Pharma/Biotech – USA, Europe Regulatory News, July 2023 Vol. 1

USA

No Big-Picture Impact for Manufacturers in CMS IRA Updates

In the face of multiple lawsuits and 7,500 public comments, CMS adjusted some aspects of the Inflation Reduction Act’s drug price negotiation provisions, but the changes don’t lessen the law’s overall power to require pharmaceutical companies to sell medications to the government at what they fear will reflect below-market rates. The revisions, for example, make it easier for companies to leave the Medicare system if they don’t want to play ball, but they don’t weaken the program’s formidable financial stick, which whacks noncompliant companies with an annual excise tax of up to 95 percent of sales, and fines of up to $1 million for every noncompliant day.

Expansion, Clarification Needed for Guidance on Incorporating COAs Into Endpoints

Feedback on the FDA’s draft guidance for incorporating clinical outcome assessments (COA) into endpoints has trickled in from a number of stakeholders, including BIO and the International Society for Cell & Gene Therapy, who feel the guidance would be well served with expansion and clarification in certain areas.

Compounders May Not Sell to Wholesalers to Qualify for 503B Exemption

The FDA’s interpretation and policies on exemption as well as prohibition of wholesaling of compounded drugs in section 503B of the Food, Drug & Cosmetic Act (FDC) are explained in a draft guidance published on June 27.

Patient Preference, Safety Evaluation, Bioequivalence New Guidance Areas for ICH

The International Council for Harmonization’s (ICH) governing group announced earlier this month it will begin work on new guidelines in three areas: patient preference, nonclinical safety evaluation for oligonucleotide-based therapies and bioequivalence for modified-release products.

Changes to Rules for LDTs, National Drug Code and Device QSR Top FDA Regulatory Agenda

The FDA’s list of regulations it plans to propose or finalize in the next 12 months, released Tuesday, includes more than 30 proposed and final rules related to drug, device and biologics products. Target release dates vary by rule.

FDA Issues Procedures for Handling Reclassification Requests

FDA’s method for assessing requests for major-to-minor reclassifications for complete response (CR) letters is described in the just-released Manual of Policies and Procedures (MAPP).

FDA Guidance Outlines GDUFA III Fee Program Changes

The FDA sketched out how it is implementing the fee structure of the Generic Drug User Fee Amendments of 2022 (GDUFA III) in a final guidance released Friday.

FDA Launches Real-World Evidence Program, Part of PDUFA VII Commitments

The FDA has selected the initial applications for participation in its Advancing Real-World Evidence (RWE) program, which allows pharmaceutical sponsors four meetings with the agency to discuss proposals to use RWE in drug development, according to Kimberly Smith, RWE analyst in CDER’s Office of Medical Policy. Speaking in a presentation at the FDA’s Regulatory Education for Industry (REdI) Annual Conference, June 5-9, Smith explained that the program launched in October 2022 as part of the agency’s commitments under the Prescription Drug User Fee Act (PDUFA VII), the program aims to identify approaches for generating RWE that can meet regulatory submission requirements.

Best Practices for Pharma Process Validation

Compliance with current good manufacturing practice (CGMP) has always been a top enforcement priority for the FDA. And lately, the agency has been taking a tougher stance on one particular CGMP area process validation.

FDA Confirms Its Cover Letter Attachments for Generic Submissions Are Voluntary

The use of FDA’s checklist-like cover letter attachments for controlled correspondence and generic drug submissions are voluntary, the agency emphasized in a final guidance released Monday.

FDA Calls for Public Comment on Revised Draft of GCP Guideline

The FDA is seeking public comment from clinical trial sponsors, sites, investigators and other interested parties on a long-awaited revision of the International Council on Harmonization’s (ICH) good clinical practice (GCP) guideline, ICH E6.

ICH paper calls for ‘stepwise’ harmonization of RWE

The International Council for Harmonization (ICH) issued a Reflection Paper outlining a “stepwise” approach to harmonization of real-world data and evidence (RWD/RWE) that includes common operational definitions, general principles for assessment, and best practices for registration of study protocols and results. The ICH Assembly endorsed the Reflection Paper in June 2023, and it is under public consultation until 30 September 2023. Any comments received by that date will be considered for inclusion in the final Reflection Paper, anticipated to be adopted in June 2024.

FDA issues revised site selection model tying surveillance inspections to location

The US Food and Drug Administration (FDA) recently issued an internal Manual of Policies and Procedures (MAPP) for its staff outlining how it will prioritize inspections under its site selection model (SSM) for routine quality related surveillance inspections. The update adds a risk factor for establishments located in countries where there is a “history of violations” related to exports. The update revises a previous version issued in September 2018 to add a “risk factor for establishments related to the compliance history of establishments in the country or region in which an establishment is located.” This can include “the history of violations related to products exported from such country or region that are subject to such regulation.”

FDA finalizes guidance on quantitative efficacy and risk info for DTC promotional labeling, ads

The US Food and Drug Administration (FDA) has published final guidance on presenting risk and efficacy for direct-to-consumer (DTC) promotional labeling and advertisements for prescription drug and biologic products for humans and drug products for animals. The aim of the final guidance is to provide recommendations for companies on how to create advertisements and promotional materials for DTC drug and biologic products with “consumer-friendly” language and presentation, which includes information on presenting probability, formatting quantitative efficacy and risk information, and use of visual aids.

EUROPE

EMA Opens Comment on ICH-Endorsed Draft Paper on RWD/RWE

Use of real-world data (RWD) and real world evidence (RWE) continues to gain traction in countries around the world, as seen in a draft reflection paper endorsed by the International Council on Harmonization and issued for comment by the European Medicines Authority (EMA).

MHRA vows to increase oversight of high-risk products

The UK Medicines and Healthcare products Regulatory Agency (MHRA) will increase oversight of high-risk products, particularly new technologies, while simultaneously reducing regulatory oversight of products “where there is clear evidence of a lower risk to patients.” The risk-based framework, plus a focus on addressing health inequalities and promoting sustainability, will inform MHRA’s pursuit of four strategic priorities through 2026. MHRA’s four strategic priorities, outlined in its corporate plan, are to: maintain public trust through transparency and proactive communication; enable healthcare access to safe and effective medical products; deliver scientific and regulatory excellence through strategic partnerships; and become an agency where people flourish alongside a responsive customer service culture.

New EFPIA leaders share wish list of changes to draft pharmaceutical legislation

The newly elected EFPIA presidency team has shared a list of requested changes to EU draft pharmaceutical legislation. EFPIA, a trade group representing large pharma companies, wants the EU to work on “further optimizing the regulatory framework and maximizing use of expedited pathways.” Industry leaders criticized the draft EU legislation before and after its publication in April. EFPIA Director General Nathalie Moll warned that the proposals “undermine research and development in Europe while failing to address access to medicines for patients” and argued that “penalizing innovation if a medicine is not available in all member states within two years is fundamentally flawed and represents an impossible target for companies.”

Guidance on Parallel EMA/HTA body (HTAb) Scientific Advice for the Interim Period

This guidance highlights ideal timelines and actions for each party undertaking a Parallel EMA/HTAb Scientific Advice. This is a multi-stakeholder procedure with EMA and HTAbs being equal partners. As a multi-stakeholder procedure, collaboration and communication between all stakeholders are important to ensure agreement and clarity on the ownership of different actions, and to deliver on the objectives of the exercise.

European Medicines Agency post-authorization procedural advice for users of the centralized procedure

This guidance document addresses a number of questions which marketing authorization holders (MAHs) may have on post-authorization procedures. It provides an overview of the Agency’s position on issues, which are typically addressed in discussions or meetings with MAHs in the post-authorization phase. This guidance information and fruitful pre-submission dialogue between MAHs and the Agency should enable MAHs to submit applications, which are in conformity with the legal and regulatory requirements and which can be validated and processed promptly.

Guideline for the notification of serious breaches of Regulation (EU) No 536/2014 or the clinical trial protocol

This document was prepared in collaboration with the UK Medicines & Healthcare products Regulatory Agency (MHRA) and was available for public consultation between May and August 2017. To outline the practical arrangements for notification of serious breaches; this document does not cover notifications related to unexpected events, other reporting obligations related to the safety of trial participants or urgent safety measures, as defined in Articles 53 and 54 of the Regulation (EU) No 536/2014.

ICH Reflection paper on proposed international harmonization of real-world evidence terminology and convergence of general principles regarding planning and reporting of studies using real-world data, with a focus on effectiveness of medicines

The objectives of this Reflection Paper are:  To engage ICH on convergence of terminology for RWD and RWE, on the format for protocols 85 and reports of study results submitted to regulatory agencies throughout the lifecycle of 86 medicinal products, and on promoting registration of protocols and reports, to inform the assessment of RWD and RWE for regulatory purposes.