Overview of compositional guidelines and templates

What is a compositional guideline

A TGA compositional guideline is a summary of descriptions, tests and acceptance criteria (such as numerical limits, ranges or other criteria) that define the characteristics and specify the composition of an ingredient permitted for use in listed medicines. For the current list of compositional guidelines – refer to the list of compositional guidelines.

Compositional guideline templates

The compositional guidelines templates below are for prospective applicants to supply with their applications to vary the Permissible Ingredients Determination. There are four templates for different ingredient types that provide guidance for the type of information that should be included.

The information in the compositional guideline will be derived from the information you provide in an application for a new ingredient such as the description, characterisation (identity, assay, impurities) analytical methods and acceptance criteria. Refer to the ‘Specifications’ under Section B – Information Requirements within the Application requirements for new substances in listed medicines.

Compositional guideline templates for:

• Chemical entities or synthetic polymers
• Herbal materials
• Microorganisms
• Substances of animal origin

How compositional guidelines are used

Compositional guidelines assist sponsors in determining if an ingredient that is being considered for use in a listed medicine is one that has been evaluated by the TGA and found to be of appropriate quality and safety. Compositional guidelines are generated where there is no applicable default standard recognised in the Therapeutic Goods Act 1989 (the British Pharmacopoeia, United Stated Pharmacopoeia-National Formulary and European Pharmacopoeia).

If an applicable new default standard is published for an ingredient where a compositional guideline exists, the ingredient must comply with the requirements of the new default standard. Sponsors should check the default standards to determine if there is an applicable default standard before manufacturing. Compositional guidelines may remain on the TGA website as a record of what was approved by the TGA at the time.

Compositional guidelines assist sponsors to:

• understand the specific nature of the ingredient that has been approved for use
• determine whether their material conforms to the requirements for that ingredient
• minimise any risks associated with the ingredient by complying with the parameters of the specification

While compliance with the compositional guideline is not a legal requirement, using an ingredient that does not meet the specifications of a compositional guideline may result in the TGA having concerns about the safety of that ingredient and any medicines containing it.

Where a sponsor wishes to include an ingredient in listed medicines that does not meet the compositional guideline a request may be made to justify the safety of that specific material and/or the safety of any listed medicines containing that material. Where an ingredient is found to be unjustifiably different from the relevant compositional guideline, a sponsor may be requested to no longer use that material.

It is expected that there will be improvements in testing methods as equipment and technology advances. Sponsors may choose to impose tighter limits, include additional tests, or use new validated analytical methods where there is a sound scientific justification that the ingredient is the same as what has been approved for use in listed medicines.

When compositional guidelines are generated

Compositional guidelines are generated as part of the application and evaluation of a new substance for use as an ingredient in listed medicines. If the new ingredient is not subject to a specific default standard, a draft compositional guideline for the substance must be submitted in the application. The information the applicant includes in the proposed compositional guideline is based on the quality data submitted in the application.

On occasion, a compositional guideline may be generated for some ingredients currently permitted for use in listed medicines, for example: ‘grandfathered’ ingredients that were available in Australia prior to the commencement of the Therapeutic Goods Act 1989 and are not subject to a default standard or have a compositional guideline. The TGA will work with relevant stakeholders, including industry stakeholders, to develop these compositional guidelines when required.

Procedure for amending compositional guidelines

Compositional guidelines are not regularly amended as they are established specifications that characterise the substance at the time a new substance is approved for use in listed medicines. A stakeholder can request the TGA to consider amending a compositional guideline. The request must be accompanied by an appropriate justification that the safety profile of the ingredient will not be compromised (which would make it unsuitable for use as an ingredient in listed medicines).

Consideration will be given to whether the compositional guideline should be amended or a separate ingredient recognised (which would require an application for evaluation of a new substance). If the amendment is considered warranted, we will seek initial comment from the original applicant prior to determining if a revised draft should be published.