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High-moderate risk changes to permissible ingredients - Caffeine

Changes to the Permissible Ingredients Determination - High-moderate risk

3 September 2019

The Therapeutic Goods (Permissible Ingredients) Determination ('the Determination') is a legislative instrument under section 26BB of the Therapeutic Goods Act 1989. This instrument specifies all of the ingredients that are available for use in listed and assessed listed medicines and their associated requirements. The Determination is continually reviewed by the TGA to ensure that all ingredients and their requirements are appropriate for use in low-risk medicines.

Following a safety review, new requirements for caffeine and caffeine-containing ingredients within listed medicines are specified in the Therapeutic Goods Amendment (Permissible Ingredients) Determination (No. 1) 2019. A delay to implementation of these changes was considered likely to pose an imminent or serious safety risk to consumers (see High-moderate risk changes). As such, the Delegate of the Minister of Health has considered it appropriate to make this change to the Determination commencing 2 September 2019.

Background

The TGA wrote to sponsors of caffeine containing ingredients on 13 March 2018 and 17 May 2018 regarding changes relating to caffeine and caffeine-containing ingredients. Feedback from stakeholders at these times referenced a review of caffeine safety conducted by the European Food Safety Authority (EFSA) and the Health Canada (HC) monograph for caffeine. We also sought advice from the Advisory Committee on Complementary Medicines (ACCM) regarding requirements for caffeine in listed medicines in 2018.

In June 2019, the TGA was contacted by the NSW Coroner's Court regarding the death of an individual associated with acute caffeine toxicity. The caffeine is suspected to have been ingested from an unlabelled pure or highly concentrated caffeine powder. Further, on 10 July 2019 Minister Colbeck and Minister Hunt wrote to Food Standards Australia New Zealand (FSANZ) to request a review of the safety of caffeine powders and high caffeine content products. The Ministers also requested that FSANZ engages with TGA to align therapeutic goods regulations with food regulation to the extent possible.

Subsequently, the TGA reviewed the current toxicology data pertaining to caffeine and reconsidered the requirements for caffeine; as an individual ingredient, when present as a component of other herbal ingredients (e.g. Camellia sinensis), and when present from both these sources (i.e. total caffeine).

New requirements for the use of caffeine

Following consideration of options to manage the safety concerns with concentrated caffeine powders and other dosage forms, and taking into account the request from Minister Colbeck and Minister Hunt, and feedback from last year's review of caffeine, highly concentrated caffeine in any dosage form will become ineligible for listing.

Caffeine as an individual ingredient remains only for oral use and at a maximum daily dose of 100mg. However, caffeine when present as a component of other herbal ingredients will now have dosage restrictions so that the medicine does not provide more than 400mg total caffeine per day. A maximum dose of 100mg per 3 hours will also be required. These limits consider consumption from other sources such as food, and the adverse effects which are seen with caffeine intake exceeding 400mg/day and more frequent dosing.

The additional restrictions have been included to be consistent with all caffeine containing ingredients and cover routes of administration where caffeine is present from other ingredients.

The warning statement (CAFF) has been adjusted to increase consumer awareness of caffeine intake. An additional warning statement of (CAFFPREG) addresses concerns for caffeine use in pregnancy and lactation. Caffeine as an individual ingredient currently has the requirement for a warning statement for 'Adults only'. The same concerns for caffeine intake for children apply to other ingredients containing caffeine and this statement has been applied to all caffeine containing ingredients above 10mg daily dose.

For doses greater than 80mg/day (which equates to a cup of instant coffee), additional warning statements will be required to address specific safety concerns of inadvertent misuse, interactions with other medicines which may lead to increased caffeine plasma levels or interactions between medicines, and potential adverse effects due to high caffeine intake.

A caffeine concentration of 1% in undivided preparations was considered acceptable given that 30 g (estimated equivalent of a heaped tablespoon) would deliver only 300 mg of caffeine, which sufficiently reduces the likelihood of inadvertent overdose. A concentration of 33% is considered acceptable in divided preparations that do not require the consumer to measure dosage. This is considered to pose a lower risk of inadvertent overdose and is in line with the highest caffeine concentration in existing OTC products.

The new requirements for caffeine below will be applied to the following ingredients for internal use or oral application in listed medicines:

  • caffeine
  • Camellia sinensis
  • Coffea arabica
  • Coffea canephora
  • coffee
  • Cola acuminata
  • Cola nitida
  • Ilex paraguariensis
  • Paullinia cupana
  • Theobroma cacao

The following requirements will have immediate effect:

  • Undivided preparations (e.g. bulk powders) must not contain a concentration of total caffeine greater than 4%.
  • Divided preparations (e.g. tablets) must not contain a concentration of total caffeine greater than 33%.

For the following requirements, sponsors of existing listed medicines will have until 2 March 2021 to bring affected products into compliance, and any new listed medicines will need to comply immediately:

  • The maximum recommended daily dose must not provide more than 400mg of total caffeine from all ingredient sources. NOTE: The existing 100mg maximum daily dose limit for caffeine as an individual ingredient still applies.
  • Undivided preparations must not contain a concentration of total caffeine greater than 1%.
  • The maximum recommended dose must not provide more than 100 mg of total caffeine within a 3 hour period.
  • When the maximum recommended daily dose provides greater than 10 mg of total caffeine, the following warning statements are required:
    • (ADULT) 'Adults only' (or words to that effect).
    • (CAFF) 'Contains caffeine [state quantity per dosage unit or per mL or per gram of product] total caffeine [per dosage unit or per mL or per gram]. A cup of instant coffee contains approximately 80mg of caffeine.'.
    • (CAFFPREG) 'Caffeine intake more than 200 mg per day is not recommended during pregnancy or breastfeeding.'.
  • When the maximum recommended daily dose provides greater than 80 mg of total caffeine, the following warning statements are required:
    • (CAFFLIMIT) 'Limit the use of caffeine-containing products (including tea and coffee) when taking this product.'.
    • (CAFFCYP) 'Caffeine interacts with the liver enzyme CYP1A2. Consult your health professional before taking with other medicines' (or words to that effect).

What the TGA will do

Following the expiration of the compliance transition period, the TGA will identify any listed medicines in the ARTG containing caffeine from any source and may initiate a review and cancel products that are not complying with the regulatory requirements that are in force at the time.

If you have any concerns or would like to discuss this issue further, please do not hesitate to contact the Complementary and OTC Medicines Branch at complementary.medicines@tga.gov.au.