Good Manufacturing Practice

Introduction
The MHRA's Good Manufacturing (GMP) Inspectorate is part of the Inspections & Standards Division of the MHRA. It assesses the compliance of organisations conducting clinical trials using investigational medicinal products with UK and EU legislation. It is one of the five medicines inspectorates at the MHRA:

Pharmacovigilance (GPvP) Inspectorate
Good Distribution Practice (GDP) Medicine Inspectorate
Good Laboratory Practice (GLP) Monitoring Authority
Good Clinical Practice (GCP) Inspectorate

In this section you will find information regarding the working of the GMP Inspectorate, its responsibilities and powers as well as details of its work. We have presented the information in an easy to follow question and answer format but if you require any further information please do not hesitate to contact us.

What is Good Manufacturing Practice?
Good Manufacturing Practice (GMP) is that part of quality assurance which ensures that medicinal products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorisation (MA) or product specification. GMP is concerned with both production and quality control.

Who we are
The chart below illustrates the Good Manufacturing Practice (GMP) team structure:

Good Manufacturing Practice (GMP) team structure (77Kb)

What do we do?
Companies that manufacture or wholesale medicinal products may only do so if they hold the appropriate licence.

For further information please see the following section:
Manufacturer's and Wholesale Dealer's Licences

The GMP Inspectorate inspects such companies and their operations to verify their compliance with the EU GMP/GDP guidelines available in:
Rules and Guidance for Pharmaceutical Manufacturers and Distributors 2007 - the 'Orange Guide'

The Good Manufacturing Practice (GMP) Inspectorate has three teams of inspectors based at the MHRA headquarters in London (Market Towers) and at two other MHRA offices (Welwyn Garden City and York).

In Northern Ireland inspections are performed under the scope of a Memorandum of Understanding between MHRA and the Department of Health, Social Services and Public Safety (external link).

Memorandum of Understanding between MHRA and the Department of Health, Social Services and Public Safety (56Kb)

Our work
Inspections of UK sites are carried out whenever a company has applied for or been named on an appropriate licence and periodically thereafter during the course of a licence. Additional inspections that may be required to be performed are, for example, to follow up deficiencies raised previously, following reports of defective products, or to follow up information received from external sources, for example "whistleblowers". Applications to vary details of the manufacturing authorisation may also trigger an inspection.

Fees are charged for inspections and they are conducted on a defined frequency in accordance with EU guidelines, unless circumstances dictate otherwise. There is no legal requirement to notify the licence holder of an intention to visit and inspections may be pre-notified or unannounced.

Whilst the UK authorities do not issue manufacturer's licences to overseas manufacturing sites supplying the UK they are inspected when named on specific marketing authorisations. Overseas inspections focus on the products to be imported, and the standards applied are the same as those applied in the UK. Additionally, sites manufacturing Active Pharmaceutical Ingredients (API) are not issued manufacturer licences, but may be inspected. Sites of manufacture of non-immunological veterinary medicinal products and storage sites for all veterinary medicines are also inspected on behalf of the Veterinary Medicines Directorate (VMD) under the scope of a Memorandum of Understanding between the MHRA and the VMD (37325Kb).

The GDP Inspectorate inspects a number of types of Wholesale Dealer companies, including both Human and Veterinary products, full line and GSL only wholesalers. Additional information is available in our GDP section.

The GMP Inspectorate inspects a number of types of manufacturing companies, including, but not limited to:

• Manufacturers of sterile and non-sterile dosage forms
• Manufacturers of ‘Specials’
• Assembly only sites
• Assemblers of parallel imported products
• Licensed hospital units including radiopharmacies
• Medical gas manufacturers
• Investigational Medicinal Products (IMP) for use in clinical trials
• Active Pharmaceutical Ingredients (API)
• Biological medicinal products eg vaccines
• Blood establishments and blood banks. Additional information is available in our How we regulate blood section.
• Plasma collection and fractionation sites
• Herbal medicinal product manufacturers. Additional information is available in our Herbal and homoeopathic medicines section.
• Importers of medicinal products
• Contract testing laboratories

External liason
International co-operation has been an important part of the Inspectorate's activities for many years. The UK Medicines Inspectorate was a founder member of the Pharmaceutical Inspection Convention and is an active participant in the Pharmaceutical Inspection Co-operation Scheme (PIC/S) (external link).

The GMP Inspectorate currently carries out regular inspections in a number of countries, including USA, India, China and Japan both in connection with national requirements and on behalf of the European Medicines Agency (EMEA) (external link), the World Health Organization (WHO) (external link) and the European Directorate for the Quality of Medicines (EDQM) (external link).

For Community marketing authorisations, for example, licences granted under the centralised procedure, initial inspection is carried out under contract to the EMEA. This is normally carried out by the Supervisory Authority concerned, i.e. the Member State in which the product is to be made or imported. Subsequent inspections are normally carried out routinely by the same authority although there is provision for one Member State to inspect in non-Member States on behalf of another.

The EC negotiates Mutual Recognition Arrangements (MRAs) between the Community and third countries, which include mutual recognition of standards of GMP and arrangements to ensure compliance by pharmaceutical manufacturers. A current list of such agreements can be found on the EMEA website (external link). Under an MRA, the Regulatory Authorities accept each other's Inspection Reports and routine inspection by one authority of manufacturers in the other's territory is not required. In addition, the re-testing of imported products are normally not required.

Consultative committee
Good Manufacturing Practice (GMP) / Good Distribution Practice (GDP) Consultative Committee

The GMP/GDP Consultative Committee has two primary objectives:

To advise and provide information to representatives of Professional and Trade Associations, the wider Department of Health and Other Government Departments (OGDs) with respect to aspects of Good Manufacturing Practice and Good Distribution Practice and the licensing of manufacturers and wholesale dealers.
To provide a forum for consultation and discussion.

The Committee hold at least one meeting each year and include representatives from Inspection, Enforcement & Standards Division of the MHRA including Inspectorate and Licensing Groups, British Pharmacopoeia (BP) and Laboratory Services, Regulatory Advice and Divisional Secretariat. The Committee also includes representatives from interested trade associations and professional bodies and wider Department of Health and other Government Departments.

The Committee meet to discuss:

Regulatory and international matters related to GMP and GDP
The performance of operation of the GMP/GDP Inspectorate and the Licensing Office for manufacturers and wholesalers
Interpretation of the Principles of GMP/GDP by the regulatory authorities
Compliance by licence holders (in general) with GMP and GDP
Technical aspects of GMP and GDP.

History
The Medicines Inspectorate was established within the Medicines Division of the Department of Health and Social Security (DHSS) in 1971 in accordance with the Medicines Acts 1968 and 1971. It was set up to inspect and ensure compliance with Standard Provisions (including GMP and GDP) by all applicants for, and holders of, manufacturer's and wholesale dealer's licences in the UK.

Over the next few years it absorbed the functions of the Department of Health (DH) Inspectorate under the repealed Therapeutic Substances Act, which was only concerned with biological products, and expanded to inspect manufacturers in other countries exporting products to the UK.

In 1975 inspections of NHS manufacturing units were begun at the behest of the then Secretary of State for Health. With the removal of Crown Immunity in 1991 these units were required to hold licences and became subject to statutory inspection.

In April 1989 the MCA was established following the Cunliffe-Evans report into the control of medicines. This brought two major changes. Firstly, the Agency was organised into multi-disciplinary functional groups. This has gradually evolved over the years to reach the present organisation based on pre- and post-licensing activities. The Inspectorate became part of the Inspection and Enforcement Division responsible for inspection, licensing, testing and other activities associated with manufacture and distribution. Secondly, the Agency was to be entirely funded by licence holders on the basis of user fees.

In 1991 requirements for manufacturing authorisations and GMP were harmonised within the European Community. The UK no longer inspected or exchanged Pharmaceutical Inspection Convention (PIC) reports on manufacturers in other EC Member States.  

Contacts for further information
For questions related to the planning of inspections please contact inspectionplanning@mhra.gsi.gov.uk and for general GMP/GDP questions please contact gmpinspectorate@mhra.gsi.gov.uk

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