Discontinuing pre-market evaluation of Herbal Component Names: Frequently asked questions (FAQs)

Previously, sponsors applied to have their HCN evaluated and approved. After approval the HCN was visible in the Electronic Listing Facility (ELF) and available for inclusion in ARTG entries. A business process had been designed and implemented around such applications, even though this is not a formal legal requirement.

To determine the correct name, the TGA reviewed the supportive information provided by an applicant which included details of the laboratory methods used for the material's analysis, along with validation data. While this process was scientifically robust with respect to the individual application, the fact that the 'approved' HCN was available in ELF for use in all future listed medicines, and no comparative analysis against the original application was required or performed, meant that there was no assurance that a particular HCN would be applied consistently across products. Furthermore, the work that was required for TGA to approve the name of herbal components across multiple branches is not legislated (mandatory) and was not commensurate with a risk-based approach to the regulation of complementary medicines.

Sponsors will no longer be able to submit new HCN applications effective immediately. After 1 October 2018, sponsors will not be able to select HCNs from the TGA list of approved HCNs for use in new listings. However, sponsors will retain the freedom to make claims on their labels about herbal components without pre-market evaluation of HCNs as long as they are true and comply with regulatory requirements. Sponsors will still be required to hold evidence to support any claims that they make about herbal components on their labels and this can be reviewed as part of a post-market compliance review.

TGA is implementing this business improvement process for the following reasons:

• The pre-market evaluation or use of a HCN is not a legal requirement for listing therapeutic goods;
• Listed medicines are generally not required to undergo any pre market evaluation and comprise the lowest risk class of regulated medicines. The pre-market evaluation of HCNs is not in step with this low risk framework;
• Industry has raised concerns about the length of the evaluation process and the lack of predictability for business planning and timing of product launches;
• The HCN evaluation process is resource intensive and is not cost recovered; and
• Discontinuation of TGA pre-market evaluation of HCNs will remove unnecessary regulatory red tape for sponsors.

Existing ARTG entries will not be affected by this change. Sponsors will not be required to amend or remove any HCNs from their ARTG entries, and will continue to be able to make variations to their medicines as usual. Sponsors will not be able to add new non-mandatory HCNs to the ARTG entry for any medicines. Sponsors can of course still use HCNs as therapeutic or quality markers as part of the product manufacturing process or as part of a claim on product labels.

Existing, non-mandatory HCNs will no longer be available for selection in new listed medicine applications.

Existing mandatory herbal components, as identified in the Therapeutic Goods (Permissible Ingredients) Determination, will be retained and still be required to be declared in the ARTG entry for listed medicines for the purposes of safety.

Existing herbal proprietary ingredients will not be amended to remove any HCNs. Non-mandatory HCNs in the Ingredients Repository will not available for selection for new proprietary ingredients.

There is no change to the assessment of HCN label claims in post-market listing compliance reviews. Sponsors must hold evidence to support claims about herbal components. This evidence can be requested as part of a compliance review to assess whether a reference to the use of any component is accurate and not misleading, as is the case with any label claim.

The naming of the component(s) is up to the sponsor as long as it can be scientifically justified and is not confusing or misleading to consumers. Note that the label should not indicate a therapeutic role for quality marker components as this is potentially misleading to the consumer.

Where a sponsor makes a label claim about the presence of a component, the sponsor will need to hold:

• evidence that the component occurs in the herbal species, such as published scientific literature or original scientific analysis showing the presence of the component; and
• details of the method of analysis used to identify and/or quantify the individual component declared on the label.

HCN claims have always been subject to post-market review because only the name was assessed pre-market. Any listed medicine that makes a label claim about a herbal component will continue to be subject to review whether a HCN has been pre-market evaluated or not. The pre-market evaluation of HCNs does not provide an assurance that HCNs are applied consistently across listed medicines or that the component is actually present in a listed medicine. It has been, and will continue to be, the responsibility of the sponsor to ensure a HCN is applied appropriately to their listing and they hold appropriate evidence to justify the presence and quantity of the component.

Discontinuation of TGA pre-market evaluation of HCNs will not in itself result in any GMP deficiencies being issued. If a product label indicates that the product contains a specific quantity of a herbal component (i.e. standardisation), the sponsor will need to hold documentation that the component has been quantified in the finished product and meets the defined manufacturing specification for that component. Batch-to-batch variation and standardisation is already expected to be controlled by the manufacturer by testing in line with product manufacturing specifications, and not by virtue of whether a HCN is or is not listed in the ARTG entry for a medicine.

Personnel conducting release for supply will still need to confirm that the product formulation is consistent with the ARTG listing in terms of the specific ingredients and their quantity. The herbal component and relative quantity will not be in new ARTG entries made after 1 October 2018, however mandatory components must still be declared in the ARTG entry for listed medicines for the purposes of safety. The person conducting release for supply must ensure that the quantity of the component meets the relevant specification for the batch of product. If the quantity of the herbal component in the batch is not specified in the documents being reviewed at the time of release, the person conducting release for supply needs to obtain copies of these documents (for example, the certificate of analysis or testing records). The product should only be released once the component is found to be present in the product at the correct concentration (within specification).

Additionally, where specifications for components in finished products are defined in Therapeutic Goods Orders or pharmacopoeial monographs, the specifications for these components should be in line with these requirements.

If an applicant selects a standardised extract preparation type without entering the standardised component then the ELF system will not validate. This process remains unchanged from the previous arrangements where if a sponsor wished to standardise to a component which is not in the Ingredients Database, the sponsor would have to select 'extract' in ELF or apply for a new HCN, in addition to maintaining evidence to show it is being standardised.

Unless a component is available to select in the Ingredients Database when using 'standardised extract', then the sponsor will need to select 'extract' to validate. The sponsor will still be required to maintain the quality of the product (whether standardised or not) throughout the product's life as described above.

Existing HCN notification forms and guidance documentation will be archived on the TGA website or amended to reflect the changes as required.