Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
EMA Proposes Changes to Vaccine Clinical Trial Guideline
The European Medicines Agency (EMA) has released a revised guideline on the clinical evaluation of vaccines for consultation. EMA’s replacement for a text adopted more than a decade ago addresses questions that have arisen over that time, including issues linked to the emergence of vaccines that contain antigens from multiple pathogens and interest in prime-boost regimens.
As EMA notes in its draft guideline, the vaccine landscape and the questions raised by sponsors and its own reviews have changed considerably since the existing document came into force in 2007. The changes have led EMA to completely rewrite the text and expand its scope. The result is a document destined to replace the vaccine guideline and other texts on adjuvants and summary of product characteristics (SPC) requirements.
In highlighting the key changes to the guideline, EMA zeroed in on sections intended to address the development of vaccines that feature antigens from multiple pathogens or multiple subtypes of one pathogen.
Typically, EMA wants developers of vaccines that contain novel combinations of antigens to compare the immune responses they trigger to those achieved by separate administrations of the antigens. However, if the vaccine contains a very large number of antigens, this approach may not be feasible. Vaccines that target multiple subtypes of an antigen could encounter this problem. EMA provides no advice specific to this situation, stating only that strategies should be designed case by case.
The interest in targeting multiple subtypes of a pathogen is evident in another new focal point of the guideline, namely the use of different products to prime and boost responses. EMA touched on the topic in a two-sentence section of the old guideline, but goes into greater detail in the new draft.
EMA wants companies pursuing this approach to compare the immune responses generated when another vaccine is added to a regimen to those achieved by the single-product course. In some cases, developers are using one vaccine to prime the immune system to and another to boost it. This can increase the response or broaden it to encompass multiple subtypes of a pathogen. In these cases, EMA wants companies to compare their regimens to repeated doses of the first vaccine construct.
The agency’s interest in prime-boost regimens grew out of requests for scientific advice. Analyzing the questions being asked by sponsors led EMA to identify these regimens, the use of vaccines during pregnancy to protect babies in their early months and immune correlates of protection as areas to address in the revised guideline. EMA also reviewed the shortcomings of recent application dossiers, resulting in a greater focus on interpreting results from comparative immunogenicity trials.
EMA is accepting feedback on the draft until the end of October.
, EMA Statement
Antimicrobial Resistance Prompts EMA to Revise Veterinary Medicine Guideline
EMA is seeking feedback on revisions to its guideline on antimicrobial veterinary products SPC. The changes to the 2008 guideline reflect the regulator’s responses to growing fears about antimicrobial resistance over the past decade.
In recent years, the Committee for Medicinal Products for Veterinary Use (CVMP) has adopted positions on antimicrobial resistance that affect its view on what information manufacturers should include in the SPC. This led CVMP to propose changes to the SPC guideline to optimize use of antimicrobials and cut the risk of resistance.
The current guideline includes provisions related to resistance — and uses the word 25 times — but the draft goes further. EMA is planning to add a warning to the labels of broad-spectrum antimicrobials that states narrow-spectrum therapies carry a lower risk of antimicrobial resistance selection and are therefore the preferred first-line treatment. The guideline also features new, specific recommendations, such as those aimed at stopping antimicrobial use in dairy cows from causing resistance in calves.
Other changes reflect scientific advances and the rise of resistance. EMA is recommending sponsors include information on the molecular genetics of acquired resistance. That suggestion is absent from the existing guideline.
EMA is accepting feedback on the draft until the end of September.
EMA Updates EudraVigilance Policy to Expand Access to Adverse Event Data
EMA is planning to provide multiple groups with more access to records held in its EudraVigilance Veterinary (EVVET) system. The changes will give healthcare professionals, the public and academics greater access to adverse event records linked to veterinary medicines sold in Europe.
EVVET launched in 2011 with an access policy fully aligned to the one covering EMA’s human pharmacovigilance system. However, a lack of resources meant EMA never established a dedicated web tool to facilitate access to EVVET, creating a divergence in the availability of information about veterinary and human medicines. That led to EMA receiving lots of requests for EVVET data.
The exact future legislative position on access to EVVET has become more uncertain in recent years, but EMA thinks it is safe to assume the veterinary policy will be very similar to a 2015 update to the human rules. This thinking has shaped EMA’s draft EVVET access document.
EMA’s changes affect multiple groups. If the document is enacted, healthcare professionals and the public will gain extended access to adverse event records on all medicinal products authorized in the European Union. EMA will provide “easy-to-use retrieval functions” on its adrreports.eu portal to facilitate access to aggregated data outputs, line listings and forms.
The proposals also extend access for academics. Once authorized, academics will have access to details withheld from the public, such as the dates submissions were made, registration identifiers, the names of marketing authorization holders (MAHs), lot numbers, dosage details and explanations relating to assessments. EMA will provide access to this information to facilitate public health research. The agency will also grant this level of access to third countries on an ad hoc basis.
MAHs retain full access to their own reports under the new policy and also gain access to defined data element sets. EMA sees access to this resource supporting signal detection and validation.
The draft is open for comment until 27 June.
Commission Plans Systems to Show Vaccine Safety, Prevent Shortages
The European Commission has set out its strategy for increasing vaccine use in the region. Officials plan to create a public portal of vaccine safety evidence and an EU-wide data warehouse to prevent shortages.
The plan addresses concerns that some EU citizens are not getting vaccinated, either because they have concerns about the safety of such products or lack access to them.
Establishing the data warehouse is intended to ease access constraints. The Commission envisions the system holding information on vaccine stocks across the region, enabling details of an impending shortage in one country to quickly spread. Forewarning regulators could enable mitigating actions.
The safety portal targets the trend toward vaccine hesitancy. The Commission’s concerns about the trend were amplified when it ran an online consultation. For the first two months, the Commission received about 50 responses a week. Then, it received almost 6,000 responses in 24 hours from people, mostly in France, who submitted anti-vaccination comments. To the Commission, the surge was testament to the role “powerful influencers” play in the vaccine hesitancy trend.
From next year, the Commission hopes to counter these influencers with a portal that provides “objective, transparent and updated evidence” on vaccine safety and benefits.
, Fact Sheet