Phase 6: Expert advisory review
5.6.1 Objective
After completion of the second round assessment phase, the evaluation reports are considered by the delegate. The delegate may seek independent advice on issues concerning the application.
The main advisory group for prescription medicines generally is the Advisory Committee on Medicines (ACM) and for vaccines specifically it is the Advisory Committee on Vaccines (ACV). Independent expert advice may also be sought by the delegate outside of the advisory committees.
Information on each of the advisory committees is available on the TGA website, including proposed meeting dates.
5.6.2 Milestone 6
The TGA notifies the applicant of the advice received from the ACM or ACV.
5.6.3 Key dates
The expert advisory review phase commences on the day the delegate's Request for ACM/ACV advice (also referred to as the Delegate's Overview for ACM/ACV) is sent to the applicant. This date is at least 23 working days prior to the proposed ACM/ACV meeting.
The Pre-ACM/ACV response from the applicant must be is received by the committee secretariat at least 13 working days before the meeting date. This is to ensure that ACM/ACV have adequate time to consider the information.
The expert advisory review phase ends when the ACM/ACV advice is sent to the applicant. This generally occurs on the Friday two weeks after the meeting (10 working days after the ACM meeting or 12 working days after the ACV meeting).
5.6.4 Advisory Committee on Medicines and Advisory Committee on Vaccines
5.6.4.1 Request for ACM/ACV advice
The delegate will review the evaluation reports and prepare a Request for ACM advice or Request for ACV advice if independent advice from the ACM/ACV is required on aspects of the application.
The delegate is not obligated to refer an application to an expert advisory committee. At the time of preparing the Planning letter it may not always be clear whether an application will require ACM/ACV advice; however, for applications other than those to register a new generic medicine, the Planning letter will identify the ACM/ACV meeting allocated to the application should the delegate decide to refer aspects of the application for advice.
When preparing the Request for ACM advice, the delegate will consider any outstanding issues from the evaluation process. The request contains a number of elements including:
- an overview of the application including key findings from the evaluation reports
- outstanding issues identified by the delegate
- an account of the risks and benefits relevant to the proposed product and proposed indication(s)
- a specific request for advice on any aspect of the application's characteristics, findings, or risk/benefit considerations
- whether special registration conditions, PI changes, or risk management plan changes would be appropriate.
On completion, a copy of the request is sent to the applicant prior to the ACM/ACV meeting to allow the applicant to compile a Pre-ACM/ACV response.
The delegate may also provide a Delegate's Overview for applications that do not require ACM/ACV advice. The purpose of this document is to summarise the evaluation and request information from the sponsor on any outstanding issues. This document will be clearly identified as not requiring ACM/ACV advice and therefore a Pre-ACM/ACV response will not be required. However a response addressing any outstanding evaluation issues may be required.
5.6.4.2 Pre-ACM/ACV response
The Pre-ACM/ACV response is the applicant's opportunity to provide comments that will be considered by the ACM/ACV. Applicants generally compile a Pre-ACM/ACV response based on the evaluation reports and the delegate's Request for ACM/ACV advice. The applicant should ensure they address any outstanding issues raised by the TGA, but should not provide new unsolicited information.
5.6.4.2.1 Guidelines for compiling the Pre ACM/ACV response
The response must be provided:
- as an electronic submission:
- via email as a zipped attachment (maximum size 20 megabytes), or
- on electronic media
- as an appropriately validated sequence using either the eCTD or NeeS specification, consistent with preceding sequence
- as sequence type 'Supplementary Information'; sequence description 'Pre-Advisory Committee response'
- as PDF files generated from electronically-sourced documents without placeholder documents. Include only the components that are necessary for the submission:
- if using eCTD specification, include only ‘new’ documents (that is, not previously submitted in an earlier sequence)
- if using NeeS specification, include a complete set of documents, even if previously submitted in an earlier sequence.
- with a cover letter, containing an address block, including:
Sponsor's name [or consultant's name] (as appropriate)
Return address
Attention: Regulatory affairs officer's name
Email address
Phone number
Regarding the format, the response must:
- be clearly marked 'PRE-ACM RESPONSE' or 'PRE-ACV RESPONSE' in bold, large upper case type at the top of the first page
- be no more than ten pages in a font no smaller than 12 point
- clearly identify upfront any changes to the indications and/or dosage and administration information from the original application.
The following should be included (as separate files) with the response:
- A tabulation of any serious unexpected adverse drug reactions which are not mentioned in the proposed Australian Product Information and have not been submitted previously - it is expected that this would normally not exceed six pages. (include under Module 1.0.3 Response to request for information).
- The updated proposed Australian Product Information and the most up-to-date Consumer Medicines Information. Please highlight changes from the version submitted with your application and reference the source of the change (e.g. clinical evaluation, company base document) in the margin. Please ensure that you comply with Form for providing product information (Module 1.3.1 Product information and Module 1.3.2 Consumer medicines information).
- statement on the current international regulatory status of the medicine. This should detail approvals (with indications), deferrals, withdrawals and rejections (including reasons). (Module 1.11.1 Foreign regulatory status).
- Where available, provide foreign equivalent to product information (in Module 1.11.2 Foreign product information)
- A copy of the latest Periodic Safety Update Report (PSUR), unless already supplied or none is available. (Module 5.3.6 Reports of Post-Marketing Experience)
The following table provides a guide to the location of the documents in CTD format:
| Pre-ACM/ACV component | CTD location* |
|---|---|
|
Pre- ACM/ACV covering letter |
Module 1.0.1 Cover letter |
|
- |
Module 1.0.2 Lifecycle management tracking table |
|
Pre-ACM/ACV response |
Module 1.0.3 Response to request for information |
|
International regulatory history |
Module 1.11.1 Foreign regulatory status |
|
Adverse reactions update |
Module 1.0.3 Response to request for information# |
|
Sponsor's comments on PI |
Module 1.0.3 Response to request for information# |
|
Sponsor's comments on foreign PI |
Module 1.0.3 Response to request for information# |
|
PSUR |
Module 5.3.6 Reports of Post-Marketing Experience |
|
PI (annotated and non-annotated) |
Module 1.3.1.1 Product information - clean |
|
Module 1.3.1.2 Product information - annotated |
|
|
CMI (annotated and non-annotated) |
Module 1.3.2.1 Consumer medicines information - clean |
|
Module 1.3.2.2 Consumer medicines information - annotated |
|
|
Foreign equivalent(s) to product information |
Module 1.11.2 Foreign product information# |
# Where multiple documents are submitted in the same CTD Module, clearly identify the different documents.
More information on Pre-ACM responses is available from the ACM Secretariat at ACM@health.gov.au, and for Pre-ACV responses from the ACV Secretariat at ACV@health.gov.au.
5.6.4.3 Withdrawing a submission: AusPAR requirements
The sponsor may withdraw the submission at any time during the expert advisory review phase.
When the withdrawal letter is received by the TGA will determine whether an AusPAR is required. Refer to the AusPAR guidance for information on AusPAR business rules.
5.6.4.4 Outcome of the ACM/ACV meeting
The ACM/ACV advice is documented in the ACM/ACV 'minutes' document, which is provided to the delegate and applicant following the meeting. This generally occurs on the Friday two weeks after the meeting (10 working days after the ACM meeting or 12 working days after the ACV meeting).
The ACM/ACV advice is independent and is primarily based on their expert opinion. Note that the ACM and ACV do not make decisions and their advice does not constitute directions to the Secretary or the TGA delegate.
The ACM/ACV advice in relation to the specific questions put to the ACM/ACV is published in the Australian public assessment report (AusPAR). The ACM/ACV minutes may also be provided to a number of overseas regulatory agencies as permitted under section 61(4) of the Act.
The ACM/ACV minutes, advice and agenda papers may also be provided to persons, bodies and authorities as permitted under section 61(5AA) of the Act.
5.6.6 What happens if an applicant misses a key date?
Where the applicant cannot provide a pre-ACM/ACV response to the ACM/ACV secretariat at least two weeks prior to the meeting date, the response will generally not be tabled for consideration by the ACM/ACV, but will be considered in the decision phase by the TGA delegate. Early contact with the committee secretariat and the case manager is advised if delays are expected.