In this Q&A, Ria Rhemrev-Boom, Lead EU Qualified Person (QP) for Sharp, offers insight into how the role of the QP has changed over time, and the additional requirements introduced by the EU in recent good manufacturing practice (GMP) guidelines.

How has the role of the QP changed over time?

The concept of the QP role was introduced in 1975 and subsequently became mandatory for companies involved in the manufacture and distribution of medicinal products in Europe. Since then, the European Union (EU) has continually updated the responsibilities held by the QP. The importance of the QP role was emphasized through EU directive 2001/83/EC in 2002, with new legislation on the annexes put into place. This version was updated in 2011, which further broadened the role of the QP and reflected the efforts of the EMA to address today’s complex global pharmaceutical supply chain, including new technologies, but also the growing problems of falsified medicines.

What is the desired outcome for the marketing authorization holders (MAHs) and the QP?

Organizations can differentiate themselves in the quality of their products but, more importantly to the public, by delivering safe and effective products. Patients today are more engaged and informed about their treatments and are able to use social media to express their opinions, criticisms, concerns and wants, and by doing so they influence the perception of the pharmaceutical industry. A good example of this is the experience with the COVID-19 vaccines and the response of a section of society who are choosing not to be vaccinated, due to their perceived concerns over the safety of the products. The industry’s priority is to help patients by delivering safe and effective medicines, this must be achieved through a collaboration between MAHs, manufacturers and regulatory bodies.

What are the QP’s responsibilities and how does annex 16 change them?

The main responsibility of the QP is to ensure that each batch released meets GMP standards and has been manufactured in compliance with the national laws of the EU member state where certification takes place.

Annex 16 to the EU Guide to Good Manufacturing Practice states much more clearly what the primary tasks and responsibilities of the QP are. This annex increased from 10 to 21 key elements for which the QP is responsible. Batch release is often mistakenly seen as the endpoint of the manufacturing process. However, the batch release process actually requires a complete review of the supply chain, with each player’s role being well defined and agreed. Qualification of the various suppliers through assessment of GMP and/or GDP, as well as related actions, such as technology transfer, validation and implementation, is also essential prior to routine batch production.

These supplier audits can either be done by the QP and/or a subcontracted Subject Matter Expert, who has expertise in a particular field. Either way, the QP must ensure that the supplier complies with GMP and/or GDP, and that the services are performed in accordance with the marketing authorization file. Once qualified and all required information is available, then the batch release protocols can be defined for the routine batch review to release. During batch review, not only are batch records reviewed but any deviations reported will be checked to ensure they are satisfactorily closed. It is also necessary to determine whether any of the changes initiated might have an impact on the batch of the drug product to be released.

As part of the process, the QP will also assess the product quality and management reviews for instance, as well as defined actions and post-registrational activities, such as ongoing stability studies, complaints, reports of adverse events and recalls, all of which may influence the product and its production process.

It’s important to note that the new Annex reinforces that QP release does not discharge the MAH from holding the ultimate responsibility for the performance and safety of a medicinal product over the duration of its lifetime.

How is innovation challenging QPs?

Due to the pressure on regulatory bodies to decrease the total review times, it seems that a lot of responsibilities are being delegated to the QPs, which demands that they need to be subject matter experts in a broad range of technologies.

Many innovative new personalized therapies are presently making their way through trial and commercialization. These novel drugs, which include cell and gene therapies, live microbial therapeutics, and second-generation antibody-based products are incredibly complex and have unique mechanisms of action. In addition, there are new, innovative technologies being used to produce medicines, such as continuous manufacturing and new analytical approaches. On top of that, the supply chain is also becoming increasingly complex. It can be very challenging for the QP to stay up to speed on all of these different, emerging technologies while also retaining knowledge of more established pharmaceuticals and processes. In summary, the role and responsibilities of the QP has grown considerably in recent years and begs the question whether this is too much for one person to handle.

In recognition of these growing requirements and challenges, Sharp has assembled a panel of QPs with different backgrounds who can also provide additional training and education opportunities both internally and externally. To ensure our industry can continue to progress safely and the promise of new therapeutics is realized, it is essential that we are open and transparent with our knowledge and information about how to ensure the quality of all products.

How can we collaborate for a better outcome?

Ultimately, it is in the interest of the MAH to have an efficient, safe batch release process.

We must collaborate with regulatory authorities when thinking through the development of new regulatory mechanisms. Improvements can also be made in the communication with MAHs and CMOs. It is not unusual for the QP to be one of the last to receive information relating to the process, which does not help any of the stakeholders in terms of costs or efficiency.

So, speaking as a QP, I would say it is essential to be involved as early as possible in the process in order to develop a trusted and transparent relationship with the marketing authorization holder and the CMO. Simple steps such as open communication, regular meetings, with a well-prepared agenda, and a list of actions to be followed up and controlled will go a long way to achieving the best outcome for all.

Sharp offers proven QP services that will allow you to streamline your product’s journey to trial and market in the EU. Working with Sharp will give you and your customers’ confidence that your products have been manufactured to the very highest standards. If you would like to hear more about Sharp’s QP services, get in touch.