Therapeutic Goods Order No.77 Microbiological standards for medicines (TGO 77) has been in force since 1 January 2010. It was automatically repealed (sunset) on 1 October 2018 in accordance with the Legislative Instruments Act 2003. A new instrument, Therapeutic Goods Order No.98 Microbiological Standards for Medicines 2018 (TGO 98) succeeded TGO 77 on this date to provide continuing clarity on the requirements for microbiological quality of medicines.
TGO 98 reflects the current requirements of TGO 77 without regulatory change. As with TGO 77, it specifies the minimum microbiological requirements with which a medicine must comply throughout its shelf life, i.e. which medicines must comply with a Test for Sterility and Bacterial Endotoxin testing; which medicines must comply with a preservative efficacy test; and the acceptance criteria for microbiological quality that apply to nonsterile medicines.
TGO 98 and its Explanatory Statement are registered on the Federal Register of Legislation and can be accessed via the following link: https://www.legislation.gov.au/Details/F2018L01287.
A guidance document to TGO 98 is being prepared. It is expected to be available on the TGA website by mid to late October.
The proposal to remake TGO 77 as a new instrument without substantially altering the current arrangements was available for public comment via the TGA website from 6 February to 6 March 2018 (refer Consultation: Remaking of TGO No. 77 - Microbiological Standards for Medicines). Eight submissions were received. Most were supportive of TGO 77 in general, but requested either one, or several technical modifications to it. One submission disagreed with the proposal to remake TGO 77 claiming microbiological requirements in the default pharmacopoeias were satisfactory and TGO 77 was not necessary. Most of the issues raised that were within the scope of TGO 77 were identical or similar to issues raised by stakeholders in relation to the 2008 consultation on the draft TGO 77 and an earlier Consultation Paper, Microbiological Standards for Medicines in the Australia New Zealand Therapeutic Products Authority (ANZTPA) - Call for Comment - July 2006.
It is evident from the recent consultation that some stakeholders would prefer TGO 98 to:
- allow multidose ophthalmic preparations, complementary medicine oral liquid dosage forms and sunscreen preparations to comply with the less stringent acceptance criteria of the United States Pharmacopeia preservative efficacy test;
- exclude probiotic medicines from all of the requirements of the new instrument;
- exclude some short shelf-life sterile medicines from the requirement to conduct bacterial endotoxin testing;
- exclude multidose low water activity preparations from the need to comply with requirements for preservative efficacy.
A minor technical amendment to Clause 8 (preservative efficacy) of TGO 98 provides clarification in relation to preservative efficacy testing of multidose medicines. This clause refers to a medicine that is an 'aqueous' multidose medicine, addressing d) above. For the same microbiological safety reasons acknowledged by the then Therapeutic Goods Committee in 2008, it is not desirable for TGO 98 to reflect the stakeholder proposals identified in a), b) and c) above.
Responses to the submissions are being prepared and will be forwarded to the respondents. A summary of the responses will be posted to the TGA website.
Questions relating to TGO 98 should be directed to the Microbiology Section by email to TGA .Laboratories@health.gov.au or by telephone to 02 6232 8921. Please include 'TGO 98' in the subject line of the email.