Regulatory Round-up - May 2022

See the latest regulatory news from around the world with the Cell and Gene Therapy Catapult regulatory newsletter.

United Kingdom

Medicines and Healthcare products Regulatory Agency (MHRA)

Open consultation: The future strategy for batch testing of medicinal products in Great Britain

Stakeholders and the UK public are invited to have their say on how, when and if Great Britain should accept batch testing results from third countries or choose to require batch testing in the UK of products intended for the UK market. The consultation seeks views on four policy options aiming to strike the optimal balance between the priority of patient safety, supporting the UK’s Life Sciences Vision, and maintaining globally harmonised standards. The consultation will run for 8 weeks, closing for responses at 11:45pm on 26 July. Full details on the consultation, the policy options, and how to respond can be found here.

Human Tissue Authority (HTA)

Consultation: a review of Code of Practice F, part two

The HTA is holding a consultation to provide an opportunity for all those working in the field of organ and tissue donation and transplantation to review the changes being made to the Code. Draft Code of Practice F, part two. The review of the Code will be focused on ensuring the changes made:

  • accurately reflect the legislative changes which introduce deemed consent for deceased organ and tissue donation in NI
  • clearly describe the circumstances where deemed consent is applicable.


European Commission (EC)

New medicines authorised - Breyanzi (lisocabtagene maraleucel)

Breyanzi received a marketing authorisation valid throughout the EU on 4 April 2022. Breyanzi is a GTMP developed for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B.

European Directorate for the Quality of Medicines (EDQM)

Revision of Chapter 2.6.7 of the European Pharmacopoeia published for Comment

A revision of the general mycoplasma guidance to bring its content in line with the current state of science and technology has been published for comment. The revision provides a statement clarifying that 2.6.7. is not limited to the study of the genus mycoplasma in the strict sense, but also includes the class "Mollicutes", with a focus on the study of mycoplasma, ureaplasma, acholeplasma and spiroplasma (using NAT-based methods). In addition, changes or additions were made in the sections on:

  • Culture method
  • Indicator cell culture method
  • Nuclear amplification techniques (NAT)
  • Validation of nucleic acid amplification techniques (NAT) for the detection of mycoplasmas: Guidelines

The draft revision can be viewed, after registration, on the EDQM/Pharmeuropa website.

European Pharmacopoeia 11th Edition

The latest edition of the European Pharmacopoeia (Ph. Eur.) has been published.

European Medicines Agency (EMA)

Upstaza (eladocagene exuparvovec) receive CHMP Positive Opinion

On 20th May 2022, the Committee for Medicinal Products for Human Use (CHMP) gave a positive opinion under exceptional circumstances for a new gene therapy, Upstaza (eladocagene exuparvovec).

Upstaza is the first medicine intended to treat adult and paediatric patients with aromatic L‑amino acid decarboxylase (AADC) deficiency, an ultra-rare genetic disorder affecting the nervous system. Upstaza consists of a modified virus (adeno-associated viral vector) that contains a functional version of the AADC gene, given to the patient by infusion into the brain, to enable AADC enzyme production in neurons.

EMA’s recommendation is based on the results of three trials including 28 children. The CHMP opinion will now be sent to the European Commission for the adoption of a decision on the EU-wide marketing authorisation. The marketing authorisation holder for this medicinal product is PTC Therapeutics International Limited.

Toolbox guidance on scientific elements and regulatory tools to support quality data packages for PRIME and certain marketing authorisation applications targeting an unmet medical need

New guidance is available for developers of medicines supported by EMA's PRIME scheme on the tools they can use to generate robust quality data packages for their MAA EMA/CHMP/BWP/QWP/IWG/694114/2019. It aims to address common challenges with meeting quality and manufacturing development data requirements during development and at the time of marketing authorisation application.

EMA and EATRIS webinar on Scientific Advice for Advanced Therapy Medicinal Products (ATMPs): what and when to ask (new)

The EMA and the European Infrastructure for Translational Research (EATRIS) are hosting a webinar discussing Scientific Advice for Advanced Therapy Medicinal Products (ATMPs) - what and when to ask. Participation is free of charge and registration can be found here. Details are:

Online, 13.00 - 14.00 Amsterdam time (CEST), 12:00 – 13:00 BST, 10/06/2022.


Food and Drug Administration (FDA)

FDA grants accelerated access for Kymriah

Novartis announced on May 28th 2022 that the US Food and Drug Administration (FDA) has granted accelerated approval for Kymriah® (tisagenlecleucel) for the treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. In accordance with the Accelerated Approval Program, continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Kymriah is now FDA approved in three indications and remains the only CAR-T cell therapy approved in both adult and pediatric settings.

FDA’s CDER launches new acceleration program, ARC

The FDA’s Center for Drug Evaluation and Research (CDER) announced (10th May 2022) the launch of the new Accelerating Rare disease Cures (ARC) Program. The vision of CDER’s ARC Program is speeding and increasing the development of effective and safe treatment options addressing the unmet needs of patients with rare diseases. This is a CDER-wide effort with leadership represented from several offices throughout the Center. In its first year, CDER’s ARC Program will focus on strengthening internal and external partnerships with stakeholders and will engage with external experts to help identify solutions for the challenges in rare disease drug development.

FDA urges drug manufacturers to develop Risk Management Plans

In an effort to improve drug shortages and improve public health, the FDA has issued draft guidance, Risk Management Plans to Mitigate the Potential for Drug Shortages, intended to help with the development, maintenance and implementation of risk management plans. The draft guidance describes a framework for stakeholders to consider when developing risk management plans that align with principles stated in the International Council for Harmonisation guidance for industry, Q9 Quality Risk Management, and identifies risk factors to consider when developing the content of risk management plans.

FDA issues new draft guidance regarding blood and blood component donations.

This draft guidance addresses certain requirements that apply to blood establishments that collect blood and blood components, including Source Plasma. Specifically, the guidance explains the conditions under which the FDA does not intend to take regulatory action for a blood establishment’s failure to comply with certain requirements in Title 21 of the Code of Federal Regulations 630.30 (21 CFR 630.30) regarding donation suitability; 21 CFR 630.10(c)(2) regarding donor eligibility; and 21 CFR 640.69(f) regarding quarantine hold for Source Plasma.

FDA issues new guidance - ‘Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and Blood Components’

This guidance supersedes the guidance of the same title dated April 2020 and updated August 2020 (2020 guidance). The FDA has removed the recommendations to defer indefinitely blood donors for 1) geographic risk of possible exposure to bovine spongiform encephalopathy for time spent in the UK from 1980-1996 and for time spent in France and Ireland from 1980-2001, and 2) receipt of a blood transfusion in the U.K., France, and Ireland from 1980-present. We also provide recommendations for requalification of individuals previously deferred for these geographic risk factors, provided they meet all other eligibility requirements.

Follow up: Annual Patient Engagement & Regenerative Medicine Meeting 2022: An FDA CBER Workshop for Patient Advocates

In the last newsletter, we mentioned a patient advocacy workshop held on the 24th of May, which brought together patients, caregivers, advocates, and other important stakeholders to discuss the purpose and importance of natural history studies. FDA staff and panellists explored how natural history studies contribute to improved understanding of diseases and drug development, including regenerative medicine treatments such as gene and cell therapies. A recording of this is now available here.

FDA hosts Education for Industry (REdI) Annual Conference 2022

Learn directly from the FDA’s regulatory experts in medical product centres: drugs, devices, and biologics. This course is designed to provide participants with a strong, basic foundation in the FDA’s regulatory requirements, and also create awareness of current activities. Registration can be found here.


International Conference on Harmonisation (ICH)

The ICH E8(R1) Introductory Training Presentation is published

The ICH E8(R1) Guideline on General Considerations for Clinical Studies reached Step 4 of the ICH Process on 6 October 2021.

The ICH E8(R1) General Considerations for Clinical Studies was finalised in October 2021 and sets out general principles on the conduct of clinical studies, with the objectives of the document being to (1) Describe internationally accepted principles and practices in the design and conduct of clinical studies that will ensure the protection of study participants and facilitate acceptance of data and results by regulatory authorities; (2) Guide the consideration of quality in the design and conduct of clinical studies across the product lifecycle; (3) Provide an overview of the types of clinical studies performed during the product lifecycle and describe study design elements; and (4) Provide a guide to the ICH efficacy documents to facilitate user's access. The modernisation of ICH E8 is the first step toward the GCP Renovation initiated in 2017.

New Version of the ICH Q3D Guideline for Impurities published to step 5 of the ICH process

The second revision of the "Guideline for Elemental Impurities Q3D(R2)" of the ICH (International Council for Harmonisation of technical requirements for pharmaceuticals for human use), which corrected PDEs for Gold, Silver and Nickel; Gold and Silver monographs; and an added limits for elemental impurities by the cutaneous and transcutaneous route, was published to step 5 of the ICH process at the end of April 2022. This version includes revisions and adaptations in Appendices 2 and 3. Appendix 5 has been added.

Comments on the new ICH Q9 Guideline Q9 (Quality Risk Management) published

Since 2005, ICH Guideline Q9 has been the state of the art when it comes to quality risk management (QRM) in the GMP environment. The draft of a revised document was published in December last year by the ICH and European Medicines Agency (EMA). The revision aims to provide more scientific and robust applications of quality risk management principles to improve quality manufacturing. The EMA has now published the comments received.

There were some important new passages on topics such as:

  • Subjectivity
  • Risk-based decision-making
  • Supply chain complexity

The comments will now be forwarded to the ICH Q9(R1) EWG for consideration as part of Step 3 of the ICH process.