Questions and answers on the authorisation of biosimilars

"Supplementary studies" mentioned in section 5.4.2 of WL Authorisation Biosimilar are, for example, non-pivotal studies on pharmacodynamics, pharmacokinetics and supplementary clinical/non-clinical studies on efficacy and safety. They provide complementary information in support of the main studies or to focus on specific aspects such as pharmacodynamics or pharmacokinetics.

This is now possible as there is no longer a “bridging” requirement. However, the suitability of the foreign comparator product must be demonstrated in accordance with section 5.4.1 of WL Authorisation Biosimilar. However, authorisation as a biosimilar is not possible if a reference product was never authorised in Switzerland. In this case, the medicinal product would correspond to new authorisation with a new active substance (NA NAS).

Yes, provided the active substances – and thus the medicinal products – demonstrate sufficient similarity.

Yes, under the revised Therapeutic Products Act and associated ordinances, it has been possible to authorise low-molecular-weight heparins as biosimilars since 2019.

¹LMWH = Low Molecular Weight Heparins

Yes, it has been possible to apply Art. 13 TPA since the beginning of 2019 provided the EU Commission or US FDA have authorised the biosimilar in question and fulfilled the requirements set out in the guidance document “Authorisation in accordance with Art. 13 TPA” (e.g. documents not more than five years old, etc.; see also Art. 17 of the Therapeutic Products Ordinance, TPO; SR 812.212.21 and sections 1.1.3 and 4 of WL Authorisation Biosimilar).

For biosimilars, the product name must be either a ‘creative’ (self-coined) name or the name of the active substance (INN) combined with a company name. If a creative name is adopted, the active substance name (INN) must be placed below the trade name. In cases where the complete (unabbreviated) active substance name is already integrated in the product name as an INN, the name of the active substance does not need to be repeated.

In its decision on whether to authorise a biosimilar, Swissmedic states that under the applicable therapeutic products legislation – particularly the provisions of the TPLRO – parts of the documentation that refer to the reference product must be modified immediately in the event of changes to the reference product.

In particular, holders of marketing authorisation for biosimilars have to monitor changes to the safety sections in the product information texts of the Swiss reference product (Contraindications, Warnings and precautions, Interactions and Undesirable effects in the case of the Information for healthcare professionals). If the changes affect their biosimilar, they then have to submit an appropriate application for modification of the texts for the biosimilar. If a holder of marketing authorisation for a biosimilar decides not to submit an application for a variation, it must notify Swissmedic of its decision immediately and without being asked, justifying the reasons for its decision (see also WL Authorisation Biosimilar, last paragraph of section 5.7).

The product information for a biosimilar is not an exact copy of that for the Swiss reference product. However, all appropriate sections of the product information text for the biosimilar must be identical to the corresponding sections of the product information for the reference product. Since a biosimilar does not need to have all the indications of the reference product, the information for healthcare professionals may differ in the "Indications / usage” section, for example.

(revised January 2024)

Applications for approval of biosimilars are not required to include an RMP.

If training materials or other additional risk minimisation measures are envisaged according to the RMP of the reference product, Swissmedic will review whether these should also be implemented for the biosimilar as part of the application for approval of the biosimilar. As a rule, it can be assumed that any measures necessary for the reference product will also be assessed as being necessary for the biosimilar; in this case, training materials or other additional risk minimisation measures will also be required as part of the application for approval of the biosimilar.

The applicant can also apply for additional risk minimisation measures directly together with the application for authorisation of the biosimilar. After review, their implementation will then be ordered as a condition.

(revised July 2024)

Yes, the revision of the Health Insurance Act (HIA, SR 832.10) with effect from 1 January 2024 and the modification of Art. 52a therein make it possible for the dispensing pharmacist to substitute biosimilars^[1].

English is not an official language of the Swiss Confederation. This translation is provided for information purposes only and has no legal force.

Art. 52a           Right of substitution

¹ If several medicinal products with the same composition of active substances are included in the list of specialities, pharmacists may dispense a less expensive medicinal product if it is equally medically suitable for the insured person, unless the doctor or chiropractor expressly requests that the original product be dispensed.

² If the dispensing person replaces the prescribed medicine with a cheaper one, he or she shall inform the prescribing person accordingly.

³ The Federal Council may specify the conditions under which medicinal products are deemed not to be equally medically suitable.

^[1] _{In the Health Insurance Ordinance (HIO, SR 832.102) of 27 June 1995 (status as of 1 January 2024) the term “biosimilar” is now defined in Article 64a paragraph 5.}

The EU Paediatric Regulation 1901/2006 (11) does not extend to biosimilars. Applying Art. 5 TPO, PIPs are not required for biosimilars in Switzerland either, because the active substance is not new.

Certain medicinal products (e.g. parenterals) do not require Patient information when they are authorised by Swissmedic (Art. 14 para. 2 of the Ordinance of the Swiss Agency for Therapeutic Products on the Licensing Requirements for Therapeutic Products, TPLRO; SR 812.212.22). Medicinal products that are not administered by patients but only by healthcare professionals do not require Patient information; the Information for healthcare professionals serves as a package insert.

Patient information is generally required and should be submitted to Swissmedic in manuscript form with the rest of the application. This does not apply to medicinal products that do not require Patient information (see question and answer 13).

The holder of marketing authorisation for the biosimilar should submit an application for a variation C.2, and Swissmedic will determine whether the conditions for authorisation are still fulfilled.

No, the date stated in the Date of revision of the text section of the Information for healthcare professionals for biosimilars is still independent of that for the reference product.

Yes, as with generics, in line with Swissmedic practice, these changes should also be submitted within 90 days for biosimilars.

The EU Commission authorisation required in Art. 17 para. 1 let. b of the Therapeutic Products Ordinance (TPO; SR 812.212.21) refers to authorisation under the centralised procedure in accordance with EU Regulation 726/2004, which is to be applied in the EU to biotech biosimilars.

Within the EU, there are very few biosimilars that member states can authorise, including low-molecular-weight heparins (LMWH), which are obtained from the mucous membranes of pigs (see https://www.ema.europa.eu/en/human-regulatory/overview/biosimilar-medicines-overview, Biosimilars in the EU – information guide to healthcare professionals). LMWH biosimilars can only be notified for authorisation in Switzerland under Art. 13 TPA if the European Commission has authorised them in a centralised procedure.

Swissmedic applies the CHF 50,000 fee in Annex 1, no. I, no. 1.2 of the Swissmedic Fees Ordinance (FeeO-Swissmedic; SR 812.214.5) to the new authorisation of biosimilars. The same fee (no. 1.2, CHF 50,000) is applied to the new authorisation of LMWH biosimilars (see also question and answer 4).

Situation:

• The preparation contains a biotech active substance (infliximab), which has been developed as a biosimilar.
• The reference product (Remicade) is authorised for IV administration in Switzerland.
• The product submitted for new authorisation is suitable for both IV and SC administration.
• The IV preparation will by definition be a biosimilar of infliximab.
• In a first stage, the SC administration route will be used in an indication of the IV product (at present, trials are only available for this indication). According to the trial, therapy will be initiated by IV administration, while maintenance doses will be administered SC.

Questions:

• How should we submit the SC administration route?
• Which preparation is the reference product?

The SC administration form cannot be classified as a biosimilar because a biosimilar must have the same dosage recommendations and administration routes as the reference product.

This is the only way that reference can be made to the documentation for the reference product (see definition of a biosimilar in Art. 4 para. 1 let. a^novies TPA).

Since the reference product is only authorised for intravenous (IV) administration, it is not possible to authorise an extension of the IV infliximab biosimilar to include the subcutaneous (SC) route (2.e) “Modification or addition of an administration route”).

The SC administration route must be submitted as a new authorisation application. There is no reference product. Adequate quality, preclinical and clinical data is required for the SC form and for every requested application (extrapolated data will not be accepted).

We recommend resolving specific questions on this point at a Scientific Advice or Presubmission Meeting.

The EMA and FDA have the most experience and/or competence in authorising biosimilars and have created and published guidelines that clearly set out the requirements that applications have to meet.This is duly reflected in Art. 17 para. 1 let. b TPO.

Yes, but only for applications for biosimilars that Swissmedic receives on/or after 1 January 2019.

Yes, as long as there are no contradicting decisions from countries with comparable medicinal product control and Swissmedic has no major objections, authorisation under Art 13 TPA can be granted.

Yes, bridging can be omitted (see also Q&A 2).

According to Art. 4 para. 1 let. a^novies TPA, biosimilars must demonstrate adequate similarity to a reference product authorised by the Agency and refer to that product’s documentation. Information for healthcare professionals is one of the documents that is relevant to authorisation. This is why a biosimilar submitted for authorisation in Switzerland must make reference to the Information for healthcare professionals of a medicinal product authorised by the Agency.

Swissmedic supports the scientific and regulatory considerations set out in the draft reflection paper, already implements the corresponding principles and – once the EMA paper has been finalised – will update the Guidance document Authorisation Biosimilar accordingly.

Yes. Please state the justification in the covering letter (with a reference to Module 2.5) and include all available scientific advice provided by EMA and the US FDA with your application.

Yes, in the context of a Meeting before application submission (see Guidance document Meetings for applicants for authorisation procedures).