The EU Qualified Person - What's it all about?

Regulations of health care products are in place to ensure they are safe to use and effective according to their intended purposes. Good manufacturing practice (GMP) or current good manufacturing practice (CGMP) guidelines are a set of regulations designed to ensure manufacturers of food, drugs, medical devices, and cosmetics consistently produce products within safe environments and in accordance with strict protocols, thereby reducing possible contamination and manufacturing errors.

If you are a non-EU based company exporting drug products into the EU, either by yourself or through a partner, it is essential to understand the role of a QP. It's also helpful to understand all other EU-GMP requirements to be better prepared for inspections.

QP Duties and Responsibilities

The European Directive 2001/83/EC defines the responsibilities of the QP. Article 51 of the Directive states that "… the QP is responsible for ensuring that each individual batch has been manufactured and checked in compliance with the laws in force in the member state where certification takes place, in accordance with the requirements of the marketing authorization (MA) with good manufacturing practice (GMP)."

Annex 16 of the EU Guidelines for GMP details the routine duties of the QP, which include for example ensuring:

• Manufacturing has been carried out in accordance with GMP regulations. The QP might need to check additional documents and take part in quality reviews.
• Manufacturing and testing processes have been validated. The QP should have access to all documentation, including deviations, investigations, change control, CAPA, etc.
• Deviations or changes in production or quality control have been authorized by the responsible persons.
• All necessary checks and tests have been performed and all production and quality control documents are complete and authorized.
• All audits are carried out as required.

The QP also needs to consider all other factors relevant to the quality of a batch. The QP can delegate the above tasks - including to a U.S.-based manufacturer and its quality control unit - except batch certification and release. Because QPs are responsible for ensuring all quality tasks are complete according to GMP regulations, they decide the extent to which certain tasks are delegated. The QP should have on-going assurance that this reliance is well founded.

Various stages of product manufacturing are often completed by external companies. The following are some of the key guidelines for managing suppliers:

• The QP of the sponsor organization will need a contract describing the arrangements for each supplier's certification.
• Supplier QPs involved in the certification, or confirmation, of a batch must have detailed knowledge of the responsibilities.
• Regardless of how many sites are involved, the QP performing certification of the finished product must ensure that all quality steps are completed according to accepted pharmaceutical GMP guidelines.
• Complete documentation must exist for all supply chain activities involving the active substance and medicinal product up to the stage of certification. The QP must have access to the documentation.
• Provided that all suppliers comply with GMP guidelines, the QP certifying the finished product may rely on confirmation from the QPs of each organization. Manufacturers employ supplier quality management systems to ensure they only receive materials that meet the required level quality.

QP Discretion on Batch Releases

Prior to certifying a batch, the QP should ensure that it complies with the provisions of the marketing authorization. Is the QP empowered to decide on the release of a batch - even in cases where deviations occurred during its manufacture or testing? For these situations, the QP can also consult EU Guidelines for GMP, Annex 16, which discusses how to deal with unexpected deviations.

A batch with an unexpected deviation concerning the manufacturing process may be certified if the result of a risk analysis performed shows that "the potential impact of the deviation on quality, safety or efficacy of the batch(es) concerned and conclusion that the impact is negligible." It is important to point out that in case of a repetition of the event this cannot be classified as unexpected any more. Correction is needed or the assessment on a decision to certify.

In cases where a deviation concerns a specification defined in the marketing authorisation as essential for the release (OOS; out of specification), the QP will have no scope left.

Why should non-EU based Companies learn about QPs?

The interpretation of a QP's position varies from company to company. What is important to know is QPs must review batch-specific data before certifying the material. A QP needs to have access to all information relevant to the batch. It's also important to have a knowledge of the company's quality system and processes.