Guidance document Procedure with prior notification

1 Terms, definitions, abbreviations

1.1 Abbreviations

FTP Fast-track authorisation procedure FeeO-Swissmedic Ordinance on the Fees charged by the Swiss Agency for Therapeutic Products of 14 September 2018 (SR 812.214.5) AI Additional Indication CC Company correction CD Calendar days eCTD Electronic submission in CTD format eDok Swissmedic application submission format, paper version + electronic version EMA European Medicines Agency FDA Food and Drug Administration (USA) FC Formal check LoQ List of Questions NA New application NAS New Active Substance ODS Orphan Drug Status PD Preliminary Decision PPN Procedure with Prior Notification TPO Ordinance of 21 September 2018 on Therapeutic Products (Therapeutic Products Ordinance, TPO) (SR 812.212.21)

2 Introduction

This guidance document describes in detail the conditions under which a PPN procedure is carried out, from the initial request, review of the request and preparatory work through to the submission of the PPN application and corresponding criteria. Swissmedic uses this guidance document first and foremost as a resource for applying the legal provisions in a uniform and equitable manner. For applicants, the document is intended to make clear the specific requirements that must be fulfilled so that corresponding applications can be processed by Swissmedic as quickly and efficiently as possible.

3 Objective

The procedure with prior notification (PPN) allows companies that submit applications for the authorisation of human medicinal products with new active substances (New API) and preparations specified in Art. 12 para. 5 TPLO (human medicinal products with a known active substance that cannot be authorised via the simplified procedure) or for an additional indication (AI) to request Swissmedic to consider whether their application with a previously agreed timeframe can be processed within a timeframe that is 20 per cent shorter. In return, the applicant is willing to pay double the fee (Art. 7 FeeO-Swissmedic). However, in contrast to the fast-track authorisation procedure (FTP) in accordance with Art. 7 of the Therapeutic Products Ordinance (TPO), the PPN procedure does not confer upon the applicant any

legal entitlement to a shorter procedure. Instead, the PPN procedure represents a special service offered by Swissmedic which, under certain conditions, makes it possible to reserve the resources required to carry out a normal authorisation procedure in advance, and thus to process the application more rapidly. PPN is not an authorisation procedure with a reduced scope of assessment or reduced requirements with regard to the documentation required.

4 Scope

This guidance document applies to the authorisation procedures for human medicinal products.

5 Description

5.1 Requests for a procedure with prior notification

5.1.1 Conditions under which a procedure with prior notification can be carried out

The following conditions must be fulfilled before an authorisation application can be processed within the framework of a PPN:

The authorisation application must concern the first authorisation of a human medicinal product with a new active substance (New API), the first authorisation of a preparation specified in Art. 12 para. 5 TPLO, an additional indication (AI) for a human medicinal product that was originally authorised as a New API or as a preparation specified in Art. 12 para. 5 TPLO, an additional pharmaceutical form and/or an additional dosage recommendation; for these last two application types, however, the applications must be submitted together with the application for the first authorisation of the New API / preparation specified in Art. 12 para. 5 TPLO.
The clinical and preclinical studies should have been fully completed by the time the application is submitted. Once the application has been received, no further trial data, trial results or other documentation relevant to the evaluation may be submitted. If the indication requires long-term data, this data must be available at the time of submission. Interim analyses must be submitted together with the planned, complete and final study report in accordance with the study protocol, reflecting the status once the primary end point of the study has been reached. Full documentation must also be submitted. The submission must be based on up-to-date data and may not contain any immature or incomplete data. The subsequent submission at a later date of further documentation that is not explicitly requested is not possible within the framework of the ongoing procedure. Any results from foreign assessments available to the applicant, and in particular assessment reports from the EMA or the FDA, must be included with the submission.
Swissmedic must have the necessary human resources available in order to complete the assessment of the application within the required time and by the date foreseen. A request for a PPN procedure can be sent to Swissmedic at the earliest six months prior to the expected submission date and must be received at the latest three months prior to the expected date. A request for an additional indication in the PPN procedure cannot be submitted until the preliminary decision (PD) on the human medicinal product with a new API / preparation specified in Art. 12 para.

5 TPLO has been issued. A PPN procedure is only possible if the authorisation application is submitted in CTD format in electronic form as an eCTD application or as a paper version with CD/DVD (eDok). If it is planned to make the submission in eCTD format, it is strongly recommended that applicants with limited or no

experience with eCTD submit a test sequence in good time (at least three weeks before submitting the application) in order to avoid exceeding the time limits as a result of technical problems. The authorisation application must then be submitted by the deadline established by Swissmedic (exact date) and fulfil all the formal requirements.

5.1.2 Documentation required for the request

A written request for a PPN procedure must include the documents listed in the Table of documents to be submitted on the Applications+Meetings sheet. The cover letter should also contain the following information:

Name of active pharmaceutical ingredient
Name of the medicinal product
For biosimilars the name of the reference preparation as well
ATC / IT group
Pharmaceutical form and, for injectable solutions, information about the primary container or – if relevant – the administration system (pre-filled syringe, autoinjector)
Indication(s) and dosage recommendation(s)
List of preclinical and clinical studies, in particular with essential information on the pivotal studies
Expected submission date for the PPN application (+/- 2 calendar weeks)
Possible date(s) for a Meeting before application submission or reasons why such a meeting is not felt to be necessary

5.1.3 Processing the request

Within 30 CD, Swissmedic decides whether it will be possible to conduct the procedure requested under the prevailing circumstances on the date proposed by the company (+/- 2 calendar weeks). The outcome of this investigation is communicated to the applicant in writing. If it is not possible to carry out a PPN procedure on the date proposed by the applicant, Swissmedic considers alternative dates and suggests an alternative in its response. If the two parties are unable to agree on an alternative submission date, the applicant is informed that a PPN procedure cannot be carried out during the proposed timeframe.

5.1.4 Combining an application for FTP with a PPN request

A request for a PPN procedure can be submitted at the same time as an application for a fast-track authorisation procedure (FTP) under the terms of Art. 7 TPO. To this end, all the required information and documentation for the FTP application and the request for a PPN must be submitted concurrently. This avoids the need to submit a request for a PPN procedure at a later stage if the application for a FTP is rejected. In the event of a negative preliminary decision on fast-track authorisation, Swissmedic requires the applicant to confirm, within 7 days of receipt of the negative preliminary decision, that they are continuing with the requested PPN procedure (with suggested deadlines for submitting the request and, where appropriate, for the Meeting before application submission). In the event of a rejection of the FTP application with simultaneous request for a PPN, the applicant will be charged for the costs of the FTP application. Furthermore, the information in the Fast-track authorisation procedure guidance document applies to the application and to the request for a FTP.

5.2 Planning the submission after approval of the PPN application

5.2.1 Stating the submission date

If the company has been informed that a PPN procedure is possible within the timeframe it has proposed, it must inform Swissmedic in writing of the definitive submission date (exact date) for the PPN application (definitive prior notification) at the latest one month before this date. If, on this definitive submission date, particular developments in the human resources situation at Swissmedic make the performance of a PPN procedure unrealistic, the Agency will inform the applicant immediately and propose an alternative submission date for the PPN application or the submission of the authorisation application in the standard procedure.

5.2.2 Meeting before application submission (optional)

If necessary, a Meeting before application submission takes place one or two months before the PPN application is submitted. The aim of the meeting is to establish whether all the documentation required to process the application is available. The following formal aspects of the authorisation application to be submitted, in particular, will be considered:

Index of scientific and administrative documentation
Any open questions about the documentation
Manufacturers involved
Date of the eCTD test submission (if an eCTD application is to be submitted and the applicant wants to submit a test sequence)
Determination of the deadlines to be respected by Swissmedic and by the applicant
Planning of sample testing, where applicable. However, the applicant can also briefly address particular problems at this meeting, e.g. special new manufacturing processes, specific statistical analyses, critical points, etc. that could affect the complexity of the evaluation. The definitive submission date (exact date) is established at the meeting. The following information / documentation must be sent to Swissmedic, with an appropriate cover letter, at the latest 2 weeks before the meeting:
List of questions: Presentation of the issues to be clarified during the meeting, usually in the form of a Briefing Book (see section 3.2 List of questions/documentation in the guidance document Meetings for applicants for authorisation procedures),
Draft agenda with the points to be discussed,
Proposal for the type of meeting: in person, teleconference or videoconference and
List of participants and their functions. Furthermore, Meetings before application submission in the PPN procedure are subject to the provisions of the guidance document Meetings for applicants for authorisation procedures. The applicant is responsible for minuting the meeting. The applicant should send a copy of the minutes to Swissmedic 14 CD at the latest after the meeting. The meeting can also be waived by mutual agreement between Swissmedic and the applicant.

5.3 Authorisation procedure with PPN

5.3.1 Submission and documentation

The applicant submits the authorisation application to Swissmedic, including all documentation, on the agreed date as an eCTD version or as a CTD paper version with CD/DVD (eDok). The requirements governing the application documentation are the same as those applicable to an authorisation application outside the PPN process (see for example guidance documents Authorisation of human medicinal product with known active pharmaceutical substance, Authorisation biosimilar, Variations and extensions and the formal requirements as laid down in guidance document Formal requirements and the Directory Overview of documents to be submitted). Any results from foreign assessments available to the applicant, and in particular assessment reports from the EMA or the US FDA, must be included with the submission. If the date provided to the Agency for the submission is not respected, or if the documentation submitted with the application has major shortcomings (which cannot be rectified by the applicant within 10 CD), with the result that the agreed schedule is unlikely to be observed, the submission will be accepted and processed as a normal authorisation application, i.e. outside the PPN procedure (subject to the normal flat fee specified in FeeO-Swissmedic and with no shortening of the processing period by 20%). The costs of examining the request and for the Meeting before application submission will be billed on an hourly basis in accordance with Art. 4 para. 2 FeeO-Swissmedic.

5.3.2 Evaluation phase and periods

The evaluation takes place in accordance with the process for first authorisation of a New API / preparation specified in Art. 12 para. 5 TPLO, variations and authorisation extensions and the guidance document Time limits for authorisation applications and is subject to the shortened periods shown in the flow chart in section 7. If a List of Questions (LoQ) is issued, the applicant informs Swissmedic within two weeks of the binding submission date for its reply to the LoQ. This information will enable Swissmedic to adapt its planning for evaluation phase II accordingly. The applicant must also inform Swissmedic, within two weeks of receipt of the preliminary decision, of the date by which it will send its reply (position statement and supporting documents) to the preliminary decision. If the applicant submits a larger volume of documentation for assessment than is required to answer the questions (e.g. in reply to the LoQ or as a position statement on the preliminary decision), the Agency shall be granted the same number of calendar days as for the preceding application phase in order to evaluate this documentation (i.e. 100 CD for a comprehensive, unsolicited answer to the LoQ and 90 or 70 CD for a comprehensive unsolicited answer to the preliminary decision) and these days shall be at the expense of the applicant. Swissmedic also reserves the right to impose a surcharge determined by the time involved (Art. 5, para. 2, Fee-O Swissmedic).

5.3.3 Sample testing

Sample testing by Swissmedic takes place in accordance with the requirements generally applicable to the authorisation procedure. The performance of sample testing and the timing and modalities for submitting the documentation and samples can be discussed and agreed upon in the Meeting before

application submission. Samples and any other documents must then be submitted in accordance with the requirements stated in the LoQ.

5.3.4 Failure to respect time limits

If Swissmedic is unable to observe the agreed processing periods / time limits, the Agency may not apply a surcharge for the authorisation procedure (time limits continue according to the PPN). However, if the applicant's failure to respect a time limit prevents adherence to the time schedule established for processing the application, the applicant will be charged the full surcharge, and the application will be treated as a normal authorisation application from the time at which the delay occurs, including the corresponding time limits and modalities. The applicant is also deemed to have failed to observe the time limits if extensions to the time limits for replying to the LoQ, PD and text correction communication are granted (see flow chart in section 7).

5.3.5 Fees for applications in the PPN procedure

FeeO-Swissmedic applies, particularly Art. 7. If there are justified reasons for halting or withdrawing the PPN procedure before processing of the application begins (i.e. specifically before the formal checks have been completed), a fee for the costs that have been incurred up to that point will be charged.

5.4 Flow chart

Before submission (request, examination, preparation for PPN) After submission (PPN application)

New authorisation Indication extension Swissmedic time Swissmedic time Time (months, weeks) (calendar day) after (calendar day) after before submission submission submission -6M 0 Submission 0 Submision

10 CD FC 10 CD FC FC completed FC completed 10 10

Request for procedure with prior max. max. NB NB 10 CD 10 CD Doc. OK 10 Doc. OK

Evaluation I Evaluation I notification 100 CD 100 CD

List of List of 110 110 Questions Questions

Deadline for

Reply to LoQ -3M Info re

Reply to LoQ Info re request* when when Examina- max. max. reply to

90 CD reply to 60 CD

tion by LoQ (14 LoQ (14 CD) CD) Swissmedic Reply to LoQ Reply to LoQ informs applicant: received received

Evaluation II Evaluation II

Confirmation of planned 90 CD 70 CD submission date (+/- 2 W)
Possible other submission Preliminary Preliminary

Preparatory work 200 180 date dicision dicision

Info re Info re

Reply to PD Reply to PD max. when max. when -1M 60 CD1

60 CD1 reply to reply to

Fix submission date PD (14 PD (14 (or during Meeting CD) CD) before application submission) Receipt of Receipt of reply to reply to preliminary preliminary Product decision Product decision 64 CD information /

36 CD information /

-3W If applicable: Submit eCTD test sequence Labelling Labelling

264 216 Decision

0 Decision

Submission

Key: Milestone / applicant s side

Milestone / Swissmedic s side

*NI in the PPn only after PD approval of the NA for NAS For a PD rejection companies have 30 CD to send a reply to the PD.

Change history Version Change sig

6.0 Requirement in section 5.2.1 deleted: Information on submission format before stg

application submission is not necessary; Section on product information / labelling phase and packaging materials deleted (reason: corresponds to the process in the standard procedure)

5.0 Clarification of submission date for authorisation application in PPN (exact date) fg

4.1 New layout, no content adjustments to the previous version. dei

4.0 Restriction in Chapter 6.3.6 lifted: Fee reduction for collective applications according to dts

Art. 11 FeeO-Swissmedic are possible

3.2 Formal adjustments to the header and footer dei

No content adjustments to the previous version.

3.1 Clarification that extensions to the time limits for the company’s reply to the letters (LoQ, stb

PD and TC) sent to them by Swissmedic are also considered as failure to observe the time limits (section 6.3.5 Failure to respect time limits).

3.0 Explanation regarding fees for applications in the PPN procedure (chapter 6.3.6): When stb

applications for indication extensions are submitted for medicinal products in the same range under the procedure with prior notification (PPN), no fee reduction (joint discount) is granted.

2.0 The procedure with prior notification (PPN) is now also possible for new authorisations of stb

medicinal products with Orphan Drug Status (ODS – section 6.1 as amended). In such cases, the supplement is payable but no flat fee is charged.