Australia has Codes of GMP and Quality System requirements for the manufacture of medicinal products, sunscreen products, human blood and tissues, 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).

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.

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.

Marketing Authorisation

The person releasing goods for supply must ensure that products meet regulatory requirements. Final release must include assurance of compliance with marketing authorisation, regardless of who carries out the release for supply. This applies to both local and overseas manufacturers. Marketing authorisations for imported products that have been fully released for supply before reaching Australia will only be checked where an overseas manufacturer is being subjected to audit by the TGA. Where an overseas manufacturer is certified by another regulatory authority as being in compliance with the PIC/S or EU GMP requirements, it will be presumed that the manufacturer complies with the requirement for holding appropriate marketing authorisations for all products manufactured.

Personnel

It is expected that training be carried out by persons with relevant training, qualifications and experience in the subject matter and should preferably be themselves trained as trainers.Training (and records thereof) should be given to people affected in all circumstances where significant change occurs in the quality management system, eg when SOPs or methods are changed. This requirement should be reflected in procedures. There are a number of people who have a direct bearing on quality outcomes. These include contractors, consultants and casual employees. Appropriate training should be provided.

Premises and Equipment

Clause 3.9 describes the physical requirements for the area being used to sample starting materials. Sampling of starting materials should be carried out in a separate room, or appropriately qualified sampling hood, under a filtered air supply to protect product from contamination. The sampling area should be designed with dust extraction or equivalent controls to prevent contamination of adjacent areas. The level of air control should be consistent with requirements under clause 115 of the 1990 Australian Code of GMP. Sampling hoods can be used provided there is no possibility of contaminating the storage area and that the hood has appropriate filtering/de-dusting facilities, has been qualified and that materials sampled are not high risk. Note that the 2002 Australian Code of GMP definition of starting material excludes packaging materials.

Primary packaging materials

Clause 3.9 also describes the physical requirements for the area being used to sample primary packaging materials. The standard of air quality is optional and HVAC is not expected. However, sampling in an open warehouse would not be allowed.

Air quality for non-sterile manufacturing areas

The Australian Standard that is/was recognised is/was AS 1386. The various (sub) parts of this standard are being progressively replaced by AS/NZS ISO 14644. However, the various grades of air quality for the production of non-sterile medicines, as outlined in Noel Fraser's presentation at the recent industry seminars, will require further consultation with industry before a TGA policy is issued on this topic.

Manufacture of sterile medicinal products

It is generally accepted by European regulatory authorities that dedicated buildings, facilities and equipment are required for penicillin manufacture. An isolator operating at negative pressure would be regarded as a 'micro-environment' and could be accepted for penicillin manufacture provided that factors such as cleaning, sanitation (noting that if the isolator is opened during cleaning this could present specific concerns), preventative maintenance, environmental monitoring (residues), spillage, etc. are adequately addressed with respect to cross contamination. However, the manufacture of 'other drugs' in the isolator used for penicillin would not be permitted.

rDNA products

Annex 2 relates to the manufacture of biological medicinal products for human use. If a material is classified as an API in Australia (if it is manufactured in Australia or used in a medicinal product in Australia), it should be manufactured according to the requirements of the ICH Harmonised Tripartite Guideline: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients. The ICH Guide excludes vaccines, whole cells, whole blood and plasma, blood and plasma derivatives (plasma fractionation) and gene therapy APIs, and the sterilisation and aseptic processing of sterile APIs. Any specific concerns regarding the interface between the API and the finished product may be discussed with the TGA.

- (Source: TGA Website)