It is a requirement under paragraph 26A (2) (e) of the Act that each step in the manufacture of a listed medicine in Australia is carried out by a licensed manufacturer (unless the therapeutic good is exempt from this requirement) - refer to Manufacturing therapeutic goods. It is an offence, carrying heavy penalties, to manufacture therapeutic goods for human use without a licence unless the manufacturer or goods are exempt. The manufacturer's licence carries details of the types of manufacture permitted under the licence.

Where a product is imported, each nominated international manufacturer must demonstrate an acceptable standard of good manufacturing practice (GMP) as would be required of an Australian manufacturer. Pre-clearance of international manufacturers is mandatory for listed complementary medicines - refer to Manufacturing standards for overseas manufacturers.

Australia has adopted manufacturing principles for medicinal products for the manufacture of therapeutic goods, including complementary medicines. 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. Compliance with GMP and the quality system requirements in Australia is determined by carrying out regular on-site inspections.

Some complementary medicines comprise relatively simple ingredients (for example: amino acids, mineral salts, vitamins) and the quality parameters applying to such products are essentially the same as for other medicines. Special considerations are required for those complementary medicines that contain complex ingredients, that are difficult to characterise, and/or certain combinations of multiple active ingredients.

Guidance on quality for complementary medicines

There are a number of scientific guidelines of particular relevance to listed medicines:

• Guideline on Stability Testing: Stability Testing of Existing Active Substances and Related Finished Products (CPMP/QWP/122/02, rev 1).
• Quality of Herbal Medicinal Products/Traditional Herbal Medicinal Products (CPMP/QWP/2819/00 Rev. 2) provides guidance to achieve consistent quality for products of herbal origin. Note herbal ingredients included in listed medicine must meet the definition of a herbal substance.
• Test procedures and Acceptance Criteria for Herbal Substances, Herbal Preparations and Herbal Medicinal Products/Traditional Herbal Medicinal Products CPMP/QWP/2820/00 Rev. 2) provides general principles for setting and justification of a uniform set of specifications for products of herbal origin.

Sponsors and potential applicants should also be aware of the following documents that provide specific guidance for complementary medicines:

• Annex 7 of the Guide to good manufacturing practice for medicinal products provides specific guidance on the manufacture of herbal medicinal products.
• Supplier qualification provides the steps by which supplier qualification may be achieved.
• Identification of herbal materials and extracts provides common questions and answers relating to identification of herbal materials.
• Sampling and testing of complementary medicines covers the sampling and testing requirements for raw materials used in the manufacture of intermediate, bulk or finished complementary medicine products. It also describes a plan for reduced sampling and testing once an approved supplier has been qualified.
• The guideline Starting material analytical procedure validation for complementary medicines describes the minimum approach acceptable to achieve validation of the test procedures used for starting materials for use in complementary medicines.
• Finished Product Specifications and certificate of analysis.
• The document Equivalence of herbal extracts in complementary medicines assists sponsors of medicines containing herbal extracts to determine how and when a herbal extract may be considered 'equivalent' to an ingredient currently included in a therapeutic good and when it may be used as a substitute without causing the product to be considered a different therapeutic good.
• Use of modified unprocessed herbal materials in complementary medicines assists sponsors in identifying situations where the composition of an unprocessed herbal material has been modified to the extent that it is significantly different from the original material approved for use in listed or registered medicines.
• On-going stability testing for listed complementary medicines provides guidance on the development of a stability protocol for complementary medicines. The approach taken by TGA in relation to stability testing of herbal and certain other listed complementary medicines, recognises the differences between these types of therapeutic products and pharmaceutical products that usually contain a single, chemically defined, active.
• Stability testing of listed complementary medicines provides common questions and answers on stability testing.
• Product quality review for listed complementary medicines provides guidance on product quality reviews, which are part of GMP requirements.
• The Process validation for listed complementary medicines document provides guidance to ensure that the validation process used is effective in producing a quality medicinal product.
• Consistent with the TGA's risk-based approach to the regulation of medicines, it may be possible to justify certain situations where it is not necessary to assay an ingredient in every batch of finished product. In such situations, the content of an ingredient, or a component within the ingredient, may be estimated from the amount dispensed during the manufacture of the product. This practice is termed 'quantified by input' (QBI). However, based on risk to consumers, it is not appropriate to apply this practice to all ingredients - refer to Guidance on use of the term 'quantified by input' for listed complementary medicines for more information.
• Sponsors and potential applicants should also be aware of information included in ARGCM Part D 'Table D6: Allowed changes to the nominal amounts of certain excipients', which is also relevant for listed complementary medicines.