Overview of evaluation of a substance for use in listed complementary medicines

ARGCM Part C: New complementary medicine substance evaluation

3 May 2018

This guidance is for applicants requesting evaluation of a substance for use in listed complementary medicines.

Applications to vary the Permissible ingredients determination

Listed complementary medicines may only contain ingredients included in the Therapeutic Goods (Permissible Ingredients) Determination (the Permissible Ingredients Determination). The Permissible Ingredients Determination is a legislative instrument made by the Minister for Health under section 26BB of the Therapeutic Goods Act 1989 (the Act).

For a substance to be included in the Permissible Ingredients Determination, an applicant must make an application to the Secretary under section 26BE of the Act for a recommendation that the Minister vary the Permissible Ingredients Determination. Applicants must use the application form: Application for evaluation of a substance for use in listed complementary medicines. An application can be submitted for:

  • A new complementary medicine substance not currently included in the Permissible Ingredients Determination.
  • A proposed new role or a change to a the existing requirements for use of a current permitted ingredient, for example:
    • for an ingredient permitted for use as an excipient to be used as an active ingredient
    • to change the permitted level of use
    • to change the permitted route(s) of administration

The Secretary will evaluate the substance taking into account whether it is of appropriate quality and safety to be permitted for use in listed complementary medicines. A TGA delegate of the Secretary must either, make a recommendation (successful applications) or refuse the application (rejected applications).

If the substance is determined to be safe, it will be recommended for inclusion in the Permissible Ingredients Determination and the Minister may vary the instrument. In some cases, 'requirements' (for example, restrictions on the concentration of an ingredient in a product or restrictions on the maximum daily dose of the product) may be attached to the use of the ingredient in a listed complementary medicine so that safety and quality can be maintained.

Once an ingredient is included in the Permissible Ingredients Determination, it may be used in any listed complementary medicine provided any requirements for use are complied with.

Route of evaluation for complementary medicines

Schedule 10 of the Therapeutic Goods Regulations 1990 (the Regulations) prescribes which area within the TGA conducts the evaluation of specific therapeutic goods.

Part 2 of Schedule 10 states that complementary medicines (including substances) that do not meet the criteria for inclusion in Schedule 4, 8 and 9 of the Poisons Standard are evaluated by the Complementary and OTC Medicines Branch.

If you are of the view that your application has been incorrectly referred to a particular TGA area for evaluation, you may make a submission in support of which route of evaluation you consider more appropriate. In making such a submission, you should provide all relevant information that would enable the assessment of the therapeutic good against Schedule 10 of the Regulations.

Substances eligible for evaluation for use in listed complementary medicines

Schedule 14 to the Regulations provides a list of designated active ingredients for complementary medicines. If a substance is of the type listed in Schedule 14 to the Regulations, it may be eligible for evaluation for use in listed complementary medicines providing:

  • The substance is not a prohibited import.
  • For a substance of herbal origin, the substance or its constituent(s) is/are not subject to the conditions of a Schedule (or applicable Appendix) to the Poisons Standard.

Some substances are subject to the conditions of a Schedule (or applicable Appendix) to the Poisons Standard only if present in a certain quantity in a finished product. Accordingly, appropriate restrictions (for example, dose or route of administration) must be placed on the use of such an ingredient in listed complementary medicines.

If the proposed new substance is not currently in a Schedule to the Poisons Standard but the substance, or its constituent, has a potential safety concern that may meet the criteria for inclusion in a Schedule, you should seek advice from the TGA prior to submitting an application. Should it be identified during the course of the evaluation that the substance meets the criteria for inclusion in a Schedule, the matter will be referred to the relevant scheduling advisory committee. It may be determined that the substance is not suitable for use in listed medicines on the basis of the scheduling decision.

If you consider the scheduling of a substance should be reconsidered, you can submit an Application to amend the Poisons Standard.

Application categories for evaluation of substances

Applications for evaluation of a substance to be used in listed complementary medicines are categorised into four application levels (IN1, IN2, IN3 and IN4). Each application category has defined submission requirements. Less supporting information is required and shorter evaluation times apply to lower level applications. IN1, IN2 and IN3 application categories require submission of pre-evaluated information from an acceptable comparable overseas regulator (COR).

Table C1 provides the application categories and the key application requirements for evaluation.

Table C1: Application categories for evaluation of substances
Category Description Evaluation and application requirements
IN1 Evaluation of safety and quality based on evaluation reports from a COR.
IN2
  • Evaluation of safety based on evaluation reports from a COR.
  • Independent evaluation of quality by the TGA.
IN3
  • Evaluation of quality based on evaluation reports from a COR; or a monograph contained in a default standard.
  • Independent evaluation of safety by the TGA.
IN4 Full independent evaluation of safety and quality by the TGA.

Where possible, the TGA makes use of COR evaluation reports for evaluation of a substance for use in listed complementary medicines. As part of the Government's reforms arising from the Medicines and Medical Devices Review (MMDR) the TGA is developing:

  • A list of countries and jurisdictions from whom TGA will accept reports for use in the COR report-based process.
  • Transparent criteria for identifying CORs.
  • A process for using overseas reports.

Please note, COR evaluation reports that are provided for IN1, IN2 and IN3 applications must be from a list of CORs that is determined by the TGA under Regulation 16GJ.

Guidance on the use of COR reports will be available on the TGA website in 2018.

Timeframes and fees for evaluation of substances

Regulation 16GI of the regulations provides for legislated timeframes for evaluation of a substance for use in listed complementary medicines. There are different evaluation timeframes for each of the four application categories (refer to Table C1). While the TGA is required to complete the assessment within the specified timeframes, applicants should not presuppose the outcome of an application.

The timeframes for evaluation of a substance for use in listed complementary medicines are provided in Table C2.

Table C2: Timeframes for the evaluation of a substance for use in listed complementary medicines
Application level Screening time Evaluation time
IN1 40 70
IN2 40 120
IN3 40 150
IN4 40 180

Within 40 working days of receiving an application, the TGA delegate of the Secretary will notify the applicant in writing, whether the application has or has not been accepted for evaluation.

The timeframes for the evaluation of a substance for use in listed complementary medicines:

  • only commence once an application is accepted for evaluation and the evaluation fee has been paid
  • apply to working days only and exclude public holidays and weekends
  • exclude the time when the evaluation clock has stopped (for example: the time taken by the applicant to provide responses to formal requests for information; or when the applicant and TGA agree to a mutual stop clock)

If the Secretary does not make a recommendation within the evaluation timeframe, the TGA must refund 25% of the prescribed application fee.

Exclusive use of new ingredients

Following an evaluation of a substance, subsection 26BB(2A) of the Act allows the Minister to permit the successful applicant to have exclusive use of that ingredient (the protected ingredient). Exclusivity periods will be specified in the Permissible Ingredients Determination as a 'requirement' relating to the use of the ingredient in listed medicines (under paragraph 26BB(1)(b) of the Act).

During the specified exclusivity period the use of a protected ingredient in a listed medicine will be restricted to:

  • the applicant who requested evaluation of the substance (who may or may not be a medicine sponsor)
  • other persons nominated by the applicant

The exclusivity period will start from the date the protected ingredient is included in the Permissible Ingredients Determination and end two calendar years later (for example, an exclusivity period starting 1 July 2018 will end 1 July 2020).

At the end of the exclusivity period, any sponsor can include the ingredient in a medicine and list that medicine in the ARTG.

An ingredient that is the subject of an exclusivity period cannot be used by other applicants to list a medicine in the ARTG unless they have been nominated by the ingredient applicant during the exclusivity period. Use of a protected ingredient within the exclusivity period without an approval from the ingredient applicant would contravene the requirement relating to the use of the ingredient and is grounds to cancel the medicine from the ARTG under section 30 of the Act.

Eligibility for exclusivity

Exclusivity will only be permitted for a new complementary medicine ingredient (active or excipient) that is not currently included in the Permissible Ingredients Determination (that is, the ingredient is a new item in Table 1 in Part 2 of Schedule 1 to the Permissible Ingredients Determination, provided that:

  • it has not previously been evaluated by the TGA for use in listed or registered medicines
  • it is not used in, or available for use in registered medicines

Exclusivity will not apply to applications submitted for a new role or a change to any existing requirements for use of a permitted ingredient, for example:

  • for an ingredient permitted for use as an excipient to be used as an active ingredient
  • to change the permitted level of use (for example, from 0.5% to 1%)
  • to change the permitted route(s) of administration (for example, from topical use to oral use)
  • to change the permitted use of a herbal ingredient (for example, to add a different plant part or preparation method)
  • to change the requirements to allow use of another strain of a species which is a permitted ingredient (for example, addition of the LA-5 strain to Lactobacillus acidophilus)