Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.

CVMP Adopts Guideline Despite Criticisms of Rising Regulatory Burden

The Committee for Medicinal Products for Veterinary Use (CVMP) has adopted a guideline on the data needed to win approval for immunological minor use, minor species (MUMS) drugs. CVMP is pushing ahead with the guideline despite the animal medicine industry raising concerns it will add to regulatory burdens, an outcome that runs counter to the primary objective of MUMS status.

Members of the European Medicines Agency’s (EMA) Immunologicals Working Party released the draft guideline for consultation in February. That text, the second draft released for consultation in 12 months, and the final version posted this week sought to “reduce data requirements where possible for products classified as MUMS.” EMA designed the text to stimulate development of such products — the veterinary equivalent of orphan drugs — without compromising on quality, safety or efficacy.

Some observers have questioned whether the guideline achieves this goal. EMA received feedback on the February draft from two organizations, Zoetis’ fish vaccine subsidiary Pharmaq and animal health trade group IFAH-Europe. Both groups raised concerns the guideline, rather than reducing data requirements, will actually increase the regulatory burdens on companies developing MUMS products.

“There is a major concern that the regulatory requirements actually increase, such as the addition of a requirement for Detailed and Critical Summaries and revision of “R&D batches” into “pilot batches” for consistency and stability, which contradicts the general principle of favoring acceptable data reduction for [marketing authorization] applications in order to increase the availability of products,” IFAH-Europe wrote in its feedback. Zoetis, a member of IFAH-Europe, made a similar point.

CVMP noted but largely rejected the concerns. The one point it conceded is that the need for Detailed and Critical Summaries (DACS) will add to data requirements. However, the addition of DACS to the list of materials companies must include in their dossiers is a legislative requirement. To mitigate the effect of the requirement on MUMS medicine developers, CVMP is only asking for one short DACS covering quality, safety and efficacy and justifying gaps in the data.

The committee thinks concerns about the revision of “R&D batches” into “pilot batches” are misplaced. As CVMP sees it, this change does not add to data requirements. Instead, it “provides the opportunity to generate data with either R&D or pilot batches providing these are representative for the manufacturing process of industrial scale batches.” The regulator also pointed to changes it expects to reduce data requirements, such as the option to skip duration of immunity studies.

As with all guidelines, the actual impact will only become fully apparent once sponsors and regulators begin using it to guide their activities. The text is due to come into force on 1 November.

Press Release, Final Guideline, Industry Comments

EMA Proposes Update to Guideline on Veterinary Bioequivalence Studies

CVMP has released a revised guideline on running bioequivalence studies of veterinary medicines. The proposed changes are intended to bring EMA’s guideline in line with an international text that came into force in the European Union in August.

EMA’s CVMP has known it would need to revise its guideline since the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) adopted its bioequivalence document late in 2015. CVMP responded to the adoption of the VICH document with a concept paper that outlined the areas of its guideline affected by text. The draft guideline builds on the concept paper.

Headline changes include the adoption of VICH’s harmonized definition of bioequivalence. The CVMP draft defines bioequivalence as “the absence of a difference (within predefined acceptance criteria) in the bioavailability of the active pharmaceutical ingredient (API) or its metabolite(s) at the site of action when administered at the same molar dose under similar conditions in an appropriately designed study.” The current adopted CVMP guideline has a different definition.

CVMP has also addressed the implications of the VICH document on the design, conduct and evaluation of bioequivalence studies. The draft text goes into greater detail on how to design and run crossover and parallel bioequivalence than the current guideline. It also provides a more thorough explanation of why a parallel study may be preferable to a crossover test.

EMA’s CVMP is proposing other changes to the section on study design, too, but it has left sections of the guideline unaltered. This reflects CVMP’s focus on incorporating the VICH changes rather than making wholesale changes to the guideline, which it adopted in 2011. 

CVMP is accepting comments on the draft until the end of October. 

Draft Guideline

Dutch MEB Raises Concerns About use of ADHD Drug Ritalin in Adults

The Medicines Evaluation Board (MEB) of the Netherlands has raised concerns about the use of methylphenidate in adults with attention deficit hyperactivity disorder (ADHD). Methylphenidate, better known by the brand name Ritalin, is not approved by MEB for use in adults.

MEB’s opposition to the use of methylphenidate in adults is based on a belief side effects including high blood pressure and psychiatric events mean the risks outweigh the benefits. However, MEB allows doctors to continue to prescribe methylphenidate to patients after they turn 18 years old if they think the benefits clearly outweigh the risks for that particular person. 

Prescribing data suggest doctors are frequently making decisions in favor of continued use of the drug into adulthood. MEB reports 57,000 people aged 25 years and older were taking the drug in 2015. This amounts to around one-third of the total market for methylphenidate in the Netherlands.

MEB has responded to the data by restating its opposition to the routine use of methylphenidate in adults. However, the regulator is not strengthening restrictions on the drug. Instead, the agency plans to talk to doctors and patients about the use of methylphenidate, a drug it acknowledges may be the best option in some cases.

MEB Notice (Dutch)

Spanish Regulator, Defense Department Agree on Disaster Response Plan

The Spanish Agency of Medicinal Products and Medical Devices (AEMPS) is working with the country’s defense department to build a stockpile of medicine for use in case of a disaster. Officials plan to procure drugs for use in the event of terrorist attacks, epidemics and other events.

AEMPS stepped up its working relationship with the Spanish department of defense by signing a document setting out the terms of their collaboration. The government agencies will work together to identify which medicines Spain needs to stockpile and in what quantities. Officials will also take coordinated actions to ensure these medicines are available in the event of an emergency.

The regulator’s role in the process will include signing off on a protocol to follow in emergency situations, such as biological, chemical and nuclear attacks, epidemics and serious but localized disease threats. The goal is for Spain to be equipped to respond quickly to such events and, in doing so, mitigate the harm they cause.

AEMPS Statement (Spanish)

Other News:

AEMPS has changed its procedure for handling modifications to marketing authorizations. The regulator has implemented the changes to address the delays that arose as a result of the volume of modification requests and complexity of the procedure. Officials in Spain think the new way of working will cut the time it takes to resolve changes. AEMPS Notice (Spanish)