Euro Roundup: EDQM adopts positions on phage therapies, CEP application content

The European Directorate for the Quality of Medicines & HealthCare (EDQM) has updated its guideline on the content of the dossier for chemical purity and microbiological quality and adopted a new chapter on phage therapy medicinal products.

The updated dossier-content guideline is effective 1 May and replaces a 2019 document. Changes are intended to align the document with the current regulatory environment and are essential to prevent a Certification of Suitability (CEP) dossier from being blocked, according to EDQM.

The directorate highlighted key changes to the three modules. In module one, the directorate advises applicants to pay particular attention to using the appropriate EMA SPOR/OMS ORG_ID and LOC_ID for the CEP holder and manufacturing sites. EDQM published a separate notice about updates to a policy document about identifying manufacturing sites by the SPOR OMS coordinates, which have been made mandatory for all CEP applications since June 2023.

For module two, EDQM updated its template for the Quality Overall Summary (QOS). The QOS “serves as a concise overview of Module 3, highlighting the control strategy applied and how regulatory requirements are met to ensure the quality of the substance, and providing assessors with a clear understanding of the substance’s specification and manufacturing process,” the directorate noted.

The QOS is a mandatory component of the CEP application, EDQM added, and “should be treated with utmost importance” The directorate warned that “a poorly crafted or incomplete QOS can hinder the assessment process and lead to delays, potentially jeopardizing the overall timelines to obtain a CEP.”

In module three, EDQM added new requirements for CEP 2.0 and introduced post-approval change management protocols. The directorate also highlighted its addition of detailed expectations for sections related to the manufacturing process, starting materials and intermediates. Companies will need to adapt to the new guideline to avoid setbacks.

“EDQM will implement a stricter validation of applications at receipt and check whether the submission is in line with the requirements described in the revised guideline and the revised QOS template,” EDQM said. “EDQM may, therefore, block applications at receipt from May 2024 in case these are considered deficient to start the assessment process.”

The directorate published the updated guideline days before adopting a new general chapter on phage therapy medicinal products. Interest in phage therapies has risen as the spread of drug-resistant bacteria has created a need for alternatives to existing antibiotics. The European Pharmacopoeia Commission (EPC) responded by making standardized phage therapy requirements a top priority for 2023 to 2025.

EPC adopted the first text last month. The new general chapter “provides a framework of requirements for the production and control of phage therapy products and allows a degree of flexibility commensurate with the complex approaches currently employed in this emerging and rapidly developing field,” EDQM said.

EPC “decided to exceptionally pre-publish the text” on the EDQM website ahead of its publication in July because of the “high interest in the subject matter.” EDQM said the chapter is “the first up-to-date text of its kind to be published in a pharmacopeia.”

CEP Guideline, Phage Chapter

MHRA shares guidance on falsified medicines, parallel distribution under Brexit deal

A pair of documents from the UK Medicines and Healthcare products Regulatory Agency (MHRA) seek to explain the effect of the disapplication of the European Union Falsified Medicines Directive (FMD) safety features and the revised Brexit agreement.

Both guidance documents describe the effect of changes that will come into force in 2025. On 1 January, the revised Brexit deal, known as the Windsor Framework, will take effect. Then, MHRA will license all medicines across the whole of the UK and the FMD will no longer apply in Northern Ireland.

Currently, Parallel Distribution Notices (PDNs) are valid in Northern Ireland, but Parallel Import Licences (PLPIs) are used across the rest of the UK. MHRA will stop accepting PDNs in Northern Ireland at the start of next year and automatically convert all existing PLPIs to cover the whole of the UK.

Starting in January, new packs placed on the market must carry a “UK Only” label to stop them from entering the EU. The guidance states the requirements for the labels and explains how companies can meet the rules by using stickers. The guidance also features a paragraph on the disapplication of FMD, a topic that MHRA covers in more depth in the other document.

“Any 2D barcode encoding an alphanumeric character sequence that has been uploaded to the European repositories system should be fully removed or covered,” MHRA said. “From 1 January 2025, PLPI license holders must ensure imported packs are decommissioned correctly and cannot re-enter the European supply chain.”

The guidance covers how to check stock from Italy and Greece, two countries that are yet to implement the FMD’s 2D barcode unique identifier system because they have their own approaches to verification.

Falsified Medicines, Parallel Distribution

European, Japanese pharmacopeias launch harmonization project

The European and Japanese pharmacopeias have started “a bilateral prospective harmonization project” aimed at standards for active substances and medicinal products.

The project will take place outside of the Pharmacopeial Discussion Group processes, the harmonization collaboration for European, Japanese, US and Indian pharmacopeias. Building on experience gained in earlier collaborations, the European and Japanese pharmacopeias plan to work to harmonize certain monographs while taking the specificities of their respective regulatory frameworks into account.

The pharmacopeias have chosen macitentan and macitentan tablets as the first candidates for the new project. Macitentan, which Johnson & Johnson sells as Opsumit, is a pulmonary arterial hypertension treatment.

“Discussions will include an overview of current and future possibilities and the challenges met when expanding the harmonization of pharmacopoeial standards to both active substances and medicinal products. The lessons learned during this project may pave the way towards further strengthened cooperation between the two organizations,” EDQM said.

EDQM Notice

EFPIA lists concerns with the workability of EU HTA as Commission closes consultation

EFPIA and other trade groups have voiced concerns over the workability of the EU Health Technology Assessment (HTA) regulations in response to a request for feedback from the European Commission.

The trade groups said the draft rules in their current format will create “an unworkable framework for [joint clinical assessments] and consequently lead to duplication of work.” Specifically, the trade groups contend that “the timelines are unworkable and too short to allow companies to provide quality input regarding evidence, analysis and comments.”

Other respondents to the consultation made similar points. AstraZeneca called the timelines “insufficient and unbalanced,” explaining that they undermine companies “capacity to produce a high-quality submission.” Novartis is also pushing for more opportunities for the developers of health technologies to contribute to the process.

Press Release

Other news

The European Medicines Agency (EMA) has warned its systems will be fully or partially inaccessible from 11 to 17 April. On those days, EMA will be loading nationally and centrally authorized product data to its Product Management Service database, an action it called a crucial step in making structured and standardized medicines data available. The agency has listed when different systems will be affected. EMA Notice

Euro Roundup: EDQM adopts positions on phage therapies, CEP application content

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