Guidance for UK Manufacturers Licence and Manufacturers Authorisation (for Investigational Medicinal Products) Holders on the use of UK Stand

Alone Contract Laboratories Introduction This document: Defines a stand alone contract laboratory in relation to quality control testing of medicinal products. Provides guidance* as to when a contract laboratory must be named on a manufacturers licence for relevant medicinal products for human and veterinary** use and/or a manufacturers authorisation for investigational medicinal products. Is applicable to all manufacturing licence holders, i.e. import, export, herbals and specials. Provides guidance as to when a contract laboratory is not required to be named on a manufacturers licence or authorisation. Outlines the MHRAs criteria for inspection of contract laboratories. *This document should be used as guidance and it is acknowledged that there may be some specific situations where this guidance may vary. **As of April 2009 responsibility for veterinary only licences lies with the Veterinary Medicines Directorate, therefore this guidance is only applicable to licence holders who manufacture both human and veterinary medicinal products. It is acknowledged that there are a number of manufacturing licence and manufacturing authorisation holders that can also offer contract quality control testing to GMP. The inspection of these QC testing activities is included within the scope of their routine GMP inspections. In this situation the licence holder who is performing the testing and acts as the contract acceptor should be named as a contract laboratory on the contract givers licence. GMP and QC Testing Stand alone contract laboratories do not hold their own manufacturers licence or manufacturers authorisation, but are named by manufacturers as a contract laboratory performing testing on their behalf. Quality control testing is regarded as part of GMP and plays a fundamental role in the production process. Quality control testing is required at various stages of manufacture: Raw material and starting material testing: which includes active pharmaceutical ingredients, excipients (including process water) and packaging materials. Intermediate product testing: bulk tablets, capsules, granules, liquids and creams etc. Finished product testing. Ongoing stability testing of products on the market. Microbiological monitoring of the manufacturing areas.

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Criteria for inspection of contract laboratories by the MHRA In accordance with the MHRAs risk based approach to inspections; fee bearing inspections of stand alone contract laboratories will be conducted against EU GMP if the laboratory is undertaking the following testing of a medicinal product (human & veterinary) or an investigational medicinal product for human use: Microbiological testing of either raw materials or finished products. Microbiological testing of manufacturing areas, i.e. Environmental Monitoring (excluding secondary packaging areas). Biological testing of finished products. i.e. final testing prior to QP certification. Chemical/physical analysis of finished products. i.e. final testing prior to QP certification. Stability testing on finished marketed medicinal products.

When contract laboratories must be named on manufacturers licences/authorisations Contract Laboratories that meet the criteria for inspection must be named on manufacturers licences or manufacturers authorisations, irrespective of the quantity or frequency of testing. This also includes any UK stand alone contract laboratory subcontracted by another stand alone contract laboratory. Stand alone contract laboratories that are testing finished products on import into the EU must be named on the manufacturers licence. When contract laboratories should not be named on manufacturers licences/authorisations Stand alone contract laboratories that produce data for research and development purposes only, where the products are not intended to be released onto the market or used in a clinical trial do not need to be named on a manufacturing licence or manufacturers authorisations. MHRA expectations of the Manufacturers Licence, Manufacturers Authorisation holders and Stand Alone Contract Laboratories The following is expected with regards to stand alone contract laboratories named on a manufacturers licence or manufacturers authorisation: The contract laboratories named should be aware that they are named and may be subject to inspection by MHRA. By way of a written contract/technical agreement the licence/authorisation holders must ensure that the laboratories are made fully aware and are in agreement with what is expected of them. Licence holders/authorisation holders must have assessed the laboratory as being fit for their purposes.

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Contract laboratories involved in quality control testing of medicinal products or investigational products for human use must do so in accordance with the marketing authorisation, product specification file and EU GMP.

Inspection Process The scope of the inspection of a stand alone contract laboratory will be to assess their GMP quality system, against EU GMP along with the specific activities they perform, i.e. Chemical/physical analysis, microbiological testing, biological testing. Within the UK there is no requirement for a stand alone contract laboratory to have a licence; however a GMP certificate will be issued to the contract laboratory following an inspection. Confirmation of the compliance status of a stand alone contract laboratory will be communicated directly to the laboratory on completion of the inspection process. Stand alone contract laboratory details will be added to the MHRAs list of inspected laboratories which can be found on the MHRA website. This list will be updated at least annually. In the event of any serious non-compliance issues, a referral will be made to the Inspection Action Group (IAG). The final outcome of the IAG process may result in: The laboratory being removed from the licence and/or authorisation. The laboratory being removed from the MHRAs list. The laboratory being issued with a notification of GMP non-compliance.

GLP and GMP The term Good Laboratory Practice (GLP) is a generic term that causes confusion when used to describe the quality control testing of medicinal products. Compliance with the OECD Principles of GLP is a regulatory requirement when conducting non-clinical, toxicology studies of new chemical or biological substances. There is no legal requirement for the quality control testing of medicinal product to be conducted in accordance with the OECD Principles of GLP and there is no requirement for laboratories involved in quality control testing of medicinal products to be members of the UK GLP Compliance programme. Quality control laboratories that are testing medicinal products including investigational medicinal products should do so in accordance with GMP and in accordance with any details specified in the product specification file or the marketing authorisations. References Eudralex volume 4 - Medicinal Products for Human and Veterinary Use: Good Manufacturing Practice. Published: June 2010

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