Technical Alerts

Transition Reminder

Members are reminded that the end of the transition period for certain ingredient changes is approaching on 28 February 2023.

Some changes relate to pregnancy warnings, or allergen warnings, which are often subject to retail or consumer level recalls if the required statements are not included.

Vitamin B6

- maximum daily dose change from 200mg to 100 mg (adults);

- maximum daily dose change for children (depending on age group)

- warning statements on labels for products containing > 10 mg pyridoxine per MRDD.

Artemisinin containing herbs

- End of transition period to include a pregnancy warning for certain existing artemisinin containing ingredients.

Mollusc derived ingredients

- Updated allergen warning

These ingredients were subject to changes following the outcomes of the 2021-22 Permissible Ingredients Consultation. Please see CMA's 27 September 2022 tech alert, the TGA Final Decisions Document and the TGA Oct 2022 publication on Vitamin B6 for more information. 

Please note: Due to recent changes in the Advertising Code ‘health warnings’, members should also ensure, as a priority, that relevant advertisements (e.g. where an advertisement facilitates directly the purchase or other supply of a medicine; and the medicine is not able to be physically inspected by a consumer before the purchase or other supply) have the required warnings.

TGA Pharmacovigilance Inspection Program (PVIP) Risk Assessment Survey closes 18 December 2022 

Pease note: Any sponsor who has at least one medicine included on the ARTG should complete this survey. Medicine sponsors that do not complete the survey will be assigned the highest survey risk score, meaning you have a very high chance of receiving a PV Inspection under the TGA's PVIP. 

The TGA's Pharmacovigilance Inspection Program (PVIP) Risk Assessment Survey is designed to inform the TGA about a sponsor's medicine portfolio, pharmacovigilance system, inspection history and compliance with Australian pharmacovigilance legislation and guidelines, and will serve as a tool to help prioritise and schedule pharmacovigilance inspections.

Sponsors are directed to complete and submit their survey responses online; the survey consists of 24 questions and must be completed in one attempt only. Partially completed surveys will not be recorded and cannot be retrieved for later use. After completing the survey, a message will be displayed on your screen saying that your response has been recorded. You may also download a copy of your responses for your own records (please note that a copy of your responses will not be sent to your e-mail).

The TGA request that stakeholders answer the questions carefully and truthfully as they may ask for evidence of responses during a pharmacovigilance inspection.

A copy of the survey questions is provided to assist stakeholders prepare their responses prior to submission.

Please visit the TGA website for more information, to access the survey questions and respond to the survey.

The TGA will be conducting targeted desktop compliance reviews of selected listed medicines that contain fennel. These reviews follow recent signals received by the TGA about the  lack of pregnancy warning statements on products that contain the following ingredients:

 -Foeniculum vulgare (fennel);

 - fennel bitter seed dry;

 - fennel sweet seed dry; and /or

 - fennel oil

This technical alert provides more information for sponsors, including background on historical TGA safety reviews of fennel ingredients.

Please see below for information on the CMA /TGA Probiotics Day at Lipa Pharmaceuticals, held in October 2022.

Today's alert for technical members provides key information for members who are involved with applications for new microorganisms in listed medicines, which are whole cell or intact - these may be probiotics (live) or postbiotics (non-viable). It also applies to the development of new listed assessed or registered medicines based on these microorganisms. A 5 page Appendix describing TGA feedback on extensive consultation with CMA on new substance microorganisms is included.

In addition, the alert contains some clarifying information for members regarding postbiotics for existing microorganisms in the Permissible Ingredients Determination, based on CMA-TGA discussion.

Member update: CMA/TGA Probiotics Day at Lipa Pharmaceuticals

CMA are pleased to report the success of the CMA/TGA meeting and facility tour, as part of a probiotics discussion day, held at Lipa Pharmaceuticals on 24 October 2022.

CMA led a delegation of industry members and TGA staff, including TGA Manufacturing Quality Branch GMP inspectors and Complementary Medicine and OTC Branch staff, to attend a member manufacturing facility. The visit included a tour of the facility and information in relation to storage, testing, validation, blending uniformity and stability. The delegation also engaged in robust discussions on critical quality topics ensuring market continuance of important products, and aspects of methods of enumeration, acceptance limits, species and genus specific enumeration, overages and multi-strain products.

This meeting saw positive and constructive discussion between the group, and provided the opportunity to hear information and perspectives from the TGA and industry on how to best regulate the probiotics process from a finished product quality and legislative / regulatory and global leading perspective. The TGA are considering producing further guidance for the quality of finished probiotics that is likely to be released during 2023.

This event assisted in bridging the gap in understanding between the TGA and industry, and contributed to building a positive relationship with the regulator on challenging areas of technical regulation. The meeting was seen to facilitate renewed TGA connections with a view to enhancing a greater understanding of industry expertise and practices.

CMA thanks Lipa and other attending regulatory professional members for their invaluable contribution.

The TGA has released a public consultation, closing 19 December 2022, seeking views on whether the dual naming of certain ingredients should end on 30 April 2023.

In relation to listed complementary medicines, only sponsors of medicines containing mecobalamin (comethylcobalamin) are affected. 

This technical alert provides information for affected sponsors of mecobalamin (comethylcobalamin), including CMA’s draft position and details on how to respond to the consultation.

The TGA has published a web page announcing changes to applying for the evaluation of a new substance. The changes apply to all complementary medicines and substances in listed medicines, and include new sections specifically for microorganisms (such as probiotics).

Mandatory requirements for applications to vary the Permissible Ingredients and accompanying guidelines are intended to come into effect in January 2023. This means that from that date, there will be a new way to apply for evaluation of a new substance for use in listed medicines.

CMA has a copy of the suite of new draft documents that have been provided to certain committees, and which we may also provide to requesting members to help prepare any applications for 2023 until the new documents are published in full: Please contact Lang@cmaustralia.org.au for a copy of the documents. We also welcome urgent feedback on these documents by late November or early December if you perceive there are any parts that cause a significant problem for certain ingredient types. 

Please read todays full technical alert for more information, including a summary of changes to new mandatory requirements and guidelines documents; details of CMA’s engagement with the TGA in the development of these documents; and a 19 page Annex describing TGA feedback on years of extensive consultation and feedback provided by CMA.

The TGA has published a web page and requested industry associations to remind affected medicine sponsors and manufacturers to be prepared that the Therapeutic Goods (Medicines Standard for Serialisation and Data Matrix Codes) (TGO 106) Order 2021 will commence on 1 January 2023 following the transition period provided. 

This instrument does not mandate the use of data matrix codes or serialisation of medicines, but sets out mandatory requirements if medicine sponsors choose to do either of these things. 

Medicines, including listed complementary medicines, released from supply from 1 January 2023 must comply with the requirements of TGO 106 if they:

 - are serialised (where each unit bears a unique identifier, allowing the unit to be identified distinctly within its batch); or

 - include a data matrix code that encodes a Global Trade Item Number (GTIN).

For medicines that must comply with TGO 106, a data matrix code must be formatted as a GS1 DataMatrix, as set out in the GS1 General Specifications. TGO 106 also sets out specific requirements including:

 - how human readable information must be formatted on the primary pack; and

 - that information in a DataMatrix must be consistent with all machine-readable and human-readable information on the label, and any relevant content of the Product Information (PI) or Consumer Medicine Information (CMI).

The guidance for TGO 106 clarifies the requirements of the standard, including readability and the need to include consistent GTINs if multiple machine-readable codes are present.

Background: The TGA introduced TGO 106 in 2021 to provide clarity for adopters of serialisation and data matrix codes on medicines supplied in Australia. TGO 106 aligns with global standards to provide consistency for sponsors and manufacturers operating in multiple jurisdictions and to enable international interoperability. The TGO 106 and the associated guidance has been developed by the TGA with stakeholder input and feedback received during consultation.

Contact:

 - Questions for TGA on the TGO 106 may be directed to  TGA.Scientific@health.gov.au

 - CMA may be contacted for industry issues at technical@cmaustralia.org.au

Prior CMA tech alert:

 - CMA 29 march 2021 Tech alert: TGO 106 -New standard for medicines serialisation and data matrix code

CMA have continued to seek clarification with the TGA on the status of titanium dioxide, in consideration of international changes that began with EFSA in 2021. The TGA have provided CMA with an update on their monitoring of domestic and international developments on the status of titanium dioxide, in response to these queries. Please note that this update is not on the TGA website.

Please read todays full technical alert for more details, including additional information for member consideration from comparable national and international regulators.

A public consultation on the interim decision for dichloromethane is now open, closing 24 November 2022.

Dichloromethane (also known as methylene chloride) is a solvent for some materials used in complementary medicines, particularly lipid soluble fractions of plant extracts, and is therefore a residual solvent relevant to some CM finished products.

In May 2022, the TGA consulted on a private applicant's proposal to change the Scheduling of dichloromethane from Schedule 5: Caution; to Schedule 10: Substances of such danger to health as to warrant prohibition of sale, supply and use, effectively prohibiting any use of dichloromethane. 

After considering the submissions from 22 entities (17 opposed) including CMA, and advice from the Advisory Committee on Chemicals Scheduling (ACCS), a Delegate of the Secretary of the Department of Health and Aged Care has made an interim decision to not amend the current Poisons Standard in relation to dichloromethane. 

While this is positive news, there are ongoing considerations for listed medicines that have not been resolved by the interim decision, which members may wish to consider in relation to making further submissions.

Please read this technical alert for more details. 

The TGA are seeking feedback, closing 5 December 2022, on proposed changed to Safety Reporting Requirements as described in the Pharmacovigilance responsibilities of medicine sponsors: Australian recommendations and requirements guidance document (the PV guidelines). 

Please ensure your officers responsible for Pharmacovigilance receive this technical alert

The intention of the proposed changes is stated to increase the quality of notifications, enabling the TGA to act on all safety issues in a timeframe proportionate to the risk to public health. The TGA also state that the aim is not to lessen the current requirements for reporting of safety issues, but to better define which issues are to be notified urgently by sponsors, supporting timely responses to new safety information by the TGA.

This technical alert provides information for members on key aspects of the proposed changes to the PV Guidelines, including related documents and resources. 

The TGA will be conducting targeted compliance reviews of selected listed medicines that contain colecalciferol (Vitamin D) and bone related indications, beginning Oct/Nov 2022. The review does not  include review of products that contain vitamin D and calcium.

This technical alert provides more information for sponsors, including additional contextual information on studies that may have informed the review, and comparable international perspectives.