Upcoming changes to the Permissible Ingredients Determination
Therapeutic Goods (Permissible Ingredients) Determination No. 5 of 2017
Permissible Ingredients Determination
All ingredients available for use in listed medicines and any restrictions pertaining to them are listed in the Therapeutic Goods (Permissible Ingredients) Determination. The Determination is continually reviewed by the TGA to ensure that all ingredients are safe for use in low-risk medicines. It is updated quarterly through the addition or removal of ingredients, and the clarification, removal or addition of restrictions or warning statements. This document outlines changes that will be made to the determination in the first half of 2018.
Please note that this list is not definitive, as other changes may be processed in the interim, depending on the progress of applications and reviews. The TGA will endeavour to provide updates as far in advance as possible.
Changes scheduled for March 2018
Subject to the approval of the Delegate of the Minister of Health, the amendments outlined in the following sections will be made to the Determination in March 2018.
1. Herbal naming standard for new herbal ingredients
Following advice from the Herbal Ingredients Naming Committee (HINC), the TGA will use the Medicinal Plant Names Service (MPNS) as the reference for new herbal ingredients in the Determination. This service, provided by Kew Royal Botanic Gardens, provides an accurate and updated naming standard for commonly used plants. The TGA will also use the Species Fungorum which provides accurate and updated naming standard for commonly used algae and fungi.
2. Addition of new ingredients
The following will be added to the determination:
- Tinospora sinensis as an active ingredient
- PEG/PPG-14/7 dimethyl ether as an excipient for topical medicines
- 2-hydroxyacetophenone as an excipient for topical medicines
An additional ingredient that had been previously approved by the Delegate, but omitted from the Determination in error, will also be added:
- chicken comb extract as an active ingredient
3. Addition of curcuminoids as a new ingredient name
There has been long-standing confusion over the naming of turmeric extracts and components in listed medicines.
The ingredient name 'curcumin' has been used historically to refer to an enriched extract of Curcuma longa. However, the British Pharmacopeia (BP) refers to 'curcumin' as 1,7-bis(4-Hydroxy-3-methoxyphenyl)hepta-1,6- diene-3,5-dione (458-37-7), and 'curcuminoids' as a mixture of curcumin, demethoxycurcumin and bis-demethoxycurcumin.
'Curcuminoids' of (Curcuma longa) is currently only a Herbal Component Name (HCN) and can only be used in conjunction with the parent herb 'Curcuma longa'. To allow sponsors to more accurately identify their active ingredient, and to align with the approach of the BP, the TGA will add 'curcuminoids' as an Australian Ingredient Name (AIN) and will add the ingredient to the Permissible Ingredients Determination.
Sponsors of current listed medicines containing Curcuma longa, curcuminoids or curcumin will have 18 months from the date of the publication of the amendment to update their listings and labels.
To allow sponsors of current listed medicines containing Curcuma longa, curcuminoids or curcumin to plan updates to their Register entries and product labels, curcuminoids is not included in the Therapeutic Goods (Permissible Ingredients) Determination No. 1 of 2018. See Updates to the Permissible Ingredients Determination for listed medicines for more information.
It is intended that curcuminoids will be included in a later 26BB Determination once the implementation issues are resolved.
4. Addition of new therapeutic purpose(s)
- Hydrolysed collagen will be made available for use as an active ingredient
- Opopanax chironium will be made available as an excipient in listed medicines
5. Removal of ingredients
'Cola cotyledon dry', and 'Cola cotyledon powder' will be removed as these are not in use and a more appropriate name (Cola acuminata) is already available. Similarly, 'Theobroma prepared' will be removed, as sponsors should use the existing ingredient Theobroma cacao.
2-octyldodecanal was recently added as a component of fragrance proprietary excipient formulations will be removed as it was incorrectly identified. Further assessment has found that there is insufficient evidence to ensure the safety of this ingredient.
6. Removal of certain (S) warning statements
The requirement for the (S) warning statement ('If symptoms persist consult your healthcare practitioner' (or words to that effect)) will be removed from the following ingredients, as it is an indication-related requirement rather than specific to the ingredient:
- Aloe ferox, Aloe perryi, Aloe vera, Aloes cape
- Cascara dry, Cascara powder
- Cassia fistula
- Frangula purshiana, Frangula bark dry, Frangula bark powder
- Rhamnus cathartica, Rhamnus frangula
- Rheum officinale, Rheum palmatum, Rheum rhaponticum, Rheum tanguticum
- Rhubarb, Rhubarb root dry, Rhubard root powder
- Senna alexandrina, Senna fruit Alexandrian dry, Senna fruit Alexandrian powder
- Senna fruit Tinnevelly dry, Senna fruit Tinnevelly powder
- Senna leaf dry, Senna leaf powder
- Senna occidentalis, Senna tora
7. Removal of certain anti-microbial warning statements
The warning statements relating to certain anti-microbial preservatives will be removed from the Determination, as these are not related to specific safety concerns. The ingredients affected are:
- Butylated hydroxyanisole
- Cetylpyridinium chloride
- Sodium dehydroacetate
- Sodium proprionate
8. Correction of warning statements for Plantago species
The PSYLL warning statement ('On medical advice' (or words to that effect)) for Plantago species will be limited to flower, seed or pollen only, based on an evaluation conducted by the European Medicines Agency (EMA). The ingredients affected are:
- Plantago afra
- Plantago arenaria
- Plantago asiatica
- Plantago major
- Plantago ovata
- Plantago lanceolata
However, a new warning statement (CHILD5 - 'Use in children under 3 years is not recommended') will be required for Plantago lanceolata based on the findings of an EMA assessment
9. Correction of tilactase requirements
The current reference to 'haemoglobin units' will be corrected to 'acid lactase units'.
10. Correction of restrictions relating to coumarin
The requirements for coumarin in a number of herbal ingredients will be amended to correctly align with the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) in referring to concentration, rather than maximum daily dose. The requirement will change from"... maximum daily dose of the medicine must contain no more than 0.001% of coumarin" to "the concentration of coumarin in the medicine must be no more than 0.001%". The ingredients affected are:
- Anthoxanthum odoratum
- Cassia cinnamon bark dry
- Cinnamomum camphora
- Cinnamomum cassia
- Cinnamomum verum
- Cinnamon bark oil
- Cinnamon dry
- Cinnamon leaf oil
- Cinnamon powder
- Dipteryx odorata
- Galium odoratum
11. Correction of restrictions relating to Piper methysticum
The requirements for Piper methysticum when for oral use will be amended to correctly align with the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) in referring to use of dried or aqueous preparation or aqueous extract of the whole or peeled root or rhizome.
Changes scheduled for June 2018
Subject to the approval of the Delegate of the Minister of Health, the amendments outlined in the following sections will be made to the Determination in June 2018.
1. Addition of therapeutic role for menthol
The TGA has recently conducted a review of menthol safety and as a result will expand the purpose of menthol to include use as an active ingredient for topical and oral administration with requisite restrictions (not more than 5% w/w) and warning statements that apply when the ingredient is for topical use.
2. Addition of a consistent maximum daily dose for caffeine
Caffeine is listed as a mandatory component in appropriate herbal ingredients. The maximum daily dose for caffeine as a component of herbal ingredients and as an individual ingredient is proposed to be not more than 600mg, with divided preparations for oral use to contain no more than 100 mg per dosage unit.
3. Ingredient name changes
The names of the following ingredients will be changed:
- Astralagus membranaceus will change to Astralagus mongholicus (as per MPNS).
- Poria cocos will change to Wolfiporia cocos (as per Species Fungorum).
4. Clarification of SUSMP requirements for arbutin
Ingredients known to contain arbutin will have arbutin listed as a mandatory component with associated specifications in line with the Poisons Standard. The affected ingredients will be:
- Achillea millefolium
- Arctostaphylos uva-ursi (leaf)
- Chimaphila umbellata
- Kalmia latifolia
- Ledum palustre
- Origanum majorana
- Pyrus communis
- Pyrus pyrifolia
- Rhododendron ferrugineum
- Turnera diffusa
- Vaccinium vitis-idaea (leaf)
5. New restrictions on poliglusam
The TGA has recently conducted a review of poliglusam safety and as a result will include a new restriction on maximum daily dosage of 1750 mg. A restriction will also apply to minimum average molecular mass, with poliglusam requiring an average molecular mass greater than 2 kilodaltons. This is due to a considerable difference in safety profile between larger and small molecular mass poliglusam.
6. New restrictions on methyl salicylate
Following a safety alert issued by the US Food and Drug Administration (FDA), the Complementary and OTC Medicines Branch (CMES) and Toxicology section of the Scientific Evaluation Branch (SEB) carried out an assessment of the safety of methyl salicylate in listed medicines.
Ingredients containing methyl salicylate will have an additional specification: 'When for use in topical medicines for dermal application, the concentration of methyl salicylate in the medicine must be no more than 25%'.
In addition, new warning statements will be required from July 2018 (or January 2020 for previously listed medicines) for herbal ingredients containing methyl salicylate. The herbal ingredients affected are:
- Betula lenta
- Betula nigra
- Betula pendula
- Birch leaf dry
- Filipendula ulmaria
- Gualtheria procumbens
- Meadowsweet herb dry
- Methyl salicylate
- Nyctanthes arbor-tristis
- Wintergreen oil
7. New restrictions on cysteine
As a result of a safety review, more restrictive requirements will be applied to cysteine, its salts and cystine. The new maximum daily dosages will be:
- Cysteine - no more than 450 mg
- Cysteine hydrochloride - no more than 585 mg
- Cysteine hydrochloride - monohydrate no more than 652 mg
- Cystine - no more than 450 mg
Timeframes and processes
Other proposed changes may be outlined as the TGA completes ongoing applications and reviews.
Changes made to the Determination are published on the Regulatory decisions and notices (complementary medicines) webpage.