European Regulatory Roundup: Denmark Follows Ireland in Dropping Fees for Brexit-Hit MAHs

Regulatory NewsRegulatory News
| 08 February 2018 | By Nick Paul Taylor 

Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
EMA Offers Advice on When to Study Effect of Obesity on PK/PD
The European Medicines Agency (EMA) has offered advice on when drug developers should assess the effect of obesity on pharmacokinetics and pharmacodynamics (PK/PD). EMA recommends sponsors test drugs in clinical trial cohorts representative of broader disease populations throughout development to ensure they understand the effect of obesity on PK/PD.
Following that recommendation should ensure that drugs destined to be used in patient populations in which obesity is prevalent come to market backed by PK/PD data relevant to these obese people.
Extra steps are needed in some cases, though. If prior research suggests obesity may have a marked effect on drug elimination and obese people make up a large proportion of the patient population, EMA wants sponsors to perform early investigations to help with dose finding. Similarly, if the patient population features a large proportion of obese people and dosing is based on body weight, EMA is advising sponsors to assess whether the recommended dose is suitable for everyone. 
Other situations in which sponsors should pay particular attention to the effect of obesity on PK/PD include development programs featuring drugs with relatively narrow therapeutic ranges. Developers of such drugs should assess PK in obese patients with different body mass indexes to generate data to guide their dosing strategies.
EMA made the recommendations in a draft reflection paper. Another section of the draft details the effects obesity can have on absorption, distribution, elimination and other aspects of a drug’s performance. EMA concludes evidence of the effect of obesity on PK/PD is limited, but enough data has emerged to justify asking sponsors to factor it into their development plans.
The agency also discusses how sponsors can investigate the effect of obesity on PK. In some cases, the population PK (PopPK) analyses typically used to support marketing authorizations will be sufficient, provided the sponsor has enough data on patients who fall into all categories of obesity. EMA points to non-compartmental analysis as a possible alternative to PopPK, and suggests that physiologically based pharmacokinetic modeling could become useful in the future.
EMA is accepting comments on the draft until the end of July.
Draft Paper
Denmark Follows Ireland in Dropping Fees for Brexit-Hit MAHs
The Danish Medicines Agency (DKMA) has offered to waive reference member state (RMS) transfer fees for companies affected by Brexit. DKMA’s offer comes shortly after the Irish drug regulator made the same pitch to Brexit-hit marketing authorization holders (MAHs).
If, as EMA’s planning assumes, the UK becomes a third country in March 2019, companies with drugs approved under the mutual recognition and decentralized procedures that use the country as their RMS will need to move their records to another agency. Ireland and now Denmark will allow MAHs to make them the RMS for free.
European rules place some limitations on which countries companies can pick as their RMS. The new RMS must already be involved with the approved drug as a concerned member state. Companies must also complete all variations and other regulatory procedures before initiating the transfer.
The willingness of the Danish and Irish regulators to waive their fees is part of a broader scramble to claim regulatory ground currently held by the UK. That scramble is reflected in hiring at agencies in Denmark, Ireland and other countries across Europe, and in the actions regulators are taking to court companies affected by Brexit.
DKMA Notice
EMA Posts Draft Texts on Vaccine Quality, Preventing BSE Transmission
EMA has released revisions to its guideline on vaccine quality and a question and answer document on bovine spongiform encephalopathies (BSE) for consultation. The draft documents update advice EMA provided as far back as 2001.
The draft guideline addresses quality aspects of human vaccine product information. The text covers similar ground to the guideline that came into force in 2004, but EMA has expanded on or revised much of the content. Some of the changes clarify EMA’s intentions. For example, the current section on strength states “it is acceptable not to include the strength where it is not straightforward.” The new draft explains exactly when it is acceptable not to include strength.
Other proposed amendments reflect changes in vaccine technology, understanding of their effects and the regulations that govern them since the early 2000s. These include a new section on clinical particulars that details the need to disclose information about production residues and excipients that are relevant clinically, contraindicated or associated with adverse events or other known effects. The new section also instructs companies to include a statement about traceability.
EMA started the public consultation on the draft on the same day it began accepting feedback on revisions to an even-older vaccine document. The agency established its position on vaccines and BSE in 2001. At that time, EMA published a statement detailing its belief the risk of vaccine-mediated BSE transmission is extremely low and a Q&A to discuss its reasoning and precautionary measures. EMA released the documents in the wake of a BSE-related vaccine recall.
Now, EMA has created a new Q&A to supercede the earlier documents. The draft version replicates the format and much of the content of the 2001 text. EMA has removed some sections that have diminished in relevance since 2001 — such as a discussion of the BSE-related recall — and revised others to reflect the emergence of new production techniques and other advances.
Both texts are open for comment until the end of July.
Vaccine Guideline, BSE Q&A
EU Position Paper Calls for Agency Powers to Apply to UK During Brexit Transition
The European Union has put forward a draft position paper that calls for its agencies to have powers over companies in the United Kingdom during the anticipated Brexit transition period.
European officials put together the position paper to guide how their negotiators approach talks with the UK. The document envisions the UK playing a limited role in EU decisions during the transition but remaining subject to the oversight of European agencies.
“During the transition period, the institutions, bodies, offices and agencies of the Union shall have the powers conferred upon them by Union law also in relation to the United Kingdom and natural and legal persons residing or established in the United Kingdom,” the European Commission wrote in the position. Legal persons refers to entities, including companies, with legal rights and obligations.
None of the document, including the above-quoted section, refers specifically to the regulation of drugs or medical devices. Yet, In discussing how EU agencies will interact with companies operating in the UK, the paper has implications for the sector.
The position paper is currently in its draft form, and the final transition terms will depend on the outcomes of upcoming negotiations between the UK and EU. That said, the minimal flexibility shown by the EU during the first round of negotiations suggests there is a reasonable chance its position now will shape the final transition terms, assuming the two sides can reach an agreement.
Position Paper
Other News:
The UK will publish updated clinical guidance on the use of surgical mesh in patients with urinary incontinence in 12 months’ time. The Parliamentary Under-Secretary for Health and Social Care disclosed the publication date during a House of Lords debate about the UK’s response to concerns about the safety of pelvic mesh implants. Lords Debate


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