Regulatory Round-up - October 2023

UNITED KINGDOM

Medicines and Healthcare products Regulatory Agency (MHRA)

Patients could have Faster Access to Ground-Breaking Stem Cell Treatment with Manufacturing Innovation

The safe manufacture of potentially life-saving stem cells through innovative automation and machine learning, could give patients faster access to stem cell treatments in the future. The MHRA’s UK Stem Cell Bank (UKSCB) is the largest source of clinical grade human embryonic stem cells in the world, providing high quality stem cells for world-leading research, with 30 stem cell lines available for clinical application. Their aim is to implement automation to alleviate the manual aspects of laboratory working with stem cells and to scale up manufacturing, without compromising on safety and quality standards. Please find further information here.

MHRA and international partners publish five guiding principles for machine learning-enabled medical devices (MLMD)

The MHRA, FDA and Health Canada have published five guiding principles for the development of PCCPs for MLMD manufacturers which aim to support manufacturers of MLMDs by reducing the regulatory burden of reassessment following certain changes and updates to their devices.

According to the five guiding principles for MLMD manufacturers a PCCP must be:

1. Focused and Bounded: Describing specific changes that a manufacturer intends to implement.
2. Risk-based: The intent, design, and implementation of a PCCP are driven by a risk-based approach that adheres to the principles of risk management.
3. Evidence-based: Demonstrating that benefits outweigh the risks throughout the product lifecycle.
4. Transparent: Provide clear and appropriate information and detailed plans for ongoing transparency to all stakeholders, from patients to healthcare professionals.
5. Total Product Lifecycle Perspective: Improve the quality and integrity of a PCCP by continually considering the perspectives of all stakeholders.

EUROPE

European Commission (EC)

Blood, Tissues and Cells: EU to Guarantee High Standards of Quality and Safety

On the 19^th of July 2022, the European Commission presented a proposal of regulation on quality and safety standards for substances of human origin intended for human application. The proposal builds upon lessons learnt and addresses the risk of disease transmission by blood, tissues and cells as well as the need for sufficiency of supply.

On the 25^th of October 2023, the Council agreed its negotiating mandate on the proposed regulation on blood, tissues and cells. The aim of the proposed new rules is to strengthen the existing legal framework as well as to add additional flexibility in order to keep up with scientific and technical developments. Further information can be found here.

Updated document - Questions & Answers: Clinical Trials Regulation (EU) No 536/2014

The EC has updated the document titled ‘Clinical Trials Regulation (EU) No 536/2014, Questions & Answers V6.6”, which is now available here. This is a document that sets out frequently-asked 'questions and answers' regarding the implementation of the rules on clinical trials. Updates to this questions and answers document are presented and discussed within the “Expert group on clinical trials” and reflects the view of the group. This group is chaired by the Commission and is composed of representatives of all EU Member States and EEA contracting parties.

Updates in the Product Lifecycle Management (PLM) Portal

New and revised guidance documents and materials relating to ePI (electronic Product Information) are now available on the EMA website under the heading "What's New in PLM?" with a comprehensive update on the progress of the web-based Human variations eAF implementation on Product Lifecycle. The ePI Guidance and Training materials are now also available here.

EMA's Questions and Answers on the Biological Medicines Marketing Authorisation Dossier Published

Questions and Answers relating to biologic medicines have been updated on the EMA website. This content has been developed and being maintained by the Biologics Working Party (BWP). Please find further information on the updated sections here.

European Directorate for the Quality of Medicines (EDQM)

Request for stakeholder feedback on the revised general chapter, Flow Cytometry (2.7.24)

The European Pharmacopoeia is seeking stakeholder feedback on the revised general chapter Flow Cytometry (2.7.24), published in this quarter’s issue of Pharmeuropa (35.4) for comment. The revision of this chapter is of high importance

and has been updated to reflect current techniques in flow cytometry, including technical considerations on sample preparation and data analysis. The deadline for feedback is 31 December 2023. Please find further information here.

OMCL Gene Therapy Working Group Study Published

The GT005 project was initiated by the Gene Therapy Working Group (GTWG) of the GEON (General European OMCL Network), coordinated by the EDQM, with the aim of validating a method that could be broadly used for the quantification of vector genomes within AAV2- based gene therapy products. The results of this study have been published online in Pharmeuropa Bio & Scientific Notes. The article, entitled “Validation of a qPCR method for determination of viral genome titres of AAV2-based vector preparations”, describes the project which makes way for promising steps to standardisation of analytical methods for the quality control of gene therapy products.

European Medicines Agency (EMA)

Revised transparency rules for the EU Clinical Trials Information System (CTIS)

EMA has adopted revised transparency rules for the publication of information on clinical trials submitted through the Clinical Trials Information System (CTIS). One of the key changes of the revised rules is the removal of the deferral mechanism, which allowed sponsors to delay the publication of certain data and documents for up to seven years after the end of the trial to protect personal data and commercially confidential information (CCI). The updated rules intended to have the following impact:

• Benefit patients as key clinical trial information is published early,
• Benefit sponsors due to process simplifications,
• Benefit healthcare professionals as the resulting system is more user-friendly, facilitating access to information about clinical trials and enrolment in clinical trials, as well as increasing awareness of possible treatment options.

USA

Food and Drug Administration (FDA)

Electronic Submission Template for Medical Device 510(k) Submissions

This final guidance, which was published in October 2023 provides the standards for the submission of premarket notification (510(k)) submissions by electronic format, a timetable for establishment of these standards, and criteria for waivers of and exemptions from the requirements to meet a statutory requirement. The development of electronic submission templates intended to serve as guided submission preparation tools for industry to improve submission consistency and enhance efficiency in the review process.

Human Prescription Drug and Biological Products - Labeling for Dosing Based on Weight or Body Surface Area for Ready-to-Use Containers - “Dose Banding”

This guidance provides recommendations to assist applicants in incorporating information into proposed human prescription drug labeling for injectable drug products and is relevant to situations when:

• Dosing for the drug product is based on weight or body surface area (BSA),
• The drug product is available in a range of strengths in ready-to-use containers, and the entire drug content of the ready-to-use container(s) is intended to be administered to a patient.

This guidance applies to proposed labeling in a new drug application (NDA) submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FD&C Act); a biologics license application (BLA) submitted under section 351(a) of the Public Health Service Act (PHS Act); or a supplement to one of these approved applications.

New General Instructions for Completing the Biological Product Deviation Report (BPDR) - Form FDA 3486/ Instructions for Using the eBPDR System

These instructions are to be used by manufacturers to report biological product deviations (BPD) to the Center for Biologics Evaluation and Research (CBER) that may affect the safety, purity, or potency of a distributed product. They may also be for use by manufactures of human cells, tissue and cellular and tissue-based products (HCT/Ps) to report HCT/P deviations. The eBPDR system should not be used for submitting BPD reports to the Center for Drug Evaluation and Research.

The General Instructions for Completing the Biological Product Deviation Report (BPDR) - Form FDA 3486 can be found here, and Instructions for Using the eBPDR System here.

National Institute of Health (NIH)

Reminders About When to Cite an NIH Grant in a Paper: Overcite Oversight

The NIH Grants Policy Statement Section 4.2.1 states “all HHS recipients must acknowledge Federal funding when issuing statements, press releases, requests for proposals, bid invitations, and other documents describing projects or programs funded in whole or in part with Federal money.” Researchers are required to acknowledge NIH grants that support the work described in their papers only if they contributed to the project. Please find further information here.

Public consultations

EUROPEAN MEDICINES AGENCY (EMA)

Food and Drug Administration (FDA)

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