Technical Alerts

Today's technical alert includes:

 - An update on Codex/international discussions on titanium dioxide; and

 - TGA Scheduling Consultation: Proposed amendments to the Poisons Standard - Cannabis and tetrahydrocannabinols for veterinary use.

Please be aware that currently, neither the Therapeutic goods Permissible Ingredients Determination (No. 2) 2021, nor the Therapeutic goods Permissible Ingredients Determination (No. 1) 2021

Do not exceed the stated dosage except on medical advice. If you have had a baby with a neural tube defect/spina/bifida, seek specific medical advice (or words to that effect).

The change occurred in March of this year, and was not subject to public or targeted consultation before it was made. Therefore listed medicine sponsors making new or updated products since March may not have been aware of the change or to the ongoing need to include the statement on products which contain the following permitted indication:

Help to prevent neural tube defects such as spina bifida and/or anencephaly (for medicines where the recommended daily dose of the medicine provides a minimum of 400 micrograms of folic acid).

We recommend that if you have listed (or re-listed) a pregnancy or folic acid product in 2021, that you check the label for the inclusion of the NEUR statement, and if currently listing products, to include the statement until such time as the TGA completes a review of the change that occurred, and conduct any updates to the above documents as needed.

Within this context of review, clarification is also being sought on required applicability of the VIT label statement as it relates to this particular indication in respect of the 2020 Pregnancy Care Guidelines and we will provide any relevant update as available.

For any questions or product related issues, please contact technical@cmaustralia.org.au for support.

This is a technical alert to highlight and clarify that the laxative warnings for products containing magnesium amino acid chelate are no longer required for this ingredient. The removal of these requirements is correctly reflected recently published an currently in force Therapeutic Goods (Permissible Ingredients) Determination (No. 2) 2021 and its explanatory statement (Note that the laxative warnings still apply to other magnesium salts that are inorganic - as always please check the in-force Determination for each ingredient in your medicine to confirm requirements before proceeding with product decisions).

On 1 March 2021, the Therapeutic Goods (Permissible Ingredients) Determination (No. 1) 2021 commenced and the ingredient magnesium amino acid chelate (not an inorganic salt) incorrectly included new requirements for inorganic magnesium salts that were determined as a result of the outcome to the 2020-2021 consultation. This TGA consultations outcomes webpage will be updated shortly to reflect that the requirements will not apply to magnesium amino acid chelate.

On 12 August the TGA advised CMA of changes to the Determination through publication of version N.2 of 2021. On 13 august, CMA conveyed this information to members through a technical alert, including links to the newly published Determination which shows that the requirements do not apply. However, this technical alert also contained a table taken from the a TGA table which incorrectly displayed in the new requirements column that the requirements still applied to the ingredient - therefore, our table in this technical alert has also been updated to correctly reflect the removal of these requirements at the provided links (Word and PDF). 

The TGA is also sending an email to sponsors whom have magnesium amino acid chelate as an ingredient in an ARTG listing, to clarify the removal of the laxative warnings. To summarise, the laxative warning statements no longer apply to this ingredient, the Permissible Ingredient Determination has been correctly updated, the TGA consultation outcomes page will be updated shortly, the CMA table in the document has also been updated, and if you have this ingredient in a medicine you should also expect a clarifying email from the TGA in the near future.

Please see below for updates on several separate issues:

1. Titanium dioxide

For evolving information on titanium dioxide, please click here. A reminder that the FSANZ consultation is closing on 17 Sep 2021 and that they are seeking specific data for a safety assessment that may be sent directly to FSANZ. If you prefer to send unidentified or redacted company data through submission by CMA, this information may be sent to us by 16 Sep 2021 at technical@cmaustralia.org.au. FSANZ has nominated the below information is eligible to be submitted as part of their safety assessment:

- Physico-chemical characteristics and composition/specification documents of titanium dioxide as currently used food additive. Characteristics include particle size, size distribution and morphology, any size-dependant properties. Nanoparticulate material should be quantified and the composition and specifications should be provided.

- Unpublishes genotoxicity studies (in vitro or in vivo) with titanium dioxide. 

 - Other unpublished studies relevant to a safety assessment.

2. Sponsors holding Section 17 consents regarding TGO 92 Section 9(2)

The TGA have provided a commitment to give an extension for all existing s14/14A consents that relate to section 9(2) of the TGO 92, without the need for another formal s14/14A consent application from the sponsor. However, an extension will be granted only if the consent is still required and once confirmation of the need is received from affected sponsors. Therefore, the TGA is contacting sponsors with current S14/14A consents (in relation to section 9(2) of TGO 92) and requesting confirmation that an extension is required. A new consent will then be given until 1 September 2022. 

TGA Stakeholder Survey

The TGA is inviting consumers, health professionals, industry and other stakeholders to share their views in their annual stakeholder survey.

The feedback received is proposed to be used to help report on the TGA’s key performance indicators and to make ongoing improvements to stakeholder engagement. The survey takes around 10-15 minutes to complete and will remain open until Friday 27 August 2021. Please click here to access the survey.

TGA Presentations: Good manufacturing Practice (GMP) Forum

The TGA GMP Forum presentations, held online on 12- 14 May 2021, are now publicly available on the TGA website. Please click here to access the the presentations.

Permissible Ingredients Determination

A new permissible Ingredients Determination (No.2) 2021 has commenced. 

This technical Alert (available in Word and PDF) contains a detailed list of changes with a Notes field for sponsors to use to assist in identifying the changes relevant to products, as part of a table which includes:

• Each new or changed ingredient
• The original (previous) requirements that applied
• New (amended) specific requirements

This alert also summarises changes to ingredients including:

• New requirements for Artemisia annua and Artemisia absinthum; 
• Changes to ingredients such as magnesium amino acid chelate and oligofructose;
• The addition of substances permissible for use in flavours /fragrances /proprietary formulas; and  
• The addition of the following 2 new ingredients for use in listed and assessed listed medicines: sodium butyrate (active and excipient) and lacto-N-neotetraose (active).

Complementary Medicines Australia is seeking expressions of interest from members with medical, research or post-graduate scientific backgrounds to contribute scientific advice and expertise to advancing the interests of the complementary medicines industry in Australia.

Assisting on the working group helps members gain insight into current affairs and issues affecting the industry, whilst contributing a small amount of time to provide the expertise to move critical issues forward for resolution.

Please share the linked member alert with any staff member you think may be interested. We look forward to working with you on these important issues.

The TGA have announced a consultation on proposed changes to advisory statements for Registered Complementary Medicines containing melatonin, closing on 17 September 2021.

The TGA is seeking comment on the addition of proposed new advisory statements for labels of over the counter (OTC) and registered complementary medicines containing melatonin for oral use, for inclusion in the Required Advisory Statements for Medicine labels (RASML).

Please note: The proposed changes will apply only in RASML to registered medicines; there are currently no RASML warning statements for melatonin. Melatonin is in included in Schedule 3 of the Poisons Standard and therefore is not eligible for inclusion in listed medicines and not currently included in the Permissible Ingredients Determination (certain homeopathic preparations may be exempt from listing requirements).

Please read today’s technical alert for more information, including details on how to respond to the consultation

The TGA have announced a consultation on proposed changes to the Permissible Indications Determination low-negligible risk ingredients, closing 15 September 2021.

The Proposed changes relate to:

- Peripheral neuropathy associated with lower dose vitamin B6 - a proposed reduction of maximum supplemental daily intake from 200mg/day to 50mg/day; and extension of a warning statement for products providing between 10 – 50 mg of equivalent pyridoxine.

- Artemisinin and pregnancy risk - proposed new label requirements for artemisinin containing products, which may also affect products that have artemisinin in a flavour or fragrance. These changes were anticipated following the ongoing review of Artemisinin containing medicines and pregnancy risk by the TGA.

- Allergen statement for mollusc-derived ingredients - proposal for ingredients on the Permissible Ingredients Determination that are derived from a marine mollusc (substances derived from squid, oyster, green lipped mussel or homeopathic Sepia) be updated to include the warning statement “Contains mollusc” or “Contains mollusc products”, in alignment with FSANZ allergen warnings.

Please read today’s full technical alert for more information

The TGA are seeking applications for a number of remunerated advisory committee appointments from professionals with expertise in relevant medical or scientific fields or consumer health. Applications close 13 August 2021.

For complementary medicines, having relevant experts with a strong understanding of CM including nutritional medicines and traditional medicines in the Advisory Committee for Complementary Medicines can appropriately inform critical TGA decisions relating to Complementary Medicine regulation. Matters this Committee have advised on in the last 2 years include:

• Vitamin B6 (pyridoxine) with peripheral neuropathy and whether the current maximum daily dose for listed medicines (200 mg eqv. pyroxidine) is appropriate.

• The relationship between taste disturbance/loss-of-taste adverse events reported for products with Andrographis paniculata and associated restrictions for listed medicines.

• Whether listed medicines containing higher doses of various forms of magnesium should carry a label warning or have additional restrictions for potential laxative effects.

• Probiotics - characterisation for the purposes of establishing the quality and safety of applications relating to microorganisms.

• Probiotics - What constitutes adequate control of the composition, strength, stability and performance characteristics of a multi-strain probiotic.

• Valeriana officinalis to cause herb-induced liver injury, and whether there is a sufficient evidence to support restrictions to mitigate the risk when used in listed medicines.

• Aspects of clinical trial data that are critical to make publicly available as part of conducting a clinical trial the TGA's proposed data protection scheme for assessed listed medicines.

• Suitability of an herbal ingredient in listed medicines indicated for use during conception, pregnancy and lactation.

Please see today’s member alert for more information on how to apply.