Guidance document Project Orbis
1 Terms, definitions, abbreviations
1.1 Abbreviations
AAid Assessment Aid ANVISA Agência Nacional de Vigilância Sanitária FDA U.S. Food and Drug Administration GSP Global Submission Plan HSA Health Sciences Authority IMOH Israel Ministry of Health MHRA Medicines and Healthcare products Regulatory Agency IR Information Requests LoQ List of Questions POP Project Orbis Partner RMP Risk Management Plan SAL Sponsor Authorization Letter SMC Swissmedic TGA Therapeutic Goods Administration TPA Federal Act of 15 December 2000 on Medicinal Products and Medical Devices (SR 812.21) TPLRO Ordinance of the Swiss Agency for Therapeutic Products of 9 November 2001 on the Licensing Requirements for Therapeutic Products (SR 812.212.22) TPO Ordinance of 21 September 2018 on Therapeutic Products (SR 812.212.21)
2 Introduction
Project Orbis is a program coordinated by the US Food and Drug Administration (FDA) to promising oncology treatments. It provides a framework for the concurrent submission and review of applications for oncology products among international partner authorities (POPs). It aims to deliver faster patient access to innovative treatments with potential benefits over existing therapies. It involves the regulatory authorities of:
Australia (TGA)
Brazil (ANVISA)
Israel (IMOH)
Canada (Health Canada)
Singapore (HSA)
Switzerland (Swissmedic)
United Kingdom (MHRA) The FDA is responsible for coordination and verifies that applications fulfil the acceptance criteria for Project Orbis. Initial enquiries should therefore be addressed to the FDA. However, each participating country retains autonomy as regards the final authorisation decision and labelling.
2.1 Legal framework
The procedure for the authorisation of medicinal products with new active substances is based on the following legislative texts in particular: TPA
Art. 9 Marketing authorisation
Art. 10 Conditions for granting a marketing authorisation
Art. 11 Application for a marketing authorisation
Art. 14 para. 1 f Important medicinal products for rare diseases TPO
Art. 7 Fast-track authorisation
TPLRO
Art. 2 General preconditions
Art. 3 Documentation on the analytical, chemical and pharmaceutical tests
Art. 4 Documentation on the pharmacological and toxicology tests
Art. 5 Documentation on clinical trials
Art. 6 Special requirements for fixed combinations of medicinal products
The procedure for the authorisation of new indications of medicinal products is a type II major variation and based on the following legislative texts in particular: TPO
Art. 23 Major variations
TPLRO
Art. 22a Classifications of the variations
Annex 7 List of amendments according to Articles 21-24 TPO
3 Objective
This guidance document describes the marketing authorisation process for medicinal products with medical applications in oncology within the framework of Project Orbis. Swissmedic uses this guidance document first and foremost as a resource for applying the legal provisions on authorisation in a uniform and equitable manner. Publication of the guidance document is intended to provide transparency for third parties on the requirements that have to be fulfilled under Swissmedic practice. It is also intended to provide a description of the requirements for obtaining authorisation of human medicinal products under Project Orbis in Switzerland.
4 Scope
This guidance document applies to the authorisation of human medical products with new active substances and new indications (type II variations) that are assessed under Project Orbis.
5 Description
5.1 Requirements
The requirements for the authorisation of medicinal products with new active substances are described in the guidance document Authorisation of human medicinal product with new active substance.The requirements for the authorisation of new indications are described in the guidance document Variations and extensions HMP. Project Orbis procedure is a special service offered by Swissmedic in collaboration with the FDA. Requests for a fast-track procedure, temporary authorisation procedure or procedure with prior notification must be submitted on deadline prior to application submission. Applications that involve a request for review under Project Orbis can be combined with these procedures. This also applies if it is not yet known, at the time of submission, that the FDA will accept the request for review under Project Orbis. The following documents outline specific criteria and requirements for the procedures of the same name:
Guidance document Fast-track authorisation procedure
Guidance document Temporary authorisation for human medicinal products
Guidance document Procedure with prior notification
5.1.1 Formal requirements
The formal requirements are based on the guidance document Formal requirements and the associated directory of Documents to be submitted.
5.1.2 Document protection
Information on documentation protection is provided in the guidance document Document protection.
5.1.3 Time limits
The time limits are based on the guidance document Time limits for authorisation applications. The time limits may vary depending on the type of application (NAS, IE) and Orbis type (see section
5.2.2 Types of Project Orbis submissions). Type A Orbis applications and fast-track Type B Orbis
applications are always subject to the Orbis procedure time limits, irrespective of whether the application was initially submitted under a different procedure (e.g. FTP).
5.1.4 Fees
The fees specified in the Ordinance on Fees Levied by the Swiss Agency for Therapeutic Products (FeeO-SMC; SR 812,214.5) apply.
5.2 Process
5.2.1 FDA Selection Process
Once topline results are available from the registrational clinical trial(s), the US applicant can make a request for review under Project Orbis to the FDA. In principle, applications that qualify for Project Orbis satisfy the conditions for FDA Priority Review. The decision on whether to accept submissions in Project Orbis lies entirely with the FDA. Applications for inclusion in Project Orbis cannot therefore be submitted to either Swissmedic or the other POPs.
5.2.2 Types of Project Orbis submissions
Type A Applications that are sent to Swissmedic within 30 days of submission to the FDA (submission gap) are classified as Orbis Type A. Orbis Type A permits parallel assessment, which maximises cooperation between the FDA and the POPs involved in the application and ensures that regulatory decisions are made concurrently or within a short period of each other. Orbis applications submitted as Type A will always be accepted as such by Swissmedic. The time limits for Orbis Type A are shorter than the standard time limits (see guidance document Time limits for authorisation applications). Questions take the form of Information Requests (IRs). Type B Applications that are sent to Swissmedic more than 30 days after submission to the FDA (submission gap) but before the FDA issues its decision are classified as Orbis Type B. They provide the possibility of cooperation with the FDA on the ongoing assessment process. Depending on the submission gap, available resources and the progress of the FDA’s review, Orbis Type B applications may be fast-tracked (fast-track Orbis Type B) in a similar way to Orbis Type A applications. Otherwise the standard assessment timelines will be applied to Orbis Type B applications (non-fast-track Orbis Type B), in a similar way to Orbis Type C applications (guidance document Time limits for authorisation applications). The applicant will be notified no later than the start of the procedure. Type C Applications on which the FDA has already made a decision and has submitted the unredacted assessment reports to the participating partner authorities are classified as Orbis Type C. Concurrent assessment with the FDA is not possible for Orbis Type C. The standard time limits, as set out in the guidance document Time limits for authorisation applications, apply and a List of Questions (LoQ) is sent to the applicant in line with customary practice.
Table 1: Types of Project Orbis submissions (as per general FDA template) Multi- POP country Near Submission Sharing Attendance Concurrent Orbis Submission review concurrent overlaps of FDA at FDA review with Type Timeline meetings action with with FDA reviews review FDA (POP FDA meetings TCONs)
Application submission to POPs ≤ 1 Type A Expected Yes Yes Yes Expected Possible1 month of FDA submission
Application submission Type B Expected Yes Yes Yes Possible No1 month of FDA submission
Any time Type C after FDA Permitted2 Yes No Unlikely Unlikely No1 submission21
5.2.3 Determination of Orbis type by Swissmedic
Swissmedic determines the Orbis type according to the criteria above (section 5.2.2) and on the basis of the submission dates for the USA and Switzerland given in the Global Submission Plan (GSP). The GSP must be submitted to the FDA by the US applicant when applying for a Project Orbis procedure. As soon as Swissmedic has determined the Orbis type and reported back to the FDA, the FDA will notify the US applicant. The latter must then notify the applicant in Switzerland of the planned submission and instruct it to contact Swissmedic (e-mail: projectorbis@swissmedic.ch).
5.2.4 Submission of the application
As a rule, submissions should be made electronically using the Common Technical Document format (i.e. eCTD) with all documents in English, with the possible exception of the country-specific Module
1 Marketing applications should comply with the specific requirements for submissions to Switzerland
(see also guidance document Formal requirements). In order to allow the exchange of information between Swissmedic and the participating Project Orbis partners over the course of the assessment, the Swiss applicant must consent to information
1 Regulatory action in other jurisdictions is unlikely to occur immediately after FDA action and will follow respective health authority timelines.
2 Dependent on Project Orbis Partner (POP) guidelines. Contact specific POP(s) regarding optimal timing for submission of Type C dossier .
exchange (see form New authorisation of human medicinal products or Variations and authorisation extensions HAM). In addition, the following documents should be submitted in Module 1: the FDA ‘Sponsor Authorization Letter’ (SAL) and the FDA ‘Assessment Aid’ document (Aaid).
5.2.5 Swissmedic assessment
5.2.5.1 Meetings
For Orbis Type A and fast-track Type B applications, the FDA organises and coordinates several online meetings with the authorities involved in the application to discuss various aspects of it (midcycle meeting and other application-specific meetings). The application-specific meetings include discussions of specialist issues such as efficacy, safety and clinical pharmacology and a general benefit-risk assessment is made. In the case of non-fast-track Orbis Type B and Orbis Type C applications, the FDA’s assessment is already at an advanced staged or has been completed, and it is therefore generally no longer possible to take part in FDA meetings.
5.2.5.2 List of Questions / Information Requests
Type A and fast-track Type B applications make no provision for Lists of Questions (LoQs). During Evaluation phase I, questions will be asked on an ongoing basis (rolling procedure) in the form of Information Requests (IRs). Swissmedic’s IRs are shared with the FDA and POPs and sent to the applicant in Switzerland. Questions are sent in English with a response deadline of 10 calendar days (see guidance document Time limits for authorisation applications). Where IRs concern the medicinal product information texts, Swissmedic may also send the revised manuscripts. The local subsidiaries submit the responses to the IRs to the FDA and all POPs except where the responses are to FDA IRs concerning raw data analyses and IRs concerning countryspecific labelling. These do not have to be submitted to Swissmedic. For Switzerland, responses to the IRs have to be uploaded as a “communication” to the Swissmedic eGov Portal. A covering letter referencing the relevant IR(s) and mentioning that the application is being reviewed under Project Orbis should be enclosed with the submission. The responses must be submitted to all authorities involved with the application as concurrently as possible. The responsible Regulatory Manager and projectorbis@swissmedic.ch must be notified by e-mail of the upload. For non-fast-track Type B and Type C applications, Evaluation phase I generally concludes with a LoQ.
5.2.5.3 Preliminary decision
For Type A and fast-track Type B applications, Swissmedic sends a preliminary decision to the applicant in Switzerland at the end of Evaluation phase I (the IRs having replaced the LoQ). For eCTD submissions a consolidated eCTD sequence containing all responses to the IRs made by all authorities has to be submitted with the response to the preliminary decision. Swissmedic will also consider responses to IRs received up to the date of the decision. Type C and non-fast-track Type B applications are subject to the standard procedure.
Annex 1 – Flow Chart
Process steps prior to application submission Company applies to FDA for inclusion of an application in Project Orbis
FDA decision: Application not accepted for Project Orbis Are Orbis criteria no → Submit application under SMC national procedures met?
yes
FDA clarifies planned application submission dates to FDA and SMC with companies (US parent company)
FDA shares application submission dates (FDA and SMC) with SMC
SMC determines Orbis type based on submission gap to FDA
Submission gap: > 30 days and FDA decision Submission gap: < 30 days Submission gap: > 30 days and FDA decision pending has been issued
Type A Type B Type C
SMC decision: Fast-track Type B or not
Process according to Process according to
SMC notifies FDA of determined Orbis Type, FDA informs US applicant, latter informs CH applicant
CH subsidiary contacts SMC
CH subsidiary submits authorisation application to SMC
Process steps after application submission
Type A / fast-track Type B Non-fast-track Type B / Type C
If appropriate: Kick-off meeting with FDA and partner authorities to determine assessment FDA shares unredacted ARS with the POPs strategy and deadlines
Meetings with the POPs on aspects of efficacy, Application is reviewed according to SMC safety, clinical pharmacology, risk-benefit requirements and processes assessment, etc.
IRs are shared with the POPs and sent to the CH applicant by SMC. CH applicant submits responses to all IRs from all POPs involved in the application to SMC
CH applicant submits IR responses to SMC and all other POPs involved in the application within 10 calendar days
After completion of assessment: Preliminary decision sent to CH applicant
CH applicant submits response to preliminary decision
Informal letter or official decision to CH applicant
Change history Version Change sig
4.0 Editorial changes, Orbis Type A and fast-track Type B processes clarified fg, cuf, ate
3.1 New layout, no content adjustments to the previous version. dei
3.0 Clarification in section 6.2: Notification of the Information Request directly to the applicant rim, ru, in Switzerland wph, fg
2.0 Section 2: Israel new partner authority in Project Orbis rim, ru, dts
Linguistic clarifications New Annex 1 with flow chart 1.0 New document rim, ru, wph, dts