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Guide to interpretation of the Australian Code of Good Manufacturing Practice for Medicinal Products (16 August 2002) applicable to the manufacture of complementary medicines
The purpose of this document is to clarify Code requirements for manufacturers of complementary medicines. This document has been developed following discussions with industry associations.
Where specified by an asterisk (*), these interpretations may also apply to manufacturers of OTC and prescription medicines.
Person(s) recognised by the authority as having the necessary basic scientific and technical background and experience to release each batch of product for supply and to certify that it is in accordance with the requirements of the marketing authorisation.
The marketing authorisation is the approval or authorisation given to the sponsor by the TGA to supply a therapeutic good in Australia. The marketing authorisation includes the formulation listed on the ARTG (for listed products) and shelf life conditions together with any other conditions of listing or registration.
Where a clause number is not listed there is no specific interpretation provided for complementary medicines.
The authorised person to release complementary medicines for supply must ensure that the product label, ARTG entry, manufacturing formula and specifications are consistent.
In regard to stability of the product, the authorised person must ensure that data exists to support the shelf life and must be based on scientific grounds.
Guidelines for assessing stability of complementary medicines will be included in the Australian Regulatory Guidelines for Complementary Medicines.
|2.3*||The authorised person may be a consultant licensed by the TGA to release product for supply.|
|3.6||The use of dedicated and self-contained facilities is not required for listable complementary medicines.|
|3.12||Air filters used in manufacturing areas where product is exposed should be at least EU7 grade or equivalent. Pressure differentials and air flows must be defined and appropriate. This is applicable for both listed and registered complementary medicines. However additional requirements would be required for a manufacturing facility producing complementary medicines and other medicines.|
|4.11||Also refer to comments re Annex 7, Section 5. Note that it is the manufacturers responsibility to ensure appropriate specifications for starting materials are in place prior to manufacture commencing.|
|4.13(e)||Refer to the Australian Regulatory Guideline for Complementary Medicines: Quantified By Input - available on this website.|
|5.19 a||The use of segregated facilities is not required for listable complementary medicines.|
|5.21-5.24||The validation policy for complementary medicines must be included in the Validation Master Plan with justifications, if relevant, for the grouping of products and selection of processes to be validated. Validations can be limited to processes that can affect product quality and should be based on a risk assessment carried out by the manufacturer.|
This requirement applies to "actives" and not to excipients. A statistically valid sampling plan for excipients is acceptable subject to verification from PIC/S. Statistical sampling can be applied to containers of in-process bulk products eg bulk tablets and capsules, obtained from TGA approved manufacturers.
Refer also to the requirements for sampling and validation of manufacturers of starting materials in Annex 8.
Analytical methods for starting materials included in the BP, EP or USP do not require additional validation where the pharmacopoeial method is employed.
Analytical methods from the BP/USP used for finished formulations need validation to eliminate any effects from the formulation. All analytical method validations should be recorded.
|7.2*||The marketing authorisation is not required to be checked at the time of each batch release. It may be performed at a single point in time, eg. at the time the GMP agreement is signed. Any subsequent changes that may impact the marketing authorisation must be communicated by the change originator to the relevant parties, eg. manufacturers, sponsors and authorised persons.|
|7.7*||It is the contract manufacturer's responsibility to ensure that the quality of all materials used are suitable for their intended purposes. Materials supplied by a sponsor for use in the sponsors product must be tested and released by a licensed manufacturer prior to use.|
|7.11*||The contract must specify the mechanism by which the authorised person ensures that the product is in compliance with the Marketing Authorisation.|
|Annex 2||Not applicable to listable complementary medicines.|
|Annex 3-6||Not applicable.|
|Annex 7.1||A separate storage area for crude plants (ie unprocessed) should be used but if common storage areas are used for crude plants and other materials, including packaging materials, then the company must be able to justify this practice.|
This section lists items normally expected to be found in the specification for medicinal crude plants (active herbs). It is not expected that the manufacturer will carry out all tests upon receipt, but where appropriate, as a minimum will perform a macro and/or microscopic examination and a specific identification test for example chromatographic profile against an authenticated reference specimen. Other results can be taken from the Certificate of Analysis provided by the supplier. Refer to the Australian Regulatory Guidelines for Complementary Medicines: Quantified by Input.
The use of ethylene oxide as a fumigant to reduce microbial and insect contamination is not permitted by the BP.
|Annex 7.6||The environment for drying, crushing and sifting of crude plants should be clean and enclosed but does not need a filtered EU7 air environment.|
|Annex 7.7||Extra care needs to be exercised in sampling, according to a documented procedure, prior to crushing and sifting to ensure a representative sample is obtained.|
|Annex 7.9||Quantitative determinations of active ingredients in the finished product will only be required if there is a label claim for these components as specified in the Australian Regulatory Guidelines for Complementary Medicines: Quantified by Input.|
The inherent variability of raw herbs presents challenges to ensuring appropriate validation of suppliers of herbs and herbal derivatives, for example extracts. A vendor's assurance based on an acceptable quality system, for example external certification of a suppliers quality system such as ISO 9000 or GMP certification (refer to clause 5.30) should be part of acceptable validation.
NB. Refer to item 30 of the Q&A Section on the GMP page of this web site. Lack of this assurance justifies the sampling of all containers for identification testing.
|Annex 8.4||Manufacturers should be aware of the variability in crude herbs when preparing a composite sample in accordance with a documented procedure. <561> of the USP could form the basis of such a procedure.|
|Annex 9.4||Purified water should be used to prepare finished products.|
|Annex 10||Not applicable.|
|Annex 14||Not applicable.|
|Annex 15.20-27||Process validation need only consider critical points. Such validations can be grouped for similar products/formulations and should be based on worst case situations re the equipment train used.|
|Annex 15. 36-42||Cleaning validations can be grouped looking at worse case situations. Acceptance criteria of "visibly" clean will be accepted for most complementary medicines. Biological ingredients and crude plants that may carry an intrinsic microbiological load prior to processing may need other acceptance criteria.|