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Mandatory requirements for an effective application

Applicable for applications lodged from 9 February 2018

21 February 2018

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Content of application dossier

The exact content of the application dossier will vary according to the:

  • application category
  • nature of the medicine
  • application type.

A dossier documents matrix is provided in CTD Module 1: Administrative information and prescribing information for Australia which provides a high-level overview of the application dossier CTD section requirements for different application types.

Overview of CTD documents

CTD Module 1: Administrative information and prescribing information for Australia establishes the Module 1 content for different application types.

CTD Module 2 is a summary module which provides an overview of the information/data provided in the quality (Module 3), nonclinical (Module 4), and clinical (Module 5) modules of the dossier. Information on the content of Module 2 is provided at the beginning of CTD Modules 3, 4, and 5.

The organisation of Modules 3, 4, and 5 is specified by the CTD Modules 3, 4, and 5. These modules contain headings and sub-sections under which applicants must insert technical data. To determine technical data requirements, applicants must consult relevant Australia-specific guidelines and EU guidelines adopted in Australia.

Technical data requirements

The application dossier must provide appropriate documentation (in the correct format and locations, as determined by the CTD modules), including outcomes of trials and studies, to allow the Delegate of the Secretary to assess quality, safety, and efficacy claims. The technical data requirements that establish the documentation to be provided in the dossier are:

The use of EU guidelines adopted in Australia and other Australia-specific guidelines is not mandated in the legislation. However, section 25(1)(d) of the Act requires that when making a decision on whether to approve a medicine for registration, the delegate determines:

"whether the quality, safety and efficacy of the goods for the purposes for which they [the goods] are to be used have been satisfactorily established;"

Where a dossier does not address the applicable requirements/guidelines, or fails to adequately justify why an applicable requirement/guideline has not been addressed in the application, we may be unable to establish satisfactorily the quality, safety or efficacy of the proposed good.


As noted above, Australia-specific guidelines and adopted EU guidelines determine the data and information required in Modules 1, 2, 3, 4, and 5 of a dossier to demonstrate quality, safety, and efficacy.

It is the applicant's responsibility to familiarise themselves with all relevant Australia-specific guidelines and EU guidelines adopted in Australia, and to advise us of instances of, and reasons for, deviation from the applicable guidelines or requirements.

A justification is a reason given by the applicant for not complying, in the application dossier, with a specific requirement or guideline, and generally fall into one of two broad categories:

  • Justifications that will determine the categories/sections of information required in the application dossier for it to be considered effective and accepted for evaluation. If a dossier does not contain a certain section, and an acceptable justification has not been provided for its absence, the application dossier may not meet the requirements for an effective application under section 23 of the Act.
  • Justifications that will determine the depth and breadth, or adherence to an adopted standard specification or guideline for the required information. This is relevant to evaluation during the 1st and 2nd round assessment phases when the content of the application dossier is being evaluated.

    If the justification provided by the applicant for not adhering to a specification or guideline is not present, not appropriate (e.g. wrong guideline is addressed), or inadequate, the application submitted may not satisfactorily establish the quality, safety and efficacy of the proposed good. That is, the application will not be considered to be effective.

Some justifications must be submitted to us prior to lodging a Pre-submission planning form (PPF) and our acceptance of the justification included with the PPF. These include:

  • justification of a new fixed dose combination
  • justification of the literature search strategy for a literature-based submission.

The PPF refers to several justifications required to be submitted with the form:

  • for a generic application, a justification where a salt/ester of the generic product is different to the Australian reference product
  • for applications where the existing ingredients intended are to be used for different purposes (e.g. new route of administration), a justification is required if not providing additional toxicology data to support the safety of the ingredient for the intended use
  • justifications for not providing data according to a particular guideline or aspect of a guideline
  • justification for including a preservative in a single dose injection.

Where the applicant chooses not to provide data according to a particular guideline or aspect of a guideline (for example, the applicant may consider the guideline is not applicable to the product), the justification must explain why the guideline is not applicable and why the proposed alternative is valid.

A justification must be scientifically robust and address the relevant requirement. For certain requirements, we provide detailed information to assist applicants in constructing a robust scientific justification (for example, the TGA Biopharmaceutic studies guideline provides information on the required content for a justification for not conducting biopharmaceutic studies).

Where we have provided such detailed information, the applicant must ensure all details have been addressed in the justification. In other cases, applicants must adhere to the principles of a robust scientific justification (see Important note below).

Important note

Where possible applicants should not deviate from the relevant guidelines.

Should an applicant submit an application that includes justifications for not meeting a relevant guideline, we will assess whether the justification provided is a robust scientific justification.

A robust scientific justification is one that:

  • clearly identifies the guideline or part of the guideline that is not being met
  • specifically addresses why the guideline is not being met
  • has a contemporary scientific basis
  • includes citations to the relevant reference documents, including TGA documents, where appropriate. Applicants must ensure all such references are included in the dossier.

This justification will be assessed in the above terms - but not evaluated - in determining whether an application is to be found effective.

Administrative requirements

Applicants must comply with (and cannot provide a justification for not complying with) the administrative requirements. These include those applying to:

  • forms to be completed for administrative purposes
  • the presentation of the electronic dossiers.
  • requirements specific to the Priority review registration pathway

Establishing bioequivalence or therapeutic equivalence

Biopharmaceutic studies of new medicines typically include the investigation of absolute bioavailability, relative bioavailability and bioequivalence of different dosage forms or formulations, and the effect of food or antacids on their bioavailability.

For new generic medicines, establishing bioequivalence with the Australian reference product allows bridging to the nonclinical and clinical studies. Applicants applying for a new generic medicine are therefore required to provide information to demonstrate bioequivalence; however, our experience is that many applicants are uncertain about how to do so.

There are several Australian and adopted EU guidelines that are relevant to establishing bioequivalence. A summary of these documents, and their relationships, is provided below.

Summary of guidelines relevant to establishing bioequivalence
Document Relevant to Comments
TGA guideline: Biopharmaceutic studies All applications to register a new medicine.

Applicants should consult this guideline to ascertain:

  • whether or not biopharmaceutic studies will be required to support their application in Australia.
  • minimal issues to be addressed if providing a justification for not submitting biopharmaceutic data.
  • issues to consider concerning the choice of reference product.

If it is unclear whether a medicine is of the category Prescription medicines which do not require biopharmaceutic data, the applicant should contact us prior to lodging the PPF.

Guideline on the Investigation of Bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1/ Corr) Applications for synthetic medicines with an immediate release formulation and systemic action.

While this guidance suggests that the design and conduct of the study should follow EU regulations on Good Clinical Practice, applicants should note that the EU Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95) has been adopted in Australia with TGA annotations.

The procedure for abridged applications claiming essential similarity to a reference product (ie, generics), which allows applications to be made to numerous Member States of the EU, based on bioequivalence with a reference product from one Member State, does not apply in Australia.

A bioequivalence study to support the registration of a generic product in Australia should use a reference product obtained in Australia. Where an overseas reference product is used, the applicant must be able to demonstrate the overseas and Australian reference products are identical (see TGA guideline Biopharmaceutic studies).

Clinical Requirements for Locally Applied, Locally Acting Products, Containing Known Constituents (CPMP/EWP/239/95) Applications for synthetic medicines that are applied locally and act at the site of application.

Locally applied products that do not act at the immediate site of application (skin, cornea etc.) are not covered by this guideline.

For example, eye drops that exert their effect beyond the cornea (i.e. the deeper tissues of the eye). Examples of such eye drops include eye drops for the treatment of glaucoma.

Requirements for establishing the bioequivalence of such products to a reference product are set out in the adopted EU Guideline on the Investigation of Bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1).

Products applied in a transdermal dosage form are not covered by this guideline – refer to the Note for Guidance on Modified Release Oral and Transdermal Dosage Forms. Section II (Pharmacokinetic and Clinical Evaluation) (CPMP/EWP/280/96)

Note for Guidance on Modified Release Oral and Transdermal Dosage Forms: Section II (Pharmacokinetic and Clinical Evaluation) (CPMP/EWP/280/96) Applications for synthetic medicines in transdermal and modified release oral dosage forms.

For multiple strengths of generic transdermal and modified release oral dosage forms, bioequivalence studies should be performed at least on the lowest and highest strengths versus the corresponding reference products.

If an applicant considers that this is unnecessary in a particular case, a justification for not submitting bioequivalence data should be submitted in accordance with the TGA guideline Biopharmaceutic studies (Justification for not submitting biopharmaceutic data).

Guideline on Similar Biological Medicinal Products (CHMP/437/04) and related guidelines

Applications for new biological medicines that are similar to an existing reference product Applications for similar biological medicinal products are not considered new generic applications. Applicants should follow the approaches developed in the adopted EU guidelines.
Various clinical guidelines for medicines for specific therapeutic products or use Applications requiring non-inferiority studies

Some clinical guidelines provide additional information about the studies needed to demonstrate therapeutic equivalence for specific therapeutic products or use. However, applicants must ensure the guidelines are relevant to their particular application/product.

For example, the guideline: Clinical Investigation of corticosteroids intended for use on the skin refers to the use of a vasoconstriction assay. This is an example of a pharmacodynamic endpoint that is not related to the therapeutic effect of the medicinal product. When using a pharmacodynamic model to replace clinical data, applicants must ensure the model chosen is internally valid. In the case of the vasoconstriction assay this endpoint may not be externally valid where the composition of the generic product differs to that of the reference product.

The use of pharmacodynamic endpoints should be justified in terms of their direct relevance to the intended therapeutic effect of the active component of the medicinal product.

Applicants should note that the TGA considers newly released and updated EU guidelines and decides whether or not to adopt them. Some of the above guidelines may therefore be amended, removed or replaced from time to time. Applicants should check the TGA website routinely and subscribe to receive email updates on new content.

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