Australian eCTD submissions: Frequently asked questions

21 October 2014
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Pilot phase

My company wants to join the Pilot - can we send an eCTD submission directly to the TGA?

During the pilot phase, we ask Sponsors to contact esubmissions@tga.gov.au if you wish to be involved for any specific application. Decisions on which applications will be included in the pilot phase are being made on a case by case basis. This allows us to find the best test cases so we can be prepared for the implementation of eCTD. Do not send your submission without first confirming your participation in the pilot for your specific application.

An application from our company has been accepted onto the Pilot, can we submit other applications to the Pilot?

During the pilot phase, we ask Sponsors to contact esubmissions@tga.gov.au if you wish to be involved for any specific application. Decisions on which applications will be included in the pilot phase are being made on a case by case basis. This allows us to find the best test cases so we can be prepared for the implementation of eCTD. Do not send your submission without first confirming your participation in the pilot for your specific application.

What is the scope of the eCTD pilot phase?

The pilot phase will test capabilities of submitting electronic Common Technical Documents (eCTD) for registered prescription medicines. The TGA will work with sponsors to identify suitable prescription medicine eCTD submissions to pilot and test aspects of the TGA electronic submission application process internally and externally.

We are looking to test the following prescription medicines application types:

  • new chemical entity
  • major variations to a prescription medicine (both with and without baseline)
  • generic medicine.

Decisions on which prescription medicine applications will be included in the pilot phase are being made on a case by case basis. This allows us to find the best test cases so we can be prepared for the implementation of eCTD.

What formats should we submit in during the pilot phase?

During the eCTD pilot phase, submissions from sponsors participating in the pilot will be in the eCTD format. If you are not participating in the pilot phase all requirements for an effective submission, including the need to submit a paper copy of the dossier, will stay the same.

What will happen when the pilot finishes in February 2015?

The TGA will conduct a readiness assessment to determine the success of the eCTD Pilot and readiness of Industry to participate further.

Will I be required to submit applications in eCTD format after February 2015?

No. The two (2) legal instruments will allow for submission of either eCTD format or as is currently accepted. The TGA encourages sponsors / applicants to move to eCTD submissions to reduce costs and regulatory burden.

General

What type of therapeutic goods will the eCTD format be acceptable for?

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.

Will an eCTD submission to the TGA require accompanying paper copies?

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.

Are there any submission types that will not need to be submitted in eCTD format (Good Manufacturing Practice certificates, Periodic Safety Update Reports, etc.)?

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.

If there is a product with more than 1 'container/vial' size and a separate ARTG entry for each of these sizes, will there need to be separate eCTD applications for each of the ARTG listings? e.g. 5ml, 10ml and a 20 ml vial of the same product?

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.

Will we have access to the eCTD once submitted to TGA i.e. online so that we can see our application live?

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

Who will have access to the eCTD information once the dossier is submitted to TGA and once the product is approved?

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

Does the TGA recommend or welcome applicants submitting 'test eCTD submissions' to the TGA?

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.

Will a submission be given review priority by virtue of it being in the eCTD format and are there going to be any incentives for submitting in eCTD?

Over time, processes may become more efficient as we use eCTD, but at this stage there are no plans to give applications submitted in the eCTD format review priority or provide any additional incentives to submit in eCTD format.

eCTD will assist the TGA and sponsors by reducing regulatory burden and removing the requirement to produce unnecessary and burdensome paperwork.

How can industry contribute to the development of new guidance material?

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

Which software products are best suited to compile eCTD submissions?

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.

Does TGA recommend the use of eCTD viewing tools and if so should this be the Lorenz tool?

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

What is the maximum file size of an entire eCTD submission that is accepted by the TGA?

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.

Can industry download a template folder structure for eCTD/NeeS from the TGA website, as the Belgium Federal Agency for Medicines and Health Products has on their website?

Currently there are no plans for this function.

Is the TGA considering moving to RPS (eCTD 4.0) in the future?

The TGA is planning for RPS (eCTD 4.0).

Information for regulatory affairs areas

Will the eCTD dossiers be submitted via the TGA eBS portal?

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.

Will all variations be submitted via eCTD or just new registration applications?

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.

How can we prepare for eCTD?

Experience from Sponsors who are using eCTD to submit to overseas regulators has shown there are four areas to manage in order to be prepared:

  1. Standards: including data standardization and harmonization, using style guides and templates (for example, authoring templates and standardising headers and footers), understand and following the guidance from the regulator and applying component authoring standards
  2. Process: having processes to support authoring and importing, review, approving, publishing and submission, lifecycle management and system validation
  3. Technology: acquiring or using document management, publishing and data management software. Knowledge of XML authoring and publishing and having the correct IT infrastructure and network capacity in place.
  4. Organisation: supporting people through global collaboration and training.

Planning for your submission needs to include the estimated time for publishing and aligning your processes to the requirements of the TGA.

Should we use tradenames in eCTD?

No, use the drug or chemical name.

Transition

When will we know about the transition phase?

An evaluation of the pilot project will occur in February 2015. Information on the transition to eCTD will be announced when the evaluation has been completed.

Can I swap between eCTD submissions and NeeS?

Once a submission for a product is submitted in the eCTD format, all future submissions for that product must be in the eCTD format.

Will the TGA need to be informed in advance of the intention to transition an application to eCTD?

No, but once commenced in the eCTD format applicants should remain in the eCTD format in order to take advantage of the lifecycle features of the eCTD standard (i.e. applicants do not have to re-submit documents already submitted to the TGA).

Submission and sequence numbers

Can we set our own eSubmission identifier numbers or does the TGA intend to issue numbers that we need to track the application with?

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.

How do I get an eSubmission Identifier from the TGA?

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).

When submitting via eCTD will correspondence to the TGA need to be in eCTD format or can industry still send documents via email?

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

If NeeS dossiers have already been submitted, does this affect the eCTD sequence number?

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.

Can we set our own sequence numbers to track our applications or does the TGA intend to generate these?

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.

Do eCTD sequence numbers need to run sequentially or can eCTD submission be sent out of sequential order (e.g. a delay submitting sequence 0012 means sequence 0013 is submitted before 0012)?

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

Will the TGA release a list of the validation criteria for eCTD?

The TGA validation criteria will be available on the website.

Will the TGA notify the sponsor if there are any validation errors after submitting the eCTD to the TGA? Will there be time for validation errors to be fixed before the eCTD is technically rejected?

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

What is the working documents folder for and what should be submitted in this folder?

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.

Will the eCTD require an electronic baseline?

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.

How will replacement of pages work in variation dossiers if the numbering of the original eCTD does not go down to that level?

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.

Does the TGA recommend the use of the 'append' operation in LifeCycle management?

No.

Does the TGA accept cross referencing to documents in previously or concurrently submitted eCTD sequences?

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.

Will TGA accept modified United States Food and Drug Administration (FDA) submissions that include Study Tagging Files (STFs)?

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.

Will the TGA accept (or require) STFs for Module 4 and Module 5 study reports?

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

Will the TGA provide any guidance regarding the use of hyperlinking and bookmarking, for example, frequency and context of hyperlinking in different modules and impact on lifecycle management?

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

How will the eCTD be stored at the TGA?

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

If the submission is electronic only, will the requirement for the sponsor's archive copy to be in electronic format only as well?

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.

Future developments

In relation to matters related to ANZTPA, is the TGA currently liaising with Medsafe on the implementation of the eCTD? Or is each agency working separately? If so, what are the implications when/if ANZTPA comes into effect?

The TGA is aligning requirements with other international regulators where this is possible. Module 1 will be the only area with Australian only requirements.

The current plan is to accept submissions with country folder AU. In future the TGA or its successor may accept submissions with country folders NZ or ANZ.