ICH E6(R3) has been restructured and is now composed of an overarching principles section, Annex 1 (interventional clinical trials), Annex 2 (additional considerations for non-traditional interventional clinical trials), Glossary and Appendices.

 

The overarching principles, Annex 1, Glossary and Appendices will replace the current E6(R2) and were released for public consultation by ICH in May 2023.

 

For the UK, the MHRA has opened public consultation on Annex-2: https://www.gov.uk/government/consultations/consultation-on-the-international-council-for-harmonisation-ich-e6-r3-guideline-for-good-clinical-practice-annex-2?utm_medium=email&utm_campaign=govuk-notifications-topic&utm_source=a7e2cf11-d99b-4536-b0e1-17fd1819d069&utm_content=immediately 

 

 

Developing Potential Cellular and Gene Therapy Products

 

The U.S. Food and Drug Administration (FDA) has issued a draft guidance document, intended to provide the industry with answers to Frequently Asked Questions (FAQs) and commonly faced issues that arise during the development of Cellular and Gene Therapy (CGT) products.

 

This guidance is intended to help facilitate the development of safe, effective and high-quality CGT products. The FAQs represent common questions directed to the Agency and span multiple disciplines, including regulatory review, chemistry, manufacturing and controls (CMC), pharmacology/toxicology (PT), clinical and clinical pharmacology. 

 

To access, see: https://www.fda.gov/media/183631/download

 

 

 

AQL (ISO 2589)

 

The ISO standard for calculating the acceptable quality limit is at the ‘draft international standard’ phase: ISO 2589 Sampling procedures for inspection by attributes — Part 1: Sampling schemes indexed by acceptance quality limit (AQL) for lot-by-lot inspection.

 

The current version was issued in 1999 (second revision).

 

The forthcoming changes for the third edition are:

 

• A new procedure for switching from normal (or reduced inspection) to skip-lot inspection
• Guidance on the requirements for producer and product qualification for skip-lot sampling 
• Guidance on the efficacy of implementing skip-lot sampling and some methods of randomly selecting lots to inspect or skip 
• The Operating Characteristic (OC) curves for each plan have been removed in favour of sharing methods to create an individual plan's OC curve and Average Sample Number (ASN) curve, both of which are now included in Annex E

 

The draft is available from national standards bodies (such as BSI).

 

 

 

Good Distribution Practice

 

The Medicines and Healthcare Products Regulatory Agency (MHRA) has published updated guidance for pharmaceutical manufacturers and wholesalers for the Windsor Framework. These rules apply from 1 January 2025.

 

The Windsor Framework sets out the long-term arrangements for the supply of medicines into Northern Ireland. It will ensure that human medicines can be approved and licensed on a UK-wide basis by the MHRA and provides for the disapplication of European Union (EU) Falsified Medicines Directive (FMD) safety features for medicines marketed and supplied in Northern Ireland.

 

The update covers the labelling, packaging and importing requirements for human medicines.

 

For details see: https://www.gov.uk/government/publications/wholesalers-manufacturers-guidance-following-agreement-of-the-windsor-framework/wholesalers-manufacturers-guidance-following-agreement-of-the-windsor-framework 

 

 

 

 

Labelling and packaging of medicinal products for human use following agreement of the Windsor Framework 

 

Companion MHRA guidance is designed to provide information on the implementation of labelling and packaging requirements for medicinal products for human use following agreement of the Windsor Framework.

 
See: https://www.gov.uk/government/publications/labelling-and-packaging-of-medicinal-products-for-human-use-following-agreement-of-the-windsor-framework/labelling-and-packaging-of-medicinal-products-for-human-use-following-agreement-of-the-windsor-framework

 

 

 

First certification of a veterinary vaccine platform technology master file

 

has issued the first certificate for a vaccine Platform Technology Master File (vPTMF) which will support and accelerate the development and authorisation of new veterinary vaccines in the EU.

 

Vaccine platform technologies play an important role in animal and public health preparedness and the ability to respond to emerging animal and public health threats. They have a set of core components common to all vaccines based on the same platform and can be adapted rapidly for use against emerging diseases.

 

For details see: https://www.ema.europa.eu/en/news/first-certification-veterinary-vaccine-platform-technology-master-file

 

 

 

Guidance on the application of the amended Variations Regulation from 1 January 2025

 

Guidance is available on the implementation of the amended Variations Regulation (EU) 2024/1701 for applications implemented and submitted to the EMA from 1 January 2025.

 

This guidance includes amendments to the Article 5 procedure, the annual update for minor variations of type IA, the procedure for grouping and super-grouping of Type IA variations, the annual update of a human influenza or human coronavirus vaccine, the mandatory (same MAH) and voluntary (different MAHs) use of the work sharing procedure, the variations to human vaccines for public health emergencies and to the Annexes.

 

The European Commission is also currently reviewing the guidelines on the details of the various categories of variations and operation of the procedures. An updated version is expected during 2025.

 

See: https://www.ema.europa.eu/en/guidance-application-amended-variations-regulation-1-january-2025

 

 

 

Removal of expiry notifications from the EDQM DCEP Sharing Tool 

 

The EDQM DCEP Sharing Tool is used to share EDQM (European Directorate for the Quality of Medicines and Healthcare) documents securely between the Certification of Substances Department (DCEP) and CEP holders or applicants. Users receive an email with a link when a document is shared with them.

 

Links expire after 60 days, after which time the documents cannot be downloaded. Following feedback from users, the tool has been updated and users will no longer receive an activity notification when the link expires. The 60-day validity period is still in place and is clearly stated in the sharing notification. The EDQM DCEP Sharing Tool user guide (PA/PH/CEP (21) 62) has been updated accordingly.

 

 

 

Resource guide for biosimilars

 

The U.S. FDA’s curriculum materials are intended to help educate students in health care professional degree programmes covering medicine, nursing, physician assistants and pharmacy. They are also used by practicing professionals to improve understanding of biosimilar, interchangeable biosimilar products and the regulatory approval pathway in the United States.

 

The Resource Guide for Teaching Faculty provides information for instructors who would like to incorporate topics related to biosimilar and interchangeable biosimilar products into the education and training they provide students.

 

See: https://www.fda.gov/drugs/biosimilars/curriculum-materials-health-care-degree-programs-biosimilars

 

 

 

Chromatography

 

The chapter in the United States Pharmacopeia (USP) on chromatography is under review in the U.S.

 

In accordance with the Rules and Procedures of the Council of Experts, this is to provide notice that the Chemical Analysis Expert Committee intends to revise General Chapter <621> Chromatography. 

 

This upcoming revision will further clarify the use and applicability of the two sections.

 

System Sensitivity: The text will indicate that the requirement is applicable to impurity tests only when a reporting threshold is stated in the procedure in the individual monograph and clarify the language further.

 

Peak Symmetry: USP will propose to introduce text indicating that this requirement is only applicable to organic impurities, related substances and the assay. 

 

 

 

Regulatory inspections

 

The European Medicines Agency has revised ‘Compilation of Union procedures on inspections and exchange of information’. This is a process for facilitating co-operation between the GMP and GDP inspectorates of the EU Member States and a means of achieving harmonisation.

 

The Compilation has two parts: procedures within the Part I and other documents (e.g., interpretation documents and forms used by regulators) and within Part II.

 

For details, see: https://www.ema.europa.eu/en/human-regulatory-overview/research-development/compliance-research-development/good-manufacturing-practice/compilation-union-procedures-inspections-exchange-information

 

 

 

 Low Global Warming Potential (LGWP) propellants in oral pressurised metered dose inhaler

 

The EMA has issued a document providing advice for manufacturers of inhalers, noting the increased awareness around the global warming potential of certain hydrofluorocarbons (HFCs) used as excipients (propellants) in pressurised Metered Dose Inhalers (pMDIs).

 

The European Commission has proposed a quota system to incentivise the use of LGWP propellants in pMDIs. Since propellant replacement constitutes a major change to the finished product formulation with potential impact also on the construction of the inhaler, guidance is required.

 

Pharmaceutical manufacturers need to provide data confirming maintenance of adequate finished product performance for each modified product. In addition, data addressing possible toxicity and local tolerance of novel propellants needs to be provided. 

 

The document is titled “Questions and answers on data requirements when transitioning to Low Global Warming Potential (LGWP) propellants in oral pressurised metered dose inhalers”.

 

It can be accessed here: https://www.ema.europa.eu/en/questions-answers-data-requirements-when-transitioning-low-global-warming-potential-lgwp-propellants-oral-pressurised-metered-dose-inhalers-scientific-guideline

 

 

 

Tattoo inks and the risk of microbial contamination

 

The US FDA has issued guidance to help tattoo ink manufacturers and distributors recognise situations in which a tattoo ink may become contaminated with microorganisms, and thus, be potentially injurious to health. 

 

This guidance also recommends certain steps that manufacturers and distributors could take to help prevent the occurrence of these conditions, or to identify and remediate insanitary conditions that already exist during manufacturing and distribution.

 

Tattooing typically involves puncturing the epidermis about 100 times per second with needles and depositing ink 1.5 to 2 millimetres below the surface of the skin, deep into the dermis. It generally causes bleeding because the needles pierce the blood vessels. Contaminated tattoo ink can cause infections and serious injuries. Since the inks are injected, pathogens or other harmful substances in these inks can travel from the injection site through the blood and lymphatic systems to other parts of the body. 

 

Tattoo-associated microbiological infections can also include impetigo, erysipelas, cellulitis, and systemic infections that can cause life-threatening complications such as endocarditis, septic shock and multi-organ failure. Indications of an infection can be difficult to recognise, as other conditions (such as allergic reactions or other sources of inflammation) may initially have similar signs and symptoms, leading to misdiagnosis and ineffective treatments.

 

To view: https://www.fda.gov/media/183019/download?attachment 

 

 

 

Review of Drug Master Files (DMF) in advance of certain ANDA submissions under GDUFA

 

New US FDA guidance has been produced for holders of Type II Active Pharmaceutical Ingredient (API) DMFs that will be referenced in an Abbreviated New Drug Application (ANDA) or a Prior Approval Supplement (PAS) to an ANDA.

 

The guidance explains how FDA incorporates a programme enhancement agreed upon by the Agency and industry as part of the negotiations relating to reauthorisation of the Generic Drug User Fee Amendments (GDUFA), as described in “GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal Years 2023-2027” (GDUFA III commitment letter). 

 

To access, see: https://www.fda.gov/media/162019/download