Guidance document Authorisation of individual teas, cough and throat lozenges and pastilles in the notification procedure HMV4

1 Abbreviations

Art. Article CTD Common Technical Document for the Registration of Pharmaceuticals for Human Use DER Drug-extract ratio DMF Drug Master File EDQM European Directorate for the Quality of Medicines FeeO-Swissmedic Ordinance on the Fees charged by the Swiss Agency for Therapeutic Products of 14 September 2018 (SR 812.214.5) GLP Good Laboratory Practice HMPC EMA Committee on Herbal Medicinal Products KPTPO Ordinance of 7 September 2018 of the Swiss Agency for Therapeutic Products on the Simplified Licensing of Complementary and Phytotherapeutic Products (Complementary and Phytotherapeutic Products Ordinance, KPTPO; SR 812.212.24) Let. Letter OGLP Ordinance of 18 May 2005 on Good Laboratory Practice (SR 813.112.1) Para. Paragraph Ph. Eur. Pharmacopoea Europaea Ph. Helv. Phamacopoea Helvetica Sec. Section TPLO Ordinance of the Swiss Agency for Therapeutic Products of 22. June 2006 on the Simplified Licensing of Therapeutic Products and the Licensing of Therapeutic Products by the Notification Procedure (SR 812.212.23) TPA Federal Act of 15 December 2000 on Medicinal Products and Medical Devices (Therapeutic Products Act, 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 the Swiss Agency for Therapeutic Products of 21 September 2018 on Therapeutic Products (TPO; 812.212.21)

2 Introduction and objective

This guidance document is aimed at administrative bodies and thus does not directly set out the rights and obligations of private individuals. Swissmedic uses the document as a resource for implementing – in a uniform and equitable manner – the legal provisions for the authorisation of individual teas in dispensing category E via the notification procedure (with corresponding health claim) as well as of cough and throat lozenges and pastilles in dispensing category E via the notification procedure (with a corresponding health claim). The publication of the Instruction is designed to make it clear to third parties what requirements must be fulfilled according to the practice of Swissmedic. The guidance document applies to new authorisations of individual teas according to Art. 12 KPTPO and of cough and throat lozenges and pastilles according to Art. 13 KPTPO. Unless otherwise noted in this guidance document, variation applications that concern medicinal products must be submitted in accordance with the guidance document Variations and extensions HAM.

3 Legal framework

The authorisation in the notification procedure for individual teas or for cough and throat lozenges and pastilles in dispensing category E is based, in particular, on the following legislative texts (provisions of laws and ordinances): KPTPO

• Chapter 2, Section 2, Art.12 Notification procedure for teas

• Chapter 3, Art.13 Cough and throat lozenges and pastilles

• Chapter 7 Notification procedure

• Annexes to KPTPO Annex 4 (List of teas drugs) and Annex 5 (“Lozenges” list) TPA

• Art. 14, para. 1 Simplified procedure TPLO

• Art. 32 para. 1 Principle of the notification procedure TPO

• Art. 3 Authorisation application TPLRO

• Art. 12, Annex 1 Information and text on containers

• Art. 22 Notification requirement

4 General requirements and assessment principles

4.1 General principles

4.1.1 Precondition for submission

Before an application for authorisation of a medicinal product in the notification procedure can be submitted, a basic company dossier based on Art. 37 and Art. 38 KPTPO must first be submitted and approved.

4.2 Basic company dossier

The required documents comprising the basic company dossier are specified in Art. 38 para. 1 KPTPO. The basic company dossier must be specific to the manufacturer and submitted to Swissmedic via a person or company domiciled in Switzerland, who/which has the necessary establishment licence. In the case of medicinal products that are manufactured abroad either in full or in part, confirmation must be provided for each company involved in the manufacture that the medicinal product concerned is manufactured in compliance with the GMP rules valid in Switzerland (see Art. 11 para. 1 let i. MPLO) as well as corresponding proof of GMP (see guidance document GMP compliance by foreign manufacturers). The form New authorisation variation in notification procedure KPTPO, which includes a checklist of the required documents and confirmations, serves as a basis and guide for compiling a basic company dossier and for variations relating to a basic company dossier (change in manufacturing site). All required forms, confirmations and documents are also listed in the guidance document Formal requirements and the directory Overview of documents to be submitted. In justified cases, Swissmedic can require further documents (Art. 38 para. 2 KPTPO). If batch release takes place at various locations, separate basic company dossiers must be submitted for each location.

4.2.1 Time limits

The time limits are based on the guidance document Time limits for authorisation applications, Annex – Overview of time limits.

4.3 Fees

The fees specified in FeeO-Swissmedic apply.

5 Authorisation of individual teas in the notification procedure

5.1 General

Individual teas in dispensing category E can be authorised in connection with a notification provided the conditions stated in Art. 15 TPA are fulfilled and, according to the information available to the Swissmedic the submission and review of documentation on the quality, efficacy and safety of the ingredients do not appear to be necessary (Art. 32 para.1 TPLO). The tea drugs eligible for this procedure are documented in Annex 4 KPTPO. According to Art. 32 TPLO, the submission and review of the application (notification) are based on Art. 3 TPO. The Swissmedic checks the authorisation application for conformity with the requirements of this guidance document, particularly as regards the respective proposed active substance (tea drugs), and also checks the wording of the indication and the health claim in relation to the respective proposed active substance, as well as the dispensing category and packaging. If no objections arise during the check, the medicinal product is authorised without the submission of further documentation.

5.1.1 Requirements

The requirements are defined in Art. 12 KPTPO.

5.1.2 Permitted indications

The health claims attributed to the individual tea drugs (e.g. helps with flatulence, diuretic, etc.) determine the specific indications that may be claimed. If several properties apply, all of them must be stated. The permitted indications are listed in Annex 4 of KPTPO (list of tea drugs).

5.2 Regulatory documentation (Module 1)

The formal requirements are based on the guidance document Formal requirements and the associated directory of Documents to be submitted.

5.3 Documentation on quality (Module 3)

The applicant must be able to demonstrate the quality of the medicinal product – at any time when requested by Swissmedic – by means of analytical, chemical and pharmaceutical documentation. The following documents must be available: 1st Active substances: Specifications and test methods that demonstrate conformity with the following specifications:

• With the valid Ph. Eur. or Ph. Helv. monograph for the respective herbal drug

• With the general Ph. Eur. monograph Herbal Drugs / Plantae medicinales 2nd Manufacture of finished product: Narrative and schematic description; documentation of the implemented in-process controls.

3rd Container: Description of the container (filter bag, outer bag), specifications and analytical methods and documentation on the safety of the materials employed with reference to the intended use. 4th Finished product: Specifications and test methods that demonstrate conformity with the following specifications:

• With the valid Ph. Eur. or Ph. Helv. monograph for the respective herbal drug.

• With the general Ph. Eur. monograph Herbal Drugs / Plantae medicinales;

• With the general Ph. Eur. monograph Herbal Teas / Plantae ad ptisanam; 5th Documentation on the stability of the finished product in the proposed packaging. If a shelf life of a maximum of 24 months is proposed, data must be available which demonstrate that the requirements of Ph. Helv. or Ph. Eur (see Points 1st and 4th) are observed over this period. The following storage conditions must be observed here as a minimum: 25°C ± 2°C/60% RH ± 5% RH. A shelf life of more than 24 months may be claimed only if the corresponding data on stability for the finished product are submitted for the full proposed shelf life.

5.4 Toxicological documentation (Module 4)

Since the toxicology of the substances listed in Annex 4 of KPTPO (list of tea drugs) is considered to be known, they are exempt from the need to submit toxicological documentation.

5.5 Clinical documentation (Module 5)

The benefit of the tea drugs listed in Annex 4 of KPTPO (list of tea drugs) can be promoted explicitly only for adults with the health claims stated in this Annex. The exclusive use of these listed health claims for the substances mentioned therefore means that clinical documentation does not need to be submitted.

5.6 Additional requirements

5.6.1 Medicinal product information and packaging materials

The information and texts specified in Annex 1 of TPLRO (see Art. 12 para. 1 TPLRO) and the mandatory information specified in Annex 4 KPTPO should be stated on the container used for dispensing, and the requirements of guidance document Packaging for human medicinal products must be fulfilled. As these herbal teas are authorised exclusively for adults (see section 5.5), the following mandatory exclusion of children must be stated on the packaging: “The use of ‘medicinal product name’ is not recommended in children and adolescents due to a lack of or insufficient data”. If all the information can be stated on the carton, a package leaflet is not required.

5.6.2 Name

Only the scientific name is permitted as the medicinal product name of an individual tea. The name of the dosage form conforms with the EDQM Standard Terms for Pharmaceutical Dose Forms and is: “herbal tea”.

5.6.3 Composition / Declaration

The requirements for the declaration are based on the guidance document Product information for human medicinal products or the declaration requirements for herbal medicinal products, see guidance document Authorisation of herbal medicinal products.

5.7 Variations to individual teas

Regulatory variations to individual teas in dispensing category E authorised in the notification procedure must be submitted in accordance with the guidance document Variations and extensions HAM and Annex 7 (Art. 22a) TPLRO in the form of the relevant variation in section E. Regulatory changes. An extension of the shelf life beyond 24 months must be submitted together with the necessary documents in the form of a variation Q.II.f.1 Change in the shelf life or storage conditions of the finished product in accordance with the guidance document Variations and extensions HAM and Annex 7 (Art. 22a) TPLRO (see Art. 10 TPO).

6 Authorisation of cough and throat lozenges and pastilles in

dispensing category E in the notification procedure

6.1 General

Cough and throat lozenges and pastilles in dispensing category E can be authorised in connection with a notification provided the conditions stated in Art. 15 TPA are fulfilled and, according to the information available to Swissmedic, the submission and review of documentation on quality, efficacy and safety of the ingredients do not appear to be necessary (Art. 32 para.1 TPLO). The permitted starting materials (herbal drugs) and ingredients are documented in Annex 5 KPTPO (“Lozenges” list). The submission and review of the application (notification) are based on Art. 3 TPO in conjunction with Art. 32 TPLO and Chapter 7 KPTPO. Swissmedic checks the authorisation application for conformity with the requirements of this guidance document, particularly as regards the qualitative and quantitative composition, the wording of the indication and the health claim in relation to the active substances, as well as the dispensing category and packaging. If no objections arise during the check, the medicinal product is authorised without the submission of further documentation.

6.1.1 Authorisation before 1 January 2019

No basic company dossier is required retrospectively for cough and throat lozenges and pastilles in dispensing category E in the notification procedure, which were authorised before 1 January 2019. Changes in manufacturing sites must be submitted in accordance with the guidance document Variations and extensions HAM as a variation E.z Other regulatory change. Applications regarding these medicinal products are subject to the Swissmedic Fees Ordinance (FeeO-Swissmedic). The medicinal products themselves are subject to the same conditions as medicinal products authorised according to Art. 15 para. 1 let. b TPA.

6.2 Criteria for application of the notification procedure

6.2.1 Requirements

The requirements are defined in Art. 13 KPTPO.

6.2.2 Permitted indications and claims

The properties attributed to the various constituents (e.g. expectorant, soothing, disinfectant) are crucial for the indication. If justified on the basis of the composition, several indications may be claimed. The medicinal products may be promoted as emollients. These determine the indication. The permitted indications and claims are listed in the "Lozenges" list (Annex 5 KPTPO). Formulations which may give the impression that the effect of the medicinal product has been proven or that the medicinal product possesses preventive or curative effects (health claims) are not permitted. Trivialising formulations that may tempt a person to use the product excessively are also not permitted.

6.3 Regulatory documentation

The formal requirements are based on the guidance document Formal requirements and the associated directory of Documents to be submitted. If applicable, a detailed, qualitative composition of the flavours used should be submitted by the flavour manufacturer. If flavours contain pharmaceutical excipients of particular interest according to Annex 3a TPLRO, the qualitative composition of these must be declared as a minimum and the relevant warnings added. If the medicinal product is to be promoted as "kind to the teeth", an expert report by a recognised dental institute must be submitted.

6.4 Documentation on quality (Module 3)

The applicant must be able to demonstrate the quality of the medicinal product – at any time when requested by Swissmedic – by means of analytical, chemical and pharmaceutical documentation. The storage instructions should also be mentioned in the cover letter and reasons for these provided. The following documents must be available: 1st Composition of finished product (full qualitative and quantitative composition); details of the function of each individual ingredient (active substance, excipient (→ flavour, colouring agent, antioxidant, preservative, etc.)). 2nd Manufacture of finished product: narrative and schematic description; documentation of the implemented in-process controls. 3rd Herbal drugs: If a monograph for a drug is published in the valid pharmacopoeia, the corresponding reference must be stated; the requirements described in the relevant monograph must be fulfilled. If no corresponding monograph exists, the manufacturer must prepare its own monograph for the primary drug concerned. This must correspond to an existing monograph in respect of content and scope and satisfy the requirements of the Ph. Eur. monograph Herbal Drugs / Plantae medicinales. 4th Active substances: If a monograph for an active substance is published in the valid pharmacopoeia, the corresponding reference must be stated; all the requirements described in the relevant monograph must be fulfilled. If no corresponding monograph exists, the manufacturer must prepare its own monograph based on the requirements documented in the relevant General Monographs in Ph. Eur. (for example Herbal Drug Extracts / Plantarum medicinalium extracta). 5th Excipients: If a monograph for an excipient is published in the valid pharmacopoeia, the respective reference to this monograph must be stated; the requirements described in this monograph must be fulfilled. If no corresponding monograph exists, reference can be made to foodstuffs legislation; the requirements described in this legislation must be fulfilled. 6th Primary container: Description of the container, specifications and analytical methods and documentation on the safety of the materials employed with reference to the intended use. 7th Finished product: Specifications including, as a minimum, information on organoleptic testing (appearance, odour) and formulation testing (dimensions, average mass, consistency) and on the

inspection of purity (water content, loss on drying, microbiological quality).

8th Documentation on the stability of the finished product in the proposed primary container. For a shelf life of up to 24 months, it must be demonstrated that the specifications are met in full until the end of the shelf life. The following storage conditions must be observed here as a minimum: 25°C ± 2°C/60% RH ± 5% RH. A shelf life of more than 24 months may be claimed only if the corresponding data on stability for the finished product are submitted for the full proposed shelf life.

6.5 Toxicological documentation (Module 4)

The toxicological risks of the substances stated in the "Lozenges" list, Annex 5 KPTPO, are considered to be known. Accordingly, reference to the herbal substances and preparations stated in this list exempts the applicant from the need to submit toxicological documentation.

If essential oils listed in chapter 2.2. of Annex 5 KPTPO are used as active substances, the cover letter must include the reasons for the quantity chosen per unit (per lozenge or per pastille).

6.6 Clinical documentation (Module 5)

The use of the substances included in the “Lozenges” list, Annex 5 KPTPO, can be promoted using only the health claims stated in this list. The use of these listed health claims for the substances stated means that clinical documentation does not need to be submitted.

6.7 Additional requirements

6.7.1 Medicinal product information and packaging materials

All mandatory information should be stated on the container used for dispensing to patients. A package leaflet is therefore not envisaged for cough and throat lozenges and pastilles authorised in the notification procedure according to Art. 14 para. 3 TPLRO. As regards the information and texts on containers and packaging materials, the requirements according to Annex 1 TPLRO (see Art. 12, para. 1 TPLRO) apply. Unless otherwise specified in this guidance document, the requirements of the guidance document Packaging for human medicinal products also apply.

6.7.2 Pack size

The determined quantity included in a pack must be such that the health of a small child cannot be harmed even after excessive consumption (particularly after the ingestion of the contents of a whole pack). The quantity of the pack contents can be stated as the full weight (i.e. the number of pastilles/lozenges in a pack does not need to be stated).

6.7.3 Name

The medicinal product name of throat and cough lozenges and pastilles is based on the guidance document Medicinal product names. Moreover, and to differentiate them from foodstuffs, the medicinal products should be designated as “cough lozenges”, “throat lozenges” or “throat pastilles”.

The name of the dosage form conforms with the EDQM Standard Terms for Pharmaceutical Dose Forms and is: pastilles/oral gum (soft consistency) or lozenges (hard consistency).

6.7.4 Composition / Declaration

The requirements for the declaration are based on the guidance document Product information for human medicinal products. The composition must be stated "per unit" (1 lozenge or 1 pastille). The declaration can also be stated in Latin. The following requirements apply: a) All active ingredients must be listed by quantity. The active substances contained must be included in the “Lozenges” list and referenced accordingly. b) The quantity of excipients of particular interest according to Annex 3a TPLRO and the quality of other excipients must be declared. Excipients should be listed in decreasing order of their content.

6.8 Variations to cough and throat lozenges and pastilles

Regulatory variations to cough and throat lozenges and pastilles in dispensing category E authorised in the notification procedure must be submitted in accordance with the guidance document Variations and extensions HAM and Annex 7 (Art. 22a) TPLRO in the form of the relevant variation in section E. Regulatory changes. Variations relating to the active substances contained in a medicinal product must be submitted as a an application for new authorisation. Variations relating to the excipients in a medicinal product must be submitted according to the guidance document Variations and extensions HAM as a variation E.z Other regulatory change. If the variation also affects the packaging texts, the amended packaging must also be submitted for assessment as part of the application for variation in addition to the Full declaration form. An extension of the shelf life beyond 24 months must be submitted together with the required documents in the form of a variation Q.II.f.1 Change in the shelf life or storage conditions of the finished product in accordance with the guidance document Variations and extensions HAM and Annex 7 (Art. 22a) TPLRO.

Change history Version Change sig

2.0 Change to the rules concerning medicinal product name and dosage form stb, tsj, Clarifications regarding the basic company dossier heb Additional instructions regarding applications for variation Clarification regarding the documentation on stability (lozenges) New layout, deletion of the “HMV4” suffix, change of phone number, more precise wording.

1.1 Chapter 6.8: Explanation regarding “Other regulatory variations” bui

1.0 Implementation of TPO4 bui