The Role of the Qualified Person in European Pharmaceutical Regulations

The authors provide a brief overview of the European pharmaceutical regulation with regard to batch certification by a qualified person and batch release for the European market.
Oct 02, 2010
By Pharmaceutical Technology Editors
Volume 34, Issue 10

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 (8). 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) (9).

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

The initial concept of one individually legally responsible person for batch certification and release dates back to the second Pharma Directive 75/318/EEC of 1975 and thus far earlier than any European approach to introduce common cGMPs (10). Role and responsibilities of the QP are therefore not (or only in parts) specified in the European GMPs. As a consequence, companies are free to define any hierarchical reporting structure of the QPs depending upon the size and structure of the company and the type of products manufactured. QPs may either be heads of, or reporting to, quality assurance or quality control, perform additional quality functions such as quality management, or they may report directly to senior management.

In fact, 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 (3).

Larger companies with several sites sometimes seek to centralize certain quality systems such as complaint management, recall management such as biological product deviation reports and field corrective actions, or audit systems to corporate headquarters or to specialized centers of competence. Whenever EU regulations require the active participation of a locally based QP in a European site, this centralization has to be carefully evaluated in its consequences and its compatibility with European National laws and regulations. This is especially true when responsibilities are transferred to the US.

lorem ipsum