EU clinical trial regulations: Key Advice for meeting post-Brexit qualified person (QP) requirements

The United Kingdom’s (UK) departure from the European Union (EU) has added a layer of complexity to the clinical trial supply chain in Europe above and beyond COVID-related disruptions. As of January 2021, the EU and UK function as separate legal and regulatory jurisdictions, and drug products must meet the relevant requirements for the market in which they will be sold.

While the UK’s Trade and Cooperation Agreement with the EU does provide for the mutual recognition of good manufacturing practice (GMP) inspections of drug product manufacturing facilities, the agreement does not stipulate mutual recognition for Qualified Person (QP) release or for product batch testing. However, in the UK batch testing and QP certification is accepted as long as it is conducted in an approved country—currently the European Economic Area (EEA).

Beginning in January 2022, a full UK QP oversight process will be required for any investigational medicinal product crossing from an approved country into Great Britain clinical sites. As has always been a requirement, QPs in the EEA must certify each batch of finished product before clinical trial or commercial release in the EEA. But, because UK-based QPs can no longer certify clinical trial batches for the EEA, companies using UK-based QPs must make substantive changes to established processes to continue to market their products in the EEA.

In a recent webinar discussing the implications of the changing regulatory landscape on QP services, Thermo Fisher’s Harry Berlanga, Senior Director of Quality, EMEA, and Alessandro Barbato, QP for drug substance, drug product, and steriles, offered the following key advice for fulfilling QP requirements and minimizing supply chain risk and clinical trial disruption under the new rules.

• Include appropriate information in study submissions. Each site of QP release is required to be listed in the submission. In addition, any site of UK QP oversight also needs to be listed by the sponsor and added to the UK site’s manufacturing license. This step is critical. The submission must mirror the supply chain, including sites of QP release. Releasing a product that does not comply with this clinical submission protocol is illegal.

• Understand your supply chain strategy for QP oversight. A significant formal process is required in order to complete UK QP oversight. This includes submission updates as noted above, written agreements, and a documented process. The deadline for finalizing all supply utilizing UK QP oversight is Jan. 1, 2022, so this should be a top priority.

• Plan for QP API and IMP declarations. When an investigational medical product (IMP) is manufactured outside the region, QPs must produce declarations confirming that the supply chain for the product complies with standards equivalent to EU. This declaration must be supported by audit and appropriate assessment/control at the manufacturing/testing facility. The supporting information should be gathered as soon as possible in case there are deficiencies that need to be resolved.

• Review quality and technical agreements. When there is a change in supply chain, the quality and technical contracts must be reviewed to ensure the activities comply with regulations and confirm that appropriate contracts exist with all outsourced manufacturing, testing, and releasing sites. This should include any QP-to-QP agreements that may need to be amended.

• Prepare for new Clinical Trials Regulation.The way clinical trials are conducted in the EU will undergo a major change beginning Jan. 31, 2022, which is the date of applicability of the Clinical Trials Regulation [EU] No 536/2014. Among the changes are those associated with clinical labeling of finished products. For example, the immediate packaging of all IMPs that will be supplied for clinical trials operating under the Clinical Trials Regulation must include the period of use/expiry date, without exception. This requirement necessitates a significant change in labeling strategies.

• Factor potential API import requirements into timelines. Because of regulatory limitations surrounding the import of active pharmaceutical ingredients (API) into certain countries, additional testing or permissions may be required and should be factored into the timelines for setup of the manufacturing supply chain and ongoing supply.

• Keep your QP updated at all times. The QP is legally responsible for certifying batches of medicinal products before they are released for use in clinical trials or made available on the market. This requires not only expertise in manufacturing practice, but also understanding all the factors that can influence the safety of medicines and supply chains. For this reason, the QP should have visibility into all conditions that might affect the supply chain to ensure the safety and quality of the product. In particular, it is essential to keep your QP apprised of any supply chain changes.

“It is imperative that pharmaceutical companies based outside of Europe really understand European GMP requirements and the role and responsibilities of the EU and UK QPs, by reviewing the supply chain quality agreements, and the QP-to-QP agreements and keeping them up to date,”