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2024 Recap: BioPharma key Regulation/Guidance in USA, EU, Asia and ROW

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USA

“Electronic Submission of Expedited Safety Reports From IND-Exempt BA/BE Studies Guidance for Industry”

The “Electronic Submission of Expedited Safety Reports From IND-Exempt BA/BE Studies” guidance provides instructions for submitting expedited serious adverse event reports (SAEs) electronically from bioavailability/bioequivalence (BA/BE) studies that are exempt from Investigational New Drug (IND) requirements. It covers methods for submitting individual case safety reports (ICSRs) electronically, including the identification of ICSRs, required attachments (such as medical records or laboratory reports), and how to handle initial and follow-up reports. Additionally, the guidance addresses the use of product names for study drugs, the description of drug exposure, and the process for receiving confirmation of the FDA’s receipt of the electronic submissions. It also includes other considerations for the electronic reporting process.

“Certification of Compliance”

Form FDA 3674 is a certification required for applications or submissions related to drugs, biologics, devices, and certain amendments or resubmissions under the Federal Food, Drug, and Cosmetic Act or the Public Health Service Act. It ensures compliance with the ClinicalTrials.gov data bank requirements under 42 U.S.C. § 282(j). The form requires the sponsor, applicant, or submitter to provide contact details, product information, and specify the type of application or submission. The key section involves certifying whether the clinical trial requirements apply to the submission, based on whether clinical trial data is included or referenced. If applicable, the National Clinical Trial (NCT) numbers for relevant trials must be provided. The form also includes declarations regarding the accuracy of the submission and the responsibilities of the person signing it, which must be completed by the sponsor or an authorized representative.

Investigational New Drug Application (IND)

An Investigational New Drug (IND) application is required for clinical trials involving new or unapproved drugs. The process involves multiple phases: Phase 1 focuses on safety, Phase 2 tests effectiveness, and Phase 3 confirms safety and efficacy in larger populations. The IND submission must include detailed information such as the clinical protocol, preclinical data, chemistry, and manufacturing controls. Any changes to the study protocol or new safety information must be reported to the FDA through amendments, and adverse events must be reported promptly. Annual safety reports summarize the progress and findings of ongoing trials. The FDA or the sponsor can withdraw the IND if safety concerns or non-compliance issues arise. These regulations ensure that investigational drugs are tested safely and effectively before approval.

APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG

The New Drug Application (NDA) is submitted to the FDA for approval to market a new drug, including detailed information on clinical and preclinical data, manufacturing, and labeling. Applicants must submit patent certifications and, if applicable, a 505(b)(2) application for new uses or changes to a listed drug. Pediatric use data is also required. Amendments to unapproved NDAs or resubmissions must follow FDA procedures, while approved NDAs require supplements for changes like formulation or labeling. If ownership changes, the new holder must notify the FDA. Postmarketing, the sponsor must report adverse drug experiences and other safety data to ensure ongoing drug safety.

General Labeling Provisions

“General labeling provisions for drugs require labels to include the manufacturer’s name and address, the National Drug Code (NDC), adequate directions for use, and a statement of ingredients. Labels must avoid misleading statements, present required information prominently, and include Spanish-language versions for certain statements. The expiration date, control numbers, and bar codes for tracking are mandatory. Labels also have specific rules for using terms like “”infant”” and must meet detailed content and format requirements for prescription drugs and biological products under 21 CFR 201.56(b)(1). These provisions ensure clarity, safety, and regulatory compliance for drug products.”

PART 201 — LABELING

“Sec. 201.25 requires manufacturers, repackers, and distributors of certain drugs to include a bar code with the National Drug Code (NDC) number on the label. This applies to prescription drugs (excluding samples, medical gases, etc.), biological products, and OTC drugs commonly used in hospitals. The bar code must meet EAN/UCC or HIBCC standards, be scannable, and placed on the drug label. Exemptions can be requested if compliance would affect the drug’s safety, effectiveness, or if alternative methods ensure patient safety, with requests submitted to the FDA.”

Labeling Requirements for Prescription Drugs and/or Insulin

Prescription drug labeling must include essential scientific information for safe use, be accurate and updated as new data becomes available, and be based on human data when possible. Labels must avoid misleading claims and clearly identify animal data. These requirements apply to drugs with an NDA, BLA, or efficacy supplement approved or pending from June 30, 2001, onward, with specific deadlines for submission of updated labeling, depending on approval dates. The regulations ensure that labeling is clear, accurate, and aligned with the latest safety and effectiveness information.

Labeling Requirements for Prescription Drugs and/or Insulin

Sec. 201.57 sets specific labeling requirements for prescription drugs and biological products under § 201.56(b)(1), to be implemented according to the schedule in § 201.56(c). The exception is the requirement to include or accompany FDA-approved patient labeling, which must be done by June 30, 2007. These rules ensure proper labeling for safety and effectiveness.

How can a waiver of the electronic submission requirement be obtained

“Information must be submitted to the FDA electronically, unless a waiver is granted. Waiver requests, submitted in writing with reasons for non-feasibility and contact details, can be approved if electronic submission is unreasonable. If granted, the waiver may have specific terms, and the FDA will provide alternative submission instructions.”

“Sec. 201.58 Waiver of labeling requirements.”

An applicant can request a waiver of labeling requirements under §§ 201.56, 201.57, and 201.80 by submitting a written request to the appropriate FDA center. The FDA will issue a written decision granting or denying the waiver.

Prescription-drug advertisements.

“Prescription drug advertisements must list ingredients in the same order as on the product label, with proprietary names appearing alongside established names. The advertisement cannot use proprietary names to suggest unique effectiveness for common substances or exaggerate the value of inactive ingredients. When a proprietary name is used, the established name must also be included, either in running text or in association with the proprietary name, and in a size that is at least half as large as the proprietary name when it appears prominently. These requirements ensure clear and non-misleading drug advertising.”

FDA Regional Implementation Guide for E2B(R3) Electronic Transmission of Individual Case Safety Reports for Drug and Biological Products

This document provides technical guidelines for submitting individual case safety reports (ICSRs) and related attachments to the FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER). It details the FDA’s process for electronic submission of ICSRs, incorporating FDA-specific terminology, and including additional regional data elements not covered by the International Conference on Harmonisation’s (ICH) E2B (R3) Implementation Guideline (IG). The document applies to FDA-regulated products such as drugs with approved NDAs and ANDAs, prescription and nonprescription drugs without approved applications, and biological products with approved biologics license applications (BLAs).

Submit an eCTD v4.0 or Standardized Data Sample to the FDA

The FDA offers a process to assist sponsors and applicants new to submitting in eCTD v4.0 by validating sample submissions and standardized study datasets. To participate, applicants must have an NDA, IND, BLA, ANDA, or MF number and plan to submit an actual application within 12 months. The process involves requesting a Sample Application Number, submitting the sample through the Test Electronic Submissions Gateway, and resolving any technical issues based on feedback from FDA. The feedback will highlight errors, but the sample submission is not an official review. This validation process ensures conformance with FDA’s electronic submission standards, but does not involve scientific content review.

Prescription drugs for human use.Volume 4

“Under Title 21, Section 201.100, prescription drugs for human use are exempt from certain labeling requirements if they meet specific conditions. The drug must be in the possession of authorized entities such as manufacturers, distributors, or licensed practitioners, and it must be dispensed in accordance with relevant regulations. The drug’s label must include the statement “”Rx only,”” dosage information, route of administration (if not oral), quantity of active ingredients, and other required information for safe usage. Additionally, the label must include a lot or control number for traceability and instructions on the proper type of container for dispensing. Labeling must also provide comprehensive details on the drug’s indications, effects, dosages, side effects, and any necessary precautions. Exemptions exist for “”reminder labeling,”” which can only mention the drug’s name without detailing its uses or dosage. However, if significant safety concerns arise, such as fatalities linked to the drug, the FDA can withdraw this exemption. Reminder labeling is prohibited for drugs with boxed warnings or those subject to specific regulatory reviews.”

Postmarketing reporting of adverse drug experiences.Volume 5

Under Title 21, Part 314.80, pharmaceutical applicants are required to report postmarketing adverse drug experiences (ADEs) to the FDA, including serious, unexpected events, as well as follow-up information within specified timeframes (e.g., 15-day “Alert Reports” for serious, unexpected ADEs). Applicants must investigate and submit detailed reports, including individual case safety reports (ICSRs), which provide comprehensive data on the patient, the adverse event, and the suspect drug. Reports must be submitted electronically, with periodic updates (quarterly for the first three years and annually thereafter) on all ADEs not previously reported. The FDA mandates the inclusion of specific data in the reports, such as the drug’s dosage, patient history, and any actions taken (e.g., labeling changes). Applicants must also maintain records for 10 years and comply with privacy regulations. Failure to report or maintain records may lead to withdrawal of drug approval. Additionally, a disclaimer clarifies that the submission of reports does not imply an admission of causality.

IND safety reporting.Volume 5

Under Title 21, Part 312.32, the FDA mandates that sponsors of Investigational New Drugs (INDs) report serious, unexpected adverse events (AEs) and suspected adverse reactions (SARs) to the agency within 15 days. These reports must include information on the event, its severity, and any potential causal relationship with the drug. Specific types of reports are required, including those for life-threatening or fatal SARs (within 7 days), as well as reports of findings from clinical, animal, or epidemiological studies suggesting significant risks. Sponsors must also investigate and provide follow-up information for any new safety concerns. Additionally, sponsors are required to report safety data from clinical trials involving marketed drugs under INDs. All reports must be submitted in an FDA-approved format and analyzed for any significant patterns, with a disclaimer clarifying that the reports do not constitute an admission of causality.

Reporting of Adverse Experiences.Volume 7

Under Title 21, Part 600.80, the FDA requires that manufacturers of biological products report adverse experiences associated with their products postmarketing. They must submit reports for all serious, unexpected adverse events to the FDA, including those that may be related to the product’s use, as soon as possible, but no later than 15 calendar days after receiving information. These reports must include detailed patient, product, and event information. Follow-up reports are also required when additional information becomes available. Manufacturers are required to maintain records of these adverse experiences for a period of 10 years and must make them available for FDA inspection. The goal is to ensure the safety of biological products after they are on the market.

Records and Reports.Volume 5

The FDA requires manufacturers, packers, and distributors of marketed prescription drugs, not subject to an approved new drug or abbreviated new drug application, to maintain records and report all serious, unexpected adverse drug experiences (ADEs) to the agency. These reports, called 15-day “Alert reports,” must be submitted electronically within 15 days of receiving information about a serious, unexpected ADE. The report should include detailed patient, drug, and reporter information, along with a description of the adverse event and relevant tests. The reports must also be followed up with additional information as it becomes available. Manufacturers, packers, and distributors are required to maintain these records for 10 years, and FDA employees must have access to them. Furthermore, patient privacy must be protected by assigning a unique code for identification instead of using personal details. Reports submitted do not constitute an admission of causality by the drug manufacturer or the FDA.

“Other postmarketing reports. Volume 5”

21CFR314.81 outlines the reporting requirements for drug applicants seeking FDA approval to market new drugs. It mandates that applicants submit various postmarketing reports, including field alert reports for product defects, annual reports summarizing new safety or efficacy information, and updates on manufacturing or labeling changes. Applicants must also report on authorized generic drugs, clinical studies, and postmarketing commitments, especially regarding pediatric studies or other FDA-required trials. Additionally, manufacturers must notify the FDA of drug shortages or discontinuations, and provide specific details about product withdrawals. Non-compliance may lead to the withdrawal of drug approval. The regulation also covers advertisements, promotional labeling, and communications related to regulatory matters. Failure to comply can result in penalties, including the removal of the drug from the market.

Applications for FDA Approval to Market a New Drug

The document provides detailed definitions and regulations under Title 21, Chapter I of the U.S. Food and Drug Administration (FDA) Code of Federal Regulations (CFR) concerning the approval process for new drugs. Key sections define terms related to drug applications, such as the 180-day exclusivity period, abbreviated new drug applications (ANDA), new drug applications (NDA), and 505(b)(2) applications. It outlines the approval process, including the requirements for bioequivalence, the roles of applicants, and the FDA’s responsibilities. The definitions cover a wide range of terms related to drug ingredients, formulations, testing, labeling, and manufacturing processes. Additionally, it includes regulations on patent certifications, clinical studies, postmarketing obligations, and resubmissions following FDA’s review of applications. The document also references the FDA’s responsibilities to ensure that drugs meet safety and efficacy standards.

Investigational New Drug Application

This part contains procedures and requirements governing the use of investigational new drugs, including procedures and requirements for the submission to, and review by, the Food and Drug Administration of investigational new drug applications (IND’s). An investigational new drug for which an IND is in effect in accordance with this part is exempt from the premarketing approval requirements that are otherwise applicable and may be shipped lawfully for the purpose of conducting clinical investigations of that drug.

“FOOD AND DRUGS CHAPTER I–FOOD AND DRUG ADMINISTRATION DEPARTMENT OF HEALTH AND HUMAN SERVICES SUBCHAPTER D – DRUGS FOR HUMAN USE”

CFR Title 21, Section 312.6 requires that the immediate package of an investigational new drug (IND) intended for human use must have a label stating, “Caution: New Drug – Limited by Federal (or United States) law to investigational use.” The labeling must not be false or misleading and cannot claim that the drug is safe or effective for its intended purpose. Additionally, the FDA may grant exceptions to the labeling requirement for certain drug products included in the Strategic National Stockpile.

“FOOD AND DRUGS CHAPTER I–FOOD AND DRUG ADMINISTRATION DEPARTMENT OF HEALTH AND HUMAN SERVICES SUBCHAPTER C – DRUGS: GENERAL”

CFR Title 21, Section 251.13 outlines labeling requirements for eligible prescription drugs imported under the Section 804 Importation Program. Manufacturers must provide written authorization for the importer to use FDA-approved labeling upon request. If not provided within 30 days, FDA may deem authorization granted. The imported drugs are exempt from certain labeling requirements if the importer or manufacturer certifies compliance with the Federal Food, Drug, and Cosmetic Act. Key labeling details include the importer’s NDC, the lot number, a statement indicating the drug was imported under the Section 804 program, and additional contact information for reporting adverse reactions. The importer is responsible for relabeling to meet these standards, with restrictions on repackaging.

“FOOD AND DRUGS CHAPTER I–FOOD AND DRUG ADMINISTRATION DEPARTMENT OF HEALTH AND HUMAN SERVICESSUBCHAPTER C – DRUGS: GENERAL”

“CFR Title 21, Section 251.17 outlines the steps for importing eligible prescription drugs under the Section 804 Importation Program:
Entry Filing: Importers must electronically file a formal entry for each shipment through a CBP system, marking the drug as imported under this program.
Authorized Ports: Shipments must enter through FDA-approved ports, and the drugs must be stored securely within 30 miles of the port until FDA decides if they can be admitted.
Testing and Relabeling: Before entry, the importer must apply for approval to relabel and test the drugs. The drugs must meet FDA standards, and a sample may need to be sent to an FDA-approved lab for testing.
Sample Testing: The first shipment and any new batches must have a sample tested. The importer or manufacturer sends the results and testing records to the FDA.
Relabeling: Once the FDA approves the testing results, the drug must be relabeled with U.S. labeling requirements.
Certification: After the drug meets FDA standards, the importer or manufacturer must submit a written certification to the FDA.”

“FOOD AND DRUGS CHAPTER I–FOOD AND DRUG ADMINISTRATION DEPARTMENT OF HEALTH AND HUMAN SERVICES SUBCHAPTER C – DRUGS: GENERAL”

“Under CFR Title 21, Section 251.12, importers of eligible prescription drugs must ensure compliance with several requirements. These include proposing an NDC for each drug, verifying Canadian labeling matches FDA-approved versions, screening for issues like tampering or counterfeiting, and ensuring U.S. relabeling with required information. Importers must also submit the necessary import documentation and report adverse events and recalls to the FDA. If the importer is relabeling the drug, they must register with the FDA, obtain a labeler code, and list the drugs. If not relabeling, they must ensure the NDC and labeler code are properly assigned and listed by the relabeling entity.”

Content and format of an NDA.Volume 5

Title 21, Chapter I, Subchapter D, Part 314 of the Code of Federal Regulations outlines the requirements for applications seeking FDA approval to market a new drug. Specifically, Subpart B (Sec. 314.50) addresses the content and format of a New Drug Application (NDA). It provides detailed guidelines on the necessary components of an NDA, which include information on the drug’s identity, manufacturing process, clinical data, labeling, and other critical details that ensure the drug’s safety, efficacy, and quality for approval by the FDA.

“Guidance for Industry Providing Regulatory Submissions in Electronic Format — Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications”

“The eCTD Technical Conformance Guide provides specifications and recommendations for submitting electronic Common Technical Document (eCTD)-based submissions to the FDA’s Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER). It supplements the eCTD Guidance, which outlines the requirements for electronic submissions of certain applications such as investigational new drug applications (INDs), new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), and master files. The guide covers technical details for creating and submitting eCTD v4.0-compliant submissions, including those for combination products where CDER or CBER is the lead center.

The purpose of the guide is to provide technical recommendations for standardized electronic submissions and to promote effective communication between sponsors and FDA’s electronic submission support staff. However, it does not replace direct communication with support staff for specific implementation issues or concerns. Sponsors and applicants are encouraged to contact FDA support teams at CDER (esub@fda.hhs.gov) or CBER (esubprep@fda.hhs.gov) before submission to address any questions.”

“FDA Adverse Event Reporting System (FAERS) Electronic Submissions – E2B(R2) Standards”

“This page provides instructions for submitting postmarketing individual case safety reports (ICSRs) for human drugs and biological products regulated by CDER using the E2B(R2) standards. Companies can continue submitting ICSRs in the E2B(R2) format for up to two years during the E2B(R3) transition period. After this period, companies must adopt the E2B(R3) standard and cannot revert to legacy methods. Submissions must be in XML format through the FDA’s Electronic Submissions Gateway (ESG), with attachments in PDF format, such as hospital discharge summaries, autopsy reports, or scientific literature. Detailed guidance on preparing and submitting electronic ICSRs and attachments is available in the document “”Specifications for Preparing and Submitting Electronic ICSRs and ICSR Attachments”” and further instructions are provided in “”Steps to Submitting E2B(R2) ICSRs Electronically in the XML Format.”

“FDA Adverse Event Reporting System (FAERS) Electronic Submissions – E2B(R3) Standards”

The FDA Adverse Event Reporting System (FAERS) Electronic Submissions, based on E2B(R3) standards, outlines the requirements for the electronic submission of adverse event reports for both premarketing and postmarketing safety data. The guidance specifies the format and content of Individual Case Safety Reports (ICSRs) for drugs and biological products, including data elements such as patient demographics, drug information, adverse reactions, and other relevant safety details. For premarketing safety reporting, sponsors are required to submit ICSRs to the FDA as part of clinical trials or IND applications, while postmarketing reports cover adverse events occurring after a product has been approved and marketed. These submissions must follow standardized protocols to ensure consistent and efficient transmission of safety data, helping the FDA monitor drug safety and take appropriate actions to protect public health.

Online Verification of Electronic Certificates of Pharmaceutical Product

Electronic Certificates of Pharmaceutical Product (eCPP) now include a unique QR code for easy verification of authenticity. Recipients, including foreign governments, can verify the eCPP for U.S.-exported human drugs through two options: Option 1 involves scanning the QR code with a mobile phone camera, which prompts a notification leading to the FDA Unified Registration and Listing System Export Certification Validator (FECV) portal for certificate verification. Option 2 allows verification through the FECV portal directly if the phone cannot scan the QR code. Detailed system requirements are provided for further assistance.

Human Drug Export Resources for Foreign Governments

The FDA supports the safe and quality export of U.S. drugs by issuing over 8,500 electronic certificates of pharmaceutical product (eCPP) annually, particularly to countries like Mexico and China. The FDA follows the World Health Organization’s (WHO) Certification Scheme to assure the quality of drugs in international trade. FDA resources include inspection classifications, compliance status databases, and tools for verifying FDA-approved drugs, such as the Orange Book. Foreign governments can verify the authenticity of eCPPs via the FDA Unified Registration and Listing System Export Certification Validator (FECV) portal or by scanning a QR code on the certificate. For inquiries, foreign governments can contact CDERExports@fda.hhs.gov.

FDA Adverse Event Reporting System (FAERS) Electronic Submissions

Starting January 16, 2024, the FDA began accepting electronic submissions of both expedited and non-expedited postmarketing individual case safety reports (ICSRs) for human drugs and biological products regulated by CDER, using the E2B(R3) standard. This change also applies to premarketing ICSR submissions for IND and IND-exempt BA/BE studies, effective April 1, 2024. Submitters can continue using the E2B(R2) standard for postmarketing ICSRs until April 1, 2026, as part of the E2B(R3) implementation period. After transitioning to E2B(R3), companies must use the new standard and cannot revert to older methods. ICSRs can be submitted via database-to-database transmission through the Electronic Submission Gateway (ESG) or via the Safety Reporting Portal (SRP) for companies without E2B capability. Additionally, the submission of Periodic Safety Reports (PSRs) involves including both a descriptive portion and non-expedited ICSRs, with the latter submitted in XML format via ESG or SRP by the PSR due date.

Electronic Common Technical Document (eCTD) v4.0

The FDA’s Centers for Drug Evaluation and Research (CDER) and Biologics Evaluation and Research (CBER) began accepting new regulatory applications in the eCTD v4.0 format on September 16, 2024. The eCTD v4.0 implementation will include future phases for handling forward compatibility with existing v3.2.2 applications and enabling two-way communication. For detailed submission guidelines, including the eCTD v4.0 Implementation Guides, Technical Conformance Guide, and validation standards, the FDA provides resources on the eCTD Submission Standards page. An optional process for submitting sample eCTD v4.0 or standardized data samples for feedback is available, focusing currently on new applications. Additional resources, including the ICH eCTD v4.0 Step 4 Implementation Package, are also provided for download.

Integrating Randomized Controlled Trials for Drug and Biological Products Into Routine Clinical Practice Guidance for Industry

“The guidance on integrating Randomized Controlled Trials (RCTs) for drug and biological products into routine clinical practice outlines key considerations for sponsors, healthcare institutions, clinical investigators, and local healthcare providers. It emphasizes the importance of collaboration among these groups in ensuring effective integration of RCTs into clinical settings. The document discusses streamlining RCTs to better align with real-world clinical practices, adopting a “”Quality by Design”” approach. This includes strategies for defining the trial population, obtaining informed consent, selecting appropriate investigational drugs, and ensuring proper randomization and blinding. It also covers considerations such as managing comorbidities, choosing study endpoints, handling adverse events, ensuring data privacy, and preparing for inspections.”

Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations Questions and Answers

This guidance recommendations regarding the requirements under 21 CFR part 11 (part 11), pursuant to which FDA considers electronic systems, electronic records, and electronic signatures to be trustworthy, reliable, and generally equivalent to paper records and handwritten signatures executed on paper

Review of Drug Master Files in Advance of Certain ANDA Submissions Under GDUFA

This guidance is intended for holders of Type II active pharmaceutical ingredient (API) drug master files (DMFs) that will be referenced in an abbreviated new drug application (ANDA), or a prior approval supplement (PAS) to an ANDA. This guidance explains how FDA incorporates a program enhancement agreed upon by the Agency and industry as part of the negotiations relating to reauthorization of the Generic Drug User Fee Amendments (GDUFA), as described in “GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal Years 2023-2027” (GDUFA III commitment letter).



EUROPE

Presubmission request Form

This document is about Request for a European Medicines Agency procedure prior to the submission of a marketing authorisation application or Article 58 Application1

CMDh Best Practice Guide on Multilingual Packaging(CMDh/413/2019/Rev. 5)

“This guidance covers the preparation of multilingual packages for MR/DC products. The principles outlined may be useful for preparing a multilingual package for purely national products where the product authorisation details e.g., SmPC, are already harmonised between MSs. It should be noted that the guidance may not be applicable in all aspects for all MSs, therefore applicants are advised to consider the additional national guidance referenced in Annex 1.”

Frequently asked questions about parallel distribution(EMA/297155/2021 Rev. 4)

“Parallel distribution (PD) involves specific procedures, including mandatory notifications via the IRIS system. It covers topics like the public register, trademark issues, biologics, packaging, and sourcing from different EU member states, with special rules for centrally authorized products.
Distributors must follow guidelines for submitting PD notices, including file formats, naming conventions, and handling multiple notifications. The guide also covers re-labeling, re-boxing, and packaging requirements, including for braille labeling and unit-dose blisters.
Once a PD notice is issued, it explains its validity, revocation conditions, and distributor responsibilities for product quality. Additionally, the guide outlines the processes for safety updates, bulk changes, and annual updates, along with administrative fees and invoicing.”

Checklist for Initial Notifications for Parallel Distribution(EMA/267299/2020 Rev. 4)

The European Medicines Agency (hereinafter ‘the Agency’) asks its applicants to use this checklist in advance of submission of an initial notification for parallel distribution. You should be able to answer “Yes” to every item listed below unless a specific point is not applicable (“n/a”) to the application in question. In order to improve the quality of submissions, it is recommended to include the checklist with your submission

“Information on the Member States requirement for the nomination of a pharmacovigilance (PhV) contact person at national level – Human medicines requirements (EMA/INS/PhV/129721/2024, Rev 3)”

Based on Pharmacovigilance Inspectors Working group survey, updated when new information available. This revision applies only to human medicinal products. The requirements for veterinary medicinal products were updated by the application of REGULATION (EU) 2019/6, Article 77(3) and they are thesame for all Member States. 

The electronic Common Technical Document (eCTD) v4.0

An updated draft version of the EU eCTD v4.0 implementation package which contains EU eCTD v4.0 Implementation Guide draft version 1.2. This version is focused on Centrally Authorised Products (CAPs) and the main changes since version 1.1 are reflected in the “Document change history” of the file, EU eCTD v4.0 Controlled Vocabularies, in .xlsx format (version 1); the genericode files (.xml format) will be published in the following weeks and EU eCTD v4.0 Accepted file formats. 

Questions and answers to Stakeholders on theimplications of Regulation (EU) 2023/1182 for centrally authorised medicinal products for human use

The UK left the EU on 31 January 2020, with a transition period until 31 December 2020. After this, the Protocol on Ireland/Northern Ireland (Windsor Framework) came into effect, meaning EU pharmaceutical law still applies in Northern Ireland. Regulation (EU) 2023/1182 was introduced to address challenges related to medicinal products for human use in Northern Ireland, particularly centrally authorised medicinal products (CAPs). This document provides guidance on the impact of the regulation, advising stakeholders to consult EU and UK authorities for specific guidance on market access and regulatory requirements in Northern Ireland.

Clinical Trials Regulation (EU) No 536/2014 in practice(March 2024, version 05)

“This quick guide outlines the key rules and procedures of the Clinical Trials Regulation (EU) No 536/2014 (CTR) for sponsors conducting clinical trials (both national and multinational) in the EU/EEA or managing ongoing trials in the region. Relevant documents for clinical trials authorized under the CTR are published on the Eudralex Volume 10 website. Sponsors should start by reading the Questions and Answers document (Q&A – CTR), particularly Chapter V, followed by additional guidelines and recommendations in Chapter 6. To determine if a study qualifies as a clinical trial, refer to the decision tree in Annex I of the Q&A – CTR.
A clinical trial can only be conducted if it ensures the protection of participants’ rights, safety, and well-being, and if it is designed to generate reliable data. The trial must comply with the CTR, the General Data Protection Regulation (GDPR), and relevant national laws. Additionally, the manufacture and distribution of Investigational Medicinal Products (IMPs) must follow Good Manufacturing Practice (GMP) and Good Distribution Practice (GDP). The trial should also be conducted in accordance with Good Clinical Practice (GCP) guidelines. In cases where the CTR and ICH GCP guidelines differ, the rules of the CTR take precedence.”

Guidance for the Transition of clinical trials from the Clinical Trials Directive to the Clinical Trials Regulation(Version 4)

Starting 31 January 2025, the Clinical Trials Regulation (EU) 536/2014 (CTR) will replace the Clinical Trials Directive (CTD), and all ongoing clinical trials must transition to the CTR framework. Trials not transitioned by this date will be non-compliant, risking corrective actions, penalties, and civil or criminal liabilities. Sponsors must submit a transition application via the Clinical Trials Information System (CTIS) before the deadline, keeping in mind that Member States may require up to three months to complete the authorization process.

“European Medicines Agency post-authorisation procedural advice for users of the centralised procedure(EMEA-H-19984/03 Rev. 109)”

This guidance document addresses post-authorisation procedures for marketing authorisation holders (MAHs). It outlines the EMA’s position on common issues and will be updated regularly with new developments and legislation, marked as “New” or “Rev.” The EMA stresses the importance of pre-submission meetings with MAHs to clarify procedural, regulatory, and legal aspects of upcoming applications. These meetings help ensure applications meet requirements for timely validation.
 MAHs are encouraged to inform the EMA and co-Rapporteur about upcoming post-authorisation submissions for the next 6-12 months to facilitate planning and identify potential issues.

European Medicines Agency pre-authorisation procedural advice for users of the centralised procedure(EMA/821278/2015)

This guidance document provides an overview of the European Medicines Agency’s (EMA) position on key issues in the centralized procedure, with a focus on pre-submission meetings. These meetings, ideally held 7 months before submission, allow applicants to get procedural, regulatory, and legal advice from the EMA. They help ensure that applications meet legal and regulatory requirements for faster validation. The document will be regularly updated to reflect new developments and legislative changes, with updates marked as “New” or “Rev”. The goal is to help applicants submit well-prepared applications and establish early contact with the EMA team.



ARGENTINA

National Pharmacovigilance System Reporting Adverse Events Form for Patients

The National Pharmacovigilance System Reporting Adverse Events Form is used to report adverse reactions to medications in Argentina. It collects patient information (name, age, sex, contact details), details of the adverse reaction (symptoms, severity, impact on daily life), and information about the suspected medication (name, dosage, batch number, where obtained). It also includes questions about treatment changes, other medications used, and any studies conducted. The form asks if the adverse event has been reported to a health professional and whether ANMAT can contact the reporter. Submitting the form is voluntary but confidential, helping improve medication safety monitoring.

ANMAT Manual reporting (version: 1.7)

“Provide information and explain the procedure for uploading reports, in XML files and manual upload,
through the e-Reporting module in the National Database of adverse reactions, to provide the largest
amount of data possible in accordance with the requirements of this Department of Pharmacovigilance
and Risk Management, and in accordance with the ICH-E2B guidelines.”

Form for requesting ANMAT tariff code error

The form to request an “ANMAT tariff code error” correction is typically used for correcting or clarifying issues related to the classification of products under the Argentine National Administration of Medicines, Food and Medical Technology (ANMAT)

Information about temporary rule of acceptance of applications for state registration of medicines by national procedure

As per the Order of the Minister of Health of Armenia (No. 4896-A, dated September 11, 2024), applications for the registration of medicines can be submitted under the national procedure until December 31, 2024. Additionally, all dossiers for medicines registered under the national procedure must be updated to meet the EAEU requirements by December 31, 2025. Further information regarding the new regulations will be provided in due course



AUSTRALIA

CTA scheme forms

The CTA Scheme is under review. All CTA forms should be submitted to clinical.trials@health.gov.au (PDF or Word format) with electronic signatures. Physical copies are not needed. The CTA application includes an application form (submitted before the trial) and supporting data (submitted as an electronic dossier). The sponsor must notify the TGA within 28 days of starting the trial or adding sites. After the trial is completed, the sponsor should notify the TGA, typically after the last patient’s visit.

Submitting a Drug Master File (DMF)

Drug Master Files (DMFs) must be submitted to the TGA in the electronic Common Technical Document (eCTD) format. There are no fees for submitting or updating DMFs. Subsequent submissions must also be in eCTD format to maintain a lifecycle. Requests for eCTD exemptions are considered on a case-by-case basis. To request an exemption, email eSubmissions@health.gov.au with justification.

Payment options

“Payment Options for Fees and Charges
Authority offer two payment options: online credit card payments (preferred) via the Commonwealth Bank of Australia, or bank transfers to the Commonwealth Bank of Australia (BSB: 062-909, Account: 10215498). Bank transfer fees are the payer’s responsibility, and the organisation’s Identification Number must be included in the payment reference. A remittance advice must be emailed within 24 hours to ‘TGARemittanceAdvices@health.gov.au’ with the relevant invoice summary. All payments must be made in Australian dollars. Overseas payments must also cover any international banking fees.”

GMP surveillance inspections and extended validity of TGA GMP certificates

“Starting 1 July 2024, the TGA will introduce surveillance inspections for GMP compliance of domestic and overseas manufacturers. These inspections will cover all aspects of the Pharmaceutical Quality System (PQS) but will be shorter in duration (about 50% less than typical inspections). Eligible manufacturers with a good compliance rating (A1 or A2) will be selected for these inspections, which may be on-site, remote, or hybrid. The goal is to reduce the backlog of inspections while maintaining oversight. TGA will also extend the validity of GMP certificates to 4 years for licensed sites without a recent inspection.”

“Request to cancel an entry/entries from the Australian Register of Therapeutic Goods (ARTG)”

The “Request to Cancel an ARTG Entry” form allows sponsors to request the cancellation of products from the Australian Register of Therapeutic Goods (ARTG). It requires sponsor details, ARTG entry information, and authorization from a nominated person. The form should be emailed to ebs@health.gov.au. Cancellation is effective once the Secretary approves it. For more information, contact TGA at 1800 010 624.

Organisation details

The form is for organisations involved in the supply, manufacture, or regulation of therapeutic goods in Australia. It collects information about the legal entity making applications under the Therapeutic Goods Act 1989 and the authority granted to others acting on its behalf. The form covers sponsors, manufacturers, and agents, with specific sections for organisation details, administrator account details, and an Australian representative if required. The form must be signed by a company director, owner, partner, or regulatory affairs agent, declaring the information is true and correct.

Request for certificates or certified copies of TGA licences and certificates

To request a certificate or certified copy of TGA licences and certificates, you can use the provided form for items such as the Certificate of GMP Compliance (for licensed Australian medicinal product manufacturers), certified copies of original GMP Licences or Quality Systems Certificates (for medical device manufacturers), or Certificates of GMP Compliance for Mutual Recognition Agreements (MRA) with agencies like the EU, EFTA, HSA Singapore, or Health Canada. For detailed fees and payment information, refer to the TGA’s fees and charges page and payment options. For assistance, contact the TGA at 1800 020 653 or email info@tga.gov.au, and for finance-related queries, reach out to 1800 241 615 or accountsrec@health.gov.au.

Request for certificate, or certified copy of TGA licences and certificates or copy of Conformity Assessment Certificates 

“To request GMP certificates or certified copies, complete the form and pay the applicable fees. The fees are as follows: $204 for a GMP Compliance Certificate, $75 for a certified copy of the GMP Compliance Certificate, $75 for a certified copy of the GMP Licence, $376 for Mutual Recognition Agreement certificates, and $204 for a Quality Systems Certificate, with $75 for a certified copy of the Quality Systems Certificate. Payments are preferred via the TGA Online Payment Portal. Once payment is made, email the completed form and proof of payment to accountsrec@health.gov.au. For further assistance, contact 1800 020 653 or GMP@health.gov.au.”

Cancellation of a therapeutic good for non-payment of an annual charge

“The TGA can cancel a product’s entry on the ARTG for non-payment of the annual charge. Non-payment within 28 days (20 days for medical devices) may lead to cancellation. Sponsors remain responsible for the outstanding charges. A notice will be published, and it’s illegal to continue supplying cancelled goods. Sponsors can request a review of the decision within 90 days. For help, contact accountsrec@health.gov.au or call 1800 020 653”

“Uniform Recall Procedure for Therapeutic Goods (URPTG)
Version 2.4″

“This document is for Australian sponsors who need to undertake actions (recall and non-recall
actions) for therapeutic goods in Australia.
It outlines the processes to respond efficiently and effectively to problems with therapeutic goods that
could pose a risk to public health and safety.
It also explains the roles and responsibilities of all stakeholders who are involved in therapeutic good
recalls.”

Important annual charge deadlines

As the new financial year approaches, TGA sponsors and manufacturers should ensure they cancel ARTG entries or revoke manufacturing licenses by 30 June or 14 June, respectively, to avoid new annual charges. Key dates include submitting the ‘Declaration of $0 Turnover’ for the ACE scheme from 1-22 July, with payment for ARTG charges due by 15 September and for manufacturing license charges by 1 October. Annual charges will be applied to active ARTG entries or licenses from 1 July. Payments can be made through the TGA Business Services portal or by bank transfer, following the required steps. For more details, visit the TGA website or contact their support.

“Clinical Trial Safety Reporting Form(SSI/USM)”

The Clinical Trial Safety Reporting Form (SSI/USM) is for reporting Significant Safety Issues (SSI) or Urgent Safety Measures (USM) related to medicines, biologicals, and medical devices. The sponsor must submit this form to the TGA within the required timeframes: 72 hours for USMs and 15 days for SSIs. The form requires details about the investigational product, impacted clinical trials, a description of the safety issue, actions taken, and communications with the Principal Investigator(s) and HREC(s). Attachments such as safety memorandums or investigator letters may be included. Submit the completed form to clinical.trials@health.gov.au.

Suspending, revoking and TGA initiated variation of conditions of a manufacturing licence

This guidance is intended to help Australian manufacturers understand how TGA manufacturing licences can be suspended or revoked. It does not apply to: Overseas manufacturers and Medical device manufacturers. For guidance on revoking manufacturing licences due to non-payment of the annual charge, please refer to the relevant section on website. If applicant wish to request a variation to the details of applicant licence, please see authority guidance on varying a manufacturing licence. When authority  revoke or suspend a licence, they will notify applicant of auhtority decision in writing and publish our decision in the Gazette or on official website (in accordance with subsection 41(6) of the Therapeutic Goods Act 1989). Authority decision is considered an ‘initial decision,’ and you may request a reconsideration under subsection 60(1) of the Therapeutic Goods Act 1989.



AUSTRIA

Application for exemption from the obligation to report serious adverse reactions pursuant to Section 41e AMG to the Federal Office for Safety in Health Care (BASG)

This form of notification is equivalent to the legal obligations under Section 41 AMG to inform the BASG.It             is hereby confirmed that all SUSAR ( Suspected Unexpected Serious Adverse Reaction ) reports pursuant to Section 41 of the Medicines Act, Federal Law Gazette No. 185/1983, in the version prior to the entry into force of the amendment Federal Law Gazette I No. 8/2022, directly to EudraVigilance Database of the European Medicines Agency (EMA) in ICH E2B (R 3) format within the legally specified time frame (7/15 days).

Quality defect reporting card(F_INS_VIE_EVEQ_I54_13)

For the reporting of a quality defect in a medicinal product by doctors , dentists, veterinarians, dental practitioners and midwives in accordance with Section 75q of the German Medicines Act as amended or Section 42 of the German Veterinary Medicines Act as amended.

Quality defect reporting card(F_INS_VIE_EVEQ_I56_16)

On the reporting of a quality defect in a medicinal product by the marketing authorisation holder pursuant to Section 75q of the German Medicines Act (Medicines Act) as amended or Section 42 of the German Veterinary Medicines Act (Veterinary Medicines Act) as amended.

Guide to filling out the eAF MAA-Human Form for new human applications

This guide is intended to make it easier for applicants of authorisation/registration applications to complete the electronic application form (eAF MAA-Human Form) . The eAF MAA-Human Form is used for authorisations of human medicinal products (including homeopathic medicinal products) and for the registration of traditional herbal, homeopathic and pharmacy-specific human medicinal products.

Guide to filling the eAF Variation Form for human medicinal products

This guide is intended to facilitate the completion of the electronic application form (eAF Variation Form) for applicants of variations under Regulation (EC) No 1234/2008 . The eAF Variation Form is used for variations of authorised human medicinal products (including homeopathic medicinal products).

Guide to filling the eAF Renewal Form for human medicinal products

This guide is intended to help applicants for extensions pursuant to Section 20 AMG to complete the electronic application form (eAF Renewal Form) The eAF Renewal form is used for renewals of authorised and registered human medicinal products.

Guidance for the Transition of clinical trials from the Clinical Trials Directive to the Clinical Trials Regulation(Version 4)

Starting 31 January 2025, the Clinical Trials Regulation (EU) 536/2014 (CTR) will replace the Clinical Trials Directive (CTD), and all ongoing clinical trials must transition to the CTR framework. Trials not transitioned by this date will be non-compliant, risking corrective actions, penalties, and civil or criminal liabilities. Sponsors must submit a transition application via the Clinical Trials Information System (CTIS) before the deadline, keeping in mind that Member States may require up to three months to complete the authorization process.

Guide to the Electronic Filing Ordinance EEVO approval and lifecycle management

The amended Electronic Submission Regulation 2011 (EEVO 2011), effective from January 1, 2016, requires electronic submission for the approval, registration, and lifecycle management of medicinal products. This guide is for applicants or holders of authorizations in this area. For clinical trials and medicinal product imports (AWE), refer to the L I206 Guide KP Submission.pdf and L_I37 Handbook AWE_IT.pdf on the BASG homepage.
The document outlines the submission process for applications to the BASG/AGES Medical Market Supervision Authority. It covers various submission types, including the Common European Submission Platform (CESP) and CD/DVD. Different submission formats are specified, such as eCTD, NeeS, and VNeeS. Applicants are required to submit several documents, including a cover letter, an application form for approval, extension, change, transfer, or revocation of a medicinal product, and the relevant dossier (Modules 1-5 or Parts I-IV). Additionally, there are guidelines for the transmission of product information (e.g., FI, GI, KE, Mockups) in cases of approval, renewal, or transfer. The document also includes instructions for transmitting the Active Substance Master File (ASMF) and notifications regarding pet products. This guide, valid from November 30, 2024, provides comprehensive details on the electronic submission process and associated documentation requirements.

Human adverse reaction notification

Healthcare professionals in Austria (including doctors, pharmacists, and others authorized to manufacture or distribute medicinal products) are required to report adverse drug reactions to the Austrian Agency for Health and Food Safety (BASG), in line with the Medicinal Products Act and the Pharmacovigilance Ordinance. Patients and their relatives can also voluntarily report adverse reactions to the BASG.
For marketing authorization holders, suspected serious and non-serious post-marketing reports within Austria must be submitted electronically to the EudraVigilance Post-Authorization Module (EVPM). The Medical Literature Monitoring (MLM) service, managed by the EMA since 2015, tracks adverse reactions from specific substances and medical literature, and results are available in the EudraVigilance database.

European Medicines Agency post-authorisation procedural advice for users of the centralised procedure(EMEA-H-19984/03 Rev. 109)

This guidance document addresses post-authorisation procedures for marketing authorisation holders (MAHs). It outlines the EMA’s position on common issues and will be updated regularly with new developments and legislation, marked as “New” or “Rev.” The EMA stresses the importance of pre-submission meetings with MAHs to clarify procedural, regulatory, and legal aspects of upcoming applications. These meetings help ensure applications meet requirements for timely validation.
 MAHs are encouraged to inform the EMA and co-Rapporteur about upcoming post-authorisation submissions for the next 6-12 months to facilitate planning and identify potential issues.

European Medicines Agency pre-authorisation procedural advice for users of the centralised procedure(EMA/821278/2015)

This guidance document provides an overview of the European Medicines Agency’s (EMA) position on key issues in the centralized procedure, with a focus on pre-submission meetings. These meetings, ideally held 7 months before submission, allow applicants to get procedural, regulatory, and legal advice from the EMA. They help ensure that applications meet legal and regulatory requirements for faster validation. The document will be regularly updated to reflect new developments and legislative changes, with updates marked as “New” or “Rev”. The goal is to help applicants submit well-prepared applications and establish early contact with the EMA team.



BAHRAIN

Checklist of Requirements for Clinical Trials Applications

The checklist for clinical trial applications includes documents such as a cover letter, application form, study protocol, and investigator’s brochure for Phase II-III trials, along with informed consent forms, clinical trial insurance, and CVs of investigators. Phase IV trials have fewer requirements, mainly ethics approval and clinical trial agreements. Certain documents, like GMP certificates and IMP labeling, are only required for specific trial phases.



BANGLADESH

Guidelines for GMP, Import, Export and Destruction of Investigational Medical Products (IMPs) for Clinical Trials Document No. NRA-CT-G-OO2 Version No. 01

The document provides guidelines for the management of Investigational Medicinal Products (IMPs), covering key areas such as GMP requirements, manufacturing, packaging, labeling, and coding. It details the responsibilities of involved parties, the role of the National Regulatory Authority (NRA) in importing and exporting IMPs, and procedures for returning or destroying unused IMPs. The annexures include essential documents like Product Specification Files, Batch Certificates, and checklists for labeling and required records, ensuring proper handling and compliance with regulations throughout the IMP process.



BELGIUM

Questions & Answers

The new Belgian Company Code requires amendments to marketing authorisation (MA) documents when corporate forms change (e.g., from bvba/SPRL to bv/SRL). To update, submit an editorial change as part of a Type IB or Type II variation. For OTC switches, submit a Type II clinical variation with the necessary overviews to meet prescription criteria. For parallel imports, changes must be promptly implemented to maintain consistency with updated authorisations, with packaging indicating the authorisation holder’s details. Any changes to the reference product’s MA require submitting a new variation. Additionally, nitrosamine risk assessments must be submitted via a web form per group of medicines, specifying the product type and completed with available information.

The FAMHP encourages healthcare professionals and patients to notify medication errors

Medication errors can occur during prescribing, dispensing, storing, preparing, or administering medicines and pose a significant public health risk. These errors can harm patients and must be reported to national pharmacovigilance systems, as required by EU legislation. The FAMHP assesses these reports and works with the pharmaceutical industry to implement corrective measures, such as changes in packaging or medicine names. Children are especially vulnerable to medication errors due to their developing organs and weight-based dosing. The FAMHP has received over 150 reports since 2016, mainly related to Look-Alike, Sound-Alike (LASA) medicines. Both healthcare professionals and patients are encouraged to report errors to improve safety.

List of requested documents in CTIS for Belgium

This document outlines the requirements for clinical trial applications in Belgium under the Clinical Trials Regulation (CTR). It covers key documents such as the cover letter, trial protocol, Investigator’s Brochure, IMPD dossier, informed consent forms, and insurance certificates. It emphasizes language requirements, the use of templates, and proper document naming for easier review. Additional details include compliance with GDPR, handling of human biological samples, financial agreements, and special instructions for combined CTR/MDR-IVDR studies and transitioning trials. Clear guidelines are provided to ensure smooth submission and approval processes.

EU Regulation 536/2014

The EU Regulation No. 536/2014 (CTR) launched on January 31, 2022, streamlines clinical trial processes through the Clinical Trials Information System (CTIS). This system centralizes submission, assessment, and monitoring across the EU/EEA. By January 31, 2025, all clinical trials, including those under the previous Clinical Trials Directive (CTD), must be transitioned to CTIS. Sponsors are advised to submit transition applications by October 16, 2024. Belgium has specific submission requirements, including templates for informed consent and trial financing.

Reporting medicinal product quality defect – Company

A medicinal product quality defect refers to any issue that impacts the quality of a medicinal product. This can include chemical or microbiological contamination, deviations in quality or quantity (such as underdosing or overdosing), or packaging defects (e.g., printing errors). These defects may not always cause harm but can affect entire or parts of batches. Manufacturers and marketing authorisation holders are required by law to report such defects to the FAMHP. To report a defect, email industry@fagg-afmps.be. For urgent issues, contact the FAMHP on-call service at rapidalert@fagg.be. Companies must keep their contact information up to date with the FAMHP via the online contact form.

Statement on financing of a clinical trial

“According to Annex I P of the CTR, the sponsor should provide 69. A brief description of the financing of the clinical trial. 70. Information on financial transactions and compensation paid to subjects and investigator/site for participating in the clinical trial shall be submitted. 71. Description of any other agreement between the sponsor and the site shall be submitted.”

Marketing authorisation holders: mandatory update of contact details in product information for reporting adverse reactions to the FAMHP

The FAMHP has updated its contact details for reporting adverse reactions. Marketing authorization holders must update the Summary of Product Characteristics (SPC) and Product Information Leaflet (PIL) accordingly. The new contact details are provided for the Vigilance Department on their websites and via email. The updates can be submitted through an ongoing variation or, if none exists, via an editorial change as part of a variation (e.g., IB or Type II). These changes should be clearly noted in the variation application. Alternatively, they can be submitted as a national Type IA C.I.Z variation.

Other procedures

The marketing authorisation process consists of four steps: 1) Dispatching, where the application is validated for completeness and legal requirements, including EDMF/ASMF files; 2) Assessment/Management, where experts assess the quality, safety, and efficacy of the product and provide guidance; 3) Administrative closure, which involves finalising procedures and ensuring all documents are in order; and 4) Updating the MeSea database, which includes legal texts, forms, and necessary updates for approval.

Guidance for the Transition of clinical trials from the Clinical Trials Directive to the Clinical Trials Regulation(Version 4)

Starting 31 January 2025, the Clinical Trials Regulation (EU) 536/2014 (CTR) will replace the Clinical Trials Directive (CTD), and all ongoing clinical trials must transition to the CTR framework. Trials not transitioned by this date will be non-compliant, risking corrective actions, penalties, and civil or criminal liabilities. Sponsors must submit a transition application via the Clinical Trials Information System (CTIS) before the deadline, keeping in mind that Member States may require up to three months to complete the authorization process.

Amendments

When substantial changes are made to a clinical trial protocol or related documents that could impact participant safety, affect scientific interpretation, or significantly alter the investigation, the investigator must report these changes to the relevant ethics committee via an amendment. Amendments must be approved by the ethics committee before implementation but do not require approval from the FAMHP. However, the FAMHP must be informed of these changes via email at ct.rd@fagg.be or through the Common European Submission Platform (CESP). The submission should include a cover letter, amended documents, and the ethics committee’s favorable opinion. Notification of amendments is free of charge.



BHUTAN

Defective Medicinal Product Complaint Form(Document Number DRA-F-D2-17-01, Version 03)

The Defective Medicinal Product Complaint Form  is used to report deficiencies or defects in medicinal products, typically related to a specific batch. It is important to note that Adverse Drug Reactions (ADR) should not be reported using this form. The form collects detailed information about the complainant (if applicable), product details including the batch number, manufacturer, and expiry date, as well as a description of the defect. Additionally, it asks for information regarding stock balance and storage conditions, including where the product was stored and the storage temperature at the time of reporting. The completed form should be submitted to the Drug Regulatory Authority (DRA) via email at dra@dra.gov.bt or pmcd@dra.go.bt. For internal use, the DRA will categorize the defect (Critical, Major, Minor, or Not Sure), and may initiate further actions such as convening a recall committee or sending the product for testing. The form must be signed and dated by the person submitting the complaint, and the DRA will verify and assess the complaint accordingly.

Self inspection Form(DRA-F-D2-08-02, Version 00)

The Self Inspection Form ) is used to assess compliance with regulations for premises handling medicinal products. It collects information about the premise, including its name, address, and the in-charge person’s details. The checklist covers various compliance areas, such as the availability and legibility of signboards, proper labeling and storage of medicinal products, adherence to storage conditions, and the security of controlled drugs. It also checks the labeling of compounded products, temperature maintenance for vaccines, and the validity of AEFI kits. The form concludes with a declaration of true findings and space for official actions. The form is valid until 27-09-2024 and helps ensure regulatory standards are met.



BRAZIL

LIBRARY OF MEDICINES

Libraries are documents that bring together all current standards for a given macro-topic,
divided by themes. The objective is to facilitate access and understanding of the Regulatory
Stock for internal and external audiences, as well as to improve the process of drafting and
reviewing regulations.The document outlines Brazil’s regulatory framework for the registration, post-registration, and notification of medicines, as governed by ANVISA. It covers general procedures for registering conventional and non-prescription medicines, as well as specific guidelines for biologics, herbal products, medicinal cannabis, radiopharmaceuticals, and experimental drugs. Key sections address quality control, bioanalytical method validation, bioequivalence, and requirements for new and innovative drugs. It includes simplified procedures for low-risk medicines, criteria for the Reference Drug List, and international alignment for analytical method validation. Additional topics include consumer information, advertising regulations, good manufacturing practices, pharmacovigilance, and guidelines for import/export. Special provisions are provided for vaccines, pandemic preparedness, and conditional approval. The document also emphasizes the control and monitoring of medicines post-market to ensure safety and efficacy.

MEDICINE LIBRARY

Library of  Medicne by National Health Surveillance Agency (Anvisa) | November 29, 2024
Provides information on regularization of products subject to health surveillance, consumer information, regularization of services and establishments subject to health surveillance and Good Practices, control, inspection, and monitoring of products subject to health surveillance and health control in foreign trade and in ports, airports, borders, and customs areas



CANADA

Performance Standards for the Fees in Respect of Drugs and Medical Devices Order

This document provides the performance standards to be used to determine whether a remission should be granted, under the Fees in Respect of Drugs and Medical Devices Order (Order), to a person who must pay a fee under that Order.
The Guideline on Service Standards developed by the Treasury Board of Canada Secretariat defines a service standard as follows: a service standard is a public commitment to a measurable level of performance that clients can expect under normal circumstances. Further to consultations from October 2017 to June 2018, Health Canada has established the following performance standards in relation to fees that are payable under the Order. The standards appropriately reflect the department’s ability to deliver its service(s) within a set timeframe.

Regulatory Requirements for Drug Identification Numbers (DINs)

When Health Canada authorizes a drug to be marketed in Canada, a Drug Identification Number(DIN) is assigned to the manufacturer and printed on the package labels. A DIN indicates that the evaluation of the drug determined that it met the relevant requirements of the Food and Drugs Act and its Regulations and the drug has a favourable risk/benefit profile. Manufacturers of prescription and non-prescription drugs must obtain a DIN before they are marketed in Canada. Market authorization of a drug may require the additional issuance of a Notice of Compliance (NOC). The DIN assigned to a drug is unique and serves as a tool to help in the post-market activities of products on the market, such as product identification and verification by health care professionals, recall of products, inspections, and quality monitoring. While the authorization of a drug includes the issuance of a DIN to the manufacturer, the DIN is the property of Health Canada. This guidance document provides:
1. assistance on the interpretation of the regulatory requirements associated with a DIN
2. guidance to manufacturers on their obligation to accurately report to Health Canada the
following notifications for a change of drug status within the required timelines:
• Market notification
• 12 months without sale notification
• Discontinuation of sale notification

Preparation of regulatory activities in non-eCTD format.

This document defines the filing requirements and provides guidance on the structure, content and transmission of regulatory transactions filed in the non-electronic common technical document (non-eCTD) format. … The objective of this document is to provide operational direction and guidance to sponsors and Health Canada staff on the requirements for the preparation of: regulatory activities for Human drugs and disinfectants pursuant to Part C – Division 1 and Division 5 of the Food and Drug Regulations; regulatory activities for Veterinary drugs pursuant to Part C – Division 1 and Division 8 of the Food and Drug Regulations; Master Files (MFs).

Validation rules for regulatory transactions provided to Health Canada in the electronic Common Technical Document (eCTD) format

Health Canada has updated the validation rules for regulatory transactions submitted in the electronic Common Technical Document (eCTD) format, to reflect recent and upcoming changes in our processes.The purpose of the validation rules is to help ensure Sponsors provide a valid electronic transaction to Health Canada, and reduce errors and follow-up with Sponsors. Sponsors are encouraged to use a commercially available tool to validate their regulatory transactions in eCTD format, prior to filing them to Health Canada.

Rules to Filing submissions electronically

Master File Application Form (Current Version 2.0.0) which provide personal information that applicant provide is protected and governed in accordance with the Privacy Act. This only collect personal information required to administer the Canadian drug registration process. The personal information is collected under the authority of the Food and Drugs Act and the Food and Drug Regulations.

Drug and Health Product Submissions Under Review (SUR)

The Submissions Under Review (SUR) Lists include new drug submissions containing new active substances (pharmaceuticals and biologics with an active ingredient not approved in Canada). This give full information about submissions currently under review list and added to the submissions formerly under review list and procedure for several external consultations. 



CZECH REPUBLIC

Ethics Committees for Multicentric Clinical Trials

In accordance with Section 54 of Act No. 378/2007 Coll. on Amendments to the Act on Pharmaceuticals and Other Acts, applications for opinions on multicentric clinical trials must also be submitted to the relevant Multicentric Ethics Committees. These committees are responsible for reviewing and providing ethical assessments of the trials conducted across multiple centers, ensuring compliance with legal and ethical standards in clinical research.



DENMARK

National Scientific Advice

The Danish Medicines Agency offers advice on clinical trial and marketing authorisation applications for human and veterinary medicines, focusing on procedural, pharmaceutical, pre-clinical, and clinical matters. National Scientific Advice meetings aim to facilitate open dialogue, especially for start-ups and small companies in early phase development. Advice can be given in person, via phone, or in writing. Requests must include an application form, a description of the questions, and background details. The advice is not legally binding. Fees range from DKK 18,540 to DKK 36,485, depending on the complexity, and must be paid within 30 days after the meeting.

Exemption from the requirements for labelling, implementation deadlines, package leaflets etc. for medicinal products

An exemption from the Danish Medicines Agency allows pharmaceutical companies to temporarily market medicinal products in Denmark that do not meet statutory labelling, package leaflet, or packaging requirements. Exemptions are granted in special cases, such as supply shortages or packaging errors, and are subject to specific terms. The application must include justification for the exemption, details on the affected packages, and the impact on patient safety. If granted, the exemption is typically for a limited period and may require additional labelling or repackaging. The agency reviews applications within 10 business days, and companies must report any supply shortages if applicable.

DKMAnet – Prices & Packages – questions and answers

If you have issues notifying changes in price or product range via DKMAnet – Prices & Packages, contact DKMAnet Support at +45 4488 9694 (9:00-15:00). After 15:00 on Mondays, email your notification, explaining the issue and attaching a screenshot. The Danish Medicines Agency will assess the email submission on Tuesday mornings.In Prices & Packages, you can view details about marketed medicines, deregister or deactivate products, and update package leaflets. The MAH is responsible for uploading leaflets and changing the marketing status. If ceasing long-term marketing, update the status to ‘Not marketed.’ Notifications via Prices & Packages are binding on the company.

Upload package leaflets to DKMAnet

Pharmaceutical companies must upload current package leaflets for medicinal products sold in Denmark to the Danish Medicines Agency’s extranet, DKMAnet. These leaflets are then made available to the public on indlaegsseddel.dk. To access DKMAnet, users need a digital certificate, such as MitID Erhverv for Danish companies or a Closed User Group (CUG) certificate for non-Danish companies. The company must appoint a security administrator to create user accounts and manage access rights. The system provides an automatic overview of all authorised medicines, which updates with changes like name changes or deregistration.

Deregistration of medicinal products

The Danish Medicines Agency requires deregistration of medicinal products to be submitted at least two weeks in advance via DKMAnet. For deregistrations to take effect by the end of the year, the notification must be received by 9 December 2024 at 20:00, with the deregistration effective from 23 December 2024. Notifications can be submitted between 25 November and 9 December 2024. For other deregistrations, submissions can also be made by writing to the agency, with the same deadline of 9 December. Additionally, if deregistration could lead to a supply shortage, the marketing authorisation holder must notify the agency separately.

Requirements and deadlines for applications for company authorisations

The key sections of the document, covering general information, the process for submitting applications to the Danish Medicines Agency, and various application types, such as for new, changed, renewed, or terminated company authorisations. It also includes details on assessment times, when changes are necessary, administrative procedures (including “clock stop”), electronic issuance, validity, and fees. Additionally, it highlights specific conditions for authorisation fees and a fee for locations with more than 500 employees, along with a change log for tracking modifications.

Report side effects of medicines for human use

The Danish Medicines Agency (DMA) has introduced a new tool for reporting suspected side effects, in line with the EU’s E2B(R3) standard. Healthcare professionals, patients, and carers can submit reports via an e-form, providing details about the medicine, suspected reaction, and patient information. The DMA uses these reports to monitor safety signals and may request additional information. Healthcare professionals must report serious or unexpected side effects, especially in the first two years of a new medicine’s market release. The DMA collaborates with the European Medicines Agency (EMA) and other EU authorities to assess and update safety information.

Variation Application  for human use

This document is about Variation Application for human use with checklist

Marketing Authorization Application for human use

This document is about Marketing Authorization Application for human use with checklist

Requirements for “Blue box” and Package Leaflets – HUMAN medicinal products

The Danish requirements for the labelling and package leaflets of human and veterinary medicinal products include several key elements. For human medicinal products, the Nordic number must be on the outer labelling (except for certain products), and a red warning triangle is required for products that may impair the ability to drive or operate machines. Specific warnings, such as dosage instructions and side effects, must also be included in the package leaflet. For veterinary products, similar labelling requirements apply, including the Nordic number and specific instructions about the veterinarian’s prescription. The Danish Medicines Agency also requires a report of side effects in specific sections of the package leaflets.

Mailboxes within licensing of medicines

For inquiries about medicine licensing, contact the appropriate mailbox: general inquiries to the main mailbox, parallel import issues to the parallel import mailbox, new marketing authorizations and slot time requests to the validation mailbox, supplementary materials to the response mailbox, and technical or format queries to the eSubmission mailbox. For DKMAnet-related issues, use the DKMAnet mailbox, and for status updates on applications, use the status mailbox. Always include the case reference in the subject for existing cases and avoid submitting to multiple recipients or resubmitting documents.

Request for MRP/RUP

The MAH should use this template for their request to prepare an updated Assessment Report in accordance with article 28.2 in Directive 2001/83/EC. The filled in template should be sent to the RMS in Word format. The RMS will then use the document in the preparation of their updated Assessment Report



ECUADOR

ARCSA Service Rates and Operating Permits for 2024

The guidelines outline various regulations and requirements for establishments involved in the manufacturing, distribution, and storage of products related to healthcare, cosmetics, food, and hygiene. This includes pharmaceutical establishments, manufacturers of medical devices, biochemical reagents for diagnostics, primary packaging for human products, and establishments dealing with cosmetic and hygiene products. It also covers food establishments, potable water suppliers, pest control companies, and places for tattoos or body piercings. The regulations specify the need for health notifications, sanitary registration, and certificates of good practices. They are governed by resolutions and ministerial agreements, detailing fees for health registration, sanitary practices, and controlled substances. Additionally, there are specific rules for the preparation of food supplements and special dietary foods, as well as laboratories for various products.



EGYPT

Publication of the special mechanism for converting the type of trading of registered and under-registered human pharmaceutical preparations

In light of the measures taken by the Central Administration of Pharmaceutical Preparations and the General Administration for the Registration of Human Preparations in order to
continue updating the decisions regulating the registration of human preparations to support pharmaceutical companies and expedite registration procedures, authority inform you:
Noting that the Technical Committee for Drug Control, in its session on 8/1/2024, approved the mechanism for transferring the type of trading for pharmaceutical preparations, after
presenting it to the Technical Committee, and in the event of its approval, the following procedures will be followed

Regulatory Guideline on Organizing the Rules and Procedures of Registration of Human Pharmaceutical Products in Accordance with the Different Cases Based on Egyptian Drug Authority Chairman Decree No. (450) of 2023

This guideline outlines the procedures for registering human pharmaceutical products with the Egyptian Drug Authority (EDA) as per Law No. 151 of 2019. It applies to locally manufactured products for domestic use, export, or those imported and packaged in licensed factories within Egypt. The guideline specifies that relevant authorities will set grace periods for processing applications and will provide detailed instructions, including required documents and submission links. The EDA’s regulatory divisions are responsible for making necessary attachments and information available for completing registration applications.

Guideline for Good Regulatory Oversight of Clinical Trials by Egyptian Drug Authority

This guideline explains how Egypt’s national GCP regulations are applied to clinical research involving human participants, including studies on new pharmaceutical, biological, medical products, and herbal medicines not yet used in humans. It covers all interventional research, as well as non-interventional trials, where IRB approval is final, and only notification to the Egyptian Drug Authority (EDA) is needed. The guideline is aimed at ensuring the proper conduct of clinical trials within the country, particularly for products not previously accredited internationally.



ESTONIA

Patient Information Sheet and Informed Consent Form

Patient Information and Informed Consent Form – Authority invite you to participate in a clinical trial aimed at [briefly describe trial purpose]. The trial will take place at three research centers in Estonia and ten other European countries, involving [XX] participants, with [XX] from Estonia. Your participation will last approximately 1 year and 2 months, and all investigational products, procedures, and visits will be free of charge. You will be randomly assigned to receive either the investigational or reference product, with a 50% chance for each. Your participation is voluntary, and you can withdraw at any time without affecting your usual treatment. All personal data will remain confidential, and you will be covered by insurance for any risks related to the trial. You may ask questions at any time, and further details will be provided. Please read and sign this form to confirm your participation

Marketing Authorization Application for human use

This document is about Marketing Authorization Application for human use with checklist

Variation Application  for human use

This document is about Variation Application for human use with checklist



FINLAND

Decree of the Ministry of Social Affairs and Health of paid services for clinical drug trials(194/2024)

This Regulation applies to fees for applications related to clinical trials conducted under Regulation (EU) 2014/536 (the Clinical Trials Regulation, CTR). It does not apply to clinical trials under Directive 2001/20/EC (the Clinical Trials Directive, CTD), as specified in Article 98 of the CTR. However, after the expiration of the transition period in Article 98, or if a trial originally conducted under the CTD is transferred to the EU portal under Article 80 of the CTR, this Regulation will apply.

CTCG Best Practice Guide for sponsors of multinational clinical trials with different Part I document versions approved in different Member States under the Directive 2001/20/EC that will transition to the Regulation (EU) No. 536/2014

The CTCG Best Practice Guide outlines the process for sponsors of multinational clinical trials transitioning from Directive 2001/20/EC (CTD) to Regulation (EU) No. 536/2014 (CTR). Key updates in version 4 (March 2024) include guidance for sponsors proposing trial categories, archiving rules, and the handling of different versions of Part I documents (e.g., protocols, Investigator’s Brochures) approved in different Member States. Sponsors must submit a harmonised or consolidated protocol and other documents in the CTIS portal, ensuring that any differences between Member States are clearly outlined. A key point is that trials cannot be classified as low-intervention clinical trials during the transition. The guide also provides specific instructions for cases involving non-investigational medicinal products (AxMPs), and sponsors should confirm that all documents are consistent with the CTD-approved versions across Member States.

New features in the CTIS portal

The CTIS portal has introduced a new mandatory field, “Individual Participant Data (IPD) Sharing Statement,” in accordance with WHO requirements. This field must indicate whether the data collected in the study will be available to other researchers in the future, with options for Yes, No, or Undefined. An optional “Plan description” field allows up to 1000 characters for more detailed information about the data sharing plan.Additionally, sponsors can now submit a non-significant change (NSM) application to update sponsor details like name, contact information, or address. Before submitting changes in the CTIS portal, users must update their Organisation Management System (OMS) data. Once the OMS change is approved, it can be reflected in the CTIS portal.

Prices of clinical trials to be lowered in special cases

Fimea and Tukija have outlined fee adjustments for clinical trials based on Section 4 of the Decree on fees (194/2024), effective from May 1, 2024. Fees can be waived if an application expires due to technical issues with the CTIS portal, and a new application is submitted within a month. Reduced fees apply in cases where Finland’s role is limited, such as when significant changes in Part I do not involve Finland or only require evaluation by Fimea. For example, fees are reduced to EUR 300 (from EUR 1,400) if Finland is a member state concerned, or EUR 500 (from EUR 2,200) if Finland is a reporting member state.

The guide to the Clinical Trials Information System (CTIS) based on the guide made by Danish GCP-unit

The document outlines key processes in the Clinical Trials Information System (CTIS), including creating and managing an EMA account, assigning user roles, and submitting Clinical Trial Applications (CTA). It covers the steps for submitting, modifying, and withdrawing applications, responding to requests for further information (RFI), and obtaining trial authorisation. The guide also includes instructions for submitting substantial modifications, annual safety reports, and summarising results for both scientific and layperson audiences. Additionally, it highlights the need for notifications post-authorisation and the importance of maintaining an updated changes log.



FRANCE

Guidance for the Transition of clinical trials from the Clinical Trials Directive to the Clinical Trials Regulation(Version 4)

Starting 31 January 2025, the Clinical Trials Regulation (EU) 536/2014 (CTR) will replace the Clinical Trials Directive (CTD), and all ongoing clinical trials must transition to the CTR framework. Trials not transitioned by this date will be non-compliant, risking corrective actions, penalties, and civil or criminal liabilities. Sponsors must submit a transition application via the Clinical Trials Information System (CTIS) before the deadline, keeping in mind that Member States may require up to three months to complete the authorization process.

Clinical drug trials: all transition requests must be submitted on the CTIS portal

Sponsors of clinical trials are encouraged to submit transition requests for their trials from Directive 2001/20/EC to Regulation No. 536/2014 (Clinical Trials Regulation, CTR) via the CTIS portal. By 30 January 2025, all ongoing trials must be transitioned, as all authorizations under the Directive will expire after this date. A transition procedure is available to move trials from the Directive to the CTR, which can take between one week (accelerated) and 76 days (standard). Sponsors must ensure compliance, as trials not authorized under the REC by 31 January 2025 may be suspended. To avoid delays, sponsors should submit their transition applications as soon as possible, especially before 16 October 2024 for accelerated assessments. Resources such as guidance documents and online training modules for sponsors and authorities are available to assist with the transition process.

Medicines – Request authorization for a trial clinical

European Regulation No. 536/2014 of 16 April 2014 relating to clinical trials (CER) came into force on 31 January 2022. It repealed Directive 2001/20/EC. Article 98 of this Regulation provides for a transitional period of three years, from 31 January 2022 to 31 January 2025 during which clinical trial authorisations (CEs) issued in accordance with Directive 2001/20/EC remain in force. At the end of this transitional period, only Regulation (EU) No 536/2014 and its delegated acts will apply. Consequently, EC authorisations issued under Directive 2001/20/EC will no longer have any basis legal as of January 31, 2025.



HONG KONG

Guidance for Pharmaceutical Industry – Adverse Drug Reaction Reporting  Requirements .
Version 1.1

The document provides detailed guidelines on Adverse Drug Reactions (ADRs) and their reporting process. It covers the purpose, scope, and types of ADRs, including serious and unexpected reactions. The report format and essential information to include in ADR reports are discussed, along with follow-up reporting procedures. It also explains the local reporting of ADRs and addresses the use of pharmaceutical products in clinical trials. Specific considerations are given to Advanced Therapy Products, including potential ADRs and traceability concerns. The document concludes with contact information and appendices summarizing ADR reporting requirements and the document’s purposes.

Guidance for Healthcare Professionals – Adverse Drug Reaction  Reporting.
Version 3.1

The document outlines the process for reporting Adverse Drug Reactions (ADRs). It starts with defining ADRs, including serious and unexpected reactions. The guide explains where to obtain the report form and what information needs to be reported, with special attention to advanced therapy products. It details what should be included in the report, including follow-up reports, and the reporting process itself. The document also describes what happens to the report after submission and provides contact information for further inquiries. Appendices include various ADR report forms, definitions of therapy products, and sample labels with specific codes.

Adverse Drug Reactions (ADR) Report Form

The AdverseDrug Reactions (ADR) Report Form is designed for healthcare professionals to report harmful, unintended reactions to drugs or vaccines. Key points from the form and instructions include ADR  Definition, Patient Details, ADR Information, Drug Therapy Information, Treatment & Outcome, Reporter Details and Personal  Data Usage. The form is submitted to the Department of Health for ADR tracking and surveillance. A follow-up report can be submitted with the previous case reference number.

Guidance for Application for Import and Export Licences for Pharmaceutical Products and Medicines

The Import and Export Ordinance (I & E Ordinance) in Hong Kong mandates that all pharmaceutical products and medicines require import and export licences issued by the Trade and Industry Department. Applications for these licences must be submitted via the online PLAMMS system, and the applicant must hold relevant trade licenses. Additional requirements apply for clinical trial-related imports and controlled chemicals, which are governed by the Control of Chemicals Ordinance. Importers and exporters must comply with strict licensing conditions, such as presenting the original licences to carriers within specified timeframes. Violations can lead to significant fines and imprisonment. The application process is free of charge, and further inquiries can be directed to the Department of Health.



HUNGARY

Administrative service fees

The administrative service fee for the authorization of a clinical trial (hereinafter referred to as the fee) is included in Section 25/B of the Gytv and Annex 1. The fee must be paid to the NNGYK by the applicant for the conduct of the procedure or the issuance of the license for each clinical trial.

Changes in reporting of adverse events in clinical trials

From 31 January 2022, SUSAR reports in Hungary must be submitted exclusively through the EVCTM of the EudraVigilance system, with parallel reporting to OGYÉI ceasing. Annual Safety Reports (ASR/DSUR) for trials under EU Regulation 536/2014 should be submitted via CTIS, and no separate submission to ETT is required. For studies under the Directive 2001/20/EC, DSURs must be submitted to both NNGYK and ETT-KFEB via traditional routes. If both EU CTR and EU CTD studies are running, parallel submission is required. Safety assessment fees are due upon ASR submission, with proof of payment required. For Urgent Safety Measures (USM), notifications for Regulation-based trials must be submitted via CTIS, while Directive-based trials follow the old process. For further details, contact Dr. Anna Hajós at clinadr@nngyk.gov.hu.



ICELAND

Rules on reduction of fees according to Tariff no. 1554/2023

The Icelandic Medicines Agency has outlined rules for fee reductions under Tariff No. 1554/2023 for medicinal products, including discounts under specific conditions. These include a fee reduction for marketing authorizations where Iceland is the Reference Member State (RMS), and no Concerned Member States (CMS) are involved, provided the product is marketed in Iceland. A 30% discount is available for products approved through the 0-day process, and only one fee will be charged for variations in such products, as long as they remain unique on the market. Generic products can apply for a 20% fee reduction for administrative renewals. Additionally, products with a turnover below ISK 1,800,000 can apply for exemption from the annual fee if specific conditions are met. These fee reductions are intended to encourage market access and competition.

Submission of Application Dossier(s) for Marketing Authorisation of Product Name(s) in the MS where the application is submitted<Full Procedure Number(s)>

This letter formally submits the Application Dossier for a medicinal product under the Mutual Recognition or Decentralised Procedure. It includes details like the product name, pharmaceutical form, strength, active substance(s), and ATC code(s), along with the Legal Basis and any differences between the Reference Medicinal Product in RMS and CMS. The letter confirms whether an Active Substance Master File (ASMF) is included and whether it participates in the EU worksharing procedure. Additional details are provided regarding the eCTD sequence number, fee payment, risk management plan, multilingual packaging, and any other relevant information. Contact details are also provided for follow-up.

Application for Certificate of a Pharmaceutical Product (CPP Type A)

The application for a Certificate of Pharmaceutical Product (CPP) Type A requires details about the applicant, the product, and its marketing authorization. Applicants must provide the product name, active ingredients, pharmaceutical form, and the marketing authorization number, along with the name and address of the authorization holder. Additional details, such as the importing country, producer information, and whether expedited processing or shipping is requested, must also be included. The processing time is 4 weeks for regular applications, or 5 working days for expedited processing, with additional fees for expedited shipping. A copy of the Summary of Product Characteristics (SmPC) and the latest approved composition version (32p1) must be submitted as well.

Access to Medicines Before Market Authorisation or Marketing

These guidelines are intended to broadly explain the available methods to provide patients with access to medicines before they are marketed or receive marketing authorization (are registered). Emphasis will be placed on early access to new medicines without marketing authorization through programmes known as Early Access Programmes or Managed Access Programmes. These include two types of pathways: Compassionate Use (CU) and Named Patient Programmes (NPP)



INDIA

Pharmacovigilance Guidance Document for Marketing Authorization Holders
of Pharmaceutical Products(Version: 2.0)

The Pharmacovigilance System Master File (PSMF) provides a description of the pharmacovigilance system used by the MAHs with respect to pharmaceutical products marketed by them. The PSMF is not a part of the Marketing Authorization
(MA)dossier and is maintained independently from the MA.
The scope of this chapter is to provide guidance for MAHs to create and maintain the PSMF at their site (located in India). This describes the dierent documents to be created, updated, controlled, archived and traceable, whenever required.

User Manual for SUGAM- An e-Governance solution Online Forms Submission NOC (Zone)- Export NOC by Central Drugs Standard Control Organization (CDSCO)

This document is a user manual for submitting online applications for the Export NOC under the NOC (Zone) category on the SUGAM platform, developed by CDAC under the Ministry of Electronics and Information Technology, Government of India. It outlines the steps for corporate users to log in, switch to the Corporate role, and access the Export NOC form. The application process involves selecting the relevant department, filling in required details such as license information, and specifying the purpose of the application (e.g., bulk drug or finished formulation). Users are guided through various sections like Buyer/Trader details, drug information, and quantity details, and are required to upload necessary documents. Once all sections are completed, the application is submitted, and a file number is generated. The document also includes screenshots to help users navigate the platform effectively.

Guidance document for export NOC

To obtain an Export NOC for unapproved, banned, or new drugs, manufacturers must submit an application with details such as the drug name, dosage, quantity, destination, and manufacturing location, along with a valid manufacturing license and a purchase order. Legal undertakings are required to ensure the drugs are solely for export, not diverted for domestic use, and meet the importing country’s quality standards. Manufacturers must also maintain records and allow inspections. If the export order is canceled, the manufacturer must destroy the unsold stock and inform the authorities.

Circular Toxicity Studies

The requirement for toxicity studies for New Drugs, Subsequent New Drugs (SNDs), Fixed Dose Combinations (FDCs) excluding biological products and Investigational New Drugs (INDs) were reviewed and the following points are reiterated from NDCT Rules, 2019.

Sugam Portal checklist for PSUR Submission of Vaccines,New Drugs ,Subsequent New Drugs,Fixed Dose Combinations for Manufacturing or Import in India

The Sugam Portal checklist for PSUR submissions outlines the required documents for various categories of drugs and medical devices in India. For vaccines, the submission should include a covering letter, executive summary, marketing status, and license information, such as CLAA approval, product labels, and a Summary of Product Characteristics (SmPC). The dossier should also include PMS or Phase IV reports and safety summaries. The PSUR report itself must contain title pages, worldwide marketing status, safety actions, estimated patient exposure, and individual case histories, including ICSRs and SAE reports. Additional sections cover studies, risk evaluations, and benefit-risk analysis.

For new and subsequent new drugs, the checklist includes similar documentation but requires extra information such as CTD Module V, Phase III clinical reports, and PMS data. Fixed-dose combinations need safety data for each active pharmaceutical ingredient (API) in the combination. New medical devices require clinical investigation reports, product labels/IFUs, and safety summaries, along with case histories and risk management plans. Additionally, pharmacovigilance documents like the system master file, SOPs, and audit reports must be provided. CDSCO will review all data to assess the ongoing safety and efficacy of the products in India.

Submission of online applications of PSURs with respect to the Marketing Authorization (MA) of NEW Drugs/SNDs/FDCs/Biologicals/Veterinary products

In continuation to circular vide F.No. PSUR-13011(14)/2/2024-eoffice dated 26.02.2024 regarding submission of Periodic Safety Update Reports (PSUR) through online SUGAM Portal to CDSCO, the SUGAM portal is updated to upload the historical data of their PSUR applications for permissions/licenses granted before the implementation of the SUGAM portal of all the Marketing Authorization Holders (New Drugs/SNDs/FDCs/Biologicals/Veterinary)
Further, the historical data with respect to the permissions granted by State Licensing Authorities (SLAs) and CDSCO for Fixed Dose Combination drugs (FDCs) with condition to submit PMS/PSUR may also be uploaded/updated in the above mentioned portal.

Submission of online applications of PSURs w.r.t Marketing Authorization (MA) of Medical Devices/ In-vitro Devices- Reg.

The Directorate General of Health Services has issued a circular informing stakeholders that, starting from April 1, 2024, the submission of Periodic Safety Update Reports (PSURs) for the marketing authorization of medical and in-vitro devices must be done through the Online System for Medical Devices portal (https://www.cdscomdonline.gov.in/). The facility for offline submissions, including hard copies, will no longer be available after this date. Applicants are required to follow the checklist provided on the portal while submitting their applications. This change aims to streamline the regulatory submission process for medical devices and in-vitro devices in India.



IRELAND

Human Medicines Adverse Reaction Report

The report includes several key sections- Reporter Information provides details about the individual reporting the adverse event, such as their name, contact information, role, and affiliation. Patient Information covers relevant data about the patient, including their age, gender, medical history, and other pertinent health conditions or treatments. Suspect Drug Information outlines details about the drug suspected of causing the adverse reaction, including the drug name, dosage, administration route, and duration of treatment. The Suspected Reaction section describes the adverse event, including symptoms, severity, onset time, and any potential side effects related to the drug. Finally, the Outcome section details the resolution of the adverse event, noting whether the patient recovered, if there were any lasting effects, or if the event led to hospitalization, disability, or death.

Guide to Labels and Leaflets of Human Medicines(AUT-G0034-2324)

The guidance in this document applies to the labels and package leaflets of medicinal products for human use, authorised nationally, through mutual-recognition (MR) or through the decentralised (DC) procedure. The guidance does not apply to medicinal products authorised through the centralised procedure.
The document covers various aspects of pharmaceutical labeling and leaflet requirements, structured as follows: Section 1 outlines the Scope of the guidelines, while Section 2 establishes the Legal Basis for these requirements. Section 3 provides an Introduction to the document, and Section 4 details the Procedure for Submitting and Approving Labels and Leaflets. Section 5 addresses the Presentation of the Product Name on the Label, followed by Section 6, which lists Specific Label Requirements. In Section 7, Specific Package Leaflet Requirements are outlined, and Section 8 discusses the inclusion of Braille and Accessible Package Leaflets. Section 9 covers the Consultation with Target Patient Groups for the Package Leaflet, and Section 10 introduces Safety Features. Finally, Section 11 provides guidance on the Provision of Additional Information on the Label and in the Package Leaflet.

IMP Immediate Notification of Variations to Annex 3 and/or 4 Application Form(AUT-F0819-4)

The “Immediate Notification of Variations to Annex 3 and/or 4 Application Form” requires applicants to provide key details such as the authorisation/licence number, contact information of the Qualified Person (QP), and the applicant’s legal details. Variations to contract manufacturers (Annex 3) and contract laboratories (Annex 4) must be listed, including changes to names, addresses, and manufacturing or testing activities. A brief background explaining the proposed changes and supporting documents must be attached. Applicants are also required to submit the appropriate application fee. In the declaration, applicants confirm that the changes won’t affect the quality, efficacy, or safety of the medicinal product. The completed form should be submitted to the HPRA’s Compliance Department via email or post. Contact details for submission are provided in the document.

IMP Expedited Assessment of Variations to Annex 3 and/or 4 Application Form(AUT-F0719-5)

The “IMP Expedited Assessment of Variations to Annex 3 and/or 4 Application Form” allows applicants to request variations related to contract manufacturers (Annex 3) or contract laboratories (Annex 4) by providing details such as authorisation/license number, Qualified Person (QP) information, and contact details. Applicants must list changes such as additions, deletions, or alterations in names, addresses, or activities of contract sites, and provide a background explanation along with supporting documents. An application fee must be submitted as per HPRA guidelines. The form also includes a declaration from the applicant confirming that the variations will not impact the product’s quality, safety, or efficacy. Additionally, Appendix 1 contains a template for the QP’s declaration of GMP compliance for investigational medicinal products manufactured outside the EU. Completed forms should be submitted to the HPRA’s Compliance Department by email or post.

Guide to Applications for a Variation to a Manufacturer’s Authorisation(AUT-G0182-1)

This document provides guidance on applying to the HPRA to vary an existing manufacturer’s authorisation. This guide should be read in conjunction with the following relevant application forms:
– Application for variation to a manufacturer’s authorisation (AUT-F0211)
– IMP expedited assessment of variations to Annex 3 and/or 4 application form (AUT F0791)
– IMP immediate notification of variations to Annex 3 and/or 4 application form (AUT F0819)
The  document include an Introduction, followed by the Annexes of the EU Format for a Manufacturer’s Authorisation. It outlines the Type of Authorisation Required and the Variations to a Manufacturer’s Authorisation. The document also covers the Applicant Details, and includes detailed annexes on Manufacturing and Importation Operations (Annex 1 and 2), Contract Manufacturer(s) (Annex 3), Contract Laboratory (Annex 4), and Qualified Person(s) (Annex 5). Additionally, it specifies the Personnel for Production Operations and Quality Control (Annex 6), and Importation of Products which are Contract Manufactured at a Site Outside the EEA (Annex 8). Annex 7 is optional and is not used by the HPRA. Contact details are provided, along with Appendix 1 for supporting documentation required for sites based in MRA partner territories, Appendix 2 on the supply of unlicensed/exempt medicinal products, Appendix 3 for declarations by the qualified person, and Appendix 4 for remote batch certification by the qualified person.

Guide to Batch-Specific Requests for Human Medicines

Guide to batch-specific requests (BSR) for human medicines. This gives indeatils information on BSR  acceptance for critical medicines which hold a marketing authorisation (MA) issued by the Health Products Regulatory Authority (HPRA) or by the European Commission



ISRAEL

Import and marketing of drugs and pharmaceutical materials Procedure number 33 Update No. 06

The document outlines the procedures for importing and marketing drugs, covering various permits and exemptions. It includes guidelines for obtaining an import license, special requests for clinical trial imports, and exemptions for customs duties. There are provisions for importing medicinal plants, plant extracts, and oils. The document also details one-time and periodic approvals, specific permits for pharmacists, and regulatory exemptions. Additionally, it includes definitions, support information, and a history of changes.

Application for Permit to Import Registered Medical Products

This service allows registration holders or pharmacists in charge who are interested in importing registered medical products to submit an online application for a permit to import registered products.

Application for Permit to Import Drugs, Raw Materials for Drug Manufacturing, and Other Goods Requiring Approval from the Pharmaceutics Division

This service allows applicants to request permits for importing drugs, raw materials for drug manufacturing, and other approved goods. Eligible applicants include permit holders, registered drug holders, pharmacists, medical institutions, and customs brokers. Applications are submitted online via the MASLUL system, with required documents attached. The service is free, and processing takes up to five business days. Applicants will be notified of approval, conditional approval, partial approval, or rejection. If additional information is needed, applicants must submit it through the MASLUL system.

Application for Drug Registration Renewal

The Drug Registration Renewal service allows you to submit and pay for your drug’s renewal online. Submit the application before your registration expires, typically by the manufacturer or authorized representative. Required materials include the current registration certificate, updated compliance documents, and post-market data. Applications are submitted online with necessary forms and document uploads, followed by payment. The renewal cost varies, and payment can be made via online methods. Once submitted, the application will be reviewed, and you will be notified if further information is needed before the registration renewal is granted.

Report adverse effects and problems associated with medications and drugs

The service allows reporting adverse effects, drug-related issues, or malpractice (e.g., faulty dispensation or misidentification of drugs). It’s available online and open to the general public, healthcare professionals, clinics, HMOs, and certified retailers. The service is free, and reports can be submitted by filling out the required fields on the Portal for Reporting Side Effects.



ITALY

Additional requirements for creating the eCTDs to be submitted on the CESP Portal

AIFA requires pharmaceutical companies submitting eCTDs via the CESP platform to include a PDF with the 6-digit AIC national code for each medicinal product in the M1 module, specifically in the Italy section. If the code is unavailable, “N/A” should be used. The file must be placed in the COUNTRY SPECIFIC part (Italy) and not in “working documents.” This requirement is mandatory from September 16, 2024, though early implementation is encouraged. For technical issues, contact: cesp.submission.ita@aifa.gov.it.

Guidelines addressed to applicants for Authorization to the Marketing Authorisation (AIC) of a medicinal product for human use through national procedure

These guidelines are for applicants seeking Marketing Authorization for medicinal products (AIC) through the national procedure. They outline the submission process, required documentation, evaluation steps, and timelines for both administrative and technical reviews. The document aims to reduce delays caused by incomplete or non-compliant dossiers, ensuring that applicants submit high-quality, fully compliant documentation. By following these guidelines, applicants can improve the quality of their dossiers, speed up the AIC process, and help the Agency optimize resource use. The Agency may amend these guidelines after a pilot phase based on its findings.
The document outlines key elements related to the submission and evaluation process for Marketing Authorization (AIC) applications. Section 1 provides the Purpose, while Section 2 covers the Submission of the Marketing Authorization Dossier in line with best practices. Section 3 describes General Policy Principles and Procedural Aspects, including administrative validation, the technical evaluation phase, notice of denial, the final phase of the AIC release, post-approval commitments, and evaluation of printed materials. Section 4 distinguishes between the Ordinary and Simplified Procedures for AIC applications. Section 5 outlines the Decree and Publication in the Official Journal, and Section 6 addresses the Publication of the Public Assessment Report and Summary of the Risk Management Plan (RMP). Lastly, Annex I identifies Main Critical Issues encountered during the regulatory validation and technical evaluation phases, with detailed sections in A11 and B.



JAPAN

Application Form (Consultation on Other Safety Measures [Drugs (excluding in vitro diagnostics]

The Consultation Application Form for the Pharmaceuticals and Medical Devices Agency is used to inquire about drug safety measures and other related matters. It requires details like the company name, brand name, generic name, drug classification number, and the consultation date and time. If consulting about a research plan using a medical information database, “Attachment” should be written. The form also asks for contact information (telephone, email, fax), and consultation content, including revisions to electronic package inserts or plans for surveys. The form allows for responses via visit, telephone, or other means, and includes sections for consultation results, wishes for future actions, and any relevant materials to support the inquiry.

Submitting documents to be attached in the application for approval of new ethical drugs.

As of September 6, 2024, the Japanese Ministry of Health, Labour and Welfare (MHLW) has issued a provisional administrative notice allowing foreign companies without a Japanese office to submit application documents for the approval of new ethical drugs entirely in English. This includes the written application for approval and the draft package insert. This trial measure aims to reduce drug-lag and facilitate the application process for foreign companies. The submission in English is initially allowed for specific drug categories, and companies must consult with the Pharmaceuticals and Medical Devices Agency (PMDA) before submitting documents. The scope of this allowance may expand in the future based on trial results.



LITHUANIA

Notice From a Healthcare or Pharmaceutical Professional About a Suspected Adverse Reaction to a Medicinal Product Other Than Vaccine Order No. Version V-43

This document provides a form for healthcare and pharmaceutical professionals in Lithuania to report suspected adverse reactions (ADRs) to medicinal products (excluding vaccines). The form collects information about the reporter (name, specialty, institution, contact details) and the patient (name, age, gender, weight, height). It includes details about the suspected medication (name, active substance, dosage, administration, and therapeutic indications) and a description of the ADR (timing, severity, treatment, and outcome). The form also asks whether the ADR was caused by medication errors, off-label use, or other factors. Additional information on other medications and relevant medical history should be provided. Reports can be submitted online or by email for further investigation by the State Medicines Control Service.

Patient Reporting of a Suspected Adverse Reaction to a Medicinal Product Other Than Vaccine  Order No. Version V-43

This form allows patients in Lithuania to report suspected adverse reactions (ADRs) to medicinal products (excluding vaccines). It collects personal details of the reporter and the affected individual, as well as information about the suspected drug (name, dosage, usage). The report includes a description of the ADR, its duration, and the patient’s current status, along with any other medications used. Patients are also asked if they have informed their doctor or pharmacist. The form can be submitted online, by email, or by phone, and all personal data is handled confidentially for pharmacovigilance purposes.

approval of the List of Specific State Fee Amounts and the Rules for Payment and Refund of State Fees

This Resolution, adopted by the Government of the Republic of Lithuania, was officially published in the Official Gazette on December 20, 2000 (No. 108-3463) and entered into force on January 1, 2001. The resolution has the registration number 1001100NUTA00001458 and the institutional number 1458. The current consolidated version is valid from November 9, 2024, to December 31, 2024. There have been no amendments or ex post evaluations, and there are no ongoing amendment projects. The document is related to Eurovoc terms and has a relationship with EU legislation.



LUXEMBOURG

Form
AMM – RENEWAL

The AMM – Renewal Form is used to request the renewal of a marketing authorization for a medicinal product. It must be submitted after the procedure is finalized, whether it’s national, MRP (Mutual Recognition Procedure), or DCP (Decentralized Procedure). The form requires details such as the drug’s name, dosage, marketing authorization holder, product procedure number, and payment information (€600). It must be completed accurately, and incomplete forms will be returned. The applicant must sign the form with “Read and approved.” The form includes an acknowledgment section confirming the update of the marketing authorization file.

Form
AMM – TYPE I VARIATION

The AMM – Type I Variation Form is used to report modifications to a medicinal product’s marketing authorization. It must be submitted after the procedure is finalized (DCP/MRP) or approved by the country of origin (national). The form requires details like the drug name, dosage, AMM number, procedure type, and variation type (Type IA, IB, or Notification). A €50 tax payment is required. The form must be signed with “Read and approved.” For Type IA, IA in, or IB variations, Luxembourg grants tacit approval without providing further acknowledgment or approval.



MALAYSIA

Appendix  I : New/ Additional Indication

Appendix I details the process for submitting applications for new or additional indications (AI) for pharmaceutical products, including new therapeutic uses, administration routes, or expanded age groups. There are two evaluation categories: AI Full (with a reliance option) for indications approved by at least one reference agency, and AI Verification (with a reliance option) for indications approved by two or more agencies. Applicants must provide various supporting documents, including approval letters and clinical studies. Submissions are made via the Quest 3+ system, and an upfront non-refundable fee applies for AI Full submissions.

Directive regarding amendments to the process of approving applications for Clinical Trial Import License (CTIL) and Authorization to Manufacture Unregistered Products for Clinical Trial Purposes (CTX) involving First-in-Human (FIH) clinical studies

The Director of Pharmacy Services’ Directive Number 5 of 2024 outlines amendments to the approval process for Clinical Trial Import Licenses (CTIL) and Authorization to Manufacture Unregistered Products for Clinical Trial Purposes (CTX), specifically for First-in-Human (FIH) clinical studies. The new procedure, effective from March 1, 2024, streamlines the approval process, allowing CTIL/CTX applications involving FIH studies to be approved at the Product Evaluation Committee (JKPP) level, followed by notification at the Drug Control Authority (PBKD) meeting. This amendment aims to speed up the approval process, which previously took 45 working days, including expert panel reviews. The directive also references earlier guidelines on CTIL/CTX applications for FIH studies, including those for COVID-19 vaccine trials and biological products, to ensure a more efficient path for clinical research in Malaysia.

Appendix 19: General Labelling Requirements.
Eighth Revision

The “General Labelling Requirements” specify that labels for immediate containers and outer cartons of products must adhere to certain guidelines. These include prohibiting the use of misleading or inappropriate visuals, graphics, or statements on the label. Such prohibited elements may include misleading health claims, false representations of the product’s effectiveness, or any visual that may mislead consumers about the product’s nature or use. The goal is to ensure that all labels provide accurate, truthful, and non-deceptive information.

Appendix 19A Prohibited Visual/ Graphics/ Statements on Label.
Eighth Revision

Appendix 19A of the Drug Registration Guidance Document (DRGD) outlines prohibited visuals, graphics, and statements on product labels. These include misleading marketing strategies (e.g., “money-back guarantee”), promotional claims for other products, consumer testimonials, unverified clinical trial results, and references to religious texts. It also bans opinions from prominent figures, logos for certifications (e.g., ISO, GMP), and labels with graphics that could confuse or mislead consumers, such as depicting internal organs or inappropriate body parts. The authority reserves the right to disallow any label content deemed misleading or improper.

Guidance Document for Preparation of Good Manufacturing Practice (Gmp) Inspections on Traditional Medicines, Health Supplements And Cosmetics Manufacturers.

FOURTH EDITION

The “Guidance Document for Preparation of Good Manufacturing Practice (GMP) Inspections on Traditional Medicines, Health Supplements, and Cosmetics Manufacturers” outlines the procedures for GMP inspections of these industries. It covers the purpose, scope, and regulatory processes, including evaluating manufacturing workflows and premises layouts, preparing quality management systems (QMS), submitting inspection application forms, and conducting inspections with follow-up actions. The document also addresses situations such as rejection, termination, or withdrawal of inspections, and provides additional information, abbreviations, and references for further clarification.

Clinical Trial Import Licence Application Form (NPRA/427/01-2)

The application form must be typed and printed on both sides of white A4 paper, except for Appendices A, B, and C, which should be printed separately on single-sided paper. Appendix D is only required for applications involving First-In-Human clinical trials. The submitted form must be the original copy, following the latest Malaysian Guideline for Application of Clinical Trial Import Licence and Clinical Trial Exemption. Applicants are also required to make payment for the Clinical Trial Import License (CTIL) at the Financial, Accounts, and Revenue Section and submit the payment receipt with the application. The form includes sections for details of the sponsor, applicant, clinical trial, trial site in Malaysia, clinical trial status in other countries, investigational product (IP), and quantity to be imported.

Clinical Trial Exemption Application Form (NPRA/427/02-2)

The application form must be typed and printed on both sides of white A4 paper, except for Appendices A, B, and C, which should be printed separately on single-sided paper. Appendix D is required only for First-In-Human (FIH) clinical trial applications. The form must be submitted in its original copy. For detailed instructions, refer to the latest Malaysian Guideline for the Application of Clinical Trial Import Licence and Clinical Trial Exemption. The form includes sections for the details of the sponsor, applicant, clinical trial, clinical trial site, trial status in other countries, investigational product (IP), and quantity to be manufactured.

Clinical Trial Import Licence / Clinical Trial Exemption Variation Application Form.(NPRA/427/03-2)

The application form must be typed and printed on both sides of white A4 paper, with only the applicable appendix for variations printed. Each variation application should be submitted separately in its original form. For variation applications involving Clinical Trial Import License (CTIL) changes, applicants must make the payment at the Financial, Accounts, and Revenue Section using the Clinical Trial Import License Processing Fee Submission Form (Form No.: NPRA/427/08), and a copy of the payment receipt must be included. For further guidance, refer to the latest Malaysian Guideline for Application of Clinical Trial Import License and Clinical Trial Exemption. The form includes sections for the applicant’s details, clinical trial details, and variation application.

Clinical Trial Import Licence Processing Fee Submission Form (NPRA/427/08)

The application form for the Clinical Trial Import License (CTIL) must be completed in capital letters in two original copies. It is required for new applications or variation applications (e.g., addition of study products, license renewal). A separate form is needed for each product. The processing fee is RM 500 per product (non-refundable) and must be paid via Money Order, Bank Draft, Debit Card, or Credit Card to the National Pharmaceutical Regulatory Agency (NPRA). Payment must be made at the Finance, Accounts, and Revenue Section counter before submitting the application to the Centre of Product and Cosmetic Evaluation (PPCE). Applications will only be processed upon submission of the payment receipt. The form includes sections for product details, applicant information, screening officer details, and a declaration confirming the accuracy of the provided information and compliance with relevant regulations.

NPRA Guidelines for Product Registration Extension and Compliance

The National Pharmaceutical Regulatory Authority (NPRA) has outlined the procedure and criteria for extending the validity period of product registrations. This includes the requirement for Bioequivalence (BE) studies to be conducted at BE research centers that are part of the NPRA Compliance Program. These centers must undergo inspections, and only those with satisfactory results will be listed in the program for three years. Additionally, ethics committees must be registered with the Drug Control Authority (PBKD) to ensure compliance with regulatory standards during the product registration extension process.

PRODUCT CLASSIFICATION APPLICATION

National pharmaceutical regulatory division (NPRA) released application for product classification which includes instructions (part I), details of product (part II), details of product owner (part III), manufacturer details (part IV), applicant’s certificate (part V) declaration of applicant and payment submission form.



NEW ZEALAND

Proposed updates to the Guideline on the Regulation of Therapeutic Products in New Zealand: Clinical Trials A summary of the major changes and rationale

The proposed updates to the Guideline on the Regulation of Therapeutic Products in New Zealand focus on clinical trials, providing important changes and clarifications. Key updates include a clearer framework for the approval of clinical trials under Section 30 of the Medicines Act, as well as enhanced requirements for the notification of clinical trial sites and adherence to Good Clinical Practice (GCP). The guideline now also emphasizes safety monitoring and reporting for investigational products, covering both medicines and medical devices. Additional sections address considerations for first-in-human (FIH) and early-phase trials, and the inclusion of specific guidance for clinical trials involving medical devices. These updates aim to improve clarity, streamline processes, and ensure robust safety and compliance in clinical trial regulation.

Guideline on the Regulation of Therapeutic Products in New Zealand: Clinical trials – regulatory approval and good clinical practice requirements.
Edition: 3.0

The guideline outlines the regulatory framework for clinical trials in New Zealand, emphasizing the approval process under the Medicines Act 1981. It details requirements such as Good Clinical Practice (GCP), which includes responsibilities for sponsors, investigators, and monitors, as well as the role of Medsafe and the Health Research Council in approving clinical trials. The document also covers ethical considerations, the application process, fee structures, and the management of investigational products, including labeling, distribution, and cold chain requirements. Additional sections focus on the preservation of records, adverse event reporting, and specific guidelines for clinical trials involving medical devices.

Guideline on the Regulation of Therapeutic Products in New Zealand: Clinical trial safety monitoring and reporting for investigational products (medicines and medical products).
Edition: 1.0

The Guideline on the Regulation of Therapeutic Products in New Zealand outlines the safety monitoring and reporting requirements for clinical trials involving investigational medicinal products (IMPs) and investigational medical devices (IMDs). Sponsors, investigators, and clinical trial monitors are responsible for ensuring the safety of participants and complying with reporting obligations. Key requirements include the prompt reporting of adverse events, especially serious or unexpected reactions, through individual case safety reports (ICSRs), as well as periodic safety updates. Any significant safety concerns or urgent safety measures must be communicated, and trial amendments impacting safety must be reported. Medsafe and the Health and Disability Ethics Committee (HDEC) oversee compliance, while the guideline provides detailed reporting timelines and responsibilities for sponsors and investigators to ensure participant safety throughout the trial process.

Schedule OF Fees Payable under the Medicines Act 1981

The Schedule of Fees Payable under the Medicines Act 1981 outlines various fees for different types of applications and notifications. These include fees for New Medicines Applications (NMA), New Medicines Application under the Abbreviated Evaluation Process, New Related Product Applications (NRPA), and Provisional Consent for New Medicine Applications. Additionally, fees are specified for Changed Medicine Notifications (CMN) for both non-biological (Form A) and biological/biotechnological medicines (Form B), as well as Change Related Product Notifications (CRPN). Clinical Trial Application fees are also included in the schedule.

Changed medicine notification Form A

The Changed Medicine Notification (CMN) Form A provides detailed instructions for notifying changes to a registered medicine in New Zealand. It outlines how applicants should describe the nature of proposed changes to the product, such as modifications to its formulation, manufacturing processes, or labeling. The form also requires the submission of relevant product and sponsor information, a summary of the changes, and declarations of compliance. Additionally, it includes guidance on calculating and paying the associated fees for processing the notification.

Changed medicine notification Form B

The Changed Medicine Notification (CMN) Form B provides instructions for notifying changes to a registered medicine in New Zealand. It guides applicants on how to detail the proposed changes, such as alterations to the product’s formulation, manufacturing, or labeling. The form also includes sections for providing product and sponsor details, a summary of the changes, and declarations of compliance with regulatory requirements. Additionally, it offers instructions on the calculation and payment of fees associated with the notification process.

Guidelines on the Regulation of Therapeutic Products in New Zealand.
Edition: 2.0

The Guideline on the Regulation of Therapeutic Products in New Zealand provides an overview of the regulatory framework for therapeutic products, aimed at assisting the industry in meeting New Zealand’s legislative and regulatory requirements. It outlines the types of therapeutic products, including medicines, medical devices, and related products, and describes the controls governing their market entry, quality, access, and information. The guideline also addresses the interfaces with other legislation and the categorization of products, offering detailed guidance on various regulatory processes and requirements for marketing therapeutic products in New Zealand.

Guidelines on the Regulation of Therapeutic Products in New Zealand

Guidelines on the Regulation of Therapeutic Products in New Zealand gives information about when is GMP documentation required, recognized documentation, classes of medicine, sites that manufacture active pharmaceutical ingredients and recognized authorities.



NIGERIA

SmPC Review Checklist

The SmPC Review Checklist is a comprehensive tool used to ensure that all necessary information for the registration of a pharmaceutical product is included in the Summary of Product Characteristics (SmPC). It covers key sections such as product identification (name, strength, form), composition (active ingredient and excipients), clinical particulars (indications, dosage, contraindications, warnings), pharmacological properties (pharmacodynamics and pharmacokinetics), and preclinical safety data. It also includes packaging details, storage conditions, and instructions for disposal. The checklist ensures that the SmPC aligns with regulatory requirements and includes all necessary data for evaluation by health authorities. Deficiencies or additional data requirements are noted for further communication with the applicant.

Patient Information Listing (PIL) Review Checklist

The Patient Information Listing (PIL) Review Checklist ensures that essential details about a medicinal product are included in the PIL, such as the product name, strength, dosage form, therapeutic indications, and how to use it. It also covers side effects, storage instructions, and disposal guidelines. The checklist ensures clarity in presenting the dosage, contraindications, potential side effects (common, uncommon, rare, and very rare), and special precautions for storage. Additionally, it requires information about the product’s ingredients, packaging, and contact details of the supplier and manufacturer. It helps identify any deficiencies and ensures regulatory compliance.



NORWAY

Norwegian guideline for packaging of human and veterinary medicinal products with marketing authorisation/registration(Version 2.4)

Labelling of medicinal products (packaging) is essential for safe and proper use of the medicinal product by the patients and healthcare professionals. The approval of the labelling information is part of the authorisation process for all medicinal products.
This guideline presents the mandatory rules and regulatory recommendations for packaging design/layout during approval of the marketing authorisation and post authorisation procedures.
The guidance in this document applies to the labelling information of medicinal products for human and veterinary use authorised in Norway through mutual recognition,decentralised and national procedure. The differences in requirements and guidance between human and veterinary medicinal products are distinctly specified in the text.

Regulations on medicinal products for human use (the Medicinal Products Regulations)

The regulations are intended to contribute to the safe and rational use of medicines through proper control of the quality, safety and efficacy of medicines, as well as their marketing and price.In case of doubt, the Directorate for Medical Products can decide whether a product should be considered a medicinal product.Unless otherwise stated in the regulations, the regulations cover medicinal products that must have a marketing authorisation in accordance with the provisions of Chapter 2. The provisions of Chapter 3 on labelling and package leaflets and Sections 7-5 and 7-6 on prescription status, etc., nevertheless apply insofar as they also apply to other medicinal products.

Ongoing clinical trials of medicines for humans must be transferred to new regulations by 30.01.2025

As of **30 January 2025**, all ongoing clinical trials of medicinal products for human use must be transferred to the new regulatory framework under **Regulation (EU) No. 536/2014** (CTR). Clinical trials that are currently active in the EU (with at least one site in operation) must be transitioned by this deadline to remain compliant. The **Norwegian Medicines Agency (DMP)** recommends that sponsors submit their **transition applications** by **16 October 2024** to allow sufficient time for processing. After **30 January 2025**, clinical trials approved under the previous **Clinical Trials Directive (EU No. 2001/20)** will no longer have a legal basis for continuation. If a trial is not transitioned by the deadline, the DMP will issue a decision to halt the trial. To avoid disruption, sponsors are strongly encouraged to submit their transition applications as early as possible.

Practical information: transition to new directorate

Starting **1 January 2024**, the **Norwegian Medicines Agency** will become the **Directorate for Medical Products (DMP)**, with the English name **Norwegian Medical Products Agency (NOMA)**. Key changes include updating the agency’s name on invoices, websites, presentations, and materials. The website will move from **www.legemiddelverket.no** to **www.dmp.no**, and email addresses will change to **@dmp.no** (though **@noma.no** will still work). For **human medicines**, updates to the **Summary of Product Characteristics (SPC)** and **Package Leaflet** regarding adverse reactions are required. Training materials should be updated by **1 January 2025**. For queries, contact **redaksjonen@dmp.no**.

Scientific Conclusions and Grounds for the Variation to the Terms Of the Marketing Authorisation

**Annex IV** provides the scientific conclusions and grounds for variations to the terms of a medicinal product’s marketing authorisation based on the **PRAC Assessment Report** for the **PSUR(s)**. If the **CHMP** agrees with **PRAC**, it confirms that the benefit-risk balance remains unchanged and recommends the proposed changes to the product information. If the **CHMP** disagrees with **PRAC**, it outlines the differences in scientific reasoning and may recommend updates to the **SmPC** and **Package Leaflet**, such as adding adverse reactions or warnings. The **CHMP** may also impose new conditions on the marketing authorisation. Additionally, the **MAH(s)** may be required to address specific issues in the next **PSUR** or submit an updated **Risk Management Plan (RMP)**.

Notification of suspected side effects when using medicine (incl. natural medicine)

This document outlines how to report suspected side effects of medicines, including natural products, to the Norwegian Medicines Agency (NOMA) and regional **RELIS** centres. Serious side effects, such as those leading to hospitalization, death, or birth defects, must be reported. The form should include patient details, suspected drug(s), and relevant medical records (e.g., autopsy reports). Reports for vaccines are sent to the **Norwegian Institute of Public Health**. Reporting does not require patient consent, but privacy regulations apply. The form can be submitted electronically via **www.melde.no** or mailed to the relevant **RELIS** centre in the patient’s health region.

Tips and advice for filling in side effect reports

The document provides tips for filling in side effect reports to ensure quality and accurate data for assessing the side effect profile of medicines. Key points include specifying the **start and end dates** of side effects, reporting suspected side effects even if unsure, and providing objective findings such as **test results** or **lab values**. It’s important to report if the medicine was purchased online, as this may help identify counterfeit drugs. For interchangeable medicines (e.g., generics or parallel imports), specify which product was switched. **Re-exposure** (when a side effect recurs after repeated use) is important for causality assessment. **Patient information** (such as birth number and underlying conditions) helps link cases, while **diagnoses**, **medications**, and **risk factors** should be clearly noted. Reports can be updated with new information later. For **biological medicines and vaccines**, the **batch number** is critical. **Electronic and paper reporting** forms are available at **www.melde.no** and **www.dmp.no/meldeskjema**.

Renewal Application for marketing authorisation – parallel imported medicinal (Version 4)

To renew the marketing authorization for a parallel imported medicinal product, an application must be submitted to the Norwegian Medical Products Agency. The application should include details such as the product’s name, pharmaceutical form and strength, Marketing Authorization Number (MT(PI)no.), the exporting country, and the product name in the exporting state, along with all valid package sizes. Additionally, the applicant must provide the name and address of the company holding the marketing authorization, the invoice address, and contact information for a responsible person within the company. The completed form must be sent to the agency at **post@dmp.no** for processing.

application-for-variation–parallel-imported-medicinal-product

The Norwegian Medicines Agency requires that a completed variation application form for a parallel imported medicinal product be submitted to **post@dmp.no**. The application must include detailed information about the medicinal product, such as its name, pharmaceutical form, strength, and marketing authorisation number in Norway, as well as the exporting state and the name of the product in the exporting country. The application should also describe any variations being made to the product, such as changes to the name of the marketing authorisation holder, manufacturer, packaging (including size, labeling, or repackaging), updated package leaflets, storage conditions, shelf life, appearance, or composition of the product. If there is a change in the marketing authorisation number or the address of the marketing authorisation holder, these must also be noted. All changes should be detailed in an attachment, and the completed form should be sent to the provided email for review by the agency.

Guidance for the Transition of clinical trials from the Clinical Trials Directive to the Clinical Trials Regulation

This document provides guidance for sponsors on transitioning ongoing clinical trials from the **Clinical Trials Directive (CTD)** to the **Clinical Trials Regulation (CTR)** (EU) 536/2014, which will fully apply starting **31 January 2025**. Any trials continuing beyond this date must transition to the CTR or risk being non-compliant, which could result in penalties or legal consequences. Sponsors are responsible for submitting transition applications through the **Clinical Trials Information System (CTIS)** before the deadline, considering that approval processes may take up to three months. The guidance outlines the necessary steps for both **mono-national** and **multi-national** trials, including updating trial documents, ensuring compliance with transparency requirements, and addressing any urgent modifications after the application submission. Ultimately, sponsors must complete the transition to maintain the legality of their trials and ensure participant safety and data integrity under the new regulatory framework.



OMAN

Controls on the import of unregistered pharmaceutical preparations

To import unregistered pharmaceutical preparations, applicants must submit a request form verifying that no registered alternative exists. The product must be marketed in its country of origin and meet specific labeling requirements. The manufacturing company must be registered, unless the product is unavailable. Required documents include proof of registration, a purchase order, therapeutic justifications, and for unregistered manufacturers, a license and analysis certificate. Import approval is granted within 10 working days and is valid for one year, but the Directorate disclaims responsibility for the product’s quality. Approval may be canceled if the product’s validity expires or if the product or company is banned or suspended.



PERU

The primary report form for medication reactions

The primary report form for medication reactions requires the user’s initials, sex, weight, and either the date of birth or age at the start of the reaction. The country where the reactions began (e.g., Peru) should also be specified, as this helps assess potential environmental factors related to the symptoms.



PHILIPPINES

Checklist of requirements for eligibility to automatic renewal registration

Under Republic Act No. 9711, automatic renewal of the Certificate of Product Registration (CPR) is granted if three conditions are met: the application must be filed before the registration expiration date, the renewal fee must be paid at the time of filing, and a sworn statement confirming no changes to the product must be attached. Additionally, the Market Authorization Holder (MAH) must ensure compliance with any post-approval commitments or special conditions from the previous CPR or Marketing Authorization (MA). Failure to comply will disqualify the application from automatic renewal, requiring it to be processed as a regular renewal.

Guidelines on the Initial Application for Certificate of Product Registration (CPR) of Generic Prescription Drugs for Human Use using the FDA eServices Portal System Website.

The guidelines for the initial application for the Certificate of Product Registration (CPR) of generic prescription drugs for human use via the FDA eServices Portal outline the application schedule, registration requirements, and the processing timeline. It includes details on the application fee, an overview of the application and review process, and the responsibilities of the applicant. Additionally, the guidelines highlight the importance of collecting feedback during the process to ensure compliance and smooth approval.

Drug Manufacturers, Traders, Distributors and the General Public : Pilot Implementation of the Electronic Certificate of Product Registration (E-cpr) Information System for the Application for Initial Registration of Generic Prescription Drugs for Human Use From 07 May 2024 to 07 August 2024

The FDA has launched the pilot implementation of the Electronic Certificate of Product Registration (e-CPR) Information System, which will streamline the application process for the initial registration of generic prescription drugs for human use. The pilot run will take place from May 7, 2024, to August 7, 2024, with submissions open on Tuesdays and Wednesdays from 7:00 AM to 6:00 PM. During this period, previous applications for initial registration that are pending pre-assessment or document submission will be canceled, and applicants must reapply via the FDA eServices Portal. Applications with acceptable pre-assessment results will continue through the manual evaluation process. The FDA also emphasizes that duplicate applications will be canceled, and payment forfeited. Other types of drug applications, such as for vaccines, biologicals, and animal health products, must still follow the traditional FDAC procedures. All marketing authorizations issued through the e-CPR system are considered official FDA actions.

Procedure on the Use of FDA eServices Portal System Website for the Initial Application for Certificate of Product Registration (CPR) of Generic Prescription Drugs for Human Use

The procedure for using the FDA eServices Portal System for the initial application for Certificate of Product Registration (CPR) of generic prescription drugs for human use includes several steps. To access the application form, applicants must log into the portal. The application form must be completed by providing details on various sections such as the declaration and undertaking, applicant and product details, formulation, packaging, diluent, device, and establishment information. Additionally, applicants must conduct a self-assessment review. Once submitted, applicants can check the status of their application directly through the eServices Portal.

General Rules and Regulations on the Registration of Pharmaceutical _Products and Active Pharmaceutical Ingredients Intended for Human Use

The General Rules and Regulations on the Registration of Pharmaceutical Products and Active Pharmaceutical Ingredients (APIs) Intended for Human Use provide the guidelines for issuing a Certificate of Product Registration (CPR), reflecting FDA authorization for various pharmaceutical products and APIs. The regulations cover Marketing Authorization, DOH-Use-Only Authorization, and Foreign Donation Authorization. The Order outlines the identification of registrable products and APIs, types of registration applications, the FDA’s regulatory review process, and decision-making on applications. It applies to all pharmaceutical products for human use and APIs intended for distribution and sale, excluding those manufactured solely for export or used exclusively by the manufacturer for its production.



POLAND

Application for extension of the validity period of a marketing authorization for a medicinal product

The application for extending the validity of a medicinal product’s marketing authorization requires detailed information about the product, its active substances, and the responsible entity. It includes data on sales status, marketing authorization numbers, and proposed renewal dates. The applicant must submit supporting documents such as the Summary of Product Characteristics, updated labeling, GMP compliance certificates, and declarations confirming no unauthorized changes. Additional documents include authorization for a proxy, proof of legal representation, and payment confirmation. The form also includes terms and abbreviations relevant to the process.

Request for MRP/RUP

The CMDh has introduced a Request Form for an MRP/RUP procedure available for the National Competent Authorities (NCA). Due to the different organisations and thereby also different working procedures for the approved medicinal products in member states, the Request form may need to be adapted at national level and is not mandatory for the NCAs to use. The Request Form is published on the CMDh website to be transparent, but marketing authorisation holders should approach the reference member state to discuss update of the AR in the MRP/RUP procedure as appropriate and use the request form available from the RMS if applicable. For further guidance the CMDh refers to the NCAs websites.

The Table of Contents outlines the procedures related to marketing authorization for medicinal products. It covers the status of authorizations, initial approval processes (MRP or DCP), repeat use procedures, variations, renewals, and PSURs (Periodic Safety Update Reports). It also includes conditions for marketing authorization, orphan drug status, product information requirements, GMP documentation, and additional relevant information. Lastly, it lists the necessary documents to be submitted for MRP or Repeat Use Procedure requests.



SINGAPORE

Appendix 2A Application Checklist (ICH – CTD NDA and GDA) .TPB-SUB-003-009 Version 10

The Guidance on Therapeutic Product Registration in Singapore: Appendix 2A Application Checklist outlines the key components for submitting an application under the ICH-CTD format for New Drug Applications (NDA) and Generic Drug Applications (GDA). It includes Module 1 for the PRISM application form and administrative documentation, Module 2 for the Common Technical Document summaries, Module 3 for quality data, Module 4 for non-clinical study reports, and Module 5 for clinical study reports. Each module provides detailed requirements to ensure a complete and compliant application for therapeutic product registration.

Appendix 3A Application Checklist (ASEAN – CTD NDA and GDA) TPB-SUB-005-009 Version 10

The Guidance on Therapeutic Product Registration in Singapore: Appendix 3A Application Checklist provides the required components for submitting a therapeutic product application under the ASEAN-CTD format for New Drug Applications (NDA) and Generic Drug Applications (GDA). It includes Part 1 for the PRISM application form and administrative documentation, Part 2 for quality data, Part 3 for non-clinical data, and Part 4 for clinical data. Each part outlines the necessary documentation and information to ensure a complete and compliant application for product registration in Singapore.

Therapeutic Products Guidance: Guidance on Therapeutic Product Registration in Singapore. TPB-GN-005-013 Version 13

The Guidance on Therapeutic Product Registration in Singapore provides a comprehensive overview of the regulatory process for the registration of therapeutic products, including both new and generic drugs. It outlines the responsibilities of applicants and registrants, patent considerations, and the protection of confidential information. The guidance covers the entire registration process, from pre-submission preparation (including product and application types) to application submission and screening. It also details evaluation routes, documentary requirements for various application types (New Drug, Generic, and Biosimilar), and the regulatory decision-making process. Post-approval procedures, including variation applications, major and minor variations, and related fees, are also explained. This document serves as a key resource for navigating Singapore’s regulatory framework for therapeutic product registration.

Guidance on Therapeutic Product Registration in Singapore :  Appendix 5 Target Processing Timelines. TPB-GN-007-003

Appendix 5: Target Processing Timelines in the Guidance on Therapeutic Product Registration in Singapore outlines the expected timeframes for various stages of application processing. It includes the screening timeline for New Drug Applications (NDA), Generic Drug Applications (GDA), and Major Variation (MAV) applications, as well as the evaluation timeline for these application types. The document also specifies the processing timeline for Minor Variation 1 (MIV-1) applications and the notification timeline for Minor Variation 2 (MIV-2) applications. Additionally, it addresses the concept of stop-clock time, which accounts for any delays in the processing timeline due to reasons outside the applicant’s control.

Guidance on Therapeutic Product Registration in Singapore  :  Appendix 7A Guidance on Electronic Labelling for Therapeutic Products. TPB-GN-021-001

Appendix 7A: Guidance on Electronic Labelling for Therapeutic Products in the Guidance on Therapeutic Product Registration in Singapore provides general guidance on the use of electronic labelling (e-labelling) for therapeutic products. It outlines the types of therapeutic products eligible for e-labelling and the acceptable formats for e-labelling. The document also details the roles and responsibilities of the registrant in ensuring compliance with e-labelling requirements and the process for notifying regulatory authorities about e-labelling implementation.

Guidance on Therapeutic Product Registration in Singapore  :  Appendix 11 Guideline on Drug Master File (DMF). TPB-GN-013-006

Appendix 11: Guideline on Drug Master File (DMF) in the Guidance on Therapeutic Product Registration in Singapore outlines the requirements for submitting and managing a Drug Master File (DMF). It specifies the documentary requirements for DMF submission, including the necessary data and information to be included. The guideline also covers the lifecycle of a DMF, detailing the process from initial submission to updates and renewals, ensuring that the DMF remains current and compliant with regulatory standards throughout its life.

Fees and turnaround time for therapeutic products

The Fees and Turnaround Time (TAT) for Therapeutic Products outlines the costs and processing times associated with various regulatory applications in Singapore. It includes fees and TAT for New Drug Applications (NDA), Generic Drug Applications (GDA), and Biosimilar Product Registration. Additionally, it covers fees and TAT for Major Variation Applications (MAV-1) and Minor Variation Applications (MIV), including MIV-1 applications. The document also addresses licensing fees for importers and wholesalers of therapeutic products, as well as the manufacturer’s license for therapeutic products. It further includes the GMP conformity assessment for overseas manufacturers.

New Clinical Trial Authorization (CTA) or Clinical Trial Notification (CTN) submission

The New Clinical Trial Authorization (CTA) or Clinical Trial Notification (CTN) Submission provides guidelines on when and how to submit a CTA or CTN for clinical trials. It outlines the regulatory roadmap for both submission types, detailing the key steps involved in the application process. The document specifies the application requirements for CTA and CTN submissions, and provides guidance on the Clinical Trial Authorization (CTA) process. It also explains how to apply for a CTA, including the necessary documentation and procedures to ensure compliance with regulatory standards.

Subsequent submissions

Subsequent submissions refer to any updates or changes required after the initial clinical trial submission. These include substantial amendments to the trial, reports on serious breaches, and notifications of urgent safety measures. It also covers adverse event reporting, product defects and recalls, and updates to the investigator’s brochure or new safety information. Other submissions include trial status reports, notifications of suspension, termination, or completion of a clinical trial, and final clinical trial reports. Additionally, submissions related to CRM non-compliances and other regulatory updates are included. The document also outlines how to make these subsequent submissions, ensuring proper and timely communication with regulatory authorities.

New Clinical Trial Certificate (CTC) submission

The New Clinical Trial Certificate (CTC) submission outlines the process for applying for approval to conduct clinical trials. It specifies when to submit a CTC, providing a clear regulatory roadmap for the submission process. The document details the application process and the requirements, including the necessary documents for submission. It also includes information on the turnaround time for processing the application. Additionally, the guidelines explain how to apply for the CTC, ensuring compliance with regulatory standards and providing clarity on the steps needed for approval.

Client Registration and Identification Service (CRIS)

The Client Registration and Identification Service (CRIS) enables clients to authorize employees or service providers to access PRISM and MEDICS on their behalf. It allows users to apply for a new CRIS account, manage the CRIS Administrator account, and handle the management of user accounts. Additionally, the service provides assistance with enquiries on CRIS, ensuring smooth access and management of regulatory systems for clients and their representatives.

PRISM (Clinical trials)

PRISM (Clinical Trials) provides a platform for users to manage various aspects of clinical trial applications. Users can apply for new submissions, withdraw applications, amend registrations or licenses, and cancel CRM notifications. These functions allow for streamlined management and updates to clinical trial processes, ensuring efficient handling of regulatory tasks and maintaining accurate records throughout the trial lifecycle.

HSA Pin

The HSA PIN is required for overseas employees or business partners who are non-SingPass holders to access PRISM and MEDICS. Through this service, users can apply for a new HSA PIN, change or reset the PIN password, and deactivate the HSA PIN when necessary. This ensures secure access to e-services for individuals involved in regulatory activities related to therapeutic products.

HSA Pin Application

The HSA PIN Application is a formal process for granting overseas individuals access to e-services in PRISM/MEDICS on behalf of a company. Applicants must provide the company’s CRIS Account Number, details of the applicant and HSA PIN holder, and a scanned copy of the HSA PIN holder’s passport. The application is submitted through Singpass (Corporate), with the Singpass and Corppass login IDs included in the form submission. For further clarification, inquiries can be directed to HSA_CRIS@hsa.gov.sg.

HSA Pin Deactivation

The HSA PIN Deactivation application is used to request the deactivation of an HSA PIN account for an individual no longer requiring access to HSA’s e-Services. The application requires the company CRIS Account Number, and the name and details of the applicant and HSA PIN holder. The form must be submitted via Singpass (Corporate), with the Singpass and Corppass login IDs included in the submission. For further clarification, inquiries can be sent to HSA_CRIS@hsa.gov.sg.

Guidance on Therapeutic Product Registration in Singapore August 2024 – Guideline on Minor Variation Applications for Chemical Therapeutic Products Health Sciences Authority – Health Products Regulation Group : Appendix 13 Guideline on Minor Variation Applications for Chemical Therapeutic Products. TPB-GN-014-005

The Guideline on Minor Variation Applications for Chemical Therapeutic Products provides an overview of the process for submitting minor variations to the Health Sciences Authority (HSA) for approval. It outlines the application process, including required documentation and criteria for what constitutes a minor variation. The guideline specifies types of changes that do not require notification to the HSA, helping to streamline regulatory procedures for pharmaceutical companies. This document is essential for ensuring compliance with HSA regulations while making changes to chemical therapeutic products.

Guidance on Therapeutic Product Registration in Singapore– Patent Declaration Forms.
TPB-SUB-002-006 Version 7

The Patent Declaration Forms in the Guidance on Therapeutic Product Registration in Singapore outline the requirements for declaring patent-related information during the registration of a therapeutic product. Form 1 is a declaration of patent-related details for product registration under the Health Products Act 2007. Form 2 serves as a notice to the proprietor of a restraining patent, while Form 3 is a declaration by the patent proprietor regarding an application for a court order or declaration related to the patent. These forms are crucial for ensuring compliance with intellectual property laws during the registration process.

Guideline on Minor Variation Application for Therapeutic Product Registration: Checklist on Dossier Requirements for MIV-1 Variation. TPB-SUB-010-006

The Checklist on Dossier Requirements for MIV-1 (Minor Variation 1) outlines the necessary documentation for various changes in the manufacturing or formulation process of therapeutic products. It covers a range of modifications including the addition or replacement of manufacturers/sites for drug substances and drug products, changes to specifications and manufacturing processes, batch size adjustments, excipient changes, primary packaging material alterations, and changes in shelf-life or storage conditions. Specific items address changes in tablet coatings, pack sizes, and the inclusion or replacement of solvents/diluents. Each variation type, such as changes to sterility testing or product labelling, requires distinct documentation, ensuring regulatory compliance in maintaining the quality and safety of the therapeutic product.

Guideline on Minor Variation Application for Therapeutic Product Registration: Checklist on Dossier Requirements for MIV-2 Variation. TPB-SUB-011-005

The Checklist on Dossier Requirements for MIV-2 (Minor Variation 2) provides a detailed list of required documentation for a wide range of minor changes in the manufacturing and formulation of drug products. These variations include changes in drug product name, product labelling, batch size, and manufacturing processes for both drug substances and drug products. It also covers minor changes such as coating weight adjustments, excipient changes, colouring/flavouring agent modifications, in-process control updates, and changes in packaging. Other updates include adjustments to storage conditions, shelf-life specifications, dimensions or shape of dosage forms, and packaging materials. Additionally, variations in supplier changes, animal-derived materials, and drug substance intermediate manufacturers also require specific documentation. The checklist ensures that all regulatory requirements are met for maintaining the product’s safety and quality.

Guidance on Therapeutic Product Registration in Singapore – Guideline on Prism Submission Health Sciences Authority – Health Products Regulation Group Appendix 17 Guideline on Prism Submission. TPB-GN-018-005

The Guideline on PRISM Submission provides detailed instructions for submitting applications through the Pharmaceutical Regulatory Information System (PRISM) for therapeutic product registration in Singapore. It covers the steps for submitting a new product application, ensuring compliance with regulatory requirements. The guideline also outlines procedures for submitting a variation product application for changes to an existing registered product. It includes instructions for responding to an Input Request (IR) from the Health Sciences Authority (HSA) and provides guidance on how to withdraw a pending application if necessary. The document ensures a clear and systematic process for managing product registrations and variations in PRISM.

Checklist on Dossier Requirements for Miv-2 (Do-and-tell) Variation
TPB-SUB-018-005

The Checklist on Dossier Requirements for MIV-2 (Do-and-Tell) Variation outlines various changes to therapeutic products that require submission under the MIV-2 variation category. These include changes related to packaging material, quality control testing sites, ownership or address changes for manufacturers, product owners, or batch release companies, and deletion of alternative manufacturers. It also covers changes in batch numbering systems, product labelling, batch size, and in-process tests for drug substances and products. Additionally, the checklist addresses changes in specifications to comply with the latest compendium, updates to the Certificate of Suitability (CEP), modifications in manufacturing processes, and excipient specifications. Other items include pack size updates, changes in the source of empty capsules, and adjustments to the ATC code. This checklist ensures all necessary documentation is provided for these variations to be processed efficiently.

Guidance on Therapeutic Product Registration in Singapore.
TPB-GN-005-013

The Guidance on Therapeutic Product Registration in Singapore (August 2024) provides comprehensive details on the registration and approval process for therapeutic products. It includes an overview of the scope of registration, applicant responsibilities, and the impact of patent protection and confidentiality. The registration process is divided into stages such as pre-submission preparation, application submission, screening, and evaluation. It covers specific types of applications, including new drug, generic drug, biosimilar product, and post-approval variations.Each chapter offers detailed information on application types, evaluation routes, and documentary requirements. It provides guidance on submission formats (e.g., PRISM application form) and the required dossiers. There are specific sections on major variations (MAV) and minor variations (MIV), outlining the necessary procedures for different types of applications like MAV-1, MAV-2, MIV-1, and MIV-2. The document also outlines fees, processing timelines, and post-approval changes, with particular attention given to the pre-submission consultation mechanisms and application types that facilitate the approval process.

Application Timeline Calculator

The Application Timeline Calculator helps estimate the key milestone timelines for therapeutic product registration and major variation applications. It provides a tool to calculate the expected processing times for different stages of the application, enabling applicants to track progress and plan accordingly. This tool is designed to assist in managing the timeline for regulatory submissions, from initial registration to approval, including major variations, based on the specific requirements of the product and application type.

Pharmaceutical Regulatory Information System (PRISM) Internet – CT Expedited Safety Report Module. Version 3.2

The Pharmaceutical Regulatory Information System (PRISM) Internet – CT Expedited Safety Report Module user manual provides detailed instructions for submitting an expedited safety report online. It covers the entire application process, including login procedures, completing the application form, and attaching necessary supporting documents. Key sections include the clinical trial application details, applicant particulars, safety report summary, and confirmation process. The manual ensures that users are proficient in navigating the system and adhering to standards and guidelines for the online submission of expedited safety reports.

Points to Consider for Singapore Labelling.TPB-GN-009-003

This document Appendix 7: Points to Consider for Singapore Labelling outlines the key requirements for the labelling of pharmaceutical products in Singapore. It covers the necessary details for the outer carton and inner/blister labels, the package insert (PI), and the patient information leaflet (PIL). These components must comply with regulatory standards to ensure proper communication of essential product information, usage instructions, and safety precautions for both healthcare professionals and patients.

Adverse events reporting in clinical trials

Adverse events reporting in clinical trials involves the submission of safety data related to Therapeutic Products (TPs), Cell and Tissue-based Gene and Therapy Products (CTGTPs), and Medical Products (MPs). The guidelines specify what to report (such as serious adverse events), when to report (timing based on event type), and the minimum criteria for reporting (severity, outcome, and causality). It also outlines the when to start and stop submitting safety reports, ensuring timely updates during the trial. The process for how to report is detailed, providing a standardized approach for investigators and sponsors to follow when submitting safety data to regulatory authorities.

Guidance on the Implementation of Good Manufacturing Practice (GMP) Evidence for Drug Substance (DS) Manufacturers

Guidance on the Implementation of Good Manufacturing Practice (GMP) Evidence for Drug Substance (DS) Manufacturers. These equirements are mandatory as of 1 October 2024 which will enable companies to better assure the quality of therapeutic products supplied in Singapore and safeguard the health and safety of  patients.



SLOVAKIA

Information for applicants / payers of administrative fees

Applicants for services like drug registration or clinical trials with ŠÚKL must pay administrative fees using the eKolok system, which allows payments through kiosks, mobile apps, or bank transfers. After submitting an application, applicants receive a payment order, valid for 30 days. If payment is not made, the proceedings are halted. Each fee corresponds to a specific eKolok, and for multiple requests, separate eKoloks are required. Applicants must ensure payment is completed to avoid delays or rejections of their submissions. Detailed procedures and fees can be found on the ŠÚKL website.

Administrative fees for clinical trials under Regulation No. 536/2014

Starting September 1, 2024, clinical trial application fees will be paid through the eKolok payment system, operated by Slovenská pošta. This system offers faster, safer payments with various methods. The State Institute for Drug Control (ŠÚKL) will issue payment orders after receiving applications, with fees determined based on the application. A discount is available for fully electronic submissions via CTIS. Payments can be made via bank transfer, kiosks, or mobile apps, and the payment order has a 30-day validity.

Methodological Instructions for Applicants/payers Administrative Fees Related to the Collection of Fees With the “Ekolok” System MP 149/2024

his document outlines the procedures for paying administrative fees to the State Institute for Drug Control (ŠÚKL) through the new eKolok system, effective from September 1, 2024. The system is operated by Slovenská pošta and is part of the central fee registration system (CSEP). Administrative fees can be paid via various methods, including cash, credit cards, mobile apps, kiosks, and bank transfers. After payment, taxpayers must attach a payment confirmation (eKolok) to their submission. Payments can be made for specific services as listed in the ŠÚKL catalog, and payment confirmations must match the service requested. Refunds for overpayments are handled by Slovenská pošta upon ŠÚKL’s decision. The system ensures payments are recorded and processed efficiently.

REQUEST FOR TRANSFER OF REGISTRATION OF HUMAN MEDICINE
(APPLICATION FOR TRANSFER OF A MARKETING AUTHORIZATION FOR A HUMAN MEDICINAL PRODUCT)

This is an application form for the transfer of marketing authorization (MA) for a human medicinal product, addressed to the State Institute for Drug Control (ŠÚKL). It includes detailed sections for both the current holder (Applicant) and the proposed new holder (Acquirer) of the registration decision. The application requests essential information about the product, including its name, registration number, pharmaceutical form, and strength. It requires documentation such as proof of residence, labeling text, patient information leaflets, and evidence of payment of administrative fees.

The form includes declarations from both the proposed and current holders of the registration decision, confirming the availability of the updated documentation and the understanding of the rights and obligations transferring with the marketing authorization. Finally, the document includes space for signatures, dates, and the confirmation of payment through the CESP system. It also requires the signature and stamp of the ŠÚKL officer upon receipt.

Annual report on the current state of the clinical trial, which is carried out according to Regulation no. 536/2014 Version-1.0

The Annual Report on the Current Status of Clinical Trials is a required submission for sponsors and applicants based on Regulation No. 536/2014 and Act No. 362/2011 Coll.. It must be submitted annually to the State Institute for Drug Control (ŠÚKL) and the Ethics Committee (EC), either in Slovak or English, within three months after each reporting period. The report should cover trial progress, including the start and termination dates, participant enrollment, deviations from the protocol, serious adverse events (SAEs), and any audits or inspections. It should also include reasons for participant dropout and changes in clinical trial personnel. Submissions should be sent via annual_report_ct@sukl.sk for ŠÚKL and eticka.komisia@health.gov.sk for the EC.

METHODOLOGICAL INSTRUCTIONS FOR APPLICANTS FOR A PERMIT TO HANDLE MEDICINES IN THE TYPE OF ACTIVITY PRODUCTION OF HUMAN MEDICINES MP 134/2024

This document, issued by the State Institute for Drug Control (ŠÚKL) in Slovakia, outlines the requirements for applicants seeking permits to produce human medicinal products. It details the necessary documents, including personal identification, criminal record extracts, proof of professional qualifications, and facility ownership. Applicants must submit these documents for a new permit or to modify an existing one. Administrative fees apply, and applicants must prove their trustworthiness and compliance with health and safety regulations. The instructions are effective from September 25, 2024, and contact information is provided for assistance.

Transfer of registration of a human medicinal product

The transfer of a registration of a human medicinal product is a change of the registration holder to another person who must have a residence or registered office in the Slovak Republic or another Member State of the European Union. It is based on the Act on Medicinal Products and Medical Devices and on Amendments to Certain Acts (hereinafter referred to as the “Act on Medicinal Products”) 362/2011 Coll. – Section 59

Methodological instructions for the holder of the marketing authorisation for a medicinal product on reporting deficiencies in the quality of a medicinal product and in the production of a medicinal product

The purpose of the Methodological Instruction is to establish a uniform procedure for holders of decisions on the registration of human medicinal products, hereinafter referred to as the holder for reporting quality deficiencies medicines, or suspicions of deficiencies in quality, which may result in the withdrawal of the medicine from the market and the development of information materials related to deficiencies in quality for the professional and lay public

REPORTING COMPLAINTS OR CLAIMS ABOUT SUSPECTED DEFICIENCIES IN THE QUALITY OF A MEDICINE

The purpose of the Methodological Instruction is to establish a uniform procedure for holders of registration of human medicinal products for reporting complaints or reclamations of Act No. 362/2011 Coll. laws as amended. At the same time, it defines the procedure for reporting suspected deficiencies in the quality of the medicine for health workers and natural persons.

EXCEPTIONS RELATED TO LABELING OF THE PRIMARY AND SECONDARY PACKAGING OF MEDICINES OR USAGE OF STATE LANGUAGE ON THE PACKAGING OR IN PILL

The purpose of the Methodological Instruction is to establish a uniform procedure for submitting a request for an exemption from the provision of data on the outer and inner packaging of a medicine or an exemption from the provision of data in the national language on the outer and inner packaging and in the written information for the user of a human medicinal product (PIL)

T A R I F F of the Public Agency of the Republic of Slovenia for Medicinal Products and Medical Devices version No. 2

The Tariff of the Public Agency of the Republic of Slovenia for Medicinal Products and Medical Devices (JAZMP) outlines fees for services related to the regulation, inspection, and certification of medicinal products. These include authorizations for manufacturing, distribution, retail sale, and clinical trials, as well as for marketing authorizations, variations, and renewals. Fees are calculated in points, with each point valued at EUR 5.8. Payment is required within 15 days of notification, with late fees applied for overdue payments. The tariff also covers professional services like expert training, consultations, and administrative tasks, all subject to fees based on specific procedures.



SOUTH AFRICA

GWP GUIDELINE FOR THE IMPORTERS AND DISTRIBUTORS OF SCHEDULED SUBSTANCES

The Guideline for Importers and Distributors of Scheduled Substances provides instructions for wholesalers on how to import and distribute scheduled substances used in manufacturing registered medicines. It covers the application process for a wholesale license under the Medicines Act (Act 101 of 1965) and outlines compliance with Good Pharmacy Practice (GPP) and Good Manufacturing Practice (GMP) regulations. The guideline applies to substances used in both human and veterinary medicines, including raw materials and intermediates. Applicants must obtain a license for importing or distributing scheduled substances, ensuring adherence to regulatory standards for safety and quality.

LICENCE APPLICATION FOR THE IMPORTING AND THE DISTRIBUTION SCHEDULED SUBSTANCES

This application form is used to apply for, renew, or amend a licence to import and distribute scheduled substances under the Medicines and Related Substances Act. The form must be accurately completed, signed, and submitted with the application fee to SAHPRA. The licence is valid for five years, with renewal and annual fees required. Applicants must provide business details, confirm regulatory compliance, and submit a Site Master File. An audit may be conducted to ensure adherence to Good Wholesaling, Manufacturing, and Distribution Practices (GWP, GMP, GDP). Any changes in details must be reported within 30 days to keep the licence valid.

GUIDELINE FOR PROFESSIONAL INFORMATION FOR HUMAN MEDICINES (CATEGORIES A AND D)

This guideline outlines the requirements for submitting Professional Information (PI) for the registration of human medicines under the Medicines and Related Substances Act. The PI, which provides crucial details about a medicine’s use, safety, and efficacy, must be included in registration applications and cannot be altered without SAHPRA approval. The guideline aims to ensure consistency and correct presentation of the PI, helping applicants meet regulatory standards. It applies to Human Medicines in Categories A and D, with specific content requirements for each. SAHPRA may request additional information as necessary, and applicants must ensure compliance with all relevant regulations for safe and effective medicine use.

Guideline on Co-Applicancy

The SAHPRA Co-Applicancy Guideline outlines the process for applicants seeking to jointly register a medicine, sharing responsibility for its quality, safety, and efficacy. Co-applicants must be separate legal entities in South Africa and must enter a binding contract that defines their roles and responsibilities. The guideline applies to new medicine registrations where joint oversight is necessary, such as when a single applicant cannot meet all regulatory requirements. The application requires a pre-submission meeting with SAHPRA, submission of a co-applicancy contract, and clear division of responsibilities between the primary and secondary applicants. Both must comply with SAHPRA’s regulatory oversight, and any changes to the contract must be reviewed by SAHPRA. This approach ensures a collaborative effort in maintaining the safety and efficacy of medicines registered in South Africa.

 Z -CODE REQUEST FORM 

The Z-Code Request Form (Doc Number: GLF-HPA-06A, Revision: 1.0) is used to request a Z-code from SAHPRA (South African Health Products Regulatory Authority). The Z-code is a unique identifier issued by SAHPRA for specific regulatory processes. The form is typically used to facilitate communication with the regulatory body and streamline the submission process for certain regulatory matters.
The effective date of this form is 26 July 2024, indicating that any requests or submissions requiring a Z-code must follow the procedures outlined in this version of the form from this date onward.

CTD CHECKLIST 

The  CTD Conversion Variation Checklist ensures that all necessary information is included when converting a product from eSubmission to eCTD format for regulatory review. It covers key sections such as the API Details, FPP Specifications, Bioequivalence & Biowaivers, and Regional Information. The checklist includes data on manufacturing, characterization, stability, and control for both the active ingredient and the final product. It also requires justification for any omitted documents and serves as an annex to the cover letter for the baseline sequence. This structured approach helps facilitate a smooth and efficient regulatory approval process.

Guidelines for eCTD Submissions: ZA-SAHPRA eCTD Specifications v3.1 and Validation Criteria v3.

The document titled 2.21 ZA-SAHPRA eCTD Specifications v3.1(to be read with 2.22 ZA-SAHPRA eCTD Validation Criteria v3.1) outlines the specifications and validation criteria for submitting regulatory applications in the eCTD format to SAHPRA. The due date for submitting comments on these documents is 31 July 2024. The template includes sections for commenter details, the current text or reference to paragraph, proposed amendments, and rationale for the suggested changes. This allows stakeholders to review and propose changes to the guidelines before they are finalized.

GUIDELINE FOR THE API MASTER FILE (APIMF) PROCEDURE

This guideline provides recommendations for applicants and Active Pharmaceutical Ingredient (API) manufacturers submitting applications for the registration and variations of medicines. It outlines SAHPRA’s current expectations regarding the safety, efficacy, and quality of medicines but allows for alternative scientifically justified approaches. The guideline covers submission and evaluation processes for both new registrations and variations, including the handling of existing or new API Master Files (APIMFs). SAHPRA reserves the right to request additional information to ensure compliance with regulatory standards. Applicants must follow administrative requirements to prevent delays in processing applications. The document also includes reference materials, templates, and detailed annexures to assist applicants.

General Guideline for the Submission of PEM Post-Registration Amendments

This guideline provides general information to applicants on the process for post-registration quality variation submissions for orthodox human medicines. Its purpose is to identify common quality deficiencies in recent applications and offer guidance to help applicants avoid these issues, ensuring quicker processing and approval. The guideline specifically applies to variations affecting the quality of human medicines and excludes veterinary, biological, and complementary medicines. It also outlines communication protocols, including where to direct queries and follow-ups. Applicants are advised to refrain from sending unnecessary status update requests and should follow up only if no feedback is received within 120 working days.

RENEWAL OF REGISTRATION OF HUMAN AND VETERINARY MEDICINES

In South Africa, the renewal of medicine registrations is governed by the Medicines and Related Substances Act and managed by SAHPRA. The renewal process begins at least six months before a product’s registration expires. Applicants must submit a detailed application through the eCTD system, including updated documents like the Professional Information, Patient Information Leaflet, a Product Quality Review, and a Risk-Benefit Assessment Report. For older products (registered before 2017), a full eCTD baseline submission is required, along with a Quality Information Summary and evidence of pharmacovigilance. The review can take up to six months and a temporary renewal certificate is issued if the registration expires during this period. The process ensures the continued safety, efficacy, and quality of medicines in the market.

Renewal-Process-Flow

The renewal process for medicines in South Africa involves several steps, starting with the applicant submitting the required documents via SAHPRA’s system. The submission undergoes admin screening, where errors are flagged and corrected, followed by technical screening with a 10-day window to address any queries. Afterward, the evaluation committee reviews the application for primary and peer review, with a final manager sign-off and CEO approval. Once reviewed, SAHPRA issues an updated registration certificate. The entire process takes up to 70 working days (about 3 months), with applicants required to respond promptly to avoid delays.

eCTD VALIDATION and TECHNICAL SCREENING FOR RENEWALS

The Validation Template is used by SAHPRA to verify that all necessary information for renewing a medicinal product’s registration is submitted in eCTD format. For products registered in 2017 or earlier, a full eCTD baseline submission is required (if not already done), while renewal applications need Sections A, B, D, and E. The process includes:
1. Administrative Validation : Confirms all required data is provided.
2. Business Validation : Ensures completeness and compliance.
3. Technical Verification : Assesses product quality for new eCTD submissions.
4. Technical Screening (Clinical) : Reviews clinical data.
5. Technical Screening (Pharmacovigilance) : Evaluates safety monitoring.
This ensures regulatory compliance before granting a renewal.

RENEWAL OF REGISTRATION OF HUMAN AND VETERINARY MEDICINES

This guideline document is intended to provide guidance on the renewal of registration of human and veterinary medicines.
 It covers:
Document History and Glossary to explain terms used.
Purpose and Scope of the renewal process.
Legal Provisions relating to the renewal.
Post-Registration Variations that might affect medicinal products.
Requirements and Procedure for renewal applications, including both general and technical requirements, and the process for handling applications.
References for further reading.
Validity of the registration post-renewal.
Annexures, including a flow diagram to illustrate the renewal process.
This document aims to provide clear, structured guidance for all stakeholders involved in the renewal of registration for human and veterinary medicines.



SOUTH KOREA

Regulations on the recall of pharmaceutical products.

This notice, issued by the **Ministry of Food and Drug Safety** (Notice No. 2024-42), outlines the regulations for the recall of pharmaceutical products in South Korea, in accordance with the **Pharmaceutical Affairs Act**. It covers procedures for risk assessment, voluntary recall, suspension of sales, and the public announcement of recovery plans. The document emphasizes the responsibility of the entity liable for the recall to prepare and implement a recovery plan, submit evaluation reports, and manage disposal procedures for affected products. It also addresses the collection and confirmation of returned products, along with requirements for document management and recommendations to pharmaceutical professionals. Additionally, the notice extends to non-medicinal products and includes provisions for objections and review by the **Ministry of Food and Drug Safety**. The overall goal is to ensure the safe and efficient recall process to protect public health.

Regulations on labeling of pharmaceutical products

This document outlines the regulations for labeling pharmaceutical products in South Korea, as per the **Pharmaceutical Affairs Act**. It sets standards for font size, line spacing, and clear labeling of essential information, including safety warnings and simplified terms, to ensure accessibility for consumers, including those with visual or hearing impairments. The regulations also specify labeling requirements for injectables and the use of identification marks on pharmaceutical products, which must be registered and coordinated by an official agency. Additionally, the **Ministry of Food and Drug Safety** is tasked with reviewing and disclosing product information to ensure compliance and consumer safety.



SPAIN

Directory of Accredited CEIm Committees in Spain

This directory provides information on Committees that can evaluate clinical trials involving medicines and medical devices in Spain. It includes data from the Spanish Medicines Agency and the competent authorities of the Autonomous Communities. For new clinical trial applications through CTIS, sponsors must select a Committee (CEIm) committed to the new Memorandum of Collaboration and CTIS participation. It is essential to contact the selected CEIm to confirm its availability for evaluation. The directory also includes Committees that can evaluate biomedical research projects unrelated to clinical trials. Additionally, it highlights CEIms participating in the fast-track evaluation procedure.

Spain’s Fast-Track Procedure for Phase I and Bioequivalence Trials

Spain has introduced an accelerated or fast-track evaluation procedure for Phase I clinical trials involving advanced therapy drugs and bioequivalence studies. This procedure is available for trials that address serious or life-threatening diseases with no therapeutic alternatives, provided the application is submitted through the Clinical Trials Information System (CTIS) only in Spain. Sponsors must contact the Spanish Agency for Medicines and Health Products (AEMPS) before submitting the application, providing details on the trial and the selected Drug Research Ethics Committee (CEIm). Once approved for fast-track evaluation, the application will be reviewed within 26 days of validation and could be authorized within 31 days if no further clarification is needed. The same deadlines apply automatically to bioequivalence trials, without the need for prior contact with AEMPS.



SWEDEN

Guidance to The regulations of the Swedish Medicines Agency (HSLF-FS 2022:8) on parallel imported human medicines Version 1,

The purpose of this guidance is to promote a uniform application of the Swedish
Medicines Agency’s regulations (HSLF-FS 2022:8) on parallel imported human medicinal
products by describing and interpreting the content of the current regulations. This
guidance is primarily aimed at the companies engaged in the parallel import of human medicines.
A guide may contain additional information compared to the binding rules, and aims to increase
understanding of the regulation’s requirements.

Guidance on labelling, package leaflets and names for medicinal products for human use Version 2

The purpose of this guidance is to promote a uniform application of the Swedish Medicines Agency’s regulations (HSLF-FS2021:96) on labeling and package leaflets for medicinal products for human use as well as a uniform application when naming medicinal products for human use.
• The guidance covers labeling and package leaflets for human medicinal products within central,mutual, decentralized and national procedure.
• The guidance covers naming of medicinal products for human use within mutual, decentralized and national (but not central) procedures.
The guidance is aimed at the companies that must prepare labeling and package leaflets as well as propose names for human medicinal products. The intention of the guidance is to describe and interpret the content of current regulations in order to obtain labeling and patient information that is clear and user-friendly, and to reduce the risk of confusion and misuse. A guide may contain additional information compared to the constitutions, with the aim of increasing understanding of the constitutions’ requirements. The guidelines are not legally binding, but contain examples and information that can be helpful in assessing and applying the constitutional provisions. The guidance does not exclude other courses of action to achieve the result intended by the statutes, but presents the Swedish Medicines Agency’s interpretation.



SWITZERLAND

Form Status of authorisation applications abroad Identification number:ZL000_00_030 Version:3.0

The document outlines the requirements for reporting the status of authorisation applications for medicinal products abroad. It specifies information about approvals, submissions, withdrawals, suspensions, and rejections in various countries, including the EMA, EU/EFTA nations, and other key countries like the USA, Canada, and Japan. It also includes details on approved indications and whether final assessment reports are attached. The form ensures transparency in the status of authorisations across different regions.

Guidance document GMP compliance by foreign manufacturers Identification number: ZL000_00_036 Version: 4.0

The objective of this guidance document is to clarify the requirements for submitting documents in the context of authorisation applications for human medicinal products. It outlines the types of variations and their submission processes: minor type IA/IAIN variations, which can be notified after the event; minor type IB variations, which must be notified in advance; and major type II variations, which require a more extensive review. The guidance is focused on ensuring compliance with Good Manufacturing Practice (GMP), particularly for foreign manufacturers of active pharmaceutical ingredients (APIs) or ready-to-use medicinal products. This is in line with the Medicinal Products Licensing Ordinance (MPLO), Art. 11, para. 1, part i.

The scope of the document applies to both authorisation holders and applicants of ready-to-use medicines, whether manufactured abroad or in Switzerland, that contain APIs from foreign manufacturers. The responsible person (RP) must ensure that GMP compliance is verified for foreign manufacturers of these ingredients and products.

Form Application for Operating License – Basic Form for Medicinal Products (including Blood)Identification number:I-301.AA.05-A02d Version:5.0

The Application for Operating License  is used to request a license for activities such as the manufacture, import, wholesale trade, export, and brokerage of medicinal products, as well as blood sampling. It includes sections for the applicant’s information, license holder’s addresses, reason for the request (e.g., new application, change of address, or company name), and the specific activities affected. Additional forms may be required for changes like company name or responsible person. The application is subject to fees as outlined in the Swissmedic Fee Ordinance, and the license holder agrees to upload GMP/GDP certificates to the SwissGMDP database. The form must be signed by authorized representatives and submitted to Swissmedic.

Form Application for operating license – additional sheet for medicinal products (including blood) Identification number:I-301.AA.05-A03d Version:7.0

The application for an operating license for medicinal products (including blood) in Switzerland, identified by requires detailed information about the business location, the scope of the permit, and the responsible person. Applicants must provide the full address of the business premises involved in handling medicinal products, including blood, and describe the specific activities carried out under the permit, such as manufacturing, distribution, or storage. Additionally, the responsible person’s full name, position, contact details, and relevant qualifications must be provided. This ensures compliance with Swiss regulations governing medicinal products and blood-related operations.

guide Import of a human medicinal product according to Art. 14 para. 2 and 3 HMG
(parallel import) Identification number:ZL106_00_888 Version: 2.0

The guideline for the approval of parallel-imported human medicinal products outlines the simplified process for submission and approval, aiming to provide clarity on the necessary documentation. It is primarily directed at administrative bodies to ensure uniform application of legal provisions. The guideline helps Swissmedic apply these provisions consistently and fairly, making the process more transparent for applicants. It specifies the requirements for obtaining approval or making changes to parallel-imported human medicinal products, in line with Articles 14, paragraphs 2 and 3 of the Therapeutic Products Act (TPA). The guideline is intended to facilitate quicker and more efficient processing of applications by Swissmedic’s Authorisation and Vigilance Medicinal Products Division.

Guidance for Industry on Electronic Exchange of ICSRs in E2B(R2) Format via PV Gateway

This guidance aims to assist marketing authorization holders (MAHs) in preparing for the electronic transmission of Individual Case Safety Reports (ICSRs) in pharmacovigilance, ensuring compliance with common standards for successful data exchange. Swissmedic supports this electronic reporting and has developed systems that comply with ICH-E2B standards for generating and receiving ICSRs. The requirements apply to all MAHs with ICH-E2B-compliant pharmacovigilance systems. For companies unable to exchange ICSRs via the B2B Gateway, Swissmedic will continue to use its ElViS (Electronic Vigilance System) in the interim.

Guidelines for Application Deadlines for Admission

The Deadlines for Applications for Admission guideline outlines the timelines that Swissmedic (SMC) and applicants must follow during the administrative process for drug approval applications. It provides clarity on how incomplete applications are handled and aims to enhance planning certainty for both SMC and applicants. While the procedures are based on the European Medicines Agency (EMA) guidelines for centralized approval, they are adapted to comply with Swiss legal requirements, which differ from EU law. The document defines key deadlines in the authorization process, including legally mandated deadlines such as appeal periods.

Guidance on Authorization of Human Medicinal Products with New Active Substances

This guidance document outlines the requirements for submitting and obtaining authorization for human medicinal products containing new active substances in Switzerland. It provides detailed instructions on the necessary documentation, including quality, preclinical, and clinical data, to demonstrate the product’s safety, efficacy, and favorable benefit-risk profile. The document helps ensure a uniform application of the law by Swissmedic and informs third parties about the requirements for product authorization. It also highlights the possibility of seeking scientific advice from Swissmedic before submission, though this advice does not replace the formal evaluation of the application.

Guidance document Time limits for authorisation applications

This guidance document outlines the timetable for authorisation procedures and the time limits observed by Swissmedic (SMC) for submitted authorisation applications. While certain time limits are legally defined (e.g., appeal deadlines), the document aligns its processes and application time limits with those of the European Medicines Agency (EMA) for the Centralised Procedure, though some Swiss legal provisions differ from European law. The objective is to clarify the time limits for both SMC and applicants and describe the procedure for handling incomplete applications. The document aims to improve planning certainty for both parties and is applicable to the authorisation procedures for medicinal products.

Guidance document Packaging for human medicinal products Identification number: ZL000_00_021 Version: 5.0

The guidance document (ZL000_00_021, Version 5.0) provides instructions for the labelling and design of packaging for human medicinal products in Switzerland. It ensures compliance with Swiss legal provisions, including the Therapeutic Products Act (TPA), Ordinance (TPO), and Labelling and Regulatory Ordinance (TPLRO), as well as additional regulations for narcotic drugs. The document applies to both primary and secondary packaging, with specific provisions for homeopathic, anthroposophic, and Asian medicinal products, as well as parallel imports. Its goal is to standardize packaging requirements, ensuring efficient application processing and legal compliance.

Guide Deadlines for Applications for Admission Identification number: ZL000_00_014
Version: 8.0

The document outlines the timing and deadlines for authorization procedures at Swissmedic (SMC) for medicinal products. It specifies legal deadlines and processes, aligned with the European Medicines Agency (EMA) where applicable, though differences in Swiss law mean the procedures can’t be directly transferred. The guideline provides clarity on the handling of incomplete applications and aims to improve planning certainty for both SMC and applicants. It applies to all authorization procedures for medicinal products.

Quality defect report form

The Quality Defect Report is a formal document used to notify Swissmedic about quality issues related to medicinal products. It requires the reporting individual or organization to provide details such as the product name, affected lot numbers, manufacturing and distribution information, and a description of the defect. The report also includes information about any actions already taken, such as recalls or notifications to regulatory authorities, and proposes further steps to address the issue. This report is submitted to Swissmedic via fax, email, or postal mail, and includes a section for tracking changes made to the document over time.

Report of a suspected adverse drug reaction (ADR) N°

The Report of a Suspected Adverse Drug Reaction (ADR) is a form used to report adverse effects after administering a medicinal product. It collects the patient’s personal details, the onset and duration of the reaction, and the suspected drugs involved. It includes sections for describing the ADR, relevant test results, therapy, consequences (e.g., hospitalization, recovery), and any other drugs used simultaneously. The report also gathers information on the patient’s medical history, including allergies and pre-existing conditions. The completed form should be sent to Swissmedic via email or post, and for quality defects, a separate reporting form is used. For toxicological emergencies, Tox Info Suisse should be contacted directly.

Guidance document Authorisation human medicinal product under Art. 13 TPA Identification number: ZL000_00_019 Version: 5.0

This guidance document outlines the process for considering the results of foreign authorisation procedures when an applicant requests the authorisation, extension, or variation of a medicinal product or procedure already authorised in a country with a comparable regulatory system. The goal is to expedite the availability of these medicinal products in Switzerland while ensuring efficient use of Swissmedic’s resources. The document is primarily for administrative bodies but also provides applicants with clarity on the preconditions and requirements for submitting authorisation applications. It applies to various applications, including new authorisation applications for known or biosimilar substances, new indications, and minor or major variations. It also covers parallel processing with foreign applications and specific criteria for extensions and variations, including document validity and translation requirements. The guidance does not apply to authorisations under the notification procedure as outlined in Article 15 TPA.

Form Information for application Art.13 TPA Identification number:ZL101_00_004 Version:4.0

The form for applying under Article 13 of the Swiss Therapeutic Products Act (TPA) gathers key information for authorising a medicinal product in Switzerland based on foreign evaluations (e.g., EMA, FDA). It includes sections on basic product details, manufacturing information, discrepancies between the product authorised abroad and in Switzerland, and specifications for vaccines or blood products. Applicants must provide data on the active substance, finished product, and storage conditions, as well as any differences between foreign and Swiss authorisations. The form also addresses pharmacokinetic data, compliance with Good Laboratory and Clinical Practice (GLP, GCP), and pharmacovigilance. The application must be signed by authorised individuals, confirming the accuracy of the submitted information.

Guidance document Authorisation in accordance with Art. 14para.1 abis-quater TPA Identification number: ZL000_00_022 Version: 9.0

This guidance document outlines the documentation requirements for the submission and simplified authorisation of medicinal products under Article 14 para. 1 letter abis-quater of the Swiss Therapeutic Products Act (TPA). It applies to both human and veterinary medicinal products and covers new and variation applications. Variation applications under this provision are restricted to clinical and preclinical aspects and can only be made if the initial authorisation was granted under the same article. Regulatory and quality-related variations are processed separately through standard procedures. The document clarifies that therapeutic equivalence or interchangeability with a Swiss reference product is not evaluated under this procedure; applicants seeking such evaluation must use the procedure under Article 14 para. 1 letter a TPA.

“Confirmation of Electronic Submission (AM_KlinV) – Clinical Trial Application”

The “Confirmation of Electronic Submission (AM_KlinV)” form is used to authorize Swissmedic to process applications for clinical trials involving medicinal products for human use, transplant products, gene therapy products, and genetically modified organisms (GMOs) based on the electronic documents submitted via CD/DVD. It requires key information such as the sponsor’s name, the Swiss representative, the clinical trial title, trial code, and Swissmedic case ID (if applicable). The form must be signed by the authorized individual and include their contact details. Once completed, the form and CD/DVD are submitted to Swissmedic’s office in Bern for review and processing.

“New Approval Application for Human Medicinal Products”

The “New Approval Application for Human Medicinal Products” form is used to submit a request for the approval of a new human medicinal product. This application is typically required by regulatory authorities to assess the safety, efficacy, and quality of the product before it can be authorized for use. The form includes details about the product, including its composition, manufacturing process, clinical trial data, and proposed indications. It is an essential step in obtaining regulatory approval for bringing new medicinal products to market.

Formal requirements guide

The general requirements for various submissions related to clinical trials, narcotics reports, laboratory orders, inspections, certificates, market surveillance cases, and legal matters emphasize the responsibility of the applicant, who is typically the future marketing authorization holder. The applicant must ensure that all relevant documentation is submitted as part of the application, as they bear legal responsibility for the authorized medicinal product. The list of documents required for each application is provided in specific guidelines (WLs). Third-party submissions are only permitted for Drug Master Files (DMF)/Active Substance Master Files (ASMF) and specific compositions of flavorings, as outlined in the respective submission guidelines.

Order Form for a Certificate of Pharmaceutical Product (CPP)

An Order Form for a Certificate of Pharmaceutical Product (CPP) is used to request the issuance of a CPP from a regulatory authority, such as Swissmedic. The form requires details about the applicant (name, contact information, and address), the pharmaceutical product (name, dosage form, strength, marketing authorization number, and country of origin), and the purpose of the request (e.g., export or regulatory submission). It also includes a section for submitting relevant documents like marketing authorization, GMP certificates, and batch release certificates. The applicant must sign a declaration confirming the accuracy of the information provided. Additionally, payment details are required, and the form must be submitted along with the necessary documents to the relevant regulatory authority.

Working Instructions for Swiss M1 Specification eCTD Version 1.5

This document defines the specifications for Module 1 of an eCTD (electronic Common Technical Document) submission to Swissmedic, the Swiss Agency for Therapeutic Products. It focuses on enabling the electronic transfer of applications from industry to Swissmedic, outlining the requirements for submitting documents in eCTD format for regulatory approval in Switzerland. The document should be used in conjunction with the ICH eCTD Specification to ensure a valid submission, but it does not address transfers between industry stakeholders or between Swissmedic and other regulatory agencies.

Guidance Document: Packaging Requirements for Human Medicinal Products

This Guidance Document on Packaging for Human Medicinal Products outlines the legal and regulatory requirements for the labelling and design of packaging for medicinal products in Switzerland. It serves as a resource for ensuring compliance with laws such as the Therapeutic Products Act (TPA), the Therapeutic Products Ordinance (TPO), and the Therapeutic Products Labelling and Advertising Ordinance (TPLRO), as well as specific regulations for narcotics and homeopathic products. The document aims to ensure that packaging provides clear, accurate, and non-misleading information, with the primary objective of safeguarding drug safety and preventing misuse. It specifies guidelines on font size, required information, and packaging design, while also covering special cases like parallel imports and certain product types (e.g., homeopathic medicines).

Variations and extensions HAM form

the HAM form for pharmaceutical products refers to the Harmonized Assessment Model used to regulate and evaluate drugs for market approval, ensuring consistency with national and international standards. Variations in this model can occur based on specific drug categories or market needs, such as orphan drugs or biologics, where the approval process may differ due to product complexity. Extensions include adopting technologies like digital health solutions or AI-based tools for monitoring drug efficacy and safety, as well as aligning with international standards like the European Medicines Agency (EMA) or International Council for Harmonisation (ICH). These adaptations help Switzerland stay at the forefront of pharmaceutical innovation while maintaining high safety standards.

Guidance document Renewal and discontinuation of authorisation or change of status (main authorisation/export licence)

This guidance document outlines the rules for the renewal or discontinuation of authorisations for medicinal products in Switzerland, detailing how these processes should be managed and the associated rights and obligations of authorisation holders. Swissmedic uses this document to ensure the uniform and equitable application of legal provisions regarding authorisation. It aims to clarify the requirements that must be met for third parties, particularly in relation to renewal requests, notifications or applications to discontinue authorisation for specific medicinal products, dosage strengths, or pack sizes, and changes of status between main authorisations and export licences for both human and veterinary medicinal products.

Form DMF Identification number:I-ZL000_00_035 Version:5.3

The DMF (Drug Master File) Form is used to submit or modify a DMF for human medicinal products in Switzerland. It consists of two parts: Part A to be completed by the marketing authorization holder, and Part B by the DMF holder. Part A includes details like the active ingredient, DMF holder’s contact information, and affected medicinal products. Part B requires the DMF holder to provide company and manufacturing details, and consent for Swissmedic to exchange assessment reports with international authorities. The form also covers information related to nitrosamine contamination risk assessments. The process ensures that Swissmedic receives accurate and complete documentation for new registrations or changes to existing products, and tracks all relevant regulatory exchanges.

Guide Renewal and waiver of admission Change of status Main and export approval Identification number:ZL201_00_001 Version: 5.0

The guide outlines the rules and procedures for the renewal and waiver of medicinal product authorisations, detailing the rights and obligations of the marketing authorisation holder. Based on provisions from the Therapeutic Products Act (HMG), it covers authorisation duration, revocation, transfer, and renewal, as well as notifications for non-marketing or cessation of distribution. The guide helps ensure uniform application of legal provisions by Swissmedic, making the requirements transparent to third parties. It applies to various authorisation scenarios, including renewals, waivers, changes in dosage strengths or packaging sizes, and status changes for human and veterinary medicinal products.

Guidance document Variations and extensions HAM

This guidance document outlines the requirements for variations and extensions of human medicinal products in Switzerland, as managed by Swissmedic. It references Annex 7 TPLRO, which categorizes variations into types IA/IAIN, IB, and II, and includes extensions, with specific sections on regulatory, quality, safety, efficacy, pharmacovigilance changes, Plasma Master Files (PMF), and complementary/herbal medicines. The document adopts European Variation Guideline standards, adapting them to Swiss laws, and specifies the conditions and documentation needed for each variation, highlighting any differences with European requirements. Switzerland-specific variations are identified with 100-series numbers, and the document is primarily a resource for Swissmedic to apply legal provisions uniformly, while also helping applicants understand the specific requirements for efficient application processing.

Guidance Document: Meetings for Applicants with the Authorisation Sector

Swissmedic organizes meetings for applicants to clarify questions related to content and procedure, with the goal of optimizing the authorization process. These meetings, which can be held in person, virtually, or in writing, are conducted when certain requirements are met and when the exchange of information is expected to be productive for both parties. The guidance document outlines the types of meetings available, including scientific advice, pipeline meetings, presubmission meetings, and LoQ clarification meetings, as well as labeling meetings initiated by Swissmedic. It also covers the necessary documentation, meeting preparation, communication, implementation, and associated fees. The document ensures a consistent, transparent, and efficient approach to these meetings.

Gguide Changes and approval extensions HAM Identification number:ZL300_00_001
Version: 9.0

This guideline (WL) outlines the requirements for changes and approval extensions of human medicinal products in Switzerland, as per Annex 7 AMZV. It categorizes changes into regulatory adjustments, quality modifications, safety/efficacy changes, plasma master file updates, and variations for complementary or phytomedicinal products, along with approval extensions. The guideline follows the European Variation Guideline, adapting it to Swiss law, with specific requirements for each type of change. Swiss-specific variations are numbered in the 100s (e.g., A.100 for changes to product information without scientific data). It aims to ensure uniform application of legal provisions by Swissmedic and helps applicants understand the necessary documentation for efficient processing of applications. This guideline is primarily intended for administrative bodies, supporting the Authorisation, Approvals, and Market Surveillance Divisions of Swissmedic.

Guideline for Drug Information on Human Medicinal Products

This guide outlines the requirements for drug information for human medicines, targeting administrative bodies and serving as a tool for Swissmedic to ensure uniform and consistent application of legal provisions. Its purpose is to help applicants understand the necessary requirements for submitting drug information texts, facilitating faster and more efficient processing. The guide aims to clarify the standards that must be met for the timely review and approval of drug information related to human medicinal products.

Guidance for Industry on Electronic Exchange of ICSRs in E2B(R3) Format via B2B Gateway

This guidance assists marketing authorization holders (MAHs) in preparing the electronic submission of Individual Case Safety Reports (ICSRs) in the E2B(R3) format for pharmacovigilance, as required by Swissmedic. It outlines the process for transitioning from the previous E2B(R2) format to the new E2B(R3) format, which complies with ICH standards and the ISO EN 27953-2:2011 standard for ICSR reporting. The guidance includes technical requirements for submitting Safety and Acknowledgement Messages through the B2B gateway and addresses the obligations for stakeholders to ensure successful electronic communication. The transition process will be aligned with European Medicines Agency (EMA) recommendations, with differences specific to Swissmedic outlined. For companies not yet ready to use the B2B gateway, the ElViS (Electronic Vigilance System) will continue to be available in the interim.

Guidance document Temporary authorisation for human medicinal products Identification number: ZL109_00_001 Version: 16.1

The Guidance Document on Temporary Authorisation for Human Medicinal Products  outlines the procedure and requirements for obtaining temporary authorisation for medicinal products. It includes definitions, abbreviations, and detailed sections on the introduction, scope, and legal framework. The document describes the process for requesting temporary authorisation, including both material and formal preconditions, required documentation, and scientific advice. It covers application procedures, review phases, and time limits, as well as risk management and post-marketing activities. The guidelines also address variations, extensions, and “ex officio” temporary authorisation. Additionally, the document provides annexes detailing specific procedures, including the Accelerated Application Hearing (AAA) process, and outlines the fees involved.

Guidance document Product information for human medicinal products Identification number: ZL000_00_027 Version: 5.1

This guidance document provides requirements for product information for human medicinal products, aimed at ensuring consistency and clarity in the application of legal provisions by Swissmedic. It covers medicinal product information texts, including those for healthcare professionals, patients, complementary medicines, herbal products, and radiopharmaceuticals. The document also clarifies how to handle packaging material requirements, which are covered separately in another guideline.

Guide Temporary Authorization for Human Medicinal Products Identification number:ZL109_00_001
Version: 16.1

The temporary authorisation procedure allows for the expedited approval of life-saving drugs, particularly for life-threatening diseases, with reduced requirements for clinical documentation. Applicants must first obtain approval to proceed with this procedure before submitting an application for a bZul or bIE. If Swissmedic finds a standard application lacking in data, it may grant a temporary authorisation “ex officio” if the criteria of Article 9a HMG and Article 18 VAZV are met, including evidence of a significant therapeutic benefit over existing treatments. The procedure applies to new approvals of medicinal products (with both new and known active substances) and extensions of indications. The process is designed to be faster and more efficient, ensuring quick access to critical treatments while maintaining safety standards.

Guidance document Authorisation of human medicinal product with known active substance Identification number: ZL101_00_007 Version: 7.0

This guidance document outlines the process for authorising human medicinal products with known active substances (KAS), including both KAS without innovation (standard formulations) and KAS with innovation (new formulations or indications). It covers requirements for application, documentation, and the evaluation process, such as proving therapeutic equivalence, bioequivalence, and the use of reference products. It includes sections on administrative, scientific, and clinical documentation, as well as time limits, fees, and legal frameworks. The document ensures that all necessary data for product approval, including quality, safety, and efficacy, are properly assessed.

Guidance document Fast-track authorisation procedure Identification number: ZL104_00_002 Version: 11.0

The Fast-Track Procedure (FTP) for the authorisation of medicinal products is available when the criteria in Article 7 of the TPO are met. Unlike the standard procedure, the FTP requires prior approval of a request to implement it before an application can be submitted. The application for FTP follows the same scientific documentation and review criteria as a standard procedure, but the review is expedited through advanced planning of resources. Section 5 of the guidance outlines the conditions and criteria for FTP approval, including the Accelerated Application Hearing (AAA) procedure detailed in Annex 1. Section 6 covers the formal and content requirements for FTP applications and the review process. This guidance ensures uniform application of legal provisions by Swissmedic and provides clarity for applicants on how to meet the necessary requirements for efficient processing. The scope of this document applies to human medicinal product authorisations within Swissmedic’s Medicinal Product Authorisation and Vigilance sectors.

Export Certificates Guide

This guide provides detailed instructions on the requirements and procedures for obtaining export certificates for pharmaceutical products in Switzerland. It is aimed at companies seeking to export medicinal products from Switzerland to other countries. The document outlines the necessary steps for requesting an **Export Certificate of Pharmaceutical Product (CPP)**, including the required documentation, forms, and compliance with both Swiss regulations and international standards. The guide also explains how to request certificates for specific purposes, such as for regulatory submissions or international trade. Additionally, it provides information on the validity and scope of the certificates, and how Swissmedic, the Swiss Agency for Therapeutic Products, processes and issues these certificates.

Application for New Authorization of Human Medicinal Products

The application for new authorization of human medicinal products, It involves submitting a comprehensive dossier containing information on the drug’s quality, safety, and efficacy, including details about the active substance, manufacturing process, preclinical and clinical trial data, and risk management. The process also requires compliance with regulatory standards such as Good Manufacturing Practice (GMP). Swissmedic evaluates the application, and if the product meets the necessary criteria, it is granted marketing authorization. After approval, ongoing pharmacovigilance and periodic safety reports are required.

Changes to the guidance document Time limits for authorisation applications

Starting from 1 September 2024, Swissmedic will no longer send written notifications regarding the achievement of the “Doc. OK” milestone after a formal objection in the application process. Previously, a notification was sent when the application for a human medicinal product was formally accepted following a prior objection. Now, after a formal objection, Swissmedic will recheck the documentation within the time limits outlined in the “Time Limits for Authorization Applications” guidance document. Once this period expires, the “Doc. OK” milestone will be considered achieved. For applicants using the Swissmedic Portal, this milestone will still be visible online. The guidance document has been revised to reflect this change.

Questions and answers on variations and extension HMP

Swissmedic has introduced new rules for issuing packaging codes, effective from 1 June 2024. The revised guidelines simplify the process by reducing the number of packaging codes issued. No new packaging codes will be issued in cases such as changes from export licence to main authorisation, modifications to medical device components in combination products, new excipients or changes to excipient composition, changes in the dispensing category, compulsory declaration changes for herbal products, changes in pack contents (e.g., omission of a solvent or dilution container), and reclassification of active substances to excipients or removal of an active substance.

Guidance document on Transfer of marketing authorisation

This guidance document describes the requirements and preconditions (including the documentation to be submitted) for an application to transfer authorisations for human and veterinary medicinal products

Guideline Amendments Clinical Trials

Guideline for Amendments Clinical Trials gives full information on submission form including changes to a running trial, reporting to a running trial, change of Swiss representative and SUSARs; changes during the conduct of a clinical trial (amendments) (Art. 34 ClinO) including protocol amendments related to the use and/or safety of the IMP or AxMP (Section 4 of the CTA dossier), changes to the pharmaceutical quality documentation (PQD) (Section 7 of the CTA dossier), quality defects and OOS of IMPs and AxMPs, changes to labels (Section 8 of the CTA dossier), updated safety documentation (Section 5 of the CTA dossier), change of sponsorship / other administrative change (Form Type CHANGE), dear Investigator Letter (Form Type CHANGE or REPORTING) and etc

Guidance for Authorisation of human medicinal product with known active substance

Guidance document on Authorization of human medicinal product with known active substance describes the requirements regarding the documentation to be submitted for the authorization of human medicinal product with known active substances (KAS). The guidance document comprises guidelines intended for administrative bodies, and thus does not directly address the rights and duties of individuals. For Swissmedic, the instructions serve primarily to provide assistance in applying the legal provisions relating to the authorization of medicinal products with known APIs in a uniform and equitable manner

Information sheet on eGov-Portal CT standard functions

This information sheet describes the basic principles of using the Swissmedic eGov Portal, with a particular focus on the eGov eSubmissions for CT applications service. A separate Questions and Answers document (Q&A) for CT addresses additional questions and issues that may arise. The Master CT eGov use contract must be signed before the portal can be accessed. Before a standard user can use the Swissmedic eGov Portal, a user administrator or account administrator at their company must set up a new standard user account



THAILAND

Application for renewal of drug registration certificate

This Application form includes Details of the applicant and the manufacturer, Product details,Sample drugs,Evidence showing the academic information of the drug formula,Drug labels and accompanying documents,Certificate of current drug production standards of the drug manufacturing facility abroad in the case of importing or ordering drugs into the Kingdom,Documents showing the patent, Other evidence as specified by the Food and Drug Administration.



TURKEY

Fee Schedule for Licensing and Regulatory Applications – Turkish Medicines and Medical Devices Agency

The Turkish Medicines and Medical Devices Agency outlines various application fees for licensing and regulatory processes. These include fees for prioritization applications, preliminary evaluation of scientific advice, and scientific advice applications. Other fees cover license applications for new or known active substances, bibliographic references, and advanced therapy medical products. Additionally, there are fees for clinical trial applications, sales permit applications, license renewals, and license transfers. The schedule also includes fees for specific chemical substances, technical service inspections and certifications, and assessments related to biocidal products regulation. Corporate payments must be made via Halkbank, and specific transactions require additional analysis fees.

Overview of Application Procedures and Fees for Medicines and Medical Devices in Turkey

This document outlines a wide range of applications and associated fees required by the Turkish Medicines and Medical Devices Agency. It includes various license and permit applications such as new drug and product licenses (for substances, combinations, and advanced therapy products), changes to existing licenses, sales permits, and variations (e.g., Type IA, IB, and II). Other applications covered are for the classification of medicines, foods for special medical purposes, allergenic products, and medical devices, both for clinical research and post-marketing studies. The document also details application fees for certifications like Good Manufacturing Practices (GMP), price evaluations, market presentation permits, and certificates for export, free sales, and health status. Additionally, there are fees for investigational product imports, cosmetic product registration, medical gas facilities, and biocidal product registration, as well as various service-related applications for permits and notifications. Corporate payments must be made through designated bank accounts, and some fees require the submission of additional documentation for specific regulatory processes.



UAE

Dubai Scientific Research Ethics Committee (DSREC) released Submission Procedure for Clinical Trial

The Dubai Scientific Research Ethics Committee (DSREC) acts as the Central Ethics Committee for the emirate of Dubai. It takes the final decision on health research proposal requests after reviewing them thoroughly during periodic meetings. Any research planned at DHA licensed facilities WITHOUT the review or approval of Local Ethics Committee must directly be submitted to the DSREC for review and approval.

Reporting Side Effects of Medicines and Medical Products Within UAE for Individuals

The “Reporting Side Effects of Medicines and Medical Products” service in the UAE allows individuals, healthcare professionals, and pharmaceutical companies to report adverse drug reactions to the Ministry of Health and Prevention (MOHAP). The service is free, completed within 3 working days, and available via the MOHAP website and mobile app. Users must log in with UAE PASS, provide the required patient data, and submit the report. The service is aimed at marketing offices, medical stores, pharmaceutical factories, patients, healthcare practitioners, and health institutions. For support, contact PV@mohap.gov.ae.

Issue of a Certificate of a Pharmaceutical Product for Export

The “Issue of a Certificate of a Pharmaceutical Product for Export” service allows UAE pharmaceutical manufacturers to apply for an export certificate. Users must log in via UAE PASS, submit the request online with required documents (product composition certificate and approved leaflet), and complete the payment. The certificate is valid for one year, provided the product’s registration is valid for up to five years. The process takes 5 working days and is free of charge. Support is available at smartservicessupport@mohap.gov.ae or drugreg.inquiries@mohap.gov.ae.



UK

Guidance on Pre-submission Advice & Support

The Medicines and Healthcare products Regulatory Agency (MHRA) offer a pre-submission service before applying for medicines Marketing Authorizations. This service aims to provide the best support possible for prospective applicants, whichever application route is chosen

Guidance on Conditional Marketing Authorisations, exceptional circumstances Marketing Authorisations and national scientific advice

Guidance on Conditional Marketing Authorisations, exceptional circumstances Marketing Authorisations and national scientific advice

Guidance on Pre-submission Advice & Support

Guidance on Pre-submission Advice & Support. This pre-submission advice is a service that provides stakeholders with the means to understand how the process of compiling and submitting applications and supporting evidence applies for their product/s. It is distinct from MHRAs Scientific Advice offering

Guidance on Rolling review for marketing authorisation applications

Guidance on rolling review for marketing authorisation applications. This provides use the rolling review route when applicant want to submit their eCTD dossier in separate parts for pre-assessment instead of making a full consolidated document submission.

Guidance on Conditional Marketing Authorisations, exceptional circumstances Marketing Authorisations and national scientific advice

Guidance on conditional marketing authorisations, exceptional circumstances marketing authorisations and national scientific advice. This gives information like until implementation of the Windsor Framework on 1 January 2025[1] CMAs can only be granted by MHRA for Great Britain (England, Wales and Scotland and etc.

Guidance on Clinical investigations guidance

Guidance on clinical investigations guidance. This gives information on how to notify the MHRA of applicant intention to carry out a clinical investigation for medical devices.

Medicines: apply for a parallel import licence

The UK Parallel Import Licence (PLPI) allows medicines authorised in the EEA to be marketed in the UK if they are therapeutically identical to UK products. Applicants must meet Good Manufacturing Practice (GMP) standards, hold a wholesale dealer’s licence, and provide documents like product composition and labels. PLPI applications fall into simple, complex, and standard categories. Licences are valid for five years and must be renewed. The MHRA oversees the licensing process, including inspections and requirements for adverse reaction reporting.

UK Parallel Import Licences Following Agreement of the Windsor Framework

The guidance explains changes to UK Parallel Import Licences (PLPIs) under the Windsor Framework, effective from 1 January 2025. PDNs are replaced by PLPIs for marketing in both Great Britain and the UK. New packaging must include the ‘UK Only’ label, and PLPIs with a GB territorial limit will be converted to UK-wide authorisation. EU Falsified Medicines Directive (FMD) requirements will no longer apply, and parallel importers must notify the MHRA for approval of any label changes, which can be done through stickering or printing on packaging.

Medicines: apply for a variation to your marketing authorisation

The MHRA guidance explains how to apply for variations to a marketing authorisation (MA) for medicines, including administrative changes, or those affecting product quality, safety, efficacy, or pharmacovigilance. Variations are classified as minor (type IA or IB) or major (type II). Applications can be for single or multiple changes to one or more MAs or products, and may include grouped changes, extensions, or revised packaging. The process also covers applicable fees and other related requirements.

Medicines: apply for a parallel import licence

The MHRA guidance for obtaining a parallel import licence allows EEA-authorized medicines to be marketed in the UK, provided they have no therapeutic differences from UK products. To import, you must ensure the product meets GMP standards, hold a wholesale dealer’s licence, and obtain the appropriate parallel import licence. If the product is controlled under the Misuse of Drugs Act, an import licence is required. Parallel import products must also comply with pharmacovigilance requirements, including reporting adverse reactions, defects, and recalls.

UK Parallel Import Licences Following Agreement of the Windsor Framework

From 1 January 2025, under the Windsor Framework, Parallel Distribution Notices (PDNs) will be replaced by Parallel Import Licences (PLPIs) for the entire UK. All Parallel Imports, including Centrally Authorised Products, will require a PLPI, and existing licences with a GB-only limitation will automatically convert to UK-wide authorisation without the need for a variation.

Advertising investigations: June 2024

The MHRA made decisions on advertising complaints for licensed medicines,Concerns can be directed to the MHRA’s Advertising Standards Unit or relevant bodies like PAGB or PMCPA. The Blue Guide offers detailed advertising guidelines for medicines in the UK.

UK-wide licensing for human medicines

The MHRA guidance outlines changes to the licensing of human medicines in the UK following the Windsor Framework agreement. Starting 1 January 2025, the MHRA will be responsible for licensing medicines across the entire UK. This guidance should be used alongside the Human Medicines Regulations 2012, as amended by the 2024 Windsor Framework Regulations, and other related MHRA guidance, such as labelling and packaging requirements published in July 2023.

Pharmacovigilance following agreement of the Windsor Framework

Starting 1 January 2025, the Windsor Framework will introduce changes to pharmacovigilance for UK-authorised medicines. This includes updated procedures for submitting safety reports, conducting post-authorisation studies, and ensuring compliance with new pharmacovigilance requirements. The guidance should be used alongside existing MHRA guidance on licensing, labelling, and packaging.

Medicines: packaging, labelling and patient information leaflets

The MHRA regulates the packaging, labelling, and patient information leaflets (PILs) for UK medicines, ensuring clarity and safety. Labels must include essential information, and PILs are required unless the label is fully informative. Warning labels and Braille are mandatory, and child-resistant packaging is required for certain medicines. Changes to labels or packaging must be submitted for approval or notification to the MHRA, with associated fees. Complaints about labelling are investigated for safety and compliance.

Clinical trials for medicines: manage your authorisation, report safety issues

The guidance from the Medicines and Healthcare products Regulatory Agency (MHRA) outlines key steps for managing clinical trials, including amending trial protocols, reporting safety issues, and submitting required documentation. It covers processes such as updating contact details, handling urgent safety measures, and reporting adverse reactions like SUSARs. It also provides instructions on preparing annual safety reports (DSURs), suspending or terminating trials, and completing end-of-trial reports.

User reference guide – Paying online before submitting an annual safety
report.

To submit an annual safety report (DSUR) to the MHRA, first pay the fee through the GOV.UK Pay service using a credit or debit card. Enter a unique submission reference number in the specified format. After payment, ensure that the emailed receipt is included with your submission, as screenshots are not accepted. The fee covers the MHRA’s review of the report and must be agreed upon between the sponsor and any third-party CRO. Submissions without proof of payment will be invalid. For queries, contact DSURfees@mhra.gov.uk.

Medicines: packaging, labelling and patient information leaflets

The MHRA regulates the packaging and labelling of medicines in the UK, ensuring they provide essential information for both consumers and healthcare professionals. Medicines must include a patient information leaflet (PIL) if the label does not fully cover the necessary details. Key requirements include clear labelling, warnings, Braille, and child-resistant packaging. These guidelines follow UK legislation and European standards, which will continue to apply after the transition.

Apply for a licence to market a medicine in the UK

This guidance explains the process for applying for a marketing authorisation for medicines in the UK, including submitting through the MHRA portal with the required documents, such as the summary of product characteristics (SmPC). Fast-track applications are available for urgent products, and fees depend on the application type. Payments must be made promptly to avoid penalties. If a submission is rejected, applicants must correct and resubmit the entire application.

Guidance Send and receive information on adverse drug reactions (ADRs)

Marketing authorisation holders (MAHs) must report adverse drug reactions (ADRs) to the MHRA using systems like ICSR Submissions or Gateway. From 28 May 2024, the MHRA’s new database will accept both R2 and R3 XML formats, with all reports and acknowledgements issued in R3 format. MAHs are also responsible for conducting literature searches and sending relevant findings to the MHRA. Any emerging safety signals should be reported to the MHRA using the Standalone signal notification form.

Labelling and packaging of medicinal products for human use following agreement of the Windsor Framework

The Windsor Framework outlines the new labelling and packaging requirements for medicinal products for human use in the UK, ensuring medicines are approved and licensed on a UK-wide basis by the MHRA. It establishes consistent packaging and labelling across the UK and removes the EU Falsified Medicines Directive (FMD) requirements for medicines marketed and supplied in Northern Ireland.

Apply for manufacturer or wholesaler of medicines licences

The MHRA guidance covers how to apply for, update, or cancel licences for manufacturing, importing, and wholesaling human and veterinary medicines. To obtain a manufacturer’s licence, you must comply with EU good manufacturing practice (GMP) and pass regular GMP inspections. The guidance also includes information on the application process, licence variations, and how to withdraw or terminate a licence, along with details on fees and payments.

Established medicines: marketing authorisation application changes

The MHRA has introduced changes to the marketing authorisation process for established chemical medicines. Key updates include stricter handling of incomplete applications, with only one request for further information (RFI) allowed, and the requirement for applicants to submit a UK public assessment report (UKPAR) lay summary. Applications may be referred to the Commission on Human Medicines (CHM) if deficiencies are found. The process aims for greater transparency and efficiency, with clear timelines for responses and outcomes.

Labelling and packaging of medicinal products for human use following agreement of the Windsor Framework

Starting 1 January 2025, all medicines in the UK must carry a “UK Only” label to prevent their movement into the EU, following the Windsor Framework. Medicines in Northern Ireland currently authorised under the EU procedure will be re-authorised by the MHRA for the UK market. The changes also include the disapplication of EU Falsified Medicines Directive (FMD) requirements for Northern Ireland, ensuring consistent packaging across the UK.

Guidance Advertising and Promotion following agreement of the Windsor Framework

Guidance on Advertising and Promotion following agreement of the Windsor Framework should be used in conjunction with the MHRA’s guidance on the Windsor Framework including UK-wide licensing for human medicines. This guidance should also be used to supplement the operational guidance in the MHRA’s existing Blue Guide on the Advertising and Promotion of Medicines in the UK. This guidance is designed to provide information on the implementation of changes to advertising and promotion of medicines authorized in the UK from 1 January 2025.

Windsor Framework agreement on the supply of human medicines in Northern Ireland

The Windsor Framework secures the long-term stability of medicines supply to Northern Ireland, ensuring that medicines will be available in the same packaging across the UK. This means that new UK-wide arrangements for medicines come into effect on 1 January 2025 . It is important that you take action now to be ready. This document explains the main changes that these new arrangements will introduce and what you need to do to prepare. It should be read in conjunction with the other Medicines and Healthcare products Regulatory Agency (MHRA) guidance on the Windsor Framework, including the UK-wide licensing guidance and labelling and packaging guidance



VENEZUALA

Standard for Marketing Authorization of Pharmaceutical Specialties Whose Innovative Product is Not Registered in the Bolivarian Republic of Venezuela

The “Standard for Marketing Authorization of Pharmaceutical Specialties” in Venezuela outlines the regulatory framework for introducing new pharmaceutical products that are not yet registered in the country. It includes provisions on health registry processes, the application requirements, and the procedures for marketing and promoting these products. The document also covers the withdrawal of products from the market, pharmacovigilance requirements, the cancellation and renewal of health registries, and guidelines for advertising and promotion. Finally, it includes specific annexes related to the application and concludes with final provisions governing the authorization process.

Payment Rules and Tariff Guidelines for Services at the National Institute of Hygiene ‘Rafael Rangel’ (Effective 01/01/2022)

The National Institute of Hygiene “Rafael Rangel” has updated its payment rules effective from January 1, 2022. Payments for services and products must be made via cash, bank transfer, or online payment to a specific account at the Bank of Venezuela. The payment must match the exact rate for each service or product, and both the original and a copy of the deposit receipt must be submitted. Each procedure must be paid separately, and combined payments for multiple requests will not be accepted. For bank transfers, payments should be made at least three business days prior to submitting the appointment request. Incomplete payments will result in the return of the procedure, with no refund for any excess amount.

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