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

EC Accepts APIs Imported, but not Manufactured, After the Expiration of a Written Confirmation

The European Commission (EC) has updated its question and answer document on the importation of active pharmaceutical ingredients (APIs) for use in human medicinal products. The update adds a section clarifying EC’s position on APIs manufactured while a written confirmation was in place but imported following its expiration.

Under the Falsified Medicines Directive, APIs can only be imported into the European Union (EU) if they are accompanied by a written confirmation from the regulatory authority in the country where the plant that manufactured the ingredient is located. The written confirmation shows the European Medicines Agency (EMA) that the API was produced to good manufacturing practices (GMP) that are equivalent to those enforced in the EU.

Since the legislation came into force, EMA has encountered a situation not covered by its original advice. The question relates to whether API batches manufactured at a time when a valid written confirmation was in place can be imported following the expiry of the regulatory clearance letter. As the guarantees of equivalence conveyed by the written confirmation were in place at the time of production, EC is willing to allow the importation of such APIs.

This allowance comes with two caveats. For an API shipment to be allowed into the EU without a written confirmation, EC wants the consignment to include paperwork that “unequivocally proves” that all of the material it contains was manufactured and released prior to the expiration of the letter. The shipment must also include a “solid justification” as to why a valid written confirmation is no longer available.

Indian API manufacturers have recently expressed concerns that they could be left in the situation described in the EC question and answer document. The Pharmaceuticals Export Promotion Council of India said earlier this month that it wants to meet with the Drug Controller General of India to discuss these concerns, which are underpinned by fears manpower shortages at the local regulator will delay the renewals of written confirmations, leaving firms unable to produce import-ready APIs.     

EC Q&A

EMA Prioritizes Increasing Involvement of Young People in Regulatory Decisions

EMA has committed to adding young people to the list of groups it consults with before making regulatory decisions. The commitment is the latest step in an engagement strategy that has already seen EMA include the views of adult patients and healthcare professionals in regulatory processes.

Young people are on the next list of groups with which EMA wants to interact. The plan got underway last year with the creation of a Patients’ and Consumers’ Working Party (PCWP) group made up of people with experience in the topic. This week, EMA emphasized the importance of these activities by putting the engagement of young people toward the top of the list of priorities in an annual report into its interactions with patients, consumers and healthcare professionals.

The desire to bring young people into regulatory discussions is underpinned by the same factors that motivated EMA to listen more to the views of adult patients. “Young people are best placed to comment on whether trials are acceptable in terms of timing, palatability of medicines and other aspects that could impact on recruitment,” Dr. Pamela Dicks, manager at the Scottish Children’s Research Network, said at an event to discuss the topic.

Guided by this statement, the topic group is looking for existing youth groups that could contribute to regulatory discussions of relevance to them, while also assessing the most appropriate ways to involve young people in the process.

The PCWP topic group has also initiated a collaboration with The European Network of Paediatric Research at the European Medicines Agency (Enpr-EMA), a group of research networks specialized in pediatric clinical trials. Enpr-EMA plans to work with the topic group to build a virtual network of young people in Europe who can comment on the design and delivery of clinical trials that enroll children. 

EMA outlined these initiatives alongside details of its work to engage with other priority groups, including general practitioners and academics. Work to increase the involvement of general practitioners is already fairly advanced. Last month, 20 general practitioners formed an expert group to liaise with EMA following a regulator-run workshop about their involvement in the drug approval process and other mechanisms. 

Annual Report

EC Clears MAHs to Delegate Certain Falsified Medicine Tasks to Third Parties

EC has said that marketing authorization holders (MAHs) can delegate some of the responsibilities placed upon them by the Falsified Medicines Directive. Specifically, EC will allow MAHs to put a third party in charge of decommissioning the unique identifier in the event one of their products is recalled, withdrawn or stolen.

MAHs became aware of the responsibility for ensuring the decommissioning of unique identifiers when regulations on safety features were published earlier this year. That text primarily set out the need for MAHs to include a unique identifier, consisting of a 20-character alphanumeric serial code and other features, on their product packaging by 9 February 2019. European officials also used the document to detail their expectations for how MAHs should handle recalls of products with unique identifiers, and it is this topic EC has sought to clarify in an update to an earlier advice document.

The update states that MAHs can delegate responsibility for decommissioning of unique identifiers of products that are recalled, withdrawn or stolen. Decommissioning of the identifiers is a vital step in the process of ensuring the unique details cannot be reused by traffickers. The regulation places the responsibility for ensuring this happens on MAHs, but provides no details as to whether they have to be involved directly in the process. This week’s update says MAHs can delegate decommissioning, provided there is a written agreement in place with the third party that is performing the work.

EC added the clarification as part a broader restructuring and expansion of its document advising on the safety features regulation. The new questions include one regarding which parties manufacturers should inform when they encounter a case of suspected falsification or tampering. EC expects manufacturers to immediately inform the competent authority and MAH when they face such a situation. The update also clarifies that responsibility for verifying the identity of repository systems will fall on the legal entities that set up and run the repositories.            

EC Q&A

EFPIA Welcomes IVD Agreement's Implications for Precision Medicine

European biopharmaceutical trade associations have voiced their support for the in-vitro diagnostic (IVD) agreement reached by politicians in the region. The groups see the agreement supporting the uptake of companion diagnostics and precision medicine.  

Confirmation that the Council of Ministers and the European Parliament Committee on Environment, Public Health and Food Safety had endorsed the texts arrived last week, bringing years of negotiation to an end. Those negotiations have resulted in regulations with far-reaching consequences for companies that sell IVDs and medical devices in the EU.

By and large, the European Federation of Pharmaceutical Industries and Associations (EFPIA) and the European Biopharmaceutical Enterprises (EBE) are content with the IVD text. “This legislation will provide a firm basis for a rapid expansion in companion diagnostics and personalised medicine, which offers huge potential for patients and public health,” Barbara Freischem, EBE executive director, said.

The trade groups’ main concern is the absence of a direct reference to next-generation sequencing.

EFPIA Statement