Technical Alerts

CMA is pleased to announce that the Therapeutic Goods Amendment (2020 Measures no. 2) Bill 2020 was passed in both houses of Parliament without amendment on 18 February 2021. This Bill introduces a 5-year data protection regime for clinical trial information used to support the TGA efficacy-assessed listed medicines, known as 'Assessed Listed' or L(A) complementary medicines. This protection of data, in effect, will:

 - prevent generic ‘copy’ AUST L(A) versions of approved medicines from being marketed, thereby ensuring the investment into clinical research reliably generates a commercial return for the sponsoring company.

 - incentivise clinical research and public recognition of the efficacy of complementary medicines

 - assist to grow the scientific evidence base for complementary medicines

Please read today’s member alert for more information on Data Protection for L(A) complementary medicines, in addition to an update on the progression of funding rounds for the Modern Manufacturing Strategy streams.

The TGA have recently published information on their website in relation to the recall of Artemisia annua and Artemisia absinthium products.

Please read today’s technical alert for more comprehensive information and details surrounding this issue and in particular, important CMA advice and information for sponsors of herbal medicines to consider.

There are 3 weeks remaining until the final date to transition to permitted indications on 5 March. There are approximately 13% of all listed medicines remaining to either transition or be cancelled.

From member inquiries and TGA feedback, CMA would like to update members on the following key information to be aware of:

 - Please make the transition before the 5 March if you are able. Leaving the change to the last few days may risk problems with a slow TGA IT system or validation issues with your product.

 - If you are waiting to transition, please ensure you have a draft listing which has been successfully validated (refer to the Application and Submission User guide). This should help to avoid last minute issues for medicines failing to validate, which could risk them being inadvertently cancelled on 6 March if time is needed to ensure the listing meets all validation requirements. Cancellations of medicines on the 6 March are unable to be appealed so it will be important to prevent unexpected issues arising.

 - Please be aware that some retailers may check to see whether there are current listings on the ARTG when assessing their inventory. It is prudent to change a listing to permitted indications to keep the AUST L listing active on the ARTG if you are concerned about retailers stock-keeping. However, changing to permitted indications on or before 5 March remains free, meaning that a listing can stay active until the expiry of the annual charge already paid by the sponsor, to the end of June. At this time sponsors may choose to cancel their products or pay the annual charge for the next year.

 - Sponsors should retain evidence of submitting their application to transition to permitted indications on or before 5 March 2021.

 - If you are intending for a discontinued medicine to be automatically cancelled by the TGA on 6 March, please be aware that it may be preferable to cancel your own medicine, if you do not wish for the cancellation to appear on this TGA cancellation webpage. 

 - From 6 March, changes to indications on existing ARTG listings will again attract a grouping application fee of $860. If you have a listing with permitted indications but you wish to make additional changes, this can be done without charge until 5 March.

Additional Resources:

 - CMA’s October 2020 technical alert  with information on transitioning during the final phase.

 - CMA’s January 2021 technical alert summarising the update to permitted indications in  with 3 new indications.

- The TGA will send sponsors another reminder in the coming week.

This Thursday, CMA and a number of key manufacturing representatives are meeting with the TGA to identify questions or issues relating to the implementation of version 14 of the PIC/S Guide to GMP (PE009, the PICS/S guide to GMP for medicinal products).

Version 14 of the PIC/S Guide was adopted last year with a transition period, and full compliance will be expected from July 2021. As a general reminder, compliance expectations for the TGO 101 Section 16 - elemental impurities and residual solvents will also come into effect at this time.

If members have questions, issues or problems relating to the implementation of  Version 14 PIC/S GMP, please email Lucy.Lang@cmaustralia.org.au by COB Wednesday. The process is to identify whether there is a need to modify any current TGA GMP guidance (to improve clarity) or to create any new TGA GMP guidance (if required) from an industry perspective.

Resources:

- Technical Alert Summary of Version 14 GMP changes

- Current TGA interpretation and expectations for demonstrating compliance

- Listed and Complementary medicine GMP guidance

- TGO 101 Standard for capsules, tablets and pills

A new Poisons Standard is in force and has been published on the Federal Register of Legislation, available here. The Poisons Standard February 2021 incorporates changes to the Poisons Standard October 2020 and also incorporates amendments to the Poisons Standard February 2021, outlined in the Poisons Standard Amendment (Boric Acid and Picramic Acid) Instrument 2021.

Changes to the Poisons Standard of interest to the complementary medicines sector include:

• The addition of cannabidiol (CBD) to Schedule 3 of the Poisons Standard (Pharmacist Only).

Important points include that oral cannabidiol medicines may only be sold to a consumer by a Pharmacist. Guidance on what constitutes supply by a Pharmacist is available from State and Territory bodies, for example, NSW. The allowable maximum recommended daily dose of 150mg is higher than the 60mg initially proposed in the Scheduling consultation. However, it must first be evaluated and approved as a Registered medicine and included on the ARTG. This means it must have evidence suitable for a registered medicine. Information on applying for registered complementary medicines is available here and further information relating to over-the-counter access to low dose cannabidiol can be found here. Please also refer to CMA's 15 December member alert for the full list of Schedule 3 requirements.

• BORON

Boron has new requirements in Schedule 5 for warning statements that apply to the following classes of products: cosmetic hand cleaning preparations, cosmetic talc preparations, cosmetic oral hygiene preparations, and in other cosmetic preparations.

Important Note: Boron in the 26BB Permissible Ingredients Determination- transition ending 

While the Poisons Standard hasn’t implemented warning statements for boron for oral or dermal preparations for human therapeutic use, please be reminded that boron warning statements were introduced into the 26BB Permissible Ingredients Determination, and that these changes apply to medicines that were listed in the Register on or after 2 March 2020; or released for supply after 2 March 2021. Please refer to the Determination if you have any oral or dermal preparations with ingredients containing boron listed onto the ARTG to ensure all the warning statements are present or being implemented on batches that will be released for supply after 2 March 2021.

Today's technical alert contains:

- Important contextual information for members on the TGA's recently published pharmacovigilance 'FAQs', including further details of sponsor pharmacovigilance obligations; and

 - Information on the TGA issued safety advisory for Eucommia ulmoides in response to one reported allergic reaction to a product containing Eucommia.

A new Therapeutic Goods(Permissible Indications Determination (No. 1) 2021 has been approved by the TGA delegate and is now available on the Federal Register of Legislation. 

The addition of 3 new indications to the new Determination means that sponsors may, if they wish, make additional fee-free changes to their indications on the ARTG entries before the end of the transition period for permitted indications on 5 March 2021.

In addition, there are other minor changes expected to reduce regulatory burden. A total of 16 changes appear in the Determination. A summary of the changes includes:

 - 3 new indications

 - Broadening the wording of the required label statement for 11 indications

 - Broadening the evidence base for one indication

 - Combining two duplicative indications into one indication

Please read today’s technical alert and the information on the TGA website to be aware of the changes, particularly, the changes to the <VIT> warning statement.

The TGA have released the public consultation on discontinuing new applications for Proprietary Ingredients (ingredient mixes) in the Proprietary Ingredients Table, specifically for Active Ingredient mixes (such as ingredients containing vitamins or minerals), Active Herbal mixes, as well as the non-specific excipient category (other excipient mix categories are unaffected).

PIs are blends of ingredients that the supplier enters into the TGA database and obtains a number which sponsors can then use to add those ingredient mixes to their ARTG listing (or registration).

Please read today’s technical alert for more information, noting that this alert contains important information relevant to CMA members that is not included in the public consultation document.

n particular, there is information about the member response to the consultation, and further information about potential effects. We welcome all member feedback by Committee and also offline.

The TGA is seeking comment on the content, presentation and usability of two draft efficacy monographs that have been developed for vitamins B6 and B12 in response to Recommendation 46 from the Review of Medicines and Medical Devices Regulation (MMDR).

These monographs document evidence which substantiates the use of these vitamins for particular indications which are appropriate for listed medicines.

The consultation period on these monographs closes 5:00 PM Friday 26 February 2021.

Please see today's technical alert for more information on the consultation and potential sponsor impacts.

Today's technical alert provides information for members on current and upcoming consultations, including:

- Evaluation of Country of Origin Labelling regulations for food

- TGA hemp seed oil down-scheduling consultation

- Upcoming FSANZ Caffeine Review June 2021.