Access Consortium: Operational procedures for New Active Substances Work-Sharing Initiative (NASWSI)

Original: June 29, 2021

On this page

• Introduction
• Application requirements
• Dossier requirements
• Phase 1: Pre-procedure/confirmation of operational approach
• Phase 2: Application submission and assessment
• Phase 3: National steps
• Target evaluation plan of the Access NASWSI standard procedure

Introduction

This document outlines operational procedures and recommendations for planning and implementing the New Active Substances Work-Sharing Initiative (NASWSI). It's intended for the regulatory agencies within the Access Consortium:

• Therapeutic Goods Administration, Australia
• Health Canada, Canada
• Health Sciences Authority, Singapore
• Swissmedic, Switzerland
• Medicines and Healthcare products Regulatory Agency, United Kingdom

As part of the NASWSI, a joint review may be considered for:

• new chemical or biological entity applications
• new indications applications that are submitted to 2 or more Access agencies

For new chemical or biological entity applications, the submission will be divided into modules. A specific agency will review each module or designated sections within a module. Other participating agencies will conduct a peer review of the assessment reports for each module. Each agency is also responsible for reviewing its respective Module 1.

For new indications applications, 1 agency will evaluate Module 5. Other participating agencies will conduct a peer review of the assessment reports.

Each agency will make its own sovereign decision based on the recommendations contained in the assessment reports. If participating agencies cannot reconcile any issues with the data, they may seek additional information and undertake further review.

Interested applicants should communicate early on with the Access agencies in the countries where they propose to submit their application to discuss the suitability of their application.

Potential applicants will be required to work with the agencies throughout the procedure.

Application requirements

Applications should be submitted simultaneously to at least 2, but preferably more, of the Access agencies. The formal work-sharing procedure described in this document will begin when an Expression of Interest form has been submitted.

A joint review may be considered for:

• new chemical or biological entity applications
• new indications applications

Applications submitted under the standard or priority review pathways may be eligible for the NASWSI. The same assessment pathway (standard or priority) must be used in all participating jurisdictions. Applicants must indicate the pathway they intend to use in the Expression of Interest.

A joint review will not be considered for:

• applications for provisional or conditional approvals
• variations to products previously authorized through the NASWSI procedure (other than new indications applications)

Dossier requirements

The dossiers submitted should fully address the requirements of all jurisdictions proposed for work-sharing.

Applicants are expected to submit the same data set for Modules 2 to 5 to all agencies. However, if there are differences, the completed "Summary of Differences" table (included in the Expression of Interest form) should be submitted. The applicant should outline the differences in the information provided to each participating agency. The participating agencies will consider these differences to determine if the application is suitable for the NASWSI.

Note: Module 1 will continue to be different for the dossiers filed in the different Access jurisdictions (as per regional requirements).

Dossiers must be submitted in eCTD format to all agencies where eCTD is allowed.

Phase 1: Pre-procedure/confirmation of operational approach

The pre-procedure covers the process steps and issues that are considered before an application is accepted for the NASWSI. These steps are to be completed concurrently within the regulatory systems of the participating agencies.

Technical (scientific) pre-submission meeting/teleconference

A bilateral technical pre-submission meeting or teleconference between each local jurisdiction and the applicant is recommended. Joint meetings with 2 or more regulators can be requested but may not be granted due to operational and resource challenges.

Applicants must follow the usual procedure of their local agency when requesting a technical pre-submission meeting. This meeting can take place after the Expression of Interest form has been submitted.

Submitting the Expression of Interest form

Interested applicants should submit an Expression of Interest form at least 3 months before their anticipated filing date to each agency proposed for work-sharing. Once this is done, the participating agencies will discuss the suitability of the application for the NASWSI and the next steps will be communicated by email and/or in a teleconference.

Priority review request

Where applicable, applicants should submit their priority review request at least 3 months before filing. (Note: Only Therapeutic Goods Administration, Health Canada and Swissmedic have formal priority pathways. However, in appropriate circumstances, Health Sciences Authority and Medicines and Healthcare products Regulatory Agency may agree to an expedited review.)

Where available, priority review status will be determined in each jurisdiction before Access partners allocate review responsibilities.

Determining the role for Access partners

Access agencies will consider their operational needs when allocating review responsibilities for the dossier.

There will be models for work-sharing 2, 3, 4 and 5 ways. For example, for a new chemical entity application involving 3 regulators, the joint review could involve each participating agency reviewing a different module (3, 4, or 5).

Responsibility for reviewing aspects related to more than 1 module (example: impurities) or data by different groups within the Access agencies (example: bioavailability) will be determined case by case. As an example, if a toxicological assessment of impurities is required, it will be directed to the agency that's responsible for the non-clinical review.

Note: The lead for the clinical review will coordinate the logistical pre-submission meeting on behalf of Access partners, where one is requested.

Developing an evaluation plan and timeline

Access agencies will develop an evaluation plan with specific milestones. The plan will allow each agency to meet its legislative obligations and/or performance standards.

Access agencies will also confirm the approach for questions raised during the assessment phase:

• Joint review of an application under the standard pathway:
  • Agency questions will be issued as part of a consolidated list of questions at the end of the round 1 evaluation (milestone 3).
  • Access agencies may indicate if they prefer to issue questions throughout the evaluation period ("rolling questions") for the module they are responsible for.
  • Note: The NASWSI does not allow rolling submission of data by applicants during the evaluation phase. Applicants must lodge a complete dossier at the time of submission.
• Joint review of an application under the priority review pathway:
  • Agency questions will be issued as "rolling questions" throughout the evaluation period (for example, during phase 2).

Logistical pre-submission teleconference

In addition to technical discussions between each agency and the applicant, a logistical pre-submission teleconference is recommended. The purpose of this teleconference is to discuss and confirm the logistics, expectations related to the requirements, timelines and work-sharing processes. It also gives agencies a chance to answer any questions from the applicant.

The teleconference should take place at least 2 months before the application is filed.

The applicant will be asked to:

• provide a list of queries for the Access agencies at least 2 weeks before the teleconference
• complete a meeting record summarizing the outcomes and actions arising within 2 weeks of the meeting

Phase 2: Application submission and assessment

The following timelines refer to "calendar days". If a milestone falls on a weekend or a national holiday, the milestone will be the preceding business day.

The evaluation timeframes outlined below are the default timeframes for a NASWSI application using the standard pathway. These target timeframes allow Access agencies to meet their legislative obligations and/or performance standards. Participating agencies may agree to modified timeframes in consultation with applicants.

If changes to the evaluation plan are required during the evaluation (for example, changes to applicant response times or delays to reviews), Access agencies will contact the applicant to seek agreement.

For NASWSI applications using the priority pathway, the evaluation plan will be customized for each application.

Milestone 1: Submission of application

Applications should be submitted to each agency at the same time or as agreed with the agencies.

Milestone 2: Acceptance of application (30 to 45 days from filing to acceptance for assessment)

After receiving the application, each agency will:

• screen the application to ensure that their own legislative and data requirements are met (for example, application forms, user fees)
• inform the local applicants of the acceptability of the application for assessment following their usual procedure

The day of acceptance of the application for assessment is "Day 0" of the NASWSI process.

Note: The screening timeframe may vary between agencies. However, the goal is to have the submission enter review on the same date in all participating jurisdictions.

Assessing the dossier (90 days)

Access agencies will review and prepare an assessment report and a list of questions for the module(s) they are responsible for using their own national guidelines.

Each agency will follow their usual procedure for reviewing its respective Module 1.

Where an application (priority review pathway) or individual module is being reviewed using rolling questions rather than a list of questions:

• Access agencies will issue rolling questions throughout the evaluation at set time points wherever possible
  • for example, starting at day 60 and then once a month until day 150 (4 rounds in total)
• applicants must provide responses to rolling questions within 15 days

Peer review (25 days)

Access agencies will conduct a peer review of the assessment report and list of questions, which involves:

• consulting the modules (as needed) and sharing additional questions on relevant modules with the lead reviewing agency
• undertaking supplemental evaluations of the relevant module(s) where there are additional country-specific requirements or guidelines that need to be considered

Evaluator teleconferences will be scheduled to discuss aspects of the review. Feedback and additional questions may be provided to the reviewing agency for consideration and discussion.

Finalizing the assessment reports and list of questions (5 days)

Access agencies will finalize:

• the consolidated list of questions on Modules 2 to 5 (excluding any questions issued by rolling questions) and
• their respective list of questions on Module 1 as applicable (including questions on product information and labelling)

Milestone 3: Consolidated list of questions issued to applicants

Each agency will send to their local applicant:

• the consolidated list of questions
• a copy of the assessments report(s) they have prepared, where this is part of their usual procedure
  • Therapeutic Goods Administration in Australia and Medicines and Healthcare products Regulatory Agency in the United Kingdom will share their assessment reports at milestone 3

Note: Agencies will not provide copies of assessment reports prepared by another agency.

The list of questions will be divided into:

• a common set of questions (common to all participating agencies)
• country-specific questions (relating to Module 1 as well as any country-specific questions for the other Modules)

Country-specific questions will be identified by prefix letters A (Australia), C (Canada), S (Singapore), CH (Switzerland), UK (United Kingdom) (for example, A1, A2).

Milestone 4: Response to the consolidated list of questions (30 or 60 days)

Applicants are required to send complete responses to the consolidated list of questions as follows:

• responses to all common questions to each agency
• responses to country-specific questions for Modules 3 to 5 to the applicable agency, unless requested as an FYI

The dossier must be updated in all jurisdictions to ensure the application is complete. If required, any updated data for Modules 3 to 5 can be provided near the end of the evaluation process.

The time for the response to the consolidated list of questions will be either 30 or 60 days, as nominated by the applicant in the Expression of Interest form.

Note: Participating agencies may agree to modify the response period for the list of questions after consulting with the applicant.

Assessment of responses to list of questions (25 days)

Access agencies will:

• review the responses to the list of questions and update the assessment reports for the modules(s) they are responsible for
• prepare an assessment report of responses to their respective list of questions on Module 1 and any supplemental evaluations of the other modules

Peer review (15 days)

Agencies will conduct a peer review of the assessment report of the responses.

Milestone 5: Finalizing the assessment reports (5 days)

When there are no outstanding issues, the report(s) will be finalized and the agencies will proceed to phase 3.

If necessary, the agencies may prepare an additional (second) list of questions to clarify any outstanding issues, of which each agency will send to their local applicant.

If the additional list of questions are country-specific, the other agencies may elect to proceed to phase 3.

Submission of responses to additional list of questions by applicant (15 days, depends on nature of unresolved issues)

If required, the applicant sends responses to any additional questions to all participating agencies via the respective local applicants.

Assessment of responses to additional list of questions (15 days, depends on nature of unresolved issues)

The reviewing agencies will review the responses to the list of questions and update the assessment reports as necessary.

Where relevant, Access agencies conduct a peer review of the assessment report related to the responses and provide feedback. Access agencies finalize the assessments report(s).

Milestone 6: Conclusion of formal work-sharing

Total maximum elapsed time from acceptance of the application to the start of phase 3:

• 225 to 255 calendar days (180 days excluding applicant time/stop-clocks)

The work-sharing process formally concludes at the end of the evaluation phase. The process then enters phase 3.

Before making a final decision (or seeking further clarification on issues first), each agency undertakes the necessary administrative steps to finalize the application process domestically.

Phase 3: National steps

National steps may include expert advisory committee meetings and finalizing product labelling. To ensure all agencies can follow their national steps in a timely manner, the agencies may customize the evaluation plan beyond milestone 5.

During the national steps, Access agencies may continue to share information, such as outcomes of expert advisory committee meetings, and discuss labelling and packaging issues.

Note: While there may be discussions between regulators about product labelling during the evaluation phase, different laws and frameworks for each country affect regulatory decisions related to product labelling. It is likely that product labelling will differ from 1 jurisdiction to another.

Milestone 7: Separate sovereign decisions

Access agencies will:

• independently inform the local applicant of their decision to grant or refuse to grant market authorization
• publish a public assessment report or similar document in accordance with their usual procedures

These communications may not be happen at the same time.

Market authorization or refusal by a regulator will not affect the decision or the timing of the decision by the other participating regulators.

For a submission that's not approved by an Access agency, its national procedures will apply.

Target evaluation plan of the Access NASWSI standard procedure

The following timelines refer to "calendar days". They include applicant time/stop-clocks (or calendar days excluding stop-clocks). If a milestone falls on a weekend or a national holiday, the milestone will be the preceding business day.