Australian eCTD submissions: Frequently asked questions

19 September 2016
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General

The eCTD format will be accepted but not made compulsory for prescription, biological and registered non-prescription medicines.

Medical devices will not be included in the initial stages of the TGA moving to accept eCTD submissions. Medical devices are likely to be included when the international standard for Regulated Product Submissions is sufficiently stable.

There is no requirement for new listable substances (active and excipient), new sunscreen active substances and new excipients in topical non-prescription medicines to follow the eCTD format.

Submissions in the eCTD format will not need to be accompanied by a paper copy of the dossier. To support this activity the TGA has added a second Section 23 instrument, which enables lodgment of an eCTD submission without paper in the pilot program.

The eCTD format is regarded as the principal electronic submission format for medicines in Australia. TGA expects that all submissions will be able to use the eCTD format including registration applications, master files and Periodic Safety Update Reports.

The normal choice should be one single eCTD application that covers multiple drug products (components), multiple dosage forms, multiple strengths and multiple manufacturers. If the applicant needs to have one eCTD application per strength, dosage form, etc., this should be explained. The cover letter should describe how the documentation may be similar or different in order to prevent the duplication of work during evaluation.

There are no plans to allow online access to TGA stored submissions.

Only authorised TGA staff will have access to submissions information. This is no different to current TGA work practices and guidelines.

The TGA expects sponsors and applicants to use validation tools to test their own eCTD applications before submitting them to the TGA. A copy of the validation report will need to be attached to the submission. Validation tools are available from software vendors or an example tool can be downloaded from the TGA website.

Interested parties are welcome to forward comments on TGA's eCTD guidance documents at any time. It is expected that guidance documents will be further modified at intervals based on comments received, experience gained, and further ICH developments. Comments may be forwarded to the TGA and we will review all requests and comments for inclusion in consultation with stakeholders.

Information for IT specialists and information managers

Sponsors and applicants are free to use any appropriate software to compile and publish eCTD submissions. The TGA also requires a validation report to be attached to each submission. Submissions must pass the TGA's validation processes to be accepted.

TGA does not recommend any specific eCTD tools. However, there are a number of software vendors in the marketplace.

The maximum size of an individual PDF file is 100MB. There is no maximum for the entire submission. The TGA will encourage submission via DVD during the Pilot and until we have a fully developed portal facility with capacity for upload.

Currently there are no plans for this function.

The TGA is planning for RPS (eCTD 4.0).

Information for regulatory affairs areas

No, not initially. eCTD submissions will be submitted via electronic media. A future project phase will examine portal requirements.

It is envisaged that registered non-prescription medicine submissions can continue to use the eBS portal as is used currently. This will be confirmed in initial testing.

TGA is piloting a range of types of submissions. Subject to the outcomes of these pilots, we expect to be able to receive all types of submissions, including variations (with and without baseline eCTD submissions), in the eCTD format. Once a submission for a product is submitted in the eCTD format, all future submissions related to that product must be in the eCTD format.

No, use the drug or chemical name.

Submission and sequence numbers

Submissions will require a TGA eSubmission Identifier, issued by TGA, in the 'envelope' information for each submission. Submissions will be referenced by this number and therefore subsequent sequences must include this identifier.

To get an eSubmission Identifier, send an email to esubmissions@tga.gov.au with the applicant's name, the Australian Approved Name, and description of the application (trade names, dose form, strength and route of administration).

Documents and significant correspondence should be via eCTD sequences (e.g. responses to requests for additional information).

No. The first eCTD submission for any product (including a new dossier or the accumulated documents to date of an existing product) normally has a sequence number of 0000, even if sequential numbers were already used for a NeeS submissions of the same product. If applicants consider that there are good reasons to use another number they should seek agreement from the TGA and provide the explanation in the cover letter.

If a baseline eCTD submission is provided, the baseline should normally be submitted as sequence 0000. The baseline is a separate submission and should not include any requests for new regulatory actions. The first new regulatory activity relating to a product, e.g. the next variation, in eCTD format should then be submitted as sequence 0001.

Sequence numbers for a particular submission start at 0000 and increment by 1 each time.

The TGA is considering the approach where baselines and New Chemical Entity (NCE) submissions start with sequence 0000. In all other cases, submissions should commence with sequence 0001. This would act as a marker that previous documents are outside the eCTD system.

If an Applicant transfers part ownership (say one of the Trade Names) then the New Applicant would receive a new eSubmission Identifier and the next sequence number would be the next sequence as per the original eSubmission Identifier. This enables the New Applicant to refer to the existing documents and not have to re-submit. Part of the transfer arrangement would be agreement to access the existing dossier.

Sequence numbers will normally run sequentially. The TGA validation process will give a warning that an out of sequence submission has been detected. If a sequence number is out of order, then the applicant should state in the cover letter why the sequence is out of order in order to minimise any delays in the process.

Validation requirements

The TGA validation criteria will be available on the website.

The TGA expects sponsors and applicants to use validation tools to test their own eCTD applications before submitting them to the TGA. A copy of the validation report will need to be attached to the submission. Validation tools are available from software vendors or an example tool can be downloaded from the TGA website.

TGA will adopt a set of technical validation criteria against which all eCTD and NeeS sequences can be checked. Two categories of validation rules apply: 'Pass/Fail', and 'Best Practice'.

The technical validation of an eCTD or NeeS formatted submission is a separate activity to the content validation of a submission and takes place irrespective of the type of the submission.

Sequences which fail to meet one or more of the 'Pass/Fail' criteria will be returned to the applicant for correction and resubmission. TGA may accept sequences which fail to meet one or more of the 'Best Practice' criteria; however, the applicant should make every effort to address these areas before the eCTD is submitted to TGA.

Document requirements

Non-PDF file formats such as rich text (RTF) or MS Word formats may be required by agencies in addition to the PDF requirements of the eCTD and NeeS, for example, the provision of Product Information documents. The files referred to above should not be added as leaf elements within the eCTD/NeeS structure. When submitted with an eCTD/NeeS formatted submission, they should always be provided in a separate folder called 'xxxx-workingdocuments' on the same media containing the electronic dossier, where the number (xxxx) matches the number of the eCTD/NeeS sequence being submitted.

Currently, TGA has not identified a need for a working document folder.

It is highly recommended but not mandatory to submit an eCTD baseline when changing from paper or NeeS to eCTD and to provide as much content as possible in the eCTD.

A baseline submission is a compiled submission of the current status of the dossier, i.e. resubmission of currently valid documents that have already been provided to TGA but in another format (paper or NeeS).

The sections provided to make up a baseline can be defined by the applicant, but any omissions should not render the submitted content misleading.

Under the ICH eCTD standard, the applicant can submit new sequences. A sequence can lifecycle complete documents (replace or delete documents), or add new documents. For example, an application for updated Product Information involves submitting a new sequence with the administrative information and the proposed new documents.

The applicant should choose the appropriate level of granularity for an electronic dossier. When relevant information is changed at any point in the product's lifecycle, replacements of complete files should be provided in the eCTD.

No.

Cross referencing to other eCTD submissions is allowed under the eCTD standard as long as the location of the file is accurately cited in the xlink:href attribute for the leaf element referencing that file.

This aspect will be subject to testing in the TGA implementation. It is not known yet if the TGA can rely on cross referencing so initially applicants should supply appropriate copies of documents.

The submission in eCTD format must adhere to the Australian Module 1 and ICH specifications. Submissions which include STFs will be accepted but are not required. However, if STFs are included, they must pass validation. If an FDA submission containing STFs is modified by removing the STFs, the study files must be organized using node extensions.

The TGA will accept, but does not require, Study Tagging Files.

Hyperlinks are recommended when they would aid the evaluation in ways not already possible through the use of the eCTD index.xml and document navigation aids. Applicants should consider when creating cross document hyperlinks that they can cause confusion later in the lifecycle and therefore be distracting for an efficient review. The recommendation is not to "over" hyperlink and rely on tables of contents in the initial pages of documents.

Storage

eCTD submissions will be preserved in the TGA's computer network file storage system according to Australian Government electronic record keeping standards.

Applicants should maintain archival copies of submissions according to their business rules. TGA recommends archiving all dossiers in the format the dossier was submitted to the TGA.