Safety studies for authorised medicinal products

A PASS can be either a clinical trial or an observational study, and may be either voluntary or a requirement via the authorisation. An observational study, known as a ‘non-interventional PASS’, is divided into various categories. It is the marketing authorisation holder (MAH) who performs the study.

Purpose of safety studies

The objective of these studies is to evaluate the safety and benefit-risk profile of a medicinal product.

They aim to:

• identify, characterise or quantify a safety risk
• confirm the safety profile of a medicinal product
• measure the effectiveness of risk management measures.

Application for an interventional safety study

An interventional PASS is a clinical trial and must be authorised by the Swedish MPA.

An application and associated protocol must be submitted to the Swedish MPA.

Non-interventional safety study

A non-interventional PASS is an observational study and may be stipulated as a condition for authorisation or carried out voluntarily by the MAH on the basis that:

• Medicinal products are prescribed in the usual manner and in accordance with the conditions for the marketing authorisation.
• The specific treatment which the patient receives is not determined in advance in a trial protocol, but is the result of customary practice.
• The prescription of the medicine is clearly distinct from the decision to include the patient in the study.
• No further diagnostic or monitoring procedures are applied to patients.
• Epidemiological methods are used to analyse the data that is collected.

Categories

Categories of PASS that the MAH may be required to carry out a:

1. PASS as a condition for a marketing authorisation, or which is introduced following authorisation, where it is key to the risk/benefit profile of the product.
2. PASS as a specific obligation in the marketing authorisation, in conjunction with a conditional marketing authorisation or in the case of authorisation in exceptional circumstances.
3. PASS which does not fall under category 1 or 2 above, but which is a requirement in order to investigate a safety problem as part of the pharmacovigilance plan within the risk management plan.

In addition to these, there are also voluntary PASS which are sponsored and carried out by the marketing authorisation holder on its own initiative.

Registration and uploading of non‍-‍interventional PASS in RWD Catalogues

• It is recommended that all non-interventional PASS is registered in the RWD Catalogues.
• Registration in the RWD Catalouges database is not the same as uploading documents.
• Uploading is not a requirement but is recommended for study protocols (and their updates), progress reports and study reports.
• Uploading may mean that the authority concerned does not need to request more protocols or reports than necessary because they can be found in the RWD Catalogues. (*can apply e.g. if there is a reference in the document submitted to the authority to a previous/other study that the relevant authority wants to investigate more closely).
• Uploading can also make it easier for the person responsible for PASS at a company, who does not need to submit more protocols/reports than necessary at the possible request of the relevant authority (see above *).
• For more details about what applies to registration and uploading of PASS in RWD Catalogues, see GVP VIII.
• Please note that neither registration nor uploading of documents in RWD Catalogs replaces the requirement to submit protocols and reports to the relevant authority, pursuant to national or European legislation according to the information below on this web page.

Authorisation of non‍-‍interventional PASS

Whether or not authorisation from the Swedish MPA is necessary depends on:

• whether the study was initiated as a result of a condition in the marketing authorisation or voluntarily initiated by the MAH
• whether the study was requested by the Swedish MPA or another authority
• whether or not the study is to be carried out in Sweden.

Study included as a condition, requested by the Swedish MPA and to be carried out in Sweden only

• authorisation from the Swedish MPA is required for the study
• the application must include a draft protocol for the study concerned
• decisions concerning non-interventional studies must be taken within 60 days.

Study included as a condition, requested by an authority other than the Swedish MPA and to be carried out in Sweden

• authorisation is granted by the Pharmacovigilance Risk Assessment Committee (PRAC)
• the approved PRAC report must be sent to the Swedish MPA before the start of the study.

Study included as a requirement in RMP

• In Sweden’s role as RMS, the Swedish MPA asks for draft reports to be sent to the Agency for review, authorisation and follow-up.
• If the study is to be carried out in Sweden, the final protocol must be sent to the Swedish MPA for information.
• All protocols are notified to EU PAS.

Voluntary study

• The protocol is notified to EU PAS, but not sent to the Swedish MPA.

Information to be sent to the Swedish MPA for non‍-‍interventional PASS

Cover letter stating:

• The study is non-interventional.
• Date of registration in the EU PAS Register and registration number.
• Whether the study is being carried out in Sweden.
• Whether the study is based on a condition in the marketing authorisation.
• Whether the study is optional.
• Where possible, Sweden’s role regarding the product in terms of both CHMP and PRAC role or RMS/CMS. The latter for products authorised under the mutual or decentralised procedure.

For studies with PASS as a condition of the marketing authorisation

• Enter PRAC’s authorisation date.
• Attach PRAC’s recommendation.
• Study protocol.

For PASS category 3

When Sweden is RMS:

• draft study protocol
• study protocol
• updated study protocol following substantial change.

When Sweden is CMS or MS

Protocol is not to be sent unless the study is carried out in Sweden, when a final protocol must be submitted for information.

Updated study protocols for non‍-‍interventional PASS

• For PASS as a condition, updates to protocols must be sent to PRAC in cases where PRAC has granted a permit (see Chapter 6, Section 7 of the Medicinal Products Act). Where authorisation has been granted by the Swedish MPA, updates to the protocol must be submitted to the MPA in accordance with Chapter 6, Section 6 of the Medicinal Products Act.
• For PASS category 3, updates should only be sent to the Swedish MPA if Sweden has the role of RMS. In other roles, no updates must be sent, regardless of whether or not the study is being carried out in Sweden.

Final report for a non‍-‍interventional PASS

• If the PASS has been implemented in Sweden (whether voluntary or as a result of a condition in the marketing authorisation), the authorisation holder shall send a final report to the Swedish MPA within 12 months of the end of data collection. (Chapter 6, Section 5, second paragraph of the Medicinal Products Act (2015: 315)).
• This final report must be submitted electronically and include a summary of the study’s results (Section 18 of the Swedish MPA’s Regulations (LVFS 2012: 14) on pharmacovigilance of medicinal products for human use).
• However, the Swedish MPA may, in the case of studies authorised by the Agency, grant an exemption from the above-mentioned requirement to submit a final report in Chapter 6, Section 5, second paragraph of the Medical Products Act to the Agency (Chapter 3, Section 10 of the Medical Products Ordinance).

Ethics review for non‍-‍interventional PASS

For non-interventional studies in Sweden, the marketing authorisation holder may have to apply for an ethics review. The Swedish MPA does not reach a decision concerning this, as the matter is handled by the Swedish Ethical Review Authority.