Good manufacturing practice for therapeutic goods
What is good manufacturing practice (GMP)?
The acronym GMP is used internationally to describe a set of principles and procedures which, when followed by manufacturers of therapeutic goods, helps ensure that the products manufactured will have the required quality. A basic tenet of GMP is that quality cannot be tested into a batch of product but must be built into each batch of product during all stages of the manufacturing process.
What is manufacture?
In relation to therapeutic goods that are not medical devices, the Therapeutic Goods Act 1989 gives the meaning of manufacture as:
- to produce the goods; or
- to engage in any part of the process of producing the goods or of bringing the goods to their final state, including engaging in the processing, assembling, packaging, labelling, storage, sterilising, testing or releasing for supply of the goods or of any component or ingredient of the goods as part of that process.
Therapeutic goods - the need for high quality
Therapeutic goods are medicinal products or therapeutic devices which are used to diagnose and treat diseases, ailments, defects or injuries in people. Unless therapeutic goods can be reliably manufactured to high standards of quality, they can be ineffective or cause harm to the consumers.
Most industrialised countries have found it necessary to develop good manufacturing practice (GMP) guidelines or codes which describe the principles and practices that are necessary to follow in order to provide assurance that each batch of a therapeutic good is safe, reliable and of consistent high quality.
Various Codes, Guides, Regulations relating to GMP have been published by different countries and trade blocks. For example, the European Union has published a GMP Guide for Medicinal Products. The published volumes of the Rules governing medicinal products in the EU in electronic format in full text, including GMP is at the website http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/index.htm. Other useful information concerning GMP may be found at the Irish Medicines Board website <http://www.imb.ie> and the UK Medicines and Healthcare Products Regulatory Agency website <http://www.mhra.gov.uk>.
These GMP requirements are enforced by Health authorities through systems of factory audits and mandatory licensing of these factories.
What is done in Australia?
In Australia, the Therapeutic Goods Act 1989 requires, with certain exceptions, that manufacturers of therapeutic goods hold a licence. It is an offence, carrying heavy penalties, to manufacture therapeutic goods for human use without a licence unless the manufacturer or goods are exempt from this requirement.
To obtain a licence to manufacture therapeutic goods, a manufacturer must demonstrate, during a factory audit, compliance with manufacturing principles which includes relevant Codes of GMP and Quality Systems. An Application for a Licence to Manufacture Therapeutic Goods form is available on this website <http://www.tga.gov.au/docs/html/gmpapp.htm>.
Overseas manufacturers of therapeutic goods supplied to Australia are also required to meet an acceptable standard of GMP comparable to that required by Australian manufacturers. Sponsors of overseas manufacturers must provide evidence acceptable to the TGA that the goods are manufactured to a standard of GMP equivalent to that expected of Australian manufacturers of the same goods. If acceptable documentary GMP evidence cannot be provided, the TGA will undertake on-site audits in the same manner as that conducted for the Australian manufacturers. Further information can be found in the Guideline document Standard of Overseas Manufacturers.
Australian codes of GMP
Australia has Codes of GMP and Quality System requirements for the manufacture of medicinal products <http://www.tga.gov.au/docs/html/gmpcodau.htm>, sunscreen products <http://www.tga.gov.au/docs/html/gmpsunsc.htm>, human blood and tissues <http://www.tga.gov.au/docs/html/gmpbltic.htm>, active pharmaceutical ingredients (APIs) and medical devices. Each Code/Quality System sets out requirements relating to quality management, personnel, premises and equipment, documentation, production, quality control, contract manufacture and analysis, complaints and product recall and self inspection. The observance of these requirements is necessary through all stages of manufacture to consistently provide a high level of assurance of the quality, safety, and efficacy of therapeutic goods.
The first edition of the Australian Code of GMP for Therapeutic Goods - Medicinal Products was prepared and issued in 1969 by the (then) National Biological Standards Laboratory of the Commonwealth Department of Health after consultation with State governments and industry associations. Further editions were issued in 1971, 1976, 1983, 1990 and 2002. The present Code of GMP for medicinal products is based entirely on the international standard entitled Guide to Good Manufacturing Practices for Medicinal Products, version PH 1/97 (Rev. 3), 15 January 2002, published by the Pharmaceutical Inspection Cooperation Scheme (PIC/S) <http://www.picscheme.org>.
A summary of the current Australian Codes of GMP and referenced Quality System requirements can be found in 'Australian Codes of GMP - Current Status' <http://www.tga.gov.au/docs/html/gmpcodes.htm>.
Compliance with the code of GMP / quality system requirements
Compliance with the Codes of GMP and / or Quality System requirements in Australia is ascertained by carrying out regular on-site audits. The purpose of the audits is to assess compliance with the relevant manufacturing standard, the conditions specified in the manufacturing licence and compliance with the relevant marketing authorisations. Each audit involves a detailed examination of the operations and procedures of the factory, and includes a detailed review of all processing activities, process validation, batch documentation and quality control testing. Product samples may be taken for testing by TGAL (Therapeutic Goods Administration Laboratories). The audit is concluded with an exit interview during which the manufacturer is provided with a summary of the findings of the audit. This summary is confirmed in writing at a later date by means of an audit report. The manufacturer is required to respond satisfactorily to the audit report before the audit is closed out.
Where critical and / or several major deficiencies have been found to warrant 'unnacceptable' compliance rating, the manufacturer's licence may be suspended or revoked, or some additional conditions imposed on the licence if there is a possibility of sub-standard and / or unsafe products being manufactured.
GMP audits of overseas manufacturers who supply therapeutic goods to Australia are also undertaken by the TGA, particularly where alternative acceptable evidence of compliance to an equivalent Code of GMP or Quality System is not available.
For more information regarding the audit of medicine manufacturers in Australia, please refer to 'Audit of medicine manufacturers' <http://www.tga.gov.au/docs/html/auditmed.htm>.