Guidance document Variations and extensions HAM
1 Definitions, terms, abbreviations
1.1 Definitions and terms
1.1.1 Minor variations to be reported subsequently, type IA/IAIN
These are minor variations which only have minimal consequences for quality, safety or efficacy. They must be reported to Swissmedic in writing by the marketing authorisation holder (MAH) after they have been implemented (Do and Tell). These are known as type IA/IAIN variations. The legal framework is provided by Art. 21 TPO. Type IA variations must be reported to Swissmedic within twelve months of their implementation. Type IAIN variations (IN stands for Immediate Notification) must be reported to Swissmedic immediately after they have been implemented.
1.1.2 Minor variations to be reported in advance, type IB
These are minor variations which are neither a minor variation of type IA/IAIN, nor a major variation of type II nor a marketing extension. These are known as type IB variations. The legal framework is provided by Art. 22 TPO. Type IB variations must be reported to Swissmedic in writing before they are implemented. If Swissmedic does not raise any objections within 60 days of receipt of a valid report and the complete documentation, the variation is considered to be approved from the first day after this period elapses. If Swissmedic does raise objections within this period, the marketing authorisation holder can submit documentation within 30 days to resolve the objections, or submit a modified report that takes account of Swissmedic's objections.
1.1.3 Major variations, type II
These are variations which may have significant implications for the quality, safety or efficacy of the medicinal product and which do not involve an extension. These are known as type II variations. The legal framework is provided by Art. 23 TPO. Type II variations must be approved by Swissmedic before they are implemented.
1.1.4 Extensions
Extensions are variations that have to be approved by Swissmedic in a new authorisation procedure before they are implemented. The legal framework is provided by Art. 24 TPO.
1.1.5 Collective application
Variations of types IA/IAIN, IB or II can be submitted jointly as a collective application, provided they involve the same variation for several medicinal products and the identical documentation is submitted for all the medicinal products concerned. For a collective application, a single Variations and extensions HMP form should be submitted. Extensions cannot be submitted as a collective application. Collective applications which also involve changes to the product information in sections 4 to 16 or the sections with the corresponding information in the patient information are permitted only if these involve collective texts. The legal framework is provided by Art. 22b TPLRO.
MAH
Medicinal product Variation IA (1)
Medicinal product Variation IA (1)
1.1.6 Collective text
A collective text applies when a marketing authorisation holder submits a collective product information text for several pharmaceutical forms of the same active substance or, if an information for healthcare professionals does not exist, a collective patient information. The legal framework is provided by Art. 22b, para. 4 TPLRO.
1.1.7 Multiple application
Differing variations of the same type (e.g. several extensions) or of differing types (IA, IB, II and extension) can be submitted jointly as a multiple application, provided all the variations involve the same medicinal product. Each variation box should be checked individually in the Variations and extensions HMP form. For a multiple application, a single Variations and extensions HMP form should
be submitted. The processing of all the variations submitted in a multiple application is based on the variation type in the multiple application with the longest time limit. All variations will be assessed and completed at the same time. Safety-related changes to the product information or patient information, and variation applications processed in the fast-track procedure (FTP), the procedure for temporary authorisation or the procedure with prior notification (PPN) cannot be part of multiple applications. The legal framework is provided by Art. 22c TPLRO.
MAH Variation IA (1)
Variation IA (2) Medicinal product Variation IB (1)
Variation II (1)
1.1.8 Collective-multiple application
This is a combination of a collective and a multiple application and exists, for example, if a marketing authorisation holder submits identical variations for two of its medicinal products. In such cases, the requirements for collective and multiple applications stated above remain unchanged.
MAH Variation IA (1)
Variation IA (2) Medicinal product
1 Variation IB (1)
Variation II (1)
Variation IA (1)
Variation IA (2) Medicinal product
2 Variation IB (1)
Variation II (1)
1.2 Abbreviations
AD Authorisation Document Auth.no. Authorisation number CD Calendar Day(s)
FeeO-Swissmedic Ordinance on the Fees charged by the Swiss Agency for Therapeutic Products of 14 September 2018 (SR 812.214.5) FTP Fast-Track authorisation Procedure IA Minor variation to be reported subsequently, reporting within a maximum of twelve months after implementation IAIN Minor variation to be reported subsequently, reporting immediately after implementation, IN stands for Immediate Notification IB Minor variation to be reported in advance II Major variation i.m. intramuscular INN International Nonproprietary Name i.v. intravenous KPTPO Ordinance of 7 September 2018 of the Swiss Agency for Therapeutic Products on the Simplified Licensing of Complementary and Phytotherapeutic Products (SR 812.212.24) MAH Marketing Authorisation Holder PMF Plasma Master File PPN Procedure with Prior Notification s.c. subcutaneous 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 and objective
This guidance document explains the requirements pertaining to variations and extensions for human medicinal products. Annex 7 TPLRO (List of variations as per Arts. 21–24 TPO) provides a list of all variations of types IA/IAIN, IB and II and the extensions that are relevant for Switzerland and for which Swissmedic is responsible. The annex is structured as follows:
E. Regulatory changes Q. Quality changes C. Safety, efficacy and pharmacovigilance changes X. Changes to Plasma Master Files (PMF) Y. Various changes relating to complementary and herbal medicines Z. Extensions The European variation numbers (e.g. Q.I.a.2) and the corresponding requirements have largely been taken over from the European Variation Guideline (Guidelines on the details of the various categories of variations, on the operation of the procedures laid down in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and on the documentation to be submitted pursuant to those procedures (C/2025/5045)) and adapted to the Swiss legislation and requirements.
The conditions to be fulfilled for the individual variations and the documentation to be submitted are listed. If, for the variations taken over from the European Variation Guideline, certain conditions and/or documentation requirements do not apply in Switzerland, these are shown as "not applicable in Switzerland" (see e.g. variation Q.II.b.2). Switzerland-specific variations start under E and C with 100 numbers (e.g. E.100 Change in the product information and/or packaging texts without the submission of scientific data). X and Y refer only to Switzerland-specific variations. As this is a guidance document aimed at administrative bodies, it does not directly specify the rights and obligations of private individuals. Swissmedic uses this guidance document first and foremost as a resource for applying the legal provisions on authorisation 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 Scope
This guidance document applies to the Authorisation, Licensing and Market Surveillance divisions of Swissmedic for applications for a change and/or extension relating to human medicinal products received by Swissmedic from the effective date of the revised Therapeutic Products Act (TPA).
4 Legal framework
Art. 21 to 25 TPO, Art. 22a to 22c and Annex 7 TPLRO and FeeO-Swissmedic (particularly Annex 1).
5 Requirements
Switzerland recognises the following application types, depending on the possible implications for quality, safety and efficacy:
Minor variations to be reported subsequently, type IA/IAIN
Minor variations to be reported in advance, type IB
Major variations, type II
Extensions The categorisation of the variations can be found in Annex 7 TPLRO (List of variations as per Articles 21–24 TPO). If a variation does not appear in the list, it can be submitted as an "Other change". An "Other change" is classed as a minor variation of type IB by default. If a more extensive variation is involved, both Swissmedic and the marketing authorisation holder can upgrade this to a variation of type II. The templates for “Other change” can be found under the individual variations (e.g. Q.I.a.1.z) and at the end of section E. Regulatory changes (E.z Other regulatory change), at the end of section Q. Quality changes (Q.I.z Other quality change to active ingredient, Q.II.z Other quality change to finished product, Q.z. Other quality change) or at the end of section C. Safety, efficacy and pharmacovigilance
changes (C.z Other change relating to safety, efficacy and pharmacovigilance) of the form Variations and extensions. When categorising an “Other change”, Swissmedic also takes account of the published list “CMDh Recommendation for classification of unforeseen variations according to Article 5 of Commission Regulation (EC) No 1234/2008”. An "Other change" can then be submitted as type IA or type IAIN only if it was also classified as such in the published CMDh list. The submission must reference the list "CMDh Recommendation for classification of unforeseen variations according to Article 5 of Commission Regulation (EC) No 1234/2008", the corresponding EU variation number and the "Date issued". As regards the distinction between extensions and type II variations, Volume 2C Regulatory Guideline “Guideline on the categorisation of extension applications (EA) versus Variations Applications (V), July 2019” is taken into account. Variations and extensions can lead to the issuing of new authorisation numbers, dosage strength numbers or packaging codes (see Chapter 9).
5.1 Formal requirements
The requirements stated in Annex 7 TPLRO, the form Variations and extensions HMP and Guidance document Formal requirements apply.
5.2 Requirements applicable to conditions to be fulfilled and documentation to be
submitted
5.2.1 Minor variations to be reported subsequently, type IA/IAIN
The applicable conditions must be fulfilled for type IA/IAIN variations, and the appropriate documentation must be submitted. By ticking the checkbox in the form Variations and extensions, the authorisation holder confirms that the conditions are fulfilled and that the documentation has been submitted. If one or more of the conditions are not met and the variation is not specifically listed as being of type II, a type IB variation should be submitted. For type IA/IAIN variations, the implementation date must be provided in the appropriate field in the form Variations and extensions1. This date must be in the past. If the time that has elapsed between the implementation date and the date the variation was submitted is more than 12 months (type IA) or more than one month (type IAIN), a type IB variation should be submitted.
5.2.2 Minor variations to be reported in advance, type IB
The appropriate documentation must be submitted for type IB variations. By ticking the checkbox in the form Variations and extensions, the authorisation holder confirms that the documentation has been submitted.
1 Exception: Not date is necessary if the type IA/IA
IN variation is part of a collective application that includes type IB or II variations or extensions.
5.2.3 Type II variations
For type II variations, it is usual not to define the documentation to be submitted, as the volume of such documentation can vary depending on the nature of the variation. There have, however, been some cases of type II variations where the documentation to be submitted has been defined (e.g. as for Q.I.e.1). Approval of certain type II variations – specifically indication extensions (C.6 Change to therapeutic indication(s)) and new dosage recommendations (see also C.101 Change in the product information and/or packaging texts due to new dosage recommendation data) – may be associated with a requirement to submit PSURs. Please see the guidance document Temporary authorisation for human medicinal products regarding the procedure for temporary authorisation.
5.2.4 Extensions
The new elements of extensions that are not currently approved in Switzerland must be documented in accordance with Art. 3, 4 and 5 TPLRO. Documentation submitted for a previously authorised medicinal product can be used as supporting material for the known elements. If an extension is being requested for a medicinal product, proof must be provided that the findings on preclinical and clinical efficacy, safety and tolerability that provided the basis for authorisation of the medicinal product can be transferred to the extension. The nature or extent of the proof required depends on the physical, chemical and pharmacological properties of the active substance, the dosage strength, pharmaceutical form and administration route. The authorisation holder must provide a summary evaluation and scientific substantiation of the proof of transferability it has chosen in the form of a statement in the Nonclinical and Clinical Overview. The cover letter should briefly explain that earlier data has been used for certain elements and point out the sections containing the substantiation of transferability. Approval of extensions may be associated with a requirement to submit PSURs. Please see the guidance document Temporary authorisation for human medicinal products regarding the procedure for temporary authorisation. The following information applies to CTD format.
5.2.4.1 Change in the active substance 1a), 1b), 1c), 1e), 1f)
Quality requirements:
Complete documentation: Section 2.3 + Module 3.
CEPs or DMFs are acceptable: reference should be made to them in section 3.2.S. Preclinical requirements:
Complete preclinical documentation: Sections 2.4, 2.6 and Module 4. Clinical requirements:
The documentation to be submitted depends on the type of variation.
5.2.4.2 Change in the active substance 1d)
Quality requirements:
Complete documentation: Section 2.3 + Module 3.
CEPs or DMFs are acceptable: reference should be made to them in section 3.2.S.
Applicants may also want to consult guideline EMEA/CHMP/BMWP/101695/2006 (comparability). Preclinical requirements:
Complete preclinical documentation: Sections 2.4, 2.6 and Module 4. Clinical requirements:
Complete clinical documentation: Sections 2.5, 2.7 and Module 5.
5.2.4.3 Change in bioavailability 2a)
Swissmedic recommends advance clarification of the formal requirements in a presubmission meeting.
5.2.4.4 Pharmacokinetic change 2b)
(e.g. change in release rate) Swissmedic recommends advance clarification of the formal requirements in a presubmission meeting.
5.2.4.5 Modification or addition of dosage strength 2c)
Quality requirements:
Complete section 3.2.P. GMP compliance requirements
Complete documentation according to document ZL000_00_036_WL GMP compliance by foreign manufacturers Preclinical requirements:
Safety-critical points should be listed in section 2.4 and a risk/benefit analysis for the new dosage strength should be prepared, taking special account of the safety margins. Clinical requirements:
Substantiation of the new dosage strength plus proof that it is appropriate and the clinical results obtained with the existing dosage strengths can be transferred to the new dosage strength.
If the new dosage strength is linked to a new dosage recommendation, see also the requirements for documentation on C.I.101 Change in the product information and/or packaging texts due to new dosage recommendation data.
5.2.4.6 Modification or addition of pharmaceutical form 2d)
Quality requirements:
Complete section 3.2.P. GMP compliance requirements:
Complete documentation according to document ZL000_00_036_WL GMP compliance by foreign manufacturers Preclinical requirements:
Experimental studies on formulation.
For topical medicinal products, care must be taken to ensure that the local tolerance (e.g. eye and skin irritation studies, investigation of the sensitising and phototoxic potential) and systemic exposure have been experimentally tested with the medicinal products submitted for authorisation. If there are indications that systemic exposure is significantly higher for the new pharmaceutical form, appropriate animal studies should be submitted. Clinical requirements:
Substantiation of the new pharmaceutical form plus proof that it is appropriate and the clinical results obtained with the existing pharmaceutical forms can be transferred to the new pharmaceutical form.
Bioequivalence studies comparing the new and existing pharmaceutical form (section 5.3.1.2)
If the new pharmaceutical form is not bioequivalent to the existing pharmaceutical form, complete pharmacokinetic data (section 5.3.3.1) must be submitted (possibly including a food-effect bioavailability study).
5.2.4.7 Modification or addition of administration route 2e)
Quality requirements:
If parts of the quality documentation change as a result of the new administration route, an updated section 3.2.P should be submitted, along with an index of changes and tabular comparison. Preclinical requirements:
Experimental studies on the new administration route (new studies with the new administration route or bridging studies).
For topical forms: experimental studies of the local tolerance (e.g. eye and skin irritation studies, investigation of the sensitising and phototoxic potential) of the medicinal product submitted for authorisation (final formulation). Clinical requirements:
Substantiation of the new administration route plus proof that it is appropriate and the clinical results obtained with the existing administration routes can be transferred to the new administration route.
Pharmacokinetic studies (sections 5.3.1 and 5.3.3), particularly bioavailability studies (sections 5.3.1.1 and 5.3.1.2).
If the pharmaceutical form has not changed (e.g. formerly subcutaneous, now to be intramuscular or vice versa, but same solution for injection) a pharmacokinetic bridging study may be adequate.
If the new administration route involves a new pharmaceutical form (or other variations such as a new dose, delayed release, etc.), safety and efficacy studies must be submitted (section 5.3.5).
6 Process
6.1 Time limits
The processing times stated in the Guidance document Time limits for authorisation applications apply, with the proviso described in Chapter 1.1.7 that all the variations submitted in a collective application will be subject to the time limit for the application with the longest time requirement.
6.2 Confirmation of receipt
The date of confirmation of receipt is considered to be the starting point for processing. An electronic confirmation of receipt (Acceptance of delivery) is generated for all applications successfully received via the Swissmedic portal. Non-portal users receive an acceptance of delivery for notifiable minor variations of types IA, IAIN and IB by post. No acceptance of delivery is sent for type II variations or extensions.
6.3 Minor variations to be reported subsequently, type IA/IAIN
The marketing authorisation holder can consider its report of an implemented variation to be accepted if Swissmedic does not send a message to the contrary by 30 CD at the latest after confirmed receipt of the report, or if the approval of the report is already visible in advance in the Swissmedic portal. The date and the decision can be viewed on the Swissmedic portal. In the event of an approval, no official decision is sent for type IA/IAIN variations. If the form or content of the report is the subject of a complaint, Swissmedic sends an interim official decision by 30 CD at the latest after the confirmed receipt of the report. Missing documentation must be submitted within the specified deadline, or the correct variation type must be submitted as a new application or new report. This deadline cannot be extended. If the correct variation type and/or documentation to be submitted are not received on deadline, Swissmedic will reject the application. The marketing authorisation holder can consider the corrected variation report to be accepted if Swissmedic does not send a message to the contrary by 30 CD at the latest after confirmed receipt of the corrected variation report, or if the approval of the report is already visible in advance in the Swissmedic portal. In the event of a rejection, a corresponding official decision will be sent and the variation must be cancelled. If product information and/or packaging texts have to be revised in connection with type IA/IAIN variations, these are merely acknowledged by Swissmedic and not returned to the marketing authorisation holder as approved by means of an official decision letter. The authorisation holder is responsible for always publishing the latest versions of these texts.
6.4 Minor variations to be reported in advance, type IB
The marketing authorisation holder can consider the report to be accepted and implement the variation if Swissmedic does not send a message to the contrary by 60 CD at the latest after receipt of
a valid report and the complete documentation (i.e. after a successful formal control2), or if the approval of the report is already visible in advance in the Swissmedic portal. The date and the decision can be viewed on the Swissmedic portal. In the event of an approval, no official decision is sent for variations of type IB, unless the approval is made subject to conditions (e.g. later submission of stability data) or a new packaging code is issued. A change relating to safety, efficacy and pharmacovigilance C.2 a) (type IB variation) for reporting the inclusion of a new indication, administration route, pharmaceutical form, dosage strength or dosage recommendation for the reference medicinal product/reference preparation in the product information of an essentially identical medicinal product as per Art. 12 TPA must not be submitted until at least one day after the document protection has expired for this indication, administration route, pharmaceutical form, dosage strength or dosage recommendation. If Swissmedic has an objection to the form of the report, it will send an interim official decision by 10 CD at the latest after the confirmed receipt of the report. Missing documentation must be submitted within 30 CD, or the correct variation type must be submitted as a new application. If the correct variation type and/or documentation to be submitted are not received within the specified deadline, Swissmedic will dismiss the application. If Swissmedic has an objection to the content of the report, it will send an interim official decision by
60 CD at the latest after the report has undergone a successful formal check. The missing
documentation must be submitted within 30 CD of the applicant receiving the interim decision. If the requested documentation is not received within the specified deadline, Swissmedic will reject the application. The deadline of 30 CD cannot be extended. The marketing authorisation holder can consider the corrected content of the variation report to be accepted if Swissmedic does not send a message to the contrary by 60 CD at the latest after confirmed receipt of the corrected variation report, or if the approval of the report is already visible in advance in the Swissmedic portal. In the event of rejection, a corresponding official decision will be sent. If product information and/or packaging texts have to be revised in connection with type IB variations, these are merely acknowledged by Swissmedic and not returned to the marketing authorisation holder as approved by means of an official decision letter. The marketing authorisation holder is responsible for always publishing the latest texts.
6.5 Type II variations and extensions
If an application passes the formal control, this is indicated in the portal as the milestone Formal control completed. Non-portal users can assume that the formal check was successful if Swissmedic has not sent them a message to the contrary by 30 CD at the latest after receipt of the application (date of postmark). Type II variations and extensions are always concluded with a corresponding official decision letter (approval, rejection or partial rejection).
2 Can be viewed on the Swissmedic portal by 10 CD at the latest after confirmed receipt of the report. Non-portal users can assume that the
formal control was successful if Swissmedic has not sent them an interim official decision by 10 CD at the latest after receipt of the interim official decision.
6.6 Handling of variations to Plasma Master Files (PMF)
For each PMF, the application is submitted for one or more PMF variations according to the highest category (type II, IB, IA/IAIN) according to the classification in the European Guideline under point "Q.V.a PMF / VAMF" or "M. PMF / VAMF" (Guidelines on the details of the various categories of variations, on the operation of the procedures laid down in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and on the documentation to be submitted pursuant to those procedures (C/2025/5045)). Submitting an annual PMF update is regarded as fulfilment of a condition of authorisation and not as an application for a variation. Annual Updates of the PMF can be submitted together with changes to the PMF as a multiple application (see section X. Changes to the PMF in the Variations and extensions form).
6.7 Implementation of variations and extensions
Before the report (variations of types IA and IAIN), after the end of the waiting period if Swissmedic has no objections (variations of type IB), or after approval (variations of type II and extensions), the variation of the medicinal product is considered to be approved. Under the Therapeutic Products Act, only the modified medicinal product can be marketed as of this point in time. Swissmedic grants a transitional period for implementation for variations and extensions:
Medicinal products that the authorisation holder had already supplied to wholesalers or retailers at the time the variation was approved may be sold in the form they were supplied.
For all other products, implementation must begin with production of the next batch or the next print-run of packaging elements, but at all events within one year following approval. Products already released for the market are exempted.
Excluded from this practice are safety-related variations for which, in line with its general practice to date, Swissmedic orders immediate implementation.
In specially applied for and sufficiently justified exceptional cases, Swissmedic can approve delayed implementation time limits for changes that have to be implemented simultaneously worldwide (Replacement Changes, in particular quality variations such as different active substance manufacturer, replacement method or column exchange). The marketing authorisation holder is responsible for always publishing the latest product information texts in the required languages.
7 Document protection
The requirements of the guidance document Document protection apply.
8 Fees
The fees stated in FeeO-Swissmedic apply.
9 Issuing of new authorisation and dosage strength numbers and
packaging codes
9.1 Issuing of a new authorisation number
A new authorisation number is issued for the following extensions or variations:
Characteristic features Examples Remarks (with no claim to completeness) Z1. New or additional Solution – tablets – - pharmaceutical form ointment. Z2. New composition: Change from bovine to Exception: Does not apply to the Annual human albumin. Update of seasonal influenza vaccines Z2.1 Change in the active Exception: Does not apply to minor substance, salt, ester chemical changes to the active substance molecule (e.g. switch from monohydrate to dihydrate), for which, by agreement with the specialist departments Quality Assessment and Clinical Assessment, bioequivalence does not need to be demonstrated. Z2.2 New formulation with Modified release: Slow the aim of modifying the Release, Extended pharmacokinetics Release, etc. Z2.3 Same medicinal product Cough preparations. with/without sugar Z2.4 Same medicinal product Eye drops, nose drops, with/without preservative anaesthetics. Z.2.5 Additional COVID-19 vaccine with modified active substance regarding a new SARS-CoV-2 variant, including the replacement or addition of a serotype, strain, antigen or coding sequence or a combination of serotypes, strains, antigens or coding sequences. Z3. New indication / new Parkinson's vs. restless This can be contrasted with a C.I.6, type II application – but same active legs syndrome. application (indication extension). substance and new name of the Erectile dysfunction vs. medicinal product pulmonary arterial hypertension.
Characteristic features Examples Remarks (with no claim to completeness) Z4. New additional primary Biotechnologicals/biological Reason: differing adsorption of the active container for parenterals or new s in the mg and μg scale, substances on the surface of the additional administration system. e.g. growth factors, immediate packaging, traceability 3 must Evaluation according to the interleukins, interferon be ensured. Standard Terms EDQM Contrast media in prefilled Considered as application for a new syringes, ampoules, etc. pharmaceutical form (new combined Immunoglobulins, insulin, pharmaceutical form, see Standard Terms vaccines, etc.: previously in EDQM) or type II variation, see note in vial, now additionally as section 5. prefilled syringe or No new auth. no. for a change in the form previously as prefilled of a primary container. syringe, now additionally as prefilled pen. Z5. Additional primary container Tube and newly additional If the first immediate packaging is with measuring device for semi- press dispenser. abandoned within 6 months, the same solid forms authorisation number can be retained. . Z6. Additional administration New medical device with system (inhaler) for inhaled additional "eFeatures" for products inhalation of the authorised medicinal product if combination packs with medicinal products and medical devices are to be authorised. Z7. Additional primary container Eye drops in multi-dose If the first immediate packaging is for ophthalmic products containers and, newly, eye abandoned within 6 months, the same drops in single-dose authorisation number can be retained. containers. Z8. Additional medicinal Parenteral dosage form Patient information required. preparation with new administration with new administration route for self-administration by route (e.g. s.c. instead of patients i.v.), which are now administered by the patients themselves (instead of by healthcare professionals as was formerly the case). Z9. Powder with/without solvent Case A Case A: Powder for solution for authorised: powder (without solvent), injection: new additional newly applied for: powder with solvent finished product powder
3 The traceability at the marketing authorisation holder is not identical to the traceability at Swissmedic (Swissmedic receives a signal and
must be able to state what medicinal product was involved in each case)
Characteristic features Examples Remarks (with no claim to completeness) and solvent for solution for → extension Z.2. d) (variation or injection extension of a pharmaceutical form) with new auth. no.
Case B: Case B: Powder and solvent for authorised:powder with solvent, solution for injection: new newly applied for: powder (without additional finished product solvent) powder for solution for → variation Q.II.z, type II with new auth. injection no.
Case C: Case C: Powder and solvent for If only the solvent is omitted from an solution for injection is authorised medicinal product, this changed to powder for constitutes a variation (Q.II.a.6) and does solution for injection not result in a new auth. no.
9.2 Issuing of a new dosage strength number
A new dosage strength number is issued for the following extensions or variations: This also always entails a modification of the packaging code:
Characteristic features Examples Remarks (with no claim to completeness) D1. New dosage strength for Tablets 5 mg and newly / solid and semi-solid forms additionally 10 mg Cream, e.g. 2% and newly 1% D2. New composition of Annual update: annual seasonal influenza vaccines modification of the virus strains based on the WHO recommendations. D3. Solutions D3.1 New concentration D3.2 New dosage strength for solutions for injection with the same concentration but differing volumes D3.3 New quantity of Also corresponds to D3.1 New active substance in powder concentration for dissolving D4. New / additional flavour D5. New / additional colouring agent
Characteristic features Examples Remarks (with no claim to completeness) D6. With / without fragrance Since fragrance is included in the declaration or composition, it is
9.3 Issuing of a new dosage packaging code
Characteristic features Examples Remarks (with no claim to completeness) P1. New or modified pack size 30 tablets + 100 tablets 30 g ointment + 100 g ointment P2. Primary container P2.1 Additional new primary Can + blister packBlister with For parenterals: see Z4. container repeat printing + perforated blister For semi-solid forms: see also Z5. with individual pocket lettering P2.2 Additional ampoule 40 mg in 25 ml ampoule + 40 mg Clarification in the information for size with unchanged quantity in 50 ml ampoule healthcare professionals in the of powder “Pack sizes” section (powder for solution for infusion in 25 ml ampoules). P2.3 New primary Only for infusions with e.g. glucose, containers for basic solutions NaCl, bicarbonate, glucosaline, etc. for infusion N.B.: new dosage strength number for new dosage strength / concentrations vs. various immediate packaging materials (bag, bottle, etc.). P3. Medicinal product given new If new marketing authorisation Exception: No new packaging code name by new or same marketing holder: INN-company A → INN- is issued if the addition “New authorisation holder company B formula”, “New formulation” etc., If same marketing authorisation which was added due to holder: INN-invented company A reformulation of the active → INN-invented company B substances for a period of at least 5 years, is removed. P4. New volume (identical For blood products and e.g. concentration) for liquid forms in Metoject (0.15 to 0.6 ml), see also multi-dose containers new dosage strength number = new pack size or dosage strength
Change history Version Change sig
10.0 New Swissmedic telephone number on page 1 of the guidance document wph, lm, Adaptation due to revised list of variations (Annex 7 TPLRO) vy, stb Section 5 Requirements – Addition of reference to “Volume 2C Regulatory Guidelines “Guideline on the categorisation of extension applications (EA) versus Variations Applications (V), July 2019”” regarding the distinction between extensions and type II variations Section 9 Issuing of new authorisation and dosage strength numbers and packaging codes – various changes Various other clarifications. 9.0 General revision of section 9 wph, lm, vas, sab, irk, vy
8.2 Changes in section 9 (powder with/without solvent) lm
8.1 New layout, no content adjustments to the previous version. dei
8.0 Section 5.2.4.5 / 5.2.4.6 – Clarification regarding required documentation/GMP stb
documents (complete documentation of verification of GMP compliance of foreign manufacturers) Section 6.7 – Introduction of delayed implementation time limits for specially applied for and sufficiently justified replacement changes HMV4 suffix deleted 7.0 Changes due to expansion of scope of temporary authorisations. stb.lm. nma.hv
6.0 Adaptation due to separation of the changes for veterinary medicinal products and those stb
for human medicinal products (revision of VMP regulations)
5.1 Clarification (P1.) and new point (P12.) regarding issuing of new packaging codes in stb
section 9 and changes to department names
5.0 Inclusion in section 9.1 (Z10) of rules on issuing new authorisation numbers for the stb
adaptation of Covid-19 vaccines to new SARS-CoV-2 variants.
4.1 Formal adjustments to the header and footer dei
No content adjustments to the previous version.
4.0 Addition / explanation in section 9.1 under Z5. stb
3.0 Addition to section 6.4 – details regarding document protection. stb, ze
2.0 Inclusion of an additional case for issuing a new authorisation number (section 9.1), stb, wer
further details in section 5 (incl. in respect of the CMDh list with unforeseen variations) and section 6.6 (changes to the PMF can be submitted together with the Annual Update of the PMF as a multiple application).