Regulatory Round-up - July 2023

EUROPE

European Commission (EC)

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

This guidance for sponsors reflects the agreement reached by the Clinical Trials Advisory Group (CTAG) Contact Points and supersedes the chapter 11 of the Q&A on the application of the CTR (version 6.4). It provides information on the type of clinical trials that sponsors have to transfer to CTIS, on the timeline and on the content of the application for mono- and multinational trials. Clinical trials will be considered regulated by CTR when they will be authorised under the CTR by a first member state (MS) on the basis of a transition application.

Phasing out of extraordinary COVID-19 regulatory flexibilities

EMA, the EC and the Heads of Medicines Agencies (HMA) are phasing out the extraordinary regulatory flexibilities for medicines put in place during the COVID-19 pandemic as the end of the COVID-19 public health emergency declared by WHO in May 2023. The extraordinary regulatory flexibilities covered areas such as marketing authorisation, related regulatory procedures, manufacturing and importation of active pharmaceutical ingredients as well as finished products, quality variations, labelling and packaging requirements and compliance. The regulatory flexibilities that were introduced jointly by the HMA, EC and EMA specifically during the COVID-19 pandemic should no longer be granted. Please find further information here.

European Directorate for the Quality of Medicines (EDQM)

CEP 2.0: implementation date

EDQM has announced that the CEP 2.0 will be implemented on 1 September 2023. From that date onwards, new dossier applications and renewal applications will receive a CEP 2.0, whereas revision applications will receive a Hybrid CEP if the content of the CEP has been impacted. Please find further information here. The replacement of the declaration of access box on the CEP document by a separate letter of access is one of the changes introduced with the implementation of the CEP 2.0. Templates for this letter can be found here.

European Medicines Agency (EMA)

The use of Artificial Intelligence (AI) in the medicinal product lifecycle

EMA has published a draft reflection paper on the use of Artificial Intelligence (AI) in the medicinal product lifecycle via an open consultation concerning human and veterinary medicines. The reflection paper is part of the joint HMA-EMA Big Data Steering Group (BDSG) initiatives to develop the European Medicines Regulatory Network’s capability in data-driven regulation. It provides considerations on the use of AI and machine learning in the lifecycle of medicinal products, including medicinal products development, authorisation, and post-authorisation.

The aim of this reflection paper is to reflect on the scientific principles that are relevant for regulatory evaluation when these emerging technologies are applied to support safe and effective development and use of medicines. This consultation aims to initiate the dialogue with all groups of stakeholders and during the consultation period an AI workshop will be held by EMA on 20-21 November 2023 in the context of medicines. The deadline for comments is 31 December 2023.

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

In order to further facilitate the joint work of EMA and HTA bodies in preparation of the joint scientific consultations under Article 16 of the HTA regulation (HTAR), the parties involved agree to offer an interim consultation approach, now referred to as Parallel EMA/HTA body (HTAb) Scientific Advice. Health technology developers (HTDs) are offered the opportunity, from September 2023 onwards, to receive Parallel EMA-HTAb Scientific Advice on a rolling basis until the HTA regulation becomes applicable. For all submitted requests, the HTAb involvement coordinating body, the Federal Joint Committee, Germany (G-BA), which will be referred to as the “HTA Coordination Contact” now facilitates a centralised HTA recruitment.

Parallel EMA-HTAb Scientific Advice provides a single gateway for requests for parallel discussions during the interim period, facilitating the transition from the completion of EUnetHTA 21 in September 2023 to the full application of the HTA regulation in January 2025.

This guidance highlights ideal timelines and actions for each party undertaking a Parallel EMA/HTAb Scientific Advice.

Guidance on the electronic submission of information on medicinal products for human use by marketing authorisation holders to the European Medicines Agency

Please find the updated v3.15 ‘Detailed guidance on the electronic submission of information on medicinal products for human use by marketing authorisation holders to the European Medicines Agency in accordance with Article 57(2) of Regulation (EC) No. 726/2004 Chapter 3.II: XEVPRM User Guidance’ here.

CTIS newsflash – 21 July 2023

As of 31 July 2023, JIRA, the current tool for CTIS User Support Service requests, will no longer be available to raise requests or incidents in CTIS and the CTIS Training Environment. Existing data related to CTIS USS tickets opened prior to this date will remain available in JIRA until the tickets are resolved.

The new ServiceNow platform will be accessible via a link and through a mobile app (QR codes for download available in annex). Please find further information here.

UNITED KINGDOM

Medicines and Healthcare products Regulatory Agency (MHRA)

MHRA puts supporting patient access to innovation at the heart of its new Corporate Plan 2023-26

On the 4th July 2023 the MHRA published a new Corporate Plan 2023-2026, which set out how the Medicines and Healthcare products Regulatory Agency plans to keep patients safe by enabling access to innovative, safe and effective medical products over the coming three years.

The four priorities of the Corporate Plan are:

• 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.
• Become an agency where people flourish alongside a responsive customer service culture.

The plan sets out the key actions the agency will take to deliver on these priorities, which will transform medical product regulation in the UK.

USA

Food and Drug Administration (FDA)

OTP Town Hall: Nonclinical Assessment of Cell and Gene Therapy Products

The FDA’s Center for Biologics Evaluation and Research (CBER) Office of Therapeutic Products (OTP) is hosting its next virtual town hall on Wednesday, 30 August 2023 to answer stakeholder questions related to nonclinical assessment of cell and gene therapy products. Experts from OTP’s Office of Pharmacology and Toxicology will be availble to answer questions. Please find further information including how to register here.

Postmarketing Studies and Clinical Trials: Determining Good Cause for Noncompliance with Section 505(o)(3)(E)(ii) of the Federal Food, Drug, and Cosmetic Act Guidance for Industry

The FDA as published a new guidance describing factors considered by the FDA when determining whether an applicant has demonstrated good cause for its noncompliance with the timetable for completion of postmarketing requirements (PMRs) milestones as required under section 505(o)(3).

This guidance also provides information on relevant procedures including how to communicate with FDA regarding PMR compliance, submission of an explanation of the circumstances that led to noncompliance, and how FDA notifies an applicant of a determination of noncompliance. Although this guidance primarily addresses noncompliance with the timetable for completion of PMR milestones, any violation of a requirement under section 505(o)(3)(E)(ii) of the FD&C Act is subject to enforcement action, in the absence of a demonstration of good cause.

This guidance refers only to PMRs required under section 505(o)(3) of the FD&C Act.

Section 505(o) of the FD&C Act applies only to prescription drugs approved under section 505(b) and biological drug products approved under section 351 of the Public Health 55 Service Act (PHS Act).

Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products

Manufacturing and control of CGT products can often be affected by unique factors such as limited knowledge of product quality attributes, limited manufacturing experience, limited variable starting materials, limited amount of product, complex manufacturing processes, as well as limited product shelf life. Therefore, the management of manufacturing changes presents more challenges for human cell or gene therapy than for other biological products.

The FDA published a draft guidance on ‘Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products’ to provide recommendations for management and reporting of manufacturing changes for CGT products based on a lifecycle approach, as well as for comparability studies to assess the effect of manufacturing changes on product quality. Comments can be submitted until 13 September 2023.

Biological Product Deviation Report (BPDR)

The FDA has published general instructions for the completion of Biological Product Deviation Report (BPDR). The FDA requires reporting of certain deviations and unexpected events in manufacturing in accordance with 21 CFR 600.14, 606.171 or 1271.350(b).

The following manufacturers, who had control over the product when an event associated with manufacturing occurred, are required to submit Biological Product Deviation (BPD) reports to the Food and Drug Administration (FDA), if the safety, purity, or potency of a distributed product may be affected:

• Manufacturers of licensed biological products other than blood and blood components (licensed non‑blood) who hold the biological product license [21 CFR 600.14];
• Licensed manufacturers of blood and blood components, including Source Plasma [21 CFR 606.171];
• Unlicensed registered blood establishments [21 CFR 606.171]; and
• Transfusion services [21 CFR 606.171].

Manufacturers of non-reproductive human cells, tissues, and cell and tissue‑based products (HCT/Ps) regulated by FDA solely under section 361 of the Public Health Service Act and 21 CFR Part 1271 are required to submit HCT/P deviation reports to the Center for Biologics Evaluation and Research [21 CFR 1271.350(b)], if the deviation or unexpected event involving a distributed product is related to a Core Current Good Tissue Practice requirement [21 CFR 1271.150(b)] and related to the prevention of communicable disease transmission or HCT/P contamination. It is required that deviation reports are submitted as soon as possible, within 45 calendar days.

Please find the general instructions for completing the Biological Product Deviation Report (BPDR) - Form FDA 3486 here.

Public consultations

Medicines and Healthcare products Regulatory Agency (MHRA)

EUROPEAN MEDICINES AGENCY (EMA)

Food and Drug Administration (FDA)

International Conference on Harmonisation (ICH)

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