According to European regulations, no batch of medicinal product can be released for sale or supply prior to certification by a Qualified Person (QP). The QP is typically a licensed pharmacist, biologist or chemist (or a person with another permitted academic qualification) who has several years of experience working in pharmaceutical manufacturing operations and has passed examinations attesting to his or her knowledge. The requirement for QP oversight has been extended to material for use in clinical trials since the introduction of EU Directive 2001/20/EC.
The basic responsibilities and duties of a Qualified Person (QP) in the EU are laid down in Article 51 (EU Directive 2001/20/EC). In general, the QP must ensure that each batch of product has been manufactured in compliance with National laws and the requirements of the Marketing Authorisation and each batch imported from outside the community has undergone within the EU the following activities: full qualitative analysis, quantitative analysis of at least all the active constituents and all other tests to show compliance with the Marketing Authorisation.
Other specific requirements of the QP are:
1. Qualification of Suppliers of Starting Materials:
The QP who is responsible for release of the final batch must satisfy themselves that the provisions of the Directive are met and that a systematic system of supplier qualification is in place to give the assurance that only GMP-compliant APIs will be used for the manufacture of medicinal products.The activities to ensure that the API manufacturer is operating an adequate quality system to ensure compliance with the directives do not have to be carried out by the QP of the MA holder personally. What the QP requires is the “assurance” that all is compliant which can be obtained by having the means to assess their effectiveness throughout the supply chain by other suitably trained personnel, which may, or may not, include other QP’s such as at the API manufacturer.
2. The QP Declaration:
A so called QP Declaration should be provided in support of an application for a new marketing authorisation, variation or renewal of a medicinal product(s) authorised in the Community, using EU or national procedures within the scope of the respective Directives.
The QP declaration is a written document that provides formal confirmation for demonstrating compliance of the active substance manufacture with GMP requirements and that the manufacturer has relevant knowledge of the supply chain.
3. Contract Manufacturer and Analysis:
Chapter 7 “Outsourced Activities” of Part 1 of the EU Guide to GMP states that contract manufacture and analysis must be correctly defined, agreed and controlled to avoid misunderstandings which could result in a product or work of unsatisfactory quality. There must be a written contract between the Contract Giver and the Contract Acceptor which clearly establishes the duties of each party. The quality management system of the Contract Giver must clearly state the way that the Qualified Person certifying each batch of product for release exercises his or her full responsibility.
4. Manufacturer of Investigational Medicinal Products (IMPs):
Annex 13 of the GMP Guide “Manufacture of Investigational Products” defines in detail the requirements in the manufacture and testing of IMPs as well as ordering, shipping and returning clinical supplies. The Qualified Person, among other duties, is responsible for:
- Ensuring that there are systems in place that meet the requirements of Annex 13. The QP should therefore have a broad knowledge of pharmaceutical development and clinical trial processes.
- Advising the sponsor in relation to packaging or labelling carried out at the investigator site assessing any potential impact of a complaint and the conclusion of the investigation on the product and the clinical trial.
5. Certification and Batch Release:
The Certification and Batch Release is defined in Annex 16 of the EU Guide to GMP. The Annex also covers those cases where a batch has had different stages of production or testing conducted at different locations or by different manufacturers. In response to the increase in outsourcing and the complexity of the supply chain, there is now a strong basis in Annex 16 for the certifying QP to rely on other QPs and the Pharmaceutical Quality System within the supply chain. The entire supply chain of the active substance and medicinal product, up to the stage of certification, must be documented and available to the QP. The certifying QP is also required to have greater awareness of audits performed at the supplier’s manufacturing sites and its outcomes.
6. Maintenance of a Quality Management System (QMS):
The key requirement for QPs according to Chapter 1 is to ensure that Medicinal Products are not sold or supplied before a QP has certified that the batch has been produced and tested in accordance with the requirements of the marketing authorisation and any other regulations relevant to the production, control and release of medicinal products. To realise this objective, a QP should be involved in the implementation and maintenance of the Pharmaceutical Quality System.
7. The Qualified Person and the Product Quality Review (PQR)
The PQR should normally be conducted and documented annually and should cover all aspects of the supply chain: starting materials, the process, process environment and the final product. The review elements are listed in the respective chapter of the EU GMP Guideline. The Qualified Person responsible for final batch certification together with the marketing authorisation holder should ensure that the quality review is performed in a timely manner and is accurate. The generation of the PQR can be performed by any of the functions however, QA, in association with the QP, should lead the way to interpret data and define any follow-up required.
8. The Qualified Person and Reference and Retention Samples:
As retention samples represent a batch of finished product as distributed in the EU, the Annex strictly advises that retention samples should be located within the EU, preferably at the site where the Qualified Person (QP) certifying the finished product batch is located.
The Qualified Person who finally certifies a batch for sale is responsible to ensure that all relevant reference and retention samples are accessible at all reasonable times. If necessary, the arrangements for such access need to be defined in a written agreement.