Regulatory Round-up - February 2024

UNITED KINGDOM

Medicines and Healthcare products Regulatory Agency (MHRA)

MHRA announces two new UK Approved Bodies to certify medical devices

LNE-GMED UK and Scarlet NB UK have joined the seven current UK Approved Bodies, increasing capacity for the certification of medical devices in the UK. Please find further information here.

EUROPE

European Commission (EC)

Swissmedic: Nitrosamine Requirements updated

Swissmedic's nitrosamine Q&A document "Update of the requirements for dealing with nitrosamine impurities in medicinal products" has been released and the latest version is now available on the Swissmedic website. The updates can be found in the ‘Market authorisation’ section of the document. Please find further information here.

European Directorate for the Quality of Medicines (EDQM)

Top 10 deficiencies observed in new CEP applications for chemical purity assessed in 2023 to improve the quality of your applications

EDQM has published a document which outlines the top ten deficiencies identified after the initial evaluation of new applications for Certificates of Suitability (CEP) for chemical purity. This summary is intended to help applicants build their application in conjunction with the EDQM guideline “Content of the Dossier for Chemical Purity and Microbiological Quality of Substances for Pharmaceutical Use”. The deficiencies are listed and details on how to avoid them are provided to users to improve the quality of their applications. Please find further information and access to to document here.

European Medicines Agency (EMA)

Progress update on pilot scheme for academic and non-profit developers of advanced therapy medicines

Since the launch in September 2022, EMA has accepted three academic and non-profit organisations developing advanced therapy medicinal products (ATMPs) into a pilot scheme, in which they benefit from enhanced support from the Agency. The aim is to guide non-commercial developers of promising ATMPs addressing unmet medical needs through the regulatory and scientific requirements in the EU and better understand their needs to enable them to advance the development of their medicines and eventually reach the marketing authorisation application stage. EMA is looking to add another two developers by the end of 2024. Please find further information here.

Launch of new HMA-EMA catalogues of real-world data sources and studies

EMA and the Heads of Medicines Agencies (HMA) have launched two public electronic catalogues: one for real-world data (RWD) sources and one for working draft (WD) studies, which is intended to help medicines regulators, researchers and pharmaceutical companies to identify the most suitable data sources to address specific research questions and support the assessment of study protocols and results. The aim is to promote transparency, encourage the use of good practices, and build trust in research based on RWD. The initiative builds on the former databases, developed by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP):

• The catalogue for RWD sources enhances and replaces the ENCePP Resources Database, an EMA-coordinated index of resources of available research organisations, networks and data sources in the fields of pharmacoepidemiology and pharmacovigilance within Europe.
• The catalogue for RWD studies expands and replaces the European Union electronic register of post-authorisationstudies (EU PAS Register®).

Please find further information here.

Non-inferiority and equivalence comparisons in clinical trials - Scientific guideline

Non-inferiority comparisons to active comparators are frequently used in drug development to provide pivotal evidence for marketing authorisation applications. Issues related to non-inferiority and therapeutic equivalence comparisons require considerations different from those encountered in superiority trials. EMA suggested merging the two currently available guidance documents on this issue, the Guideline on the Choice of Non-Inferiority Margin, adopted by the CHMP in 2005, and the Points to consider on Switching between Superiority and Non-Inferiority, adopted by the CHMP in 2000. It is recognised that the generation of a single guideline on non-inferiority and therapeutic equivalence comparisons would facilitate the compilation of the related regulatory requirements. The public consultation on the proposed guidance will end on 31 May 2024.

USA

Food and Drug Administration (FDA)

Human Gene Therapy Products Incorporating Human Genome Editing

In recent years, human genome editing (GE) as a scientific technology used in the treatment of human disease has substantially increased, and there has been rapid development of gene therapy products incorporating GE. To assist in the translation of these products to clinical trials, the FDA has issued a final guidance which provides recommendations to sponsors developing human gene therapy products incorporating genome editing (GE) of human somatic cells. It provides recommendations regarding information that should be provided in an Investigational New Drug (IND) application in order to assess the safety and quality of the investigational GE product, as required in Title 21 of the Code of Federal Regulations 312.23 (21 CFR 312.23) and includes information on product design, product manufacturing and testing, non-clinical safety assessment, as well as clinical trial design.

FDA Accelerated Approval: AMTAGVI

The FDA has issued an accelerated BLA approval of lifileucel (AMTAGVI), a tumor-derived autologous T cell immunotherapy, for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor.

Use of Data Monitoring Committees in Clinical Trials

This draft guidance by the FDA is intended to assist sponsors of clinical trials in determining when a data monitoring committee (DMC) (also known as a data and safety monitoring board (DSMB), a data and safety monitoring committee (DSMC), or an independent data monitoring committee (IDMC)) would be useful for trial monitoring and what procedures and practices should be considered to guide their operation. Once finalised, it will supersede the final guidance for clinical trial sponsors entitled “Establishment and Operation of Clinical Trial Data Monitoring Committees,” issued in 2006. Comments can be submitted until 16 April 2024.

Charging for Investigational Drugs Under an IND Questions and Answers Guidance for Industry

The FDA issued a guidance providing information for industry, researchers, physicians, institutional review boards, and patients about the implementation of FDA’s regulations on charging for investigational drugs under an IND for the purpose of either clinical trials or expanded access for treatment use (21 CFR 312.8), which went into effect in 2009. FDA has received several questions concerning its implementation of the charging regulation. As a result, FDA issued the guidance for industry “Charging for Investigational Drugs Under IND — Questions and Answers” (June 2016; revised draft August 2022). This guidance finalizes the revised draft guidance of the same title issued in August 2022 and replaces the 2016 guidance.

Reporting Amount of Listed Drugs and Biological Products Under Section 510(j)(3) of the FD&C Act

The FDA has issued a final guidance to assist registrants of drug establishments in submitting reports to FDA on the amount of each listed drug manufactured, prepared, propagated, compounded, or processed for commercial distribution, as required by section 510(j)(3) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360(j)(3)), as added by section 3112(e) of the Coronavirus Aid, Relief, and Economic Security Act (CARES Act).

Notifying FDA of a Discontinuance or Interruption in Manufacturing of Finished Products or Active Pharmaceutical Ingredients Under Section 506C of the FD&C Act

The FDA has issued a draft guidance for industry entitled “Notification of a Permanent Discontinuance or Interruption in Manufacturing Under Section 506C of the FD&C Act.” This draft guidance is intended to assist applicants and manufacturers in providing FDA timely notifications about changes in the production of certain finished drugs and biological products as well as certain active pharmaceutical ingredients (API) that might help the Agency to prevent or mitigate shortages.

Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products

This FDA final guidance is intended to assist sponsors, including industry and academic sponsors, developing CAR T cell products by providing CAR T cell specific recommendations regarding chemistry, manufacturing, and control (CMC), pharmacology and toxicology, and clinical study design.

Select Updates for the Medical Device User Fee Small Business Qualification and Certification Guidance

The FDA has issued a draft guidance to propose selected updates to the FDA guidance document “Medical Device User Fee Small Business Qualification and Certification”. It provides additional information on how small businesses can show financial hardship to qualify for a small business registration fee waiver. The existing Small Business Guidance remains in its current form, until this draft guidance is finalized. FDA is seeking feedback on revisions proposed in this select update. Comments can be submitted until 23 April 2024.

INTERNATIONAL

International Conference on Harmonisation (ICH)

The ICH E2D(R1) draft Guideline presentation available now on the ICH website

The ICH E2D(R1) draft guideline on “Post-Approval Safety Data: Definitions and Standards for Management and Reporting of Individual Case Safety Reports (ICSRs)” has reached Step 2b of the ICH Process and entered the consultation period. A Step 2 Informational Presentation developed by the Expert Working Group and is now also available for download on the E2D(R1) page.

Public consultations

European Medicines Agency (EMA)

Food and Drug Administration (FDA)

Click here to download the PDF