Updates to legislative instruments exempting monographs as standards

The Therapeutic Goods Administration (TGA) has updated legislative instruments specifying that certain monographs of the United States Pharmacopeia-National Formulary (USP) are not accepted as default standards.

These instruments were due to sunset on 1 April 2022, providing TGA with the opportunity to review requirements.

Remade legislative instrument: Therapeutic Goods (Standard for Human Albumin) (TGO 111) Order 2022

The TGA has remade Therapeutic Goods Order No. 90 Standard for human albumin - external site (TGO 90), as the Therapeutic Goods (Standard for Human Albumin) (TGO 111) Order 2022 - external site with no technical amendments.

TGO 111 commences on 31 March 2022 and continues to specify that albumin from humans must comply with the monograph for human albumin in the British Pharmacopoeia (BP) or the European Pharmacopoeia (Ph. Eur.). The USP monograph for human albumin is not accepted as a default standard. TGO 111 reflects the requirements of TGO 90 and is not intended to alter existing arrangements.

The TGA assessed the performance of TGO 90 and found it was fit for purpose and was operating effectively and efficiently.

TGO 90 was introduced in 2011 due to significant differences between the requirements for human albumin in the USP compared to the BP and Ph. Eur. The TGA has remade TGO 90 as many of these differences in the USP remain including:

• not being stand alone, due to references to, or relying on, United States of America (US) legislation and/or decisions of the US Food and Drug Administration (FDA)
• lacking a requirement for mandatory Nucleic Acid Amplification Testing (NAT) of starting plasma, which could present an increased risk of infectious disease
• inadequate product characterisation in comparison to the Ph. Eur./BP.

Updated legislative instrument: Therapeutic Goods (Exempting Monographs) Determination 2021

The TGA has amended Therapeutic Goods (Exempt Monographs) Determination 2021 - external site to include the content of the sunsetting Therapeutic Goods (Exempting monographs of pharmacopoeias) Determination No. 1 of 2011 - external site, with minor amendments.

Therapeutic Goods (Exempt Monographs) Amendment Determination 2022 - external site (‘the Amendment Determination’), amends the Therapeutic Goods (Exempt Monographs) Determination 2021 to continue to set out specific monographs of the USP that are not accepted as default standards as they are exempt from the definition of ‘standard’ in the Therapeutic Goods Act 1989 - external site.

The TGA assessed the performance of the sunsetting legislative instrument and found it was fit for purpose and was operating effectively and efficiently. However, many of the monographs in the sunsetting instrument were no longer official and had been removed from the USP since 2011, so did not need to continue to be exempted. Rather than remaking the sunsetting instrument, the TGA has amended the Therapeutic Goods (Exempt Monographs) Determination 2021 to provide a single consolidated instrument to exempt monographs from the definition of standard.

The monographs of the USP exempt from the definition of standard in the Amendment Determination are:

• Antithrombin III Human
• Factor IX Complex
• Pancreatin
• Pancrelipase
• Plasma Protein Fraction.

Reasons for continuing to exempt these as accepted standards include:

• expressions of potency, including 'USP Units', that are different to units used in the BP/ Ph. Eur. with established use in Australia, with potential for product labelling in USP Units to be confusing to users
• not being stand alone, due to references to, or relying on, US legislation and/or decisions of the US FDA
• lacking a requirement for mandatory NAT of starting plasma, which could present an increased risk of infectious disease
• inadequate product characterisation in comparison to the Ph. Eur./BP.

Therapeutic Goods (Exempting monographs of pharmacopoeias) Determination No. 1 of 2011 has been repealed in Amendment Determination as the content has been included in Therapeutic Goods (Exempt Monographs) Determination 2021.

Standard no longer in force: Therapeutic Goods Order No. 89 Standard for water for injections for parenteral medicines

Therapeutic Goods Order No. 89 Standard for water for injections for parenteral medicines - external site (TGO 89) will sunset on 1 April 2022. This means it will no longer be in force and goods previously subject to TGO 89 can now be supplied in Australia.

TGO 89 specified that water for injections (WFI) must comply with the BP or the Ph. Eur. WFI monographs, and therefore could not be manufactured according to the USP WFI monograph.

TGO 89 was introduced in 2011 due to concerns about the microbiological quality of water produced by methods permitted in the USP WFI monograph. Following an extensive review of the evidence and international debate, the Ph. Eur. and BP WFI monographs have since been updated to allow additional production methods in line with the USP. As the requirements for WFI in the Ph. Eur., BP and the USP are now aligned, the TGA considers that TGO 89 is no longer needed and can be allowed to sunset.