HD-Guidance document Formal requirements

Transcription

1 List of contents 1 Prologue Terms, definitions, abbreviations Abbreviations Definitions Description of the requirements Symbols used and their meaning Purpose of this guidance document Scope Legal basis Structuring of the requirements General requirements Submission formats Time limits Signatures / Signatory authority onfirmation of reception Module 1 / Part I over letter Forms Medicinal product information Packaging elements urriculum vitae of the experts Documentation of Environmental Risk Assessment Decisions by foreign authorities PVP / RMP / Pharmacovigilance planning documents (human medicinal products only) PIP / PDP / Documentation for the paediatric investigation plan (human medicinal products only) Information on the bioequivalence trial / reference product GMP/ertificates/Establishment licences Manufacturing information: flow chart for vaccines and blood products Evidence that the obligation to notify pursuant of the Nagoya Ordinance is satisfied Information on combination products (medicinal products with a medical device component) Modules List of contents and labelling of binders References Answers to communications from Swissmedic during the ongoing application process VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

2 3 Special requirements Scientific Advice meeting Pre-Submission meeting larification meeting Recognition of important medicinal product status Recognition of orphan drug status (ODS) (human medicinal products only) MUMS status (veterinary medicines) Request for fast-track procedure (human medicinal products only) Request for procedure with prior notification (human medicinal products only) New applications, new APIs and major variations New applications, known APIs Similar biological medicinal products (biosimilars) human medicinal products only Applications under Article 13, TPA o-marketing Variations requiring notification Variations requiring approval with scientific assessment Variations requiring approval without scientific assessment onditions imposed by Quality Review, Preclinical Review and linical Review Notification procedure for sample packs Extension, no extension, no marketing and interruption to distribution Extension and no extension Discontinuation of authorised products Discontinuation of dosage strength number Notification in accordance with Art. 8a, VAM: No marketing / interruption to marketing and Placing on the market / Renewed placing on the market omplementary medicinal product: Reduced dossiers omplementary medicinal product: notification procedure HOMANT Asian medicinal products Authorisation / variations, veterinary medicinal products by the notification procedure in accordance with Art. 39, VAZV / Arts , VAM Market monitoring PSUR/PBRER Advertising permission DMF/ASMF and Plasma Master Files DMF/ASMF Plasma Master Files (Human medicinal products only) Special product types and the corresponding submission Radiopharmaceuticals Allergen products VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

3 Antidotes Medicinal gases Antivenins Parallel import Traditional herbal medicinal products hange history Version Valid and binding as of: Modified without version change Description, comments (by author) Author s initials More detailed instructions in section packaging fi elements More detailed instructions in hapter A on marking nma, stb changes and 2.5.8, PVP/RMP/pharmacovigilance planning documents. More detailed instructions in hapter A following update to Guidance Document Authorisation Biosimilar Additional information on the medicinal product information (information for healthcare professionals and patient information) working documents and packaging elements in sections and Requirement to provide information for healthcare professionals on medicinal gases added to section nma larification of Section 2.1, table Summary of submission formats wja The formal requirements for omplementary medicinal product have been updated. New chapter ; Information on combination products (medicinal products with a medical device component) Owing to the launch of the esubmissions platform, which facilitates exclusively electronic document exchange and electronic handling of authorisation and variation requests for the applicant, corresponding changes have been made. Section A : Inclusion of requirement to send a covering letter to accompany replies. In order to standardise document names, the published "Administrative Ordinances" (VV) are being replaced by "Guidance documents" (WL). The function and effects of the document are not changed as a result of the name change Section A : Based on the new guidance document on the co-marketing of medicinal products, the Guidance document will also be corrected. Section under A and A : for marking/highlighting changes in manuscripts of medicinal product information (information for healthcare professionals and for patients) adapted. hanges in medicinal product information now only accepted if inserted using Word s Track hanges function. Section 3.12 and 3.13: New rules for the joint submission of variations requiring notification and variations requiring approval (what are known as mixed applications ). rin wph, jec, na pfc lac cis vy wph VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

4 Section A : larification of requirements Section A : Deletion of duplicated table Section onfirmation of GMP compliance deleted (duplication to section ) As a result of the complete revision of the form Manufacturer information, the requirement in section A on the subdivision of "Basic form, Part A or Part B" has been deleted. Section A : Adaptation following the introduction of a template for RP Declaration for foreign manufacturer. Simplified submission of GMP certificates. Section : Extension of time limit for submitting Drug Master Files and Active Substance Master Files before submitting application Addition to section 2.1: Tables on document exchange via the Swissmedic Portal inserted. Duplications deleted from section A and section A Section 2.1, "Submission formats" table: linguistic clarification regarding submission of working documents. Sections and 2.5.4: requirements brought into line with "Submission formats" table in section 2.1. New chapter : Evidence that the obligation to notify pursuant of the Nagoya Ordinance is satisfied Explanation in chapter 3.23: Swissmedic must receive the Drug Master Files (DMF) and Active Substance Master Files (ASMF) no earlier than seven calendar days before and no later than three calendar days after it has received the application for first authorisation or a variation. Explanation of amendment to change of practice with regard to processing packaging elements. hapter A : Reference to biosimilar deleted because no environmental risk assessment need be submitted for a biosimilar. Modifications after evaluation of the pilot phase, including shortening of the notification period, option to change from an application for a fast-track authorisation procedure to a procedure with prior notification (PPN) and option for earlier preliminary correction of relevant sections in the Information for healthcare professionals. There is no need to supply an additional hard copy of entirely paper-based submissions. Amendment to change of practice with regard to processing packaging elements. Time limit for submitting Drug Master Files and Active Substance Master Files shortened Section : Modification Number of copies to be sent modified: 1 copy instead of 5 copies and explanatory statement of Submission formats added cis cis gme fi dts dts dts / stb cis VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

5 Section 2.1 "Summary of submission formats" table adapted in respect of the "Bioequivalence trials" form and the number of copies of draft information for healthcare professionals/patient information texts Section 2.1 New note stating that published documentation cited in paper-based applications can be submitted exclusively by electronic means Section A Note stating the "Bioequivalence trials" form no longer needs to be submitted as a Word document Section A Requirement extended ("forms" replaced by "documents") Section A Additional information for applications for parallel import supplemented and consecutive numbering of the subsections corrected Section A If no submission / authorisation for the relevant preparation exists in other countries, there is no need to submit the "Status abroad" form Section onsecutive numbering of subsections corrected Section 3.1 Scientific Advice meeting / Section 3.2 Pre- Submission meeting: Specify the address of the requesting company and the procedure with prior notification has been deleted. hapter A Explanatory statement that, for applications under Art. 13 TPA, the Assessment Report of the Restricted Part, the LoQ and the company's answers to the Restricted Part must be submitted by the DMF holder. Section 3.12 end / Section 3.13 end: The documentation for collective applications in paper format does not need to be submitted separately for each authorisation, but only once (original/copy). New section : Additional specific requirements added for section A Applications for parallel import. Section A : In the event of approval, no official decision is sent for variations requiring notification. Variations can be implemented unless the applicant receives information to the contrary within 30 days of the date of receipt by Swissmedic (cf. Art. 11, para. 2 VAM). Greater detail provided on the submission of notifications no in accordance with Annex 8, section 2 para.1 numbers AMZV. Section A : The reference to the form ZL000_00_009e_FO_Human_blood_components has been deleted spb dts abe 1 Prologue 1.1 Terms, definitions, abbreviations Abbreviations ASMF DS DS EP HM L TD DMF DMF/ASMF Holder edok Active Substance Master File Introduction ompany ore Data Sheet ore Data Sheet ertificate of Product omplementary and herbal medicines hecklist ommon Technical Document: format for authorisation applications, divided into Modules Module 1-5 Drug Master File Holder of the Drug Master File / Active Substance Master File (active pharmaceutical ingredient manufacturer) Swissmedic application submission format, paper version + electronic version (see Swissmedic website) VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

6 etd Fast-track GMO HP info. HP IH Known API LoA LoQ MUMS NA New API NTA ODS PBRER PDP Patient info. PIP PMF PSUR/PBRER PVP RD RP RMP SAP number SmP Definitions Data carrier Binder Loose-leaf binder Dividers over sheets Description of the requirements electronic ommon Technical Document Fast-track authorisation procedure genetically modified organisms Product information for healthcare professionals Healthcare Professional ommunication International onference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Known active pharmaceutical ingredient Letter of Access List of Questions Minor Use and Minor Species New application New active pharmaceutical ingredient Notice to Applicants, format for authorisation applications, divided into Parts I-IV Orphan Drug Status Periodic Benefit-Risk Evaluation Report Pediatric Development Plan, FDA Product information for patients Paediatric Investigation Plan, EMA Plasma Master File Periodic Safety Update Report/Periodic Benefit Risk Evaluation Report Pharmacovigilance Plan Reference document Responsible Person Risk Management Plan Identification number in the Swissmedic's AP business case application, e.g. for medicinal products, applications, products Summary of Product haracteristics D, DVD, blu-ray disc A4 rigid ring binder with two sets of holes, 50mm or 80mm spine Plastic folder for hole-punched documents, A4, two sets of holes Set of dividers with light cardboard or plastic tabs The cover sheets made available online by Swissmedic, with the titles and the bar codes for separating the individual sections within the authorisation documentation, Modules 1-5 (TD) and Parts I-IV (NTA) respectively. The requirements are described in tabular form, and are numbered. Only those items defined as requirements are relevant for the formal control. All of the other text passages are explanations only. Format used for the description of the requirements: A Description of the subject Explanation of the requirement =compulsory O=optional (=subject to objections ) Descriptions of special cases and requirements VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

7 1.1.4 Symbols used and their meaning This symbol means "Please note!" Information marked with this symbol is explanatory and provides additional information. This symbol means: "Example / Summary". Examples and summaries are intended to help clarify the requirements, and serve as additional information. 1.2 Purpose of this guidance document This document is to provide guidance and is intended for administrative entities: it does not therefore address the rights and duties of individuals. The guidance above all serves to assist Swissmedic in applying the legal provisions uniformly and equitably. The publication of this document demonstrates transparency regarding how applications should be structured so that they can be handled efficiently and completed in accordance with Swissmedic's practices and system. The guidance document comes into force on 19 May The previously valid guidance documents will be adjusted by Swissmedic before the end of This document also takes into account all publications on this subject in the Swissmedic Journal in recent years. In the case of divergences between the formal requirements specified in previous documents and those specified in the present guidance document, the present document takes precedence. 1.3 Scope The guidance document applies to all submissions to Swissmedic. It does not, however apply to: Requirements related to the content of applications Medical device Market monitoring cases Legal cases Inspections ertificates linical trials Notifications for narcotics Submission of laboratory orders 1.4 Legal basis This guidance document is aligned with the following legislation in particular (provisions of Federal Acts and Ordinances): Federal Act of 15 December 2000 on medicinal products and medical devices (Therapeutic Products Act, TPA; SR 812.2) Ordinance of the Swiss Agency for Therapeutic Products of 9 November 2001 on the requirements for the authorisation of medicinal products (Medicinal products authorisation ordinance, AMZV; SR ) Ordinance of 17 October 2001 on medicinal products (Medicinal products ordinance, VAM; SR ) Ordinance of the Swiss Agency for Therapeutic Products of 22 June 2006 on the simplified authorisation of medicinal products and the authorisation of medicinal products by the authorisation procedure (VAZV; SR ) Ordinance on the fees charged by the Swiss Agency for Therapeutic Products (Ordinance on Fees for Therapeutic Products, HGebV; SR ) VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

8 1.5 Structuring of the requirements The requirements stated in this guidance document and those in the table Documents to be submitted (separate document) are valid with regard to the submission of applications. The forms and information sheets mentioned under the requirements do not all exist in English, which is not an official language of the onfederation. VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

9 2 General requirements 2.1 Submission formats A Paper submission in TD format There are two options: Entirely paper-based submission: - Module 1-5: One original as hard The individual sections of Modules 2-5 of the paper original must be marked by dividers/tabs. In addition, the paper original must be subdivided using the cover sheets provided electronically by Swissmedic. In addition, the information for healthcare professionals / patients / veterinary medicinal product information / packaging elements must be submitted electronically on a data carrier. Paper submission with edok copy: One paper original for Modules 1-5 plus an identical electronic copy on a data carrier The individual sections must be submitted as an edok copy on the data carrier in accordance with the instructions (see Guidance edok) The paper original (with the modules submitted separately) must not contain dividers or cover sheets. In addition, the information for healthcare professionals / patients / veterinary medicinal product information / packaging elements must be submitted on a data carrier. A Paper submissions in NTA format There are two options: Entirely paper-based submission: One original as hard The individual sections of the paper original (Parts Ic-IV) must be marked by dividers/tabs. In addition, the paper original must be subdivided using the cover sheets provided electronically by Swissmedic. In addition, the information for healthcare professionals / patients / veterinary medicinal product information / packaging elements must be submitted electronically on a data carrier. Paper submission with edok copy: One paper original for Parts I-IV plus an identical electronic copy on a data carrier. The individual sections must be submitted as an edok copy on the data carrier in accordance with the instructions (see Guidance edok) The paper original (with the modules submitted separately) must not contain dividers or cover sheets. In addition, the information for healthcare professionals / patients / veterinary medicinal product information / packaging elements must be submitted electronically on a data carrier. VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

10 A Binding of the Paper documents for Modules 1-5 or Parts I-IV paper documents respectively) must be submitted in binders or folders, by module A Prioritisation sheet A prioritisation sheet must be placed on top of each dispatch, and provide information on the submission format and type of transmission. Swissmedic will provide the priorisation sheet electronically. The priorisation sheet is not part of the submission (it does not have to be incorporated into the etd or the edok). A over sheets Swissmedic provides cover sheets with the section titles and barcodes for separating the individual sections of paper submissions in the TD or NTA structure (these cover sheets are available for download on the Swissmedic website) These cover sheets must be printed out by the applicant and placed in the authorisation documents, always in front of the corresponding section All of the sections must also be separated by dividers The priorisation sheet is not part of the submission (it does not have to be incorporated into the etd or the edok). A Numbering system TD / NTA The official structure (TD, NTA) for the numbering of the individual sections must remain unchanged A etd The special requirements for an etd submission are published on the Swissmedic website The following documents should be taken into consideration: Guidance for industry on providing regulatory information in etd Format Questions and answers by Swissmedic on etd implementation Swiss Module 1 Specification for etd Swiss etd validation criteria Guidance on applications according to paragraph 13, TPA for etd applications A Additional Word documents ompanies that do not work with the Swissmedic Portal must submit Word versions of the information for healthcare professionals and patient or the information for veterinarians on an electronic data carrier. The cover sheets are not required for the submission of an edok copy. Requirements other than those stated in this guidance document with regard to the forms required (depending on application type) can be found in the table Documents to be submitted. For further details on the requirements relating to content, please see the other applicable instructions and documents on the Swissmedic website. Entirely paper-based submissions: Staples must not be used for entirely paper-based submissions. Staples may also be used for paper documents submitted with etd or edok. No transparent folders may be used. When using the cover sheets, please note: VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

11 Paper applications, submission of publications: In connection with the submission of documentation, the reference documents do not need to be submitted in paper form if they are publicly available, free of charge, at all times. In this case electronic submission of the published data alone is sufficient. The applicant should clearly state what references can be found on the D and specify the corresponding versions and dates. VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

12 Summary of submission formats egov Portal etd Paper Paper original with edok copy Entirely paper-based submission: over letter, forms, etc. of each copy 1 copy 1 copy Module 1 / Parts Ia/Ib in paper form Draft healthcare professional / patient information / veterinary product information copy 1 copy Packaging elements (mock up) copy 1 copy staples --- permitted permitted Not permitted Paper documentation (Modules 2-5 / Parts 1c to IV ) Electronic documentation on D/DVD (Modules 1-5 / Parts I to IV) Electronic documentation by egov Portal (Modules 1-5 / Parts I to IV) copy 1 copy copy 1 copy - 1 copy over sheets (Modules 1-5 / Parts I to IV ) Dividers (Modules 2-5 / Parts 1c to IV ) cover sheet per section 1 set of dividers per section Additional word documents Packaging elements (mock up) (also accepted in PDF) and / or healthcare professional / patient information / veterinary product information ontained in the electronic submission. on etd data carrier On data carrier with electronic documentation on data carrier Prioritisation cover sheet copy 1 copy 1 copy VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

13 2.2 Time limits A General The time limits stated in the Guidance document Time limits for authorisation applications and the Directory of time limits for authorisation applications (see Swissmedic website) A Time limits for resolving shortcomings regarding formal requirements In the case of objections on the part of Swissmedic, a target date by which the applicant should resolve the shortcoming is set. This time limit is communicated to applicants in writing A Extended time limit to resolve shortcomings regarding formal requirements 2.3 Signatures / Signatory authority The applicant may request an extension of the time limit O In the case of objections regarding formal requirements for an application for first authorisation, the time limit of 120 days cannot be extended 1 A Signatory authorised to commit the firm Applicants may delegate third parties to submit applications for authorisation and variations. In such cases, the corresponding power of attorney must be provided when the application is submitted A Signatures over letters, forms and other documents requiring an original signature must be submitted in paper form, with the original signature (except in the case of portal users). A A Signatures for DMF/ASMF applications Eligible authorised signatory The documentation required for a DMF/ASMF (Form Part B and Letter of Access) must bear the original signature of the DMF/ASMF holder for each new application. It is not mandatory for the signature to be that of the responsible person or of a person authorised to sign in accordance with the list of sectorial responsibilities. It may also be that of a person duly authorised by the applicant to sign documents for the corresponding operation. Swissmedic does not accept scanned, electronic or printed out signatures. 1 Article 3, para. 1, Medicinal Products Ordinance, VAM VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

14 2.4 onfirmation of reception A onfirmation of reception Swissmedic does not send confirmations of receptions by post Swissmedic sends confirmations of reception by post for variations requiring notification, for job applications and for licence applications. The authorisation holders may consult the application status online on the Swissmedic Portal. For details of the Portal, see the Swissmedic website and the Guidance for the Swissmedic Portal. 2.5 Module 1 / Part I A Packaging Module 1 (TD)/ Part I (NTA) Module 1 (TD) / Part I (NTA) must be placed at the top of a packet or on a pallet. The corresponding container must be clearly marked with "Module 1" or "Part 1" on the outside over letter A Original signature The cover letter must be submitted on paper, with an original signature (except in the case of portal users). A Documents not If certain documents required are not submitted, this submitted must be stated in the cover letter or in the hecklist, Formal ontrol, with the reason for the omission A General aspects Product name plus appropriate details if other product designations are used (e.g. other product names, chemical name, development code no.) Name of the active pharmaceutical ingredient If known: AT / IT group, or AT vet group If known: Authorisation number If known: Application ID Application type (for applications for variation, including the type of variation) and short scientific justification If no hecklist, Formal ontrol is included: List of all administrative documents and other documentation submitted (for each Module/Part, with number of binders) A A A Additional information for new applications for new / known APIs and major variations Additional information for similar biological medicinal products (Biosimilars) Additional information for Short presentation of the clinical trials conducted and if applicable, of the pharmaceutical characteristics and the manufacturing For known APIs with bioequivalence trials: state the foreign comparator product Justification for requesting an authorisation process in accordance with the Guidance document Authorisation Biosimilar Short presentation of the clinical trials conducted and if applicable, of the pharmaceutical characteristics and the manufacturing processes State where the comparability studies between the biosimilar and the comparator product can be found in the documentation Justification of the divergence if the dosage form, dosage strength and / or the excipients of the biosimilar are different from those for the reference product omment if specific requirements are foreseen for implementing the spontaneous recording of VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

15 applications under suspected adverse drug reactions in Switzerland Article 13, TPA (e.g. special questionnaires within the framework A A A A A A A A Additional information for fast-track requests (human medicines only) Additional information for requests for procedure with prior notification (human medicines only) Additional information for Scientific Advice and Pre-submission Meetings Additional information for larification Meeting Additional information for out of stock situations Additional information for comarketing application Additional information for applications for parallel import Additional information for radiopharmaceuticals of enhanced pharmacovigilance) Mention authorisation applications or any questions or decisions on the part of other authorities, if applicable Short justification for the request, indicating the documentation Possible date for the Pre-submission Meeting or reason why this is not considered necessary Planned submission date for the test etd sequence (if applicable) Planned date of the actual submission of the application (state within a time frame of +/- 2 calendar weeks) Draft agenda with the points to be discussed Proposed form of the meeting: in person, by telephone or video conference Proposal for various possible dates (within a time frame of 4-8 weeks following reception of the request for a Pre-Submission Meeting) Draft agenda with the points to be discussed Proposed form of the meeting: in person, by telephone or video conference Proposal for various possible dates (within a time frame of 4-8 weeks following reception of the request for a larification Meeting) Presentation of the problems regarding answers to the List of Questions, plus presentation of the outcomes the applicants wish to achieve (on 2 4 pages) Pharmaceutical form, authorisation holder Information on the medicinal product to be imported (foreign authorisation number, product name, pharmaceutical form, authorisation holder Name and address of the firm in the country of export from which the medicinal product to be imported will be obtained Name and address of the repackaging company ontact details for responsible person for authorisation holder 24-hour emergency number Name and authorisation of the basic preparation and any admissible differences compared to the basic preparation Information on the medicinal product to be imported: name and authorisation number of the medicinal product Information on the Swiss originator / reference product (product name, pharmaceutical form and authorisation number) Name and address of the company in the country of export from which the medicinal product will be obtained Name and address of the repackaging company Responsible person who can be contacted in the event of quality problems (name, address, telephone and fax numbers, address, 24- hour contact phone number). Name of the active pharmaceutical ingredient or the radionuclide (if possible, use the INN) Area(s) of use in diagnostics and / or treatment. For kits, the marker nuclide must also be stated Dosage form(s) VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

16 A Additional information for the simplified authorisation of medicinal gases See Guidance document Authorisation medicinal gas, (available in French and German) A A Forms Additional information for changes to the product information requiring approval Additional information for NA for a traditional herbal medicine Version on which the text submitted is based (i.e. the latest version approved by Swissmedic) For changes to the texts and corrections in an ongoing procedure (e.g. answer to preliminary decision or answer to the text correction communication), confirmation that all changes are clearly marked as such. For safety-relevant changes: In the subject line: "Safety-relevant change to the product information" Discussion regarding enhanced measures (e.g. HP) State the justification for the safety relevance in the text If the safety-relevant changes are in connection with a national or international safety signal, mention this in the cover letter Brief description of the proof of traditional use Information on the directly comparable herbal medicine A Form Application for authorisation / variation Use the corresponding form depending on whether the application is for human or veterinary medicinal products The original of the form Application for authorisation / variation must be submitted for each authorisation number and for each application type Only one application type box may be checked Dosage strength number: state the various dosage strengths Under "Additional documents", the attachments that can be submitted for the application are listed: check the appropriate box to show whether or not A A A Form Application for authorisation / variation for collective applications Form Full declaration Form Manufacturer information they are submitted ("yes" or no") omplete once per authorisation number, original copy Section "Authorisation number". State one of the authorisation numbers concerned by the collective application per form Section "ollective application": state all of the authorisation numbers concerned by the collective application on each form The complete qualitative and quantitative composition of the medicinal products must be stated For herbal medicinal products, the information on declaring extracts in the Information Sheet Extract declaration, herbal medicinal products should be taken into consideration Information on the various manufacturers For medicinal products with herbal active pharmaceutical ingredients, the special requirements in accordance with the Information Sheet Details required regarding manufacturers of herbal active substances must be met For homeopathic and anthroposophic medicinal products without indication, with reduced dossier, VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

17 the requirements stated in the Information Sheet Simplification of the information to be provided on the manufacturer information form for the authorisation of homeopathic and anthroposophic medicinal products without indication, with reduced dossier (available in German and French) must be taken into consideration A A A A A Form Status of authorisation applications abroad Form Substances of animal and human origin Form Pharmaceutical information: product information, parenteral preparations (human medicinal products only) Form Site Master File for foreign manufacturing sites Form Declaration of radiopharmaceutic als If the status changes during an ongoing application, Swissmedic must be notified accordingly by means of a newly completed form. This can take place in conjunction with the answer to the List of Questions or the answer to the preliminary decision If a product contains no substances of animal or human origin, the "no" box for the corresponding question must be checked in the form Application for authorisation / variation In this case, it is not necessary to submit the form Substances of animal and human origin This form must be submitted for all first authorisations of parenterals and any variations to parenterals Only vaccines and blood products The form must be submitted for all applications for radiopharmaceuticals for which a full declaration is also submitted If no submission / authorisation for the relevant preparation exists in other countries, there is no need to submit the "Status abroad" form. The non-submission should be justified in the cover letter. Form Application for authorisation / variation for collective applications: A collective application for authorisation numbers x, y and z. a) Form for authorisation number x: Under "authorisation number", enter authorisation number x in the upper part. Enter all of the authorisation numbers concerned (x, y and z) in the section "ollective application". b) Form for authorisation number y: Under "Authorisation number," enter authorisation number y in the upper part. Enter all of the authorisation numbers concerned (x, y and z) in the section "ollective application". c) Form for authorisation number z: Under "Authorisation number" enter authorisation number z in the upper part. Enter all of the authorisation numbers concerned (x, y and z) in the section "ollective application". The form Manufacturer information may only be submitted for application types that require this form to be processed. If the form is submitted for other application types, Swissmedic will neither check it nor approve it. The currently valid versions of the forms are available on the Swissmedic website for download. Only these versions must be used for the application to be submitted. If forms are submitted that are no longer valid, Swissmedic will issue a formal objection after the corresponding transitional period stated expires. Old versions of forms are usually valid for 3 months following the entry into force of newer versions. VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

18 If so required, the forms must be signed. Unsigned forms (e.g. the form onfirmation of substances from GMOs) are not accepted Medicinal product information Mandatory submission A Submission is Information for both Patient information is not required for mandatory for Dosage forms in accordance with Art. 14, para. 2, healthcare dispensing AMZV that are exclusively administered by doctors categories A and B professionals and or dentists (e.g. products for injection or infusion). (human medicinal products only) patients is required For these products, the information for healthcare professionals is inserted in the packaging; Veterinary medicinal products No medicinal product information is required for homeopathic and anthroposophic medicinal products without indication, for individual treatment, in accordance with Art. 17, para. 1 and Art. 19 et. seq., KPAV No information for healthcare professionals is required for homeopathic and anthroposophic medicinal products in accordance with Art. 16, Art.17 and Art. 19 et. seq., KPAV or for Asian medicinal products without indication for individual treatment in accordance with A Submission is mandatory for products of dispensing categories and D (human medicinal products only Information for both healthcare professionals and patients is required VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39 Art. 27 et. seq., KPAV Patient information is not required for Dosage forms in accordance with Art. 14, para. 2, AMZV that are exclusively administered by doctors or dentists (e.g. products for injection or infusion). For these products, the information for healthcare professionals is inserted in the container; Medicinal products for which the required information is placed on the container. Veterinary medicines No medicinal product information is required for homeopathic and anthroposophic medicinal products without indication, for individual treatment, in accordance with Art. 17, para. 1 and Art. 19 et. seq., KPAV On application, information for healthcare professionals need not be included for the following groups of medicinal products: Baby foods Bath additives and compresses (healing clay, poultices) Disinfectants Dietary supplements Intimate hygiene products Products for sensitive skin Tear substitutes Nasal products (with secretolytic and moistening effect) laxatives (only bulking and filling agents) Vitamin products (only those with water-soluble vitamins) Dental products (products for the gingiva and the other oral mucosa, products with fluoride, products to prevent tooth decay, tooth surface and to desensitise the dentine) Homeopathic and anthroposophic medicinal products in accordance with Art. 16, KPAV Asian medicinal products in accordance with Art. 25, KPAV No information for healthcare professionals is required for:

19 Homeopathic and anthroposophic medicinal products in accordance Arts. 16 and 17 and Art. 19 et. seq., KPAV or for Asian medicinal products without indication, for individual treatment in accordance with Art. 27 et. seq. KPAV Herbal medicinal products with the exception of laxatives containing anthrachinone and products containing St. John's wort A A Requirements Submission is mandatory for products of dispensing category E (human medicinal products only Veterinary product information Information for healthcare professionals or patients is not required Veterinary product information must be included for every veterinary medicinal product VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39 With the approval of Swissmedic, and if all the required information is placed on the container used for dispensing, product information is not required (Art. 15, paras. 1 and 2, AMZV). The requirements for the information and texts on containers and packaging material must comply with Art. 12, in connection with Annex 1, AMZV) A References in the medicinal product information A A Marking of changes Safety-relevant changes to the medicinal product information Statements made in the medicinal product information must be scientifically justified and proved. Suitable references are study reports, publications, or other scientific documentation For references to study reports, publications, other scientific documentation, a summary or an overview, the corresponding page number must always be stated Example: Study xyz, binder 3, page 736. Or Binder 2, Reference 38: Müller et al, title etc., page 13 Reference to the firm's internal ore Data Sheet (DS) of the ompany DS (DS) or the Summary of Product haracteristics (SmP) is not permitted, since these are not scientific references All changes compared to the last approved version must be clearly marked as such The marking must be shown in the manuscripts throughout the entire application process. hanges must be marked/highlighted using Word s Track hanges function. No other forms of marking/highlighting will be accepted. All changes to pending applications must be inserted, clearly marked as such in a different colour and identified by the application ID. If an application for a variation contains changes to texts that take place during several rounds of text corrections, and if the text has not yet been approved, confirm that the corrections suggested by Swissmedic in the previous version have been made. orrections by Swissmedic that have not yet been agreed upon must be clearly marked as corrections made to the text by Swissmedic, e.g. by inserting a comment. The application requires either a Health Professional ommunication (HP) or a justification for not submitting an HP Within the framework of an application for safetyrelevant changes, no further changes to the last approved text may be made in addition to the Veterinary medicinal products: Reference to EU-SmP is possible in exceptional cases Veterinary medicinal products: As of the answer to the preliminary decision, only those changes that do not correspond to the proposed corrections by Swissmedic must be marked. Veterinary medicinal products: Only changes concerning serious and life-threatening reactions or irreversible

20 justified, safety-related changes. Other changes must be applied for separately The content of safety-relevant changes mainly concerns new, more restrictive statements in the sections "Dosage / use", "ontraindications", "Warnings and precautionary measures", "Pregnancy / breast feeding" and "adverse reactions" If the patient information is also concerned, the corresponding changes must be submitted at the same time as those concerning the information for healthcare professionals A Information for healthcare professionals from other countries, EU-SmP For EU-SmPs: submit the last version approved in the EU, stating the date on which the approval was granted For products or changes that have not yet been approved: the applicant's proposals for the SmP in the EU must be clearly marked as the applicant's draft O damage are considered to be safety-relevant A A omposition of the medicinal product information for medicinal products with known active pharmaceutical ingredients (without innovation) and biosimilars Handling of information for healthcare professionals and patient information It must be confirmed that the medicinal product information corresponds to the currently published texts of the information for healthcare professionals and for patients for the originator product (name of the originator product), product information version dated (month / year) and that only the following authorised differences or deletions (state only as applicable) compared with the originator product have been made and are marked accordingly in the medicinal product information. Format and number of copies to be submitted in accordance with the Summary of submission formats table in section 2.1. M Paper copies are not required when making a submission in etd format. Swissmedic Portal users do not have to submit information for healthcare professionals and patient information on an additional electronic data carrier. Uploading as a working document is still mandatory, however. For medicinal products that are authorised exclusively for export, a manuscript for the basic information is checked and approved. Depending on the requirements (according to dispensing category), this basic information can be for healthcare professionals or patients, or can be information on the outer packaging Packaging elements Submission methods for packaging elements (folding boxes, labels, sachets, etc.) The format and number of copies to be submitted are as specified in the "Submission formats" table in section 2.1. olour laser printouts, in the original format, may be submitted instead of original prints of the No paper copies are required for submission in etd format. Swissmedic Portal users do not need to VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

21 packaging elements (folding boxes, labels, sachets, etc.) In addition, packaging elements must be submitted per medicinal product on a digital data carrier via the Swissmedic Portal as a single file with searchable text (OR). submit an additional electronic data carrier for the packaging elements. But it is still necessary to upload the working document urriculum vitae of the experts A urriculum vitae of the experts Required for: The overview (TD: Module 2.3, 2.4, 2.5)) Statement by an expert The original of the document is not required Documentation of Environmental Risk Assessment A Environmental Risk Assessment (ERA) Decisions by foreign authorities Human medicinal products: required for applications for new APIs and Biosimilars. If an ERA is not submitted, justification for the omission must be provided Veterinary medicinal products: An ERA (at least a Phase I assessment) is a part of every new authorisation For applications for major variations or known APIs, the submission of an ERA is only required if the impact on the environment is expected to increase For Art. 13 applications, an ERA is only required if the authorisation was granted in a non-eu country. If an ERA is not submitted, the omission must be justified. A All applications Assessment reports and decisions by foreign O authorities that are available should be submitted A Applications under Article 13, TPA Final assessments reports and decisions by foreign authorities must be submitted. For details, see Instructions: Authorisation of human medicinal products already authorised in foreign countries (Art. 13, TPA), and the hecklist, Formal ontrol, authorisation applications for human medicinal products, Art.13, TPA PVP / RMP / Pharmacovigilance planning documents (human medicinal products only) General aspects Documentation on pharmacovigilance planning should be submitted in accordance with IH E2E. This constitutes a Risk Management Plan (RMP) in accordance with EU directives or comparable documents. Swissmedic prefers that if an EU RMP is available, it should be submitted To be submitted: 1. First authorisations New active substances for synthetic human medicines and herbal human medicines Human medicines manufactured using biotechnology (including biosimilars) Human vaccines VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39

22 2. Applications that represent a major variation to the existing authorisation Paediatric indication/other significant variation to the authorisation New dosage recommendation New administration route / dosage form New manufacturing process (for substances manufactured by biotechnology) If so requested by Swissmedic: e.g. in the case of relevant safety problems The US REMS format (Risk Evaluation and Mitigation Strategy) is not accepted as implementation of the IH Guideline PIP / PDP / Documentation for the paediatric investigation plan (human medicinal products only) A PIP If a Paediatric Investigation Plan approved by the EMA is available, it must be submitted A PDP The FDA Pediatric Development Plan may be submitted O Information on the bioequivalence trial / reference product A Information on the bioequivalence trial (human medicinal products only) A A Information on the reference product (human medicinal products only) Veterinary medicinal products: Information on the bioequivalence trial and the reference product If the proof of the transferability of the test results for the reference product is based on pharmacokinetic bioequivalence trials, it is necessary to submit a fully completed Swissmedic Bioequivalence Trial Information Form) both as a printed version and as an electronic document A signed statement confirming that the test product used in the bioavailability trial is identical to the product submitted to Swissmedic for authorisation must be submitted Information required: Product name, name and address of the authorisation holder of the reference product, country of origin, authorisation number, batch number and expiry date of the packs used for the bioequivalence trial If the proof of the transferability of the test results for the reference product is based on pharmacokinetic bioequivalence trials, confirmation must be provided that the test product used in the bioavailability trial is identical to the product submitted to Swissmedic for authorisation Documents concerning the reference product must be submitted with Part 1 of the application documentation (product name, name and address of the authorisation holder of the reference product, country of authorisation, source country, authorisation number, batch number and expiry date of the packs used in the bioequivalence trial) GMP/ertificates/Establishment licences Alternative: orresponding information as described in Appendix IV of the Guideline on the Investigation on Bioequivalence (PMP/EWP/QWP/140 1/98 Rev.1) may be submitted in Module 1 A Proof of GMP For foreign manufacturer, to be submitted in compliance, accordance with: Information sheet: GMP VM-ID: ZL000_00_001e_WL / V18.0 / rin, lac, wph, jec, na, pfc, dts, tsj / sni / / 39