Administrative information and prescribing information for Australia
Module 1 of the CTD describes the administrative information and prescribing information (for example, the application form, the proposed product information and labelling) for Australia to support:
This guidance:
A summary of CTD document requirements for applications to the TGA is shown in the eSubmission Document matrix, available at: Australian eCTD regional specification and validation criteria 3.0
The following documents provide further information about the regulatory requirements for applications for prescription medicines:
| Version | Description of change | Author | Effective date |
|---|---|---|---|
| V1.0 | First version | Office of Medicines Authorisation | 28/09/2007 |
| V2.0 | Second version to reflect outcomes from the public and stakeholder consultation and the revised prescription medicine registration process. | Office of Medicines Authorisation | 16/05/2013 |
| V2.1 | Editorial amendments | Office of Medicines Authorisation | 30/05/2013 |
| V2.2 | Alignment with revised PPF, editorial changes. | Office of Medicines Authorisation | 30/04/2014 |
| V2.9 | Revisions to align with introduction of eCTD format | Office of Medicines Authorisation | 05/09/2014 |
| V3.0 | Third version to reflect electronic dossiers | Medicines Authorisation Branch | 01/07/2015 |
Regulatory activity category is identified by a number, for example, category 1 and category 2 applications, and refers to the overall legislated time-frames for decisions about regulatory activities.
Regulatory activity type relates to the fees associated with an application and is identified by a letter, for example, A, B or C applications.
Examples include:
A sequence is a package of information bundled together in an electronic structure providing information to the agency. The contents of a sequence will depend on the regulatory activity type and whether it is the initial sequence of the regulatory activity or a follow-up providing additional data or changes (see also Module 1.0.2 Lifecycle tracking table).
The Common Technical Document (CTD) is a set of specifications for a dossier for the registration of medicines. The CTD was developed by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and adopted by the TGA in 2004.
The CTD prescribes:
Under the CTD format:
The format and content of Module 1 (Administrative information and prescribing information for Australia) are described in this document.
The electronic Common Technical Document (eCTD) is the electronic version of the CTD and is described by the following documents:
This section of Module 1 holds the cover sheet, the Cover letter, the Lifecycle management tracking table, and the applicant's response to request/s for information (answers to questions) from TGA.
| Section | Description | Category 1/Category 2 | Category 3 | ||
|---|---|---|---|---|---|
| New registration | Variation | New registration | Variation | ||
| 1.0.1 | Cover letter | mandatory | mandatory | mandatory | mandatory |
| 1.0.2 | Lifecycle management tracking table | mandatory | mandatory | mandatory | mandatory |
| 1.0.3 | Response to request for information (if questions raised) | mandatory | mandatory | mandatory | mandatory |
Include in Module 1.0.1 for all regulatory activities and for each sequence associated with that regulatory activity.
Prepare the letter on company letterhead and sign by an authorised officer of the company.
The Cover letter should not contain any evaluable information. Do not include responses to questions raised by TGA in the Cover letter, since they have been assigned a specific location in Module 1.0.3.
Include the signed Cover letter in Module 1.0.1.
Ensure the letter contains the following information:
Include the following information in the initial Cover letter for a regulatory activity:
'No aspects of the quality information have been changed, including manufacturing procedures and equipment, raw material, finished product specifications, other than the changes nominated in this application.'
Include the following information in the Cover letter for all sequences:
A Note to evaluators is not a requirement, but sponsors occasionally include them to provide further information to facilitate navigation (e.g. on hyperlinking) etc. To promote a consistent approach to naming them and placing them within the regulatory activity, a Note to evaluators should be filed as a leaf element under the m1-0-1-cover heading. The title of the leaf should be "Note to evaluator".
The Lifecycle management tracking table will support transparency and ease tracking of sequences regardless of the format.
The sequence number is a four digit number referring to a package of information bundled together in an electronic structure for eCTD submissions to TGA. Sequence numbers, as defined for eCTD submissions, are not applicable for non-eCTD electronic submissions (NeeS) format dossiers; however, the use of a four digit number in the top level folder name is recommended.
The initial application should normally have a sequence number of 0000. As additional data are submitted, for example, in response to questions, the sequence number will advance, 0001, 0002, etc.
An updated Lifecycle management tracking table should be placed in Module 1.0.2 any time a new sequence is submitted.
Prepare a table listing sequences submitted to the TGA. An example is shown below.
| Sequence | Sequence Type | Sequence Description | Related Sequence |
|---|---|---|---|
| 0000 | Baseline | Reformat | 0000 |
| 0001 | C-Extension of Indication of COPD | Initial | 0001 |
| 0002 | Supplementary information | Response to Request for Information | 0001 |
| 0003 | H-Minor Variation, Not Resulting in a New Register Entry | Initial | 0003 |
| 0004 | F-Major Variation - New Strength | Initial | 0004 |
Include only when responding to a TGA request for information after dossier lodgement.
Do not include this document in the dossier:
For example, if the answer requires a revised version of the Product Information:
An appropriate response to a request for information is one that:
In an eCTD dossier, provide hyperlinks to references previously submitted in the eCTD format.
When referencing CTD documents that were provided previously to the TGA as part of a hard copy dossier or NeeS dossier, include detailed references to CTD documents:
For example: See PM-2012-12345-6-7, Module 3, 3.2.P.4.3 Method validation, p 23.
All dossiers not in the eCTD format must include a comprehensive table of contents for the complete dossier.
| Section | Description | Category 1/Category 2 | Category 3 | ||
|---|---|---|---|---|---|
| New registration | Variation | New registration | Variation | ||
| 1.1 | Comprehensive table of contents (for dossiers not in the eCTD format) | mandatory | mandatory | mandatory | mandatory |
Include a comprehensive table of contents in all dossiers not in the eCTD format.
The comprehensive table of contents is a complete list of all documents in the dossier, arranged by Module, and with location references for each document.
Specify the titles of studies in the table of contents, indicating the type of study and topic in the title. Study codes alone are not acceptable.
All documents in a NeeS dossier should be referenced from a hyperlinked table of contents. Hyperlinks for each document should always be provided to the first page of the appropriate file.
Do not use page numbers for document location as page numbering is at the document level only.
This section of Module 1 contains the application forms, pre-submission details, patent certification documents and change in sponsor information for prescription medicine applications.
| Section | Description | Category 1/Category 2 | Category 3 | ||
|---|---|---|---|---|---|
| New registration | Variation | New registration | Variation | ||
| 1.2.1 | Application form | mandatory | mandatory | mandatory | mandatory |
| 1.2.2 | Pre-submission details | mandatory | mandatory | not required | not required |
| 1.2.3 | Patent certification | requirement defined by the regulatory activity | not required | requirement defined by the regulatory activity | not required |
| 1.2.4 | Change in sponsor (if change in sponsor) | mandatory | mandatory | mandatory | mandatory |
Download and complete the appropriate application form from the TGA website:
If there is insufficient room in any field/section on the paper application form:
The information entered in the application form is the basis of the new/revised ARTG entry. It is critical that this information is entered accurately and is an accurate reflection of the information provided in the dossier.
Before the application is approved, the information that forms the basis of the new/revised ARTG entry is called the provisional ARTG record (PAR). The information included on the PAR is updated as required during evaluation of the application.
At the conclusion of the evaluation, the final information becomes the ARTG entry for the product.
The indications recorded on the application form for the registration of a new chemical entity, new biological entity or an extension of indications must be identical across:
The manufacturing steps shown on a manufacturing licence or GMP clearance issued by the TGA are not necessarily identical to the manufacturing steps that need to be entered on the prescription medicine application form.
The non-proprietary ingredients in the formulation must be specified using either:
A list of AANs and ABNs is available on the TGA website at: TGA approved terminology for medicines.
For new ingredients and new proprietary ingredients, the completed Application form for proposing a chemical/biological name or Notification of a New Proprietary Ingredient form (respectively) must be lodged with the TGA before the Pre-submission planning form is lodged.
New medicines cannot be registered until all ingredients have either an AAN or ABN, or have been included as a proprietary ingredient in the ARTG.
When a Pre-submission planning form (PPF) has been lodged for a category 1 or a category 2 application, a copy of the PPF must be included at Module 1.2.2.
(A PPF is not required for category 3 applications.)
After lodging a PPF via TBS:
It is not necessary to include the attachments to the PPF as these will be held by the TGA.
Before a newly approved registration can be included in the ARTG, one of the following forms is required to satisfy legislative requirements under section 26B of the Act:
All regulatory activities for new registrations, including formulation changes, changes in trade name, and extensions of indication, require the applicant to provide one of the above forms before the registration process can be finalised.
Applications for a similar biological medicinal product or a generic medicine which result in a new registration must complete the Certification in relation to patents required in relation to registration or listing under Sections 25, 26 and 26A of the Therapeutic Goods Act 1989.
A certificate about relevant patents is required prior to registration under section 26B of the Act in relation to regulatory activities made under section 25 of the Act. If a certificate will not be provided, a notification must be lodged advising that a certificate is not relevant.
For Category 1 and 2 applications, the sponsorship of an application can be changed prior to the milestone 5 date indicated in the evaluation plan, regardless of whether or not evaluation reports have been received by the applicant.
For other regulatory activities or after milestone 5 of a category 1 or 2 application, the sponsor's name should only be changed after the regulatory activity has concluded.
For a transfer of sponsorship include:
Also include the following documents:
For a change in sponsor name (same legal entity but change of name) include:
This section of Module 1 holds multiple documents relating to the presentation and packaging of the medicine(s).
| Section | Description | Category 1/Category 2 | Category 3 | ||
|---|---|---|---|---|---|
| New registration | Variation | New registration | Variation | ||
| 1.3.1.1 | Product information - clean | mandatory | mandatory | mandatory | requirement defined by the regulatory activity |
| 1.3.1.2 | Product information - annotated | requirement defined by the regulatory activity | mandatory | mandatory | requirement defined by the regulatory activity |
| 1.3.1.3 | Package insert | requirement defined by the regulatory activity | requirement defined by the regulatory activity | requirement defined by the regulatory activity | requirement defined by the regulatory activity |
| 1.3.2.1 | Consumer medicines information - clean | mandatory | requirement defined by the regulatory activity | mandatory | requirement defined by the regulatory activity |
| 1.3.2.2 | Consumer medicines information - annotated | requirement defined by the regulatory activity | requirement defined by the regulatory activity | mandatory | requirement defined by the regulatory activity |
| 1.3.3 | Label mock-ups and specimens | mandatory | requirement defined by the regulatory activity | mandatory | requirement defined by the regulatory activity |
Include in all regulatory activities which:
Include a proposed package insert with all regulatory activities which:
The form for the product information has been approved by a delegate of the Secretary of the Department of Health under subsection 7D(1) of the Therapeutic Goods Act 1989 (the Act) for use by applicants for the registration of:
other medicines for which the Secretary has given notice to the applicant that product information is to be provided to the Secretary (see section 25(1)(da) of the Act).
The information below is provided to assist applicants in producing an Australian PI and is to be read in conjunction with the instructions on the form.
Ensure the Australian PI is updated and maintained based on the format and contents specified in guidance for PI and package inserts.
Where there is an amendment to an existing PI:
Include in all regulatory activities which:
For example, an application to include important safety information in the PI and which needs to be reflected in the CMI.
The CMI:
If the CMI is based on an existing CMI, include:
CMIs are referred to as 'patient information' in the legislation.
In addition to the requirements of the Regulations, the TGA strongly encourages applicants to follow Writing about medicines for people: Usability guidelines for consumer medicine information when developing a CMI. These guidelines outline the correct procedure for writing, testing, implementing and monitoring CMI.
It is the applicant's responsibility under the Regulations to ensure that the CMI remains consistent with the PI and the format specified in the Regulations.
Schedule 12 of the Therapeutic Goods Regulations 1990 requires the CMI to be:
Include the proposed Australian labelling with all regulatory activities that:
Labels are evaluated under:
Therapeutic Goods Order - General requirements for labels of medicines made under section 10 of the Act sets out requirements for labels for medicines. Labels are assessed against the requirements in this order.
This section of Module 1 holds multiple documents providing information about the experts who have reviewed the supporting data for the submission and prepared the summaries and overviews that constitute Module 2.
| Section | Description | Category 1/Category 2 | Category 3 | ||
|---|---|---|---|---|---|
| New registration | Variation | New registration | Variation | ||
| 1.4.1 | Quality (if Module 2.3 included) | mandatory | mandatory | mandatory | mandatory |
| 1.4.2 | Nonclinical (if Module 2.4 included) | mandatory | mandatory | not required | not required |
| 1.4.3 | Clinical (if Module 2.5 included) | mandatory | mandatory | not required | not required |
Include where any subsection of Module 2.3 has been provided in the dossier.
The expert responsible for compiling Module 2.3 must:
The following table provides instruction on creating and completing the declaration.
| Expert | Instruction |
|---|---|
| Australian expert |
Download the Module 1.4 form Information about the experts and complete the section for the 'Local (Australian) expert' as per the instructions on the form. The declaration must be signed by the expert who is the subject of the declaration. |
| Expert from European Union |
Provide a copy of the expert's declaration from the application lodged with EMA. Alternatively, the 'Overseas expert' part of the Module 1.4 form can be completed. |
| Other overseas expert | Complete the 'Overseas expert' part of the Module 1.4 form. |
Module 1.4.1 must include, in the following order:
Module 2.3 is required for the following regulatory activity types:
Include where any subsection of Module 2.4 and/or Module 2.6 has been provided in the dossier.
The expert(s) responsible for compiling Module 2.4 and Module 2.6 must:
The following table provides instruction on creating and completing the declaration.
| Expert | Instruction |
|---|---|
| Australian expert |
Download the Module 1.4 Information about the experts form and complete the section for the 'Local (Australian) expert' as per the instructions on the form. The declaration must be signed by the expert who is the subject of the declaration. |
| Expert from European Union |
Provide a copy of the expert's declaration from the application lodged with EMA. Alternatively, the 'Overseas expert' part of the Module 1.4 form can be completed. |
| Other overseas expert | Complete the 'Overseas expert' part of the Module 1.4 form. |
Module 1.4.2 must include, in the following order:
Module 2.4 (nonclinical overview) is required when:
Where the applicant claims essentially similarity to a registered product, the nonclinical overview should focus on the grounds for claiming essential similarity and, if applicable, the additional data to demonstrate evidence of the equivalence of safety and efficacy properties of different salts, esters, or derivatives of an authorised active substance are to be provided.
Module 2.6 (nonclinical summary) is required for the following regulatory activity types:
Include where any subsection of Module 2.5 and/or Module 2.7 has been provided in the dossier.
The expert(s) responsible for compiling Module 2.5 and Module 2.7 must:
The following table provides instruction on creating and completing the declaration.
| Expert | Instruction |
|---|---|
| Australian expert |
Download the Module 1.4 Information about the experts form and complete the section for the 'Local (Australian) expert' as per the instructions on the form. The declaration must be signed by the expert who is the subject of the declaration. |
| Expert from European Union |
Provide a copy of the expert's declaration from the application lodged with EMA. Alternatively, the 'Overseas expert' part of the Module 1.4 form can be completed. |
| Other overseas expert | Complete the 'Overseas expert' part of the Module 1.4 form. |
Module 1.4.3 must include, in the following order:
Module 2.5 and Module 2.7 are required for the following regulatory activity types:
For an application to register a new generic medicine:
This section of Module 1 holds multiple documents required for specific types of regulatory activities.
| Section | Description | Category 1/Category 2 | Category 3 | ||
|---|---|---|---|---|---|
| New registration | Variation | New registration | Variation | ||
| 1.5.1 | Literature-based submission documents (if literature-based submission) | mandatory | mandatory | not required | not required |
| 1.5.2 | Orphan drug designation (if orphan drug) | mandatory | not required | mandatory | not required |
| 1.5.3 | Genetically modified organisms consents | requirement defined by the regulatory activity | requirement defined by the regulatory activity | not required | not required |
| 1.5.4 | not required | ||||
| 1.5.5 | Co-marketed medicines declarations (if applicable) | mandatory | requirement defined by the regulatory activity | mandatory | requirement defined by the regulatory activity |
| 1.5.6 | Combination medicine consent (if submission for a new combination) | mandatory | not required | not required | not required |
| 1.5.7 | OTC product assurances | Refer to OTC Guidance document. Not required for prescription medicine applications. | |||
| 1.5.8 | Umbrella brand assessment | Refer to OTC Guidance document. Not required for prescription medicine applications. | |||
Include where the application partially or completely relies on a literature-based data set to support the application.
For literature based submissions involving a systematic literature search, three items need to be prepared:
For literature based submissions NOT involving a systematic literature search, Module 1.5.1.1 and Module 1.5.1.3 only need to be prepared.
A literature-based submission uses literature references, rather than studies, for part or all of the supporting data required in the dossier to establish quality, safety, and efficacy.
Generally, the TGA will only accept literature-based submissions for medicines with an extensive registration history either in Australia or overseas.
A submission comprising a mix of conventional and literature-based data is treated in the same manner as a pure literature-based submission.
When completing the application form:
Include when the medicine has been designated an orphan drug and the applicant wishes to request the fees be waived for an application under section 23 of the Act.
Locate the TGA letter granting orphan drug designation and check the designation letter and the application to ensure:
Include a copy of the TGA letter granting orphan drug designation in Module 1.5.2.
Fees for variations to the registration of a medicine, that is, regulatory activities under section 9D of the Act, cannot be waived for an orphan drug.
If the indications proposed in the application are wider than those stated in the orphan drug designation letter, then either:
A new orphan drug designation request must be lodged with the TGA.
Orphan drug designation is granted under regulation 16J of the Therapeutic Goods Regulations 1990 where the applicant has made an application under regulation 16I that demonstrates why the drug satisfies the criteria set out in regulation 16H.
Regulation 45(12) allows for the waiving of a 'fee that would have been payable' for the Secretary considering the application under regulation 16J or 'as part of the registration of a designated orphan drug'.
Information about how to apply for orphan drug designation may be found on the TGA website.
Include where the application seeks the registration of:
TGA Guidance 21: Medicines produced by genetic manipulation.
Include this document in Module 1.5.5 when:
The third party sponsor must provide the applicant lodging the submission with a letter that:
Where the application concerns a copy of medicine registered on the ARTG to a third party sponsor, the applicant of the submission must provide:
or
information on any differences together with a declaration that all other quality (Module 3) aspects are identicalor
a complete list of the differences.Ensure the third party has lodged their data before lodging the application. Failure to provide a third party's data may result in an application being considered not effective.
To avoid delays in evaluating the application, requests to make corrections or variations to the ARTG entry for the third party's already registered product must be submitted to the TGA well in advance of lodging a submission for the co-marketed medicine.
If the proposed product(s) is a new fixed combination, attach a copy of the TGA's letter advising that the justification for fixed combination is acceptable.
Fixed combination products may be presented as composite packs (i.e. with multiple dosage forms), multiple ingredients within a single dosage form, or a combination of both.
Module 1.5.6 does not apply to fixed combination regulatory activities for new generic medicines.
For a new fixed combination product the applicant must justify, prior to lodging a PPF, the particular combination and the type and extent of data to be provided in the dossier. This is done by preparing and lodging with the TGA a 'justification for fixed combination' as described in the TGA guidance on Fixed combination prescription medicines. If your justification is accepted, attach a copy of the letter advising this in Module 1.5.6.
Refer to OTC Guidance document. Not required for prescription medicine regulatory activities.
Refer to OTC Guidance document. Not required for prescription medicine regulatory activities.
This section of Module 1 holds multiple documents relating to the use of drug master files (DMFs), plasma master files (PMFs) and Certificates of Suitability of Monographs of the European Pharmacopoeia (CEPs) to establish the quality of active substances in the medicine, novel excipients and excipients of animal and human origin.
| Section | Description | Category 1/Category 2 | Category 3 | ||
|---|---|---|---|---|---|
| New registration | Variation | New registration | Variation | ||
| 1.6.1 | Relevant external sources | requirement defined by the regulatory activity | requirement defined by the regulatory activity | requirement defined by the regulatory activity | requirement defined by the regulatory activity |
| 1.6.2 | Applicant's declaration | requirement defined by the regulatory activity | requirement defined by the regulatory activity | requirement defined by the regulatory activity | requirement defined by the regulatory activity |
| 1.6.3 | Letters of access | requirement defined by the regulatory activity | requirement defined by the regulatory activity | requirement defined by the regulatory activity | requirement defined by the regulatory activity |
Include this document when the application makes reference to one or more:
Obtain the relevant DMF/PMF/CEP details from the active substance manufacturer, including the eSubmission Identifier and any other TGA reference numbers.
Where a DMF, PMF or CEP is referenced, download and complete the relevant part/s of the DMF/PMF/CEP details form. Include the completed form(s) in Module 1.6.1.
Declaration(s) and Letter(s) of access are required—see Module 1.6.2 and Module 1.6.3.
The applicant's (open) part of the DMF must be included in Module 3.2.S of the quality documentation in the dossier.
The active substance manufacturer's restricted (closed) part is supplied to the TGA directly by the active substance manufacturer.
Ensure that the active substance manufacturer's part of the DMF/PMF has been submitted to the TGA before lodging the application dossier.
For medicines that contain either a raw material or an excipient that is derived from plasma a PMF must be included in Module 3 or have been previously approved by the TGA.
For variations to a registered medicine involving a modified DMF/PMF/CEP it is not necessary to provide this document again, unless a new DMF/PMF/CEP is to be provided.
European Union Guidelines adopted in Australia.
Include when the application makes reference to one or more:
Establish a formal agreement with the active pharmaceutical ingredient manufacturer to ensure the manufacturer communicates any changes to the applicant and the TGA before any significant change is made to the drug substance. This agreement is independent of the TGA.
Once the agreement has been established, download the Applicant declaration form
The declaration must be signed by an authorised officer of the company.
For regulatory activities subsequent to the initial registration application involving the same DMF/PMF/CEP it is not necessary to provide the declaration again, unless a new DMF/PMF/CEP is to be provided or there has been a change in sponsor.
Include when the application makes reference to one or more:
Each manufacturer providing a DMF/PMF for the application:
Each manufacturer providing a CEP for the application:
All manufacturers:
The finished product applicant must have written permission from the manufacturer to access their DMF/PMF/CEP to enable the TGA to proceed with the evaluation.
Where reference is made to a CEP, the finished product applicant must provide to the TGA a copy of the certificate and any annexes (see Module 3.2.R).
For regulatory activities subsequent to the initial registration application involving the same DMF/PMF/CEP it is not necessary to provide the declaration again, unless a new DMF/PMF/CEP is to be provided or there has been a change in sponsor.
Applications are made under either section 23 (new registrations) or section 9D(3) (requests for variations) of the Therapeutic Goods Act 1989 (the Act) and where the relevant legislative and business requirements are met, are approved under section 25 or section 9D(3), respectively.
Section 25(1)(d) of the Act requires that the TGA determine whether the quality, safety and efficacy of the goods for the purposes for which they are to be used have been satisfactorily established.
Section 9D(3)(c) requires that 'the Secretary is satisfied that the variation requested does not indicate any reduction in the quality, safety or efficacy of the goods for the purposes for which they are to be used'.
Assessing the quality of the goods includes establishing the quality of the active substance.
Where quality relating to the active substance cannot be established solely by the information provided by the applicant in Module 3.2.S, the applicant may make reference to external sources to establish the quality.
Acceptable external sources are a drug master file, plasma master file or an EDQM Certificate of Suitability of Monographs of the European Pharmacopoeia.
As a condition of registration it is a requirement that, apart from specified minor variations, no changes are made to the active substance without the prior approval of the TGA.
To receive approval for some changes, revised and/or new DMFs, PMFs and/or CEPs need to be provided to the TGA and assessed, by reference to section 9D(3) of the Act.
This section of CTD Module 1 holds documents relating to pre-submission meetings held between the TGA and the applicant and identifies how any issues raised by the TGA in the Planning letter have been addressed in the dossier.
| Section | Description | Category 1/Category 2 | Category 3 | ||
|---|---|---|---|---|---|
| New registration | Variation | New registration | Variation | ||
| 1.7.1 | Details of compliance with pre-submission meeting outcomes (if meeting held) | mandatory | mandatory | mandatory | mandatory |
| 1.7.2 | Details of any additional data to be submitted (if agreed) | mandatory | mandatory | not required | not required |
| 1.7.3 | Declaration of compliance with Pre-submission planning form and Planning letter | mandatory | mandatory | not required | not required |
Include when one or more scientific advice meetings and/or pre-submission meetings with the TGA have resulted in outcomes that the applicant must address to comply with application requirements. See also TGA Guidance 5: Pre-submission meetings with TGA.
Identify:
Meetings include all relevant meetings requested by an applicant or TGA and include meetings conducted in any format (i.e. face to face, teleconference or videoconference). There may be multiple meetings before PPF or dossier lodgement.
Ensure the information provided in Module 1.7.1 is an accurate reflection of the meeting(s) and any outcomes that need to be addressed.
All meetings provide guidance only and outcomes are without prejudice and are not considered binding on the TGA.
The TGA will only agree to the lodgement of additional data where the medicine is of critical importance to the Australian community to address emergency or safety situations..
No additional data should be submitted during the course of the evaluation of an application, other than relevant safety data and data specifically requested by the TGA.
Include details of additional data to be submitted when discussions have resulted in the TGA agreeing to accept additional data during the course of evaluation.
Include:
Additional data:
Include when the application is one for which a Pre-submission planning form (PPF) was lodged with the TGA.
After reviewing the PPF, TGA’s Planning letter and the dossier to be submitted, prepare a declaration that:
Information for applicants completing a pre-submission planning form
The TGA will check the application for consistency with the PPF. Any differences between the information provided on the PPF and the resulting application may result in the TGA considering the application not effective. For example, the inclusion of an additional indication in the application at the submission phase increases the scope of the application and will not be accepted.
If an application will differ in scope and scale from that indicated in the PPF, contact the Medicines Authorisation Branch before lodging the dossier.
This section of Module 1 holds documents relating to the pharmacovigilance activities for a new medicine, or significant changes to a registered medicine.
| Section | Description | Category 1/Category 2 | Category 3 | ||
|---|---|---|---|---|---|
| New registration | Variation | New registration | Variation | ||
| 1.8.1 | Pharmacovigilance systems | mandatory | requirement defined by the regulatory activity | mandatory | not required |
| 1.8.2 | Risk management plan for Australia | requirement defined by the regulatory activity | requirement defined by the regulatory activity | not required | not required |
Include in all regulatory activities which result in one or more new ARTG entries under section 16 of the Act, for example:
The summary of the pharmacovigilance system should be provided in Module 1.8.1 of the application and includes the following elements:
Include in all regulatory activities for:
Unless TGA has agreed that it is not required, include a risk management plan (RMP) for regulatory activities involving:
In some circumstances products which do not fall into the above categories may require a RMP. These include:
It is strongly recommended that discussions with the TGA on the need for, and content of, an RMP take place in advance of PPF lodgement, especially for situations where the submission of a RMP is not mandatory but may nevertheless be required.
Where a RMP waiver has been given by the Post-Market Surveillance Branch, include the relevant document from TGA in this module (see Risk management plans for prescription medicines).
Provide a detailed description of a risk management system in the form of a RMP, as outlined in:
This section of Module 1 holds documents relating to biopharmaceutic studies included in the dossier.
| Section | Description | Category 1/Category 2 | Category 3 | ||
|---|---|---|---|---|---|
| New registration | Variation | New registration | Variation | ||
| 1.9.1 | Details of compliance with pre-submission meeting outcomes (if meeting held) | requirement defined by the regulatory activity | requirement defined by the regulatory activity | not required | not required |
| 1.9.2 | Details of any additional data to be submitted (if agreed) | requirement defined by the regulatory activity | requirement defined by the regulatory activity | requirement defined by the regulatory activity | requirement defined by the regulatory activity |
Include for all regulatory activities which include a bioavailability or bioequivalence study in the dossier.
Australia's requirements for biopharmaceutic studies are aligned with the CHMP Guideline on the investigation of bioequivalence (CPMP/EWP/QWP/1401/98 Rev1/Corr) which has been formally adopted in Australia (with annotation).
Include when biopharmaceutic studies are required as outlined in the TGA guidance on Biopharmaceutic studies, but have not been provided.
For example, when:
The justification for not providing appropriate biopharmaceutic data, including the absence of biopharmaceutic data for all strengths of the product, must:
The justification for providing biopharmaceutic data for a generic medicine that was not generated against a reference product obtained from Australia needs to:
A BCS-based biowaiver approach should be justified in terms of the criteria listed in CHMP Guideline on the investigation of bioequivalence (CPMP/EWP/QWP/1401/98 Rev1 Corr) which has been formally adopted in Australia (with annotation).
Section. 25(1) of the Act requires medicines to be assessed for safety, quality and efficacy.
For an application to register a new generic product, as defined in Schedule 9 of the Therapeutic Goods Regulations 1990, the applicant must be able to demonstrate that the proposed medicine is bioequivalent to a registered medicine.
The Secretary must be 'satisfied that the variation requested does not indicate any reduction in the quality, safety or efficacy of the goods for the purposes for which they are to be used'.
Variations that have the potential to affect the quality of the goods may require the provision of Module 1.9.2, as described above.
This section of Module 1 holds information relating to the applicant’s paediatric development program.
| Section | Description | Category 1/Category 2 | Category 3 | ||
|---|---|---|---|---|---|
| New registration | Variation | New registration | Variation | ||
| 1.10.1 | Information relating to paediatrics | requirement defined by the regulatory activity | not required | not required | not required |
Include in all regulatory activities to register:
Complete the form Module 1.10 Information relating to paediatrics and include the form in Module 1.10 of the dossier.
The form includes advice as to whether there is a paediatric development program for this medicine and provides TGA with information, relevant to the Australian application, about the data submitted, paediatric clinical study commitments given and waivers received in the European Union and United States of America.
A paediatric investigation plan (PIP) is a development plan aimed at ensuring that the necessary data are obtained through studies in children, when it is safe to do so, to support the authorisation of a medicine for children. All applications for marketing authorisation for new medicines that were not authorised in the EU before 26 January 2007 have to include the results of studies carried out in children of different ages as described in the PIP. This requirement also applies when a company wants to add a new indication, pharmaceutical form or route of administration for a medicine that is already authorised and patented.
The Pediatric Research Equity Act (PREA) authorizes the FDA to require paediatric studies of drugs or biologics. Under PREA, a paediatric assessment is required for new applications, except when waived or deferred, and is designed to provide data needed to evaluate the safety and efficacy of a drug or biologic and to support dosing and administration for each paediatric subpopulation for which the product has been found safe and effective.
The Best Pharmaceuticals for Children Act (BPCA), enacted in 2002, encourages the manufacturers, or applicants, of drugs that still have marketing exclusivity, that is, are on-patent, to conduct paediatric drug studies, as requested by the Food and Drug Administration (FDA). If they do so, FDA may extend for 6 months the period during which no equivalent generic drugs can be marketed.
The TGA has adopted internationally recognised ICH/European guidelines concerning paediatric data generation and facilitating the extrapolation of data from one patient population to another, including:
This section of the Module 1 holds information regarding the foreign (overseas) regulatory status for the medicine and the supporting data for the dossier.
| Section | Description | Category 1/Category 2 | Category 3 | ||
|---|---|---|---|---|---|
| New registration | Variation | New registration | Variation | ||
| 1.11.1 | Foreign regulatory status | mandatory | mandatory | not required | not required |
| 1.11.2 | Foreign product information | mandatory | requirement defined by the regulatory activity | not required | not required |
| 1.11.3 | Data similarities and differences | mandatory | requirement defined by the regulatory activity | not required | not required |
| 1.11.4 | Foreign evaluation reports: | requirement defined by the regulatory activity | not required | ||
| Category 1 | requirement defined by the regulatory activity | requirement defined by the regulatory activity | |||
| Category 2 | mandatory | mandatory | |||
Include with all category 1 and category 2 regulatory activities.
If an application is rejected by overseas authorities during the Australian evaluation process, the applicant must immediately inform the TGA.
The format for providing information to the TGA on foreign regulatory status should be consistent whenever an update to the information is provided for a given submission.
Information on the foreign regulatory status of similar applications may be provided in tabular form, as shown below:
| Country/region | Submission date | Status | Indications (approved or requested) | Other relevant information |
|---|---|---|---|---|
| EU - centralised procedure | 1 June 20xx | Pending | [details] | |
| USA | 1 June 20xx | Approved Day, month year | [details] |
Provide an update on the overseas status of the application in the pre-ACPM response.
Provide an update on the overseas status of the application to the TGA Delegate at the decision phase as defined in the Planning letter.
Include with all category 1 and category 2 regulatory activities where a similar application has been lodged in:
Prepare copies of each of the following documents from the similar overseas application(s):
A draft document may be included in this part of the dossier if the overseas SmPC, monograph, or prescribing information has not been approved at the time the application is lodged in Australia.
If the overseas SmPC, monograph, data sheet, or prescribing information is approved after dossier submission in Australia, the documents should be submitted as they become available.
Provide updated overseas prescribing information documents or SmPC documents as part of a pre-ACPM response.
Provide updated overseas prescribing information documents or SmPC documents to the TGA Delegate at the decision phase as defined in the Planning letter.
Include with all category 1 and category 2 regulatory activities for which a similar application has been lodged in:
Prepare a summary of the similarities/differences between the data in the Australian submission and the data packages submitted in:
Identify and account for any significant differences.
Category 2 regulatory activities may be rejected if any significant or substantial undisclosed differences are found by the TGA.
Include for:
Regulations 16C and 16D of the Therapeutic Goods Regulations 1990 provide for shorter evaluation timeframes if
Module 1.12 holds the antibiotic resistance data for new antibacterial medicines, extensions of indication to currently registered antibacterial medicines, and updated data for currently registered antibacterial medicines.
| Section | Description | Category 1/Category 2 | Category 3 | ||
|---|---|---|---|---|---|
| New registration | Variation | New registration | Variation | ||
| 1.12 | Antibiotic resistance data | requirement defined by the regulatory activity | requirement defined by the regulatory activity | ||
Module 1.12 applies to:
It is recommended applicants review the adequacy of data relating to the potential of an antibacterial medicine to promote resistance and cross-resistance for applications:
The risk assessment of microbial resistance consists of the following steps:
The risk assessment may be qualitative in part, although quantitative data should be provided where possible.
It is acceptable for this document to refer to data supplied elsewhere in the dossier. References need to include module, tab identifier, and page number.
Include any Australian human antibiotic-resistance prevalence data in the pharmacology section of the Australian product information document.
Any additional drug substance/active substance and/or drug product information specific to Australia should be provided in section R of the application. Applicants should consult the appropriate TGA guidelines for additional guidance.
A brief description of the information specific to the region, as provided under 3.2.R should be included, where appropriate.
Any additional drug substance and/or drug product information specific to Australia should be provided in section 3.2.R of the application.
Where similar or relevant information has been provided in another section of Module 3 or where there is supporting or related information from other modules of the application, the applicant is encouraged to clearly cross-reference to the location of that information. Cross-referencing should be sufficiently detailed, so as to allow the appropriate information to be easily located within the dossier.
Applicants should include the following information in Module 3.2.R, where appropriate:
Include when: