Regulatory Round-up - August 2024

UNITED KINGDOM

Medicines and Healthcare products Regulatory Agency (MHRA)

MHRA pre-submission advice & support guidance

The MHRA offers a pre-submission service before applying for medicines Marketing Authorisations. It is a service that provides stakeholders with the means to understand how the process of compiling and submitting applications and supporting evidence applies for their product/s. The pre-submission service is distinct from MHRAs Scientific Advice offering. Please find further information on the process and access to relevant forms here.

Medicines pipeline data

MHRA is requesting that current or potential medicines Marketing Authorisation Holders (MAH) provide information on planned or potential future submissions to the MHRA. This page holds information detailing how, what, and why this data is required to be submitted.

EUROPE

European Medicines Agency (EMA)

Guidelines on good pharmacovigilance practices (GVP)

On 6 August 2024, revision 3 of Module XVI on risk minimisation measures and its Addendum II on methods for the effectiveness evaluation of such measures were published in their final versions, taking into account the comments received from the public consultation, recent experiences and research on risk minimisation measures and the overall advances in the field drawing from the implementation science. Given the new terminology in GVP Module XVI and the recent coming into application of Regulation (EU) No 536/2014, revision 5 of GVP Annex I on definitions was also published the same day.

EMA account management, what's new?

EMA's Account Management portal is the gateway to using EMA applications such IRIS PLM, electronic application forms (eAF), EudraVigilance, the Clinical Trials Information System and Union Product Database. EMA will hold an online webinar on 20 September 2024 for industry and national competent authorities to learn more about access-management aspects and procedures for requesting and managing access to EMA applications. Please find further information here.

USA

Food and Drug Administration (FDA)

FDA grants accelerated approval to afamitresgene autoleucel for unresectable or metastatic synovial sarcoma

FDA has granted accelerated approval to afamitresgene autoleucel (TECELRA, Adaptimmune, LLC), a melanoma-associated antigen A4 (MAGE-A4)-directed genetically modified autologous T cell immunotherapy, for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumour expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices.

Container closure system and component changes: glass vials and stoppers

Guidance for Industry

FDA has issued a revised guidance providing recommendations to holders of approved new drug applications (NDAs), biologics license applications (BLAs), and abbreviated new drug applications (ANDAs) regarding the reporting and implementation of some common changes to container closure system (CCS) components consisting of glass vials and stoppers for approved sterile drug products, including biological products, administered parenterally. This guidance also discusses pathways available to application holders to obtain Agency feedback. Additionally, this guidance discusses risk-based tools available to facilitate the implementation of changes to CCSs consisting of glass vials and stoppers.

FDA’s latest regulatory agenda adds proposed rules for pediatric study plans, GMPs and DSCSA

The US Department of Health and Human Services (HHS) recently published its semiannual regulatory agenda for Spring 2024 that includes 12 proposed and 10 final rules the FDA plans to propose or finalize in the near future. The agenda includes:

• plans to propose new regulations covering the submission of initial pediatric study plans (iPSPs) by October 2024. This would implement provisions under the Federal Food, Drug, and Cosmetic Act (FD&C Act) which incorporate the Pediatric Research Equity Act (PREA) relating to pediatric study plans giving FDA the authority to require pediatric studies for certain drugs and biological products.
• plans to propose a new rulemaking that would establish a new 21 CFR 321 to clarify FDA's expectations for sponsors conducting clinical pharmacology, and clinical and analytical bioavailability (BA) and bioequivalence (BE) studies supporting marketing applications for drugs and biological products.
• proposed rule, set to be published in February 2025 which would amend current Good Manufacturing Practice (GMPs) for drugs to “clarify and modernize the regulations by adding requirements for quality management systems and controls over components and drug product containers and closures”.
• plans to publish its final rule establishing uniform licensing standards for wholesale distributors and third-party logistics providers (3PLs) mandated under the 2013 Drug Supply Chain Security Act (DSCSA)

Optimising the dosage of human prescription drugs and biological products for the treatment of oncologic diseases guidance for industry

This guidance released in August 2024 is intended to assist sponsors in identifying an optimised dosage(s) for human prescription drugs or biological products for the treatment of oncologic diseases during clinical development and prior to submitting an application for approval of a new indication and usage. It should be considered along with the International Conference on Harmonisation (ICH) E4 guidance on Dose-Response Information to Support Drug Registration (November 1994) when identifying an optimized dosage(s).

BCG-unresponsive nonmuscle invasive bladder cancer: developing drug and biological products for treatment Guidance for industry

The FDA has issued a draft guidance which provides recommendations for the development of drug and biological products for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC) and is intended for pharmaceutical sponsors, the academic community, and other interested parties. This guidance discusses pathological diagnosis and staging, risk stratification, and trial design, including assessment of appropriate clinical endpoints. The deadline for comments is 9 October 2024.

International

New Zealand Medicines and Medical Devices Safety Authority (Medsafe)

Asia-Pacific Roundup: Medsafe seeks feedback on changes to clinical trial regulation

New Zealand’s Medicines and Medical Devices Safety Authority (Medsafe) is holding a consultation into planned changes to the regulation of clinical trials. Medsafe is seeking feedback on proposed revisions to an existing document and two new texts, titled ‘Guideline on the Regulation of Therapeutic Products in New Zealand on specific aspects of clinical development’ and ‘Clinical Trial Safety Monitoring and Reporting for Investigational Products (Medicines and Medical Devices)’. Medsafe wants to make the following updates:

• add details of new or updated legislation and relevant guidance issued in New Zealand and overseas, reflect changes to best practices such as the involvement of patients in trial design and clarify requirements.
• expanded definition of clinical trial that includes additional criteria intended to help distinguish studies from usual clinical practice as well as clarify the scope of the guideline and better align its position with international definitions.
• clarify the fee waiver eligibility criteria and application process, the requirements for labelling investigational medicines and the rule on reporting fatal or life-threatening suspected unexpected serious adverse reactions (SUSARs). Sponsors should report on such SUSARs within 15 days of learning of the event.

The request for feedback includes a question about whether people agree with Medsafe’s proposals to encourage patient-centric clinical trial design and conduct. Medsafe’s position is informed by the Council for International Organizations of Medical Sciences’ publications on the topic. The documents are open for comment until 27 October 2024. Please find further information on how to submit comments here.

International Conference on Harmonisation (ICH)

Prospective ICH Pharmaceutical Quality Knowledge Management (PQKM) Task Force Request for Information (RFI)

The ICH has announced that it will be releasing a Request for Information (RFI) expected in October to determine interest and potential approaches to support the ICH Pharmaceutical Quality Knowledge Management (PQKM) Task Force’s initial assessment for a secure standardised regulatory platform. Please find further information here.

The ICH E11A Guideline reaches Step 4 of the ICH Process

The E11A Guideline provides recommendations and promotes international harmonisation of paediatric extrapolation to support the development and authorisation of paediatric medicines. It provides a framework for using extrapolation to support paediatric drug development. The framework describes the process for understanding the existing information available, the gaps in information needed to inform development, and ways to generate additional information when required and recommends approaches to assessing factors that influence the determination of similarity of disease, drug pharmacology, and response to treatment between a reference and paediatric target population. In addition, it discusses how the characteristics of the disease, drug pharmacology and response to treatment may influence this determination. This guideline has now reached step 4, adoption stage of the ICH process.

Public consultations

European Medicines Agency (EMA)

Food and Drug Administration (FDA)

New Zealand Medicines and Medical Devices Safety Authority (Medsafe)

Click here to download the PDF.