Euro Roundup: EMA finalizes guideline on chemistry of active substances

The European Medicines Agency (EMA) has finalized updated guidance on the information required for the manufacture and control of active substances used in medicinal products, with a 1 September date of application.

EMA published the previous version of the guideline in 2016. In 2022, the agency proposed updating the text based on the discovery of N-nitrosamine impurities. The substances were found in sartans and other active pharmaceutical ingredients (APIs), despite the original guideline covering the assessment and control of mutagenic and potentially mutagenic impurities.

The final guideline is mostly the same as the draft version shared for consultation in 2024. Changes include adding a new introductory paragraph to a section on impurities. In the new paragraph, EMA explained that applicants should share the maximum daily dose, route of administration, and treatment duration considered for the control strategy and specification of the active substance.

EMA also revised a subsection on reprocessing. In the final guideline, EMA said any reprocessing should be conducted in line with the International Council for Harmonisation Q7 guideline or the second part of the EU good manufacturing practice document.

“If reprocessing is used for a majority of batches, such reprocessing should be included as part of the standard manufacturing process,” EMA wrote. “The cases where occasional reprocessing is carried out should be clearly described in the dossier and justified. Any data to support this justification should be either referenced or presented.”

Overall, the final guideline provides the industry with more recommendations on cohorts of concern impurities, primarily N-nitrosamines, and expanded guidance on starting materials, recovery, and reprocessing. EMA has yet to publish the feedback it received on the 2024 draft guideline.

EMA Guideline

EDQM shares guidance on reliance-based and fast-track CEP filings

The European Directorate for the Quality of Medicines and HealthCare (EDQM) has published guidelines on how Certification of Suitability (CEP) holders or prospective applicants can request reliance-based or fast-track assessments.

Both pathways offer accelerated assessments of new applications for chemical purity while maintaining the regulatory diligence and rigor of standard CEP reviews. The circumstances in which the pathways can be used are different, with EDQM opening the reliance-based route to companies with certain regulatory approvals and creating the fast-track mechanism to address medicine shortages.

The reliance pathway is open to applicants with Active Substance Master Files (ASMFs) or Drug Master Files (DMFs) that have been assessed and accepted in the EU, European Economic Area, Switzerland, UK, Australia, or Canada since October 2012. The manufacturing process must be the same for the existing and requested approvals. EDQM expects the CEP dossier to be identical to the ASMF or DMF dossier, although it may accept minor updates to the original file.

Applicants may be eligible for a fast-track review when EMA or a national regulator has asked EDQM to help address an active substance or excipient shortage. EDQM will also consider fast-tracking the review of active substances that EMA lists as being subject to an ongoing shortage. The directorate will refuse requests for fast-track assessment based solely on commercial grounds.

On a case-by-case basis, EDQM will consider fast-tracking requests from prospective CEP holders that can clearly show an accelerated review would deliver significant benefit to patients or align with the objectives of the EU Critical Medicines Act. EDQM will consider the criticality, therapeutic indication, and availability of the active substance when assessing the impact of a fast-track review on patients.

EDQM has established the same timelines for reliance-based and fast-track reviews. The directorate will complete the initial evaluation within 46 working days, after which the applicant will have 30 calendar days to respond. EDQM has 23 working days to complete its subsequent evaluation. Initial assessments take up to 115 working days under the standard procedure.

EDQM Notice

MHRA moves to de-risk development strategies that exclude animals

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published guidance on its approach to assessing drug applications that rely on alternatives to animal testing.

MHRA published its document to support the UK government’s long-term strategy for phasing out animal testing days after the US Food and Drug Administration (FDA) posted draft guidance on new approach methodologies (NAMs) (RELATED: FDA drafts guidance on animal testing alternatives, Regulatory Focus, 18 March 2026).

MHRA’s guidance sets out how the agency will help drug developers understand the requirements imposed by the planned staggered transition away from animal testing, including a commitment to provide early reviews of study data on products developed without animal studies. By the end of the year, MHRA will establish a mechanism for reviewing Module 4 of the marketing authorization application before full submission. Module 4 contains nonclinical study reports.

After the early review, MHRA will provide a non-binding written opinion, either accepting the data as adequate or explaining perceived deficiencies. Applicants will submit the same Module 4 and MHRA’s written opinion when they seek marketing authorization or file a revised Module 4 including any data generated since the original review.

The agency is creating the early-review mechanism to de-risk drug development strategies that exclude animals and to support the use of NAMs. MHRA will charge a fee for early Module 4 reviews to recover costs and discourage unsuitable applications. The mechanism applies to marketing authorizations, not submissions to run clinical trials.

Other parts of the guidance provide general and product-specific considerations for companies assessing whether to use animal models. Products with well-recognized pharmacological profiles may enter clinical trials without being tested on animals, MHRA said, and generic and biosimilar medicines should not be tested on animals.

MHRA Guidance, Press Release

EMA updates guidance on providing information via QR codes

EMA has updated guidance on using technologies such as QR codes and near-field communication to provide electronic information to patients.

The agency published the original guidance on mobile scanning technologies in 2015 and updated the text in 2018. EMA’s latest update clarifies that the marketing authorization holder (MAH) is responsible for ensuring information is available electronically when its product launches in a Member State and for keeping the materials up to date for as long as the medicine is on the market.

Information provided via mobile technology should be based on the latest approved product materials. If batches with different information coexist in the market, for example, because of changes to excipients or storage conditions, the MAH should ensure that the information for those batches is available.

EMA said it will consider requests to delete mobile technologies, as with any post-authorization change. If the platform provided by mobile technology is decommissioned and there are still batches on the market, the MAH is responsible for informing users accordingly when they scan the feature.

The agency also updated its advice on the URLs of platforms that host content linked to via QR codes and other mobile scanning technologies. EMA said the URL should ideally identify the medicinal product, for example, by using the format www.productname.eu. If that is not feasible, MAHs should choose a URL that is simple and easy to type, non-promotional, and as concise as possible. 

EMA Guidance