Technical Alerts

Further to CMA's 6 February 2024 tech alert on the TGA's proposal to adopt certain international scientific guidelines in Australia, this alert is updated to include further information on the relevance of 11 of the 13 proposed international scientific guidelines to some Listed, Listed Assessed and Registered Complementary Medicines, and some New Substance (or changed substance) applications. Updates are included in green highlights.

Residual Solvents

Raw Material Suppliers, Sponsors and Manufacturers should review the following information. 

All Listed Medicines that are subject to the TGO 101 (tablets, capsules and pills) will need to apply the ICH Q3C as it is incorporated in Ph. Eur. 5.4 referred to in Section 16(2) of the TGO 101.

As noted in this alert, CMA has included a comparison of the current Q3C (R6) and the proposed Q3C (R8) documents. The changes predominantly relate to:

- The removal of methyltetrahydrofuran from Table 4. -  Solvents for which no adequate toxicological data was found.

- The addition of Part VI: PDE for 2-Methyltetrahydrofuran, Cyclopentyl Methyl Ether, and Tertiary-Butyl Alcohol (pp 41-51).   

- Cyclopentyl Methyl Ether: 15.0 PDE (mg/day); 1500PPM

- Tertiary-Butyl Alcohol: 35 PDE (mg/day); 3500PPM

- 2-Methyltetrahydrofuran 50 PDE (mg/day).

Members are encouraged to review the information in this tech alert  and the guidelines to determine suitability to complementary medicines within Australia and provide any relevant comment to CMA by 28 Feb and/or through the TGA public consultation survey, which closes 4 March 2024. 

Please read today’s update  for more details.

The TGA have published a consultation, closing  4 March 2024, on proposals to adopt certain international scientific guidelines. This technical alert provides a summary of each of the proposed guidelines that are relevant to Listed medicines, and are likely to be of relevance to new applications for new (or changed) substances for listed medicines and Listed Assessed, or Registered complementary medicines.

Members are encouraged to review the information in this tech alert and the guidelines to determine suitability to the complementary medicine applications within the Australian regulatory framework.

Please read today’s full tech alert for more information, including a comparison of current and proposed guidelines that are applicable to all complementary medicines, and details on how to respond to the consultation.

The TGA has published a web page providing information on the updated TGA acceptable intake (AI) for nitrosamine impurities in medicines.

The update includes the addition of internationally determined AI limits for Calcium folinate / Calcium levofolinate, which is listable complementary medicine ingredient.

Please read today’s full alert for more details, including additional background information on the TGA’s approach to nitrosamine impurities in medicines.

The TGA is conducting a public consultation, closing Friday 23 February 2024, on the TGA’s proposed increase to fees and charges for the 2024-25 financial year by a total of 6.71% for medicines and 6.30% for manufacturing licenses.

This member alert provides further information on the TGA Fees and Charges Proposal 2024-25, which describes the reasons for the proposed fee increases, including an increase of the indexation factor by 4.7% and the proposal to apply additional percentage increases on fees and charges relating to digital transformation costs among others, and additional information about TGA cost-recovery framework and public interest activities. It also includes information on a future major review of fees and charges.

The TGA have stated they prefer consolidated industry feedback through representative peak bodies such as CMA, so that the overall industry view can also be considered before finalising next financial year's fees and charges. CMA is developing a position based on knowledge of TGA regulatory activities and performance, and Committee and member feedback.

Members may provide any feedback to the consultation to CMA by Mon 19 Feb2024 via technical@cmaustralia.org.au and respond to the public consultation independently based on the details in this alert.

In March 2023, the TGA introduced new label advisory statements for Valerian (Valeriana officininalis, Valerian dry, Valerian powder), Greater Celandine (Chelidonium majus), or Chaparral (Larrea tridentata), following a decision announced in December 2022.

The 12 month transition period for existing medicines that contain these ingredients is coming to an end. All existing products with these ingredients that are released for supply from 1 March 2024 must include the label advisory.

Please read this tech alert for details.

The TGA has published  updated GMP Clearance Guidance (Version 18.4), and a new Sponsor Information Dashboard giving sponsors real-time information on GMP clearance processing timeframes providing industry with the best indication of how long an application will take. The Dashboard was initiated by the need to remove all references to GMP Clearance target timeframes, in acknowledgement that these timeframes are not currently being met for certain application types.

Based on TGA feedback at the TIWGG forum, this alert also includes some tips for industry on how to ensure Clearance applications are progressed as efficiently as possible.

Please read this tech alert for more details.

The TGA has published new guidance on boundary and combination products.

The guidelines were updated following public consultation in Oct-Nov 2022, as the previous guidance was out of date and required updating to reflect significant changes in the regulation of therapeutic goods since 2005.

The new guidelines discuss key concepts that aim to assist manufacturers and sponsors to understand which regulatory pathways and requirements will apply to boundary and combination products, depending on how they are categorised. 

Please read today’s alert for more details.

Today's tech alert provides information for sponsors on the TGA’s new published Checklists for 9D(1)(a) requests to change (vary) an ARTG entry.

The new checklists are designed to be used by a sponsor (or agent) who wants to request the following changes to their medicine's ARTG entry under paragraph 9D(1)(a) of the Act: the checklists will assist sponsors who want to make the following changes:

1. Correct an omission or mistake made at the time the medicine was listed; and/or

2. Replace a Proprietary Ingredient (PI) with the individual ingredients included in the PI’s formulation (where there is no change to the formulation, ingredients or quantity).

This tech alert also clarifies the TGA’s interpretation of ‘separate and distinct’ with regard to Section 9D applications, and provides additional information to assist sponsors in determining the circumstances under which their application to change (vary) an ARTG entry may be eligible.

Examples of what are potentially eligible and ineligible for section 9D(1)(a) applications are included at the end of this alert.

Please read the full alert for all information and details.

The TGA has published outcomes of the consultation on proposed low-negligible risk changes to the Permissible Ingredients Determination, which occurred in August - September 2023.

These changes relate to:

New warning statements for - 

- Curcuma species/curcumin (turmeric)

- Camellia sinensis (green tea)

Changed requirements for - 

- soy phosphatidylserine

- Kakadu plum

New Adverse Event Management System launched

In response to feedback to the TGA's 2022 sponsor survey on Improving access to medicine adverse event data, the TGA have now finalised their launch of a new search functionality, the Adverse Event Management System (AEMS).

Sponsors can now access TGA-held adverse event reports relevant to their own medicines to:

- search for reports

- filter results using multiple data attributes

- download de-identified Public Case Detail (PCD) and Case Line Listing (CLL) reports for inclusion into your own pharmacovigilance systems.

Sponsors can use the feature through the AEMS portal or TGA’s Business Services Sign In using your TBS account. 

As specified in the AEMS guidance for sponsors, once a new TBS user account is created, it can only be used to access AEMS the next day. See New medicine Adverse event search for sponsors. 

Electronic notification form updates

Following the update to the Pharmacovigilance responsibilities of medicine sponsors: Australian recommendations and requirements guidance in August, the TGA have made the following improvements to the medicine safety issues electronic notification form in response to stakeholder feedback.

1. A secondary email address field - an email address provided in this field will also receive a copy of the submitted safety issue notification.

2. A preview page - this will allow the reporter to review the details of their safety issue notification as the final step prior to submission of the form.  

TGA Webinar: Understanding changes to the Pharmacovigilance (PV_ Guidelines

The TGA held 2 webinars in August, outlining and explaining the changes contained in version 3.0, with the opportunity for Q&A. A third and final TGA webinar is now set for Thursday 14 December at 1:00pm AEDT and will be a further opportunity for Q&A on the changes to the PV guidelines. The TGA are inviting stakeholders to submit questions prior to the webinar, as these will be addressed first and questions may not be accepted live during the webinar. Register for the webinar and submit questions here.

Reminder - implementation period

The 6-month implementation period of the changes to the PV, during which adoption of the changes included in this update are strongly encouraged but not mandatory and will not be inspected against, will conclude on Wednesday 31 January 2024. During this time, the TGA expect significant safety issues (SSIs) to continue to be reported. The TGA has advised that changes to reporting requirements will not be enforced or inspected against until February 2024. All existing requirements in the PV Guidelines are excluded from this implementation period and will continue to be enforced.