QUALIFIED PERSONS AS PER EUROPEAN PHARMACEUTICAL REGULATIONS
Qualified person (QP):- It is a technical term used in European Union pharmaceutical regulation (Directive 2001/83/EC for Medicinal products for human use). The regulations specify that no batch of medicinal product can be released for sale or supply prior to certification by a QP.
The QP is typically a licensed pharmacist, biologist or chemist (or a person with another permitted academic qualification) who has several years’ 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.
In countries that are part of the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S), the same role may be termed responsible person (RP) or authorized person (AP).
Differences in the United States’ and European Union’s good manufacturing practices (GMPs):- For example, the responsibilities of the quality control unit according to FDA’s guideline 21 CFR 210/211 are comparable to the responsibilities of the head of manufacturing and the head of quality control as described in the European GMPs. However, there is one major difference in the European pharmaceutical legislation—the additional personal responsibility and liability of the “qualified person” (QP) as defined in the superior European pharmaceutical directives. This function is unknown within the US pharmaceutical legislation as well as in almost all other countries outside the EU.
In today’s international pharmaceutical supply chains, it is important to know the specific requirements in the various markets worldwide. In Europe, no single batch of a finished pharmaceutical product can be released without the certification of the QP.
Legal basis for QPs in Europe:- The legal basis for the qualified person is detailed in the European Directive 2001/83/EC issued on Nov. 6, 2001, relating to medicinal products. For veterinary products, the requirements are defined in the European Directive 2001/82/EC.
Qualification of the QPs: – The required qualification to become a QP in a member state of the EU is a completed four years theoretical and practical university study in pharmacy. A shorter study (e.g. of three years) recognized as equivalent by the member state concerned is also acceptable in some cases. A university study in medicine, veterinary medicine, chemistry, pharmaceutical chemistry and technology, or biology may also qualify the applicant. In this case, however, all missing basic subjects from the curriculum of a full pharmaceutical study must be completed by additional studies or training courses. The adequacy of these additional studies or training will be determined by the relevant national authority.
To qualify as a QP in Europe, the applicant must provide evidence about successful university studies in experimental physics; general, inorganic, organic and pharmaceutical chemistry; analytical chemistry, including analysis of medicinal products; general and applied (medical) biochemistry; physiology; microbiology; pharmacology; pharmaceutical technology; toxicology; and pharmacognosy (the study of medicines derived from natural sources).
In addition to coursework in these areas, the qualified person must have acquired practical experience during at least two years at one or more companies authorized to manufacture medicinal products in the EU. The practical experience should cover the topics of qualitative analysis of medicinal products, quantitative analysis of active substances, and testing and checking the quality of medicinal products. The duration of practical experience may be reduced to one year in case of a five-year university program or to a half year in case of a six-year university course.
Responsibilities of the QP:- To perform his or her responsibilities successfully, a qualified person must be registered (or approved, depending on the member state’s legislation) by the competent authority of the EU member state where the manufacturing license of the pharmaceutical company was issued and the QP is acting.
According to article 51 of Directive 2001/83, the QP must certify prior to the release for sale, placing on the market, or export in a register or equivalent document provided for that purpose, that each batch of the medicinal product has been manufactured and checked in compliance with the laws of that member state and in accordance with the requirements of the marketing authorization.
The corresponding article of Directive 2005/28/EC (good clinical practice) requires (in case of human medicinal products only) certification of the QP before release for use in clinical trials or export that each batch of investigational medicinal product has been manufactured and checked in accordance with cGMPs and its product specification file.
In the case of medicinal products coming from third countries (i.e., countries outside the EU), the QP has to certify that each production batch has undergone in a member state a full qualitative analysis, a quantitative analysis of at least all the active constituents, and all the other tests or checks necessary to assure its quality in accordance with the requirements of the marketing authorization.
For investigational medicinal products coming from third countries, the QP must certify that each batch has been manufactured and checked in accordance with standards of cGMP at least equivalent to those of the European Union, in accordance with the product specification file.
The QP must ensure that the said register or equivalent document is kept up to date as operations are carried out. The documentation must remain at the disposal of the agents of the competent authority for the period specified in the provisions of the member state concerned and in any event for at least five years. This provides the competent national authorities a tool to immediately come back to the responsible QP in case of any issue with the batch that was certified and released.
The certification process for batch release is described in Annex 16 of the EU Guide to GMP, and addresses the complexity of manufacturing and supply chains stretching across several production sites, companies, and countries within and outside the European Union. In addition, the European Medicine Agency (EMA) published a reflection paper laying down expectations of how QPs should respond if batches intended to be released show minor deviations from the details described in the marketing authorization for human and veterinary medicinal products (including biological products) .
In general, the tasks and responsibilities of a QP, especially the process of batch certification and release, can only be delegated to another QP who is registered at the responsible authority for supervision of the marketing authorization and/or supervision. Some companies may use contract QPs providing independent service. The duties and responsibilities—especially the requirement to be registered or approved—do not differ from those applicable to QPs who are full-time employees of a company. Contract QPs should have a detailed agreement to ensure clear assignment of all duties and responsibilities.
Organizational and reporting structures:- According to the European regulations, the head of manufacturing could be assigned as QP, given that he or she meets the requirements. In addition, the heads of production and quality control must be independent from each other. This is not further specified in EU GMPs, but according to the authors’ inspection experience, having separate heads of departments reporting to one site director or one hierarchical level higher is considered sufficient to comply with this requirement.
Conclusion:- The concept of the qualified person according to EU regulations is unique. It does not exist in the US or in any other state outside of the European Union. The personal responsibility and liability of the QP is a very specific requirement. Every qualified person needs to be registered or appointed or approved with the competent authority of the EU member state in which he or she is operating. Therefore not only the pharmaceutical company for which he or she is acting, but also the registered qualified person, is personally responsible for his or her duties.
All holders of a manufacturer’s licence for licensed products, including for the purposes of import, are required to have available the services of a Qualified Person (QP), who must be named on the licence. When considering a nomination, the licensing authority (the MHRA) routinely takes into account the assessment of the nominee’s eligibility made by the joint assessment panel of the Institute of Biology, the Royal Pharmaceutical Society of Great Britain and the Royal Society of Chemistry.
Exceptionally, the MHRA will assess a nominee directly if he or she is not a member of any of these professional bodies.
Title IV of Directive 2001/83/EC as amended lays down the requirements for QPs in relation to products for human use:-
Article 51 defines the duties of the QP;
Articles 49 and 50 define the requirements for eligibility under the permanent and transitional arrangements respectively, and
Article 52 requires Member States to ensure that the duties of QPs are fulfilled,
By inspection and other means the licensing authority routinely assesses whether or not QPs are fulfilling their duties. In making this assessment, reference is made to the Code of Practice for Qualified Persons produced jointly by the Institute of Biology, the Royal Pharmaceutical Society of Great Britain and the Royal Society of Chemistry in collaboration with the MHRA and the Veterinary Medicines Directorate.
All QPs should be guided in fulfilling their duties by the Code of Practice.
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