Clinical trials

If the ATMP classification is not established, application to the CAT for classification is recommended. Classification is a non-mandatory, free-of-charge, non-legally binding procedure. Classification helps developers to clarify the applicable regulatory framework. It provides clarity on the development path and scientific regulatory guidance to be followed. It is recommended that this is done before submitting requests for scientific advice/protocol assistance or other discussions with the EMA. ATMP classification also sometimes may be a useful tool for applicants in initiating a tailored dialogue on product development with the regulators.

Presubmission request form

The applicant shall provide information about the product:

Active substance

• Description of the active substance (including starting materials, when relevant)
• Description of any additional substances (e.g. any applicable structural components such as scaffolds, matrices, biomaterials, biomolecules and/or other components)
• Description of the medical device or active implantable medical device (when applicable)

Finished product

• Qualitative and quantitative composition
• Mode of administration
• Pharmaceutical form (use standard term as applicable) and description of the finished product ready for clinical use

Mechanism of action/proposed use

• Claimed mechanism of action
• Properties (including pharmacological, immunological or metabolic, if applicable)
• Proposed use/indication (including therapeutic, prophylactic, diagnostic)

In addition, information on the status of development shall be provided (including the element of manufacturing, quality aspects and outline of the non-clinical and clinical development) where this is relevant for ATMP classification. Applicants should also substantiate their positions on the classification of their product in light of the legal definitions in force.

Essential documents are those documents which individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced and serve to demonstrate the compliance of the investigator, sponsor and monitor with the standards of GCP and with all applicable regulatory requirements. The essential documents also serve several other important purposes. Filing the essential documents at the investigator/institution and sponsor sites in a timely manner can greatly assist in the successful management of a trial by the investigator, sponsor and monitor. These documents are also the ones which are usually audited by the sponsor’s independent audit function and inspected by the regulatory authorities as part of the process to confirm the validity of the trial conduct and the integrity of data collected.

The IMPD, IB and Clinical Study Protocol are described briefly below. For the complete list of essential documents, please see Section 8 of ICH guideline E6 on GCP, available from the ICH website.

INVESTIGATIONAL MEDICINAL PRODUCT DOSSIER (IMPD) IMPD GUIDELINE AND TEMPLATE

IMPD is the basis for approval of clinical trials by the competent authorities in the EU. The IMPD includes summaries of information relating to the quality, manufacture and control of the investigational medicinal product (IMP). An overall risk-benefit assessment, including reference safety information, and critical analyses of the non-clinical and clinical data in relation to the potential risks and benefits of the proposed study must be included in the IMPD.

The applicant may either provide a stand-alone IMPD or cross-refer to the IB for the pre-clinical and clinical parts of the IMPD.

INVESTIGATORS BROCHURE (IB) ICH-GCP GUIDELINES FOR IB (SECTION 7)

The IB is a compilation of the clinical and non-clinical data on the IMP(s) relevant to the study of the product(s) in human subjects. Its purpose is to provide the investigators and others involved in the trial with the information to facilitate their understanding of the rationale for, and their compliance with, many key features of the protocol, such as the dose, dose frequency/interval, methods of administration and safety monitoring procedures. The IB also provides an insight for supporting the clinical management of the study subjects during the course of the clinical trial. The information should be presented in a concise, simple, objective, balanced and non-promotional form that enables a clinician or potential investigator to understand it and make his/her own unbiased risk-benefit assessment of the appropriateness of the proposed trial. For this reason, a medically qualified person should generally participate in the editing of an IB, but the contents of the IB should be approved by the disciplines that generated the described data.

The IB should be reviewed at least annually and revised as necessary in compliance with a sponsor’s written procedures. More frequent revision may be appropriate depending on the stage of development and the generation of relevant new information.

CLINICAL STUDY PROTOCOL

The clinical study protocol should comply with the scientific, regulatory, statistical and GCP requirements, see guidelines for GCP (section E6). The protocol describes the objective(s), design, methodology, statistical considerations and organisation of a trial. The protocol also contains the background and rationale for the trial. It is essential to include a detailed flow chart of the trial in the clinical study protocol. Basic advice on the clinical study protocol from Läkemedelsverket (in Swedish).

CLINICAL STUDY PROCEDURE

The procedures for clinical trial planning, application, execution, analysis, reporting and archiving have been outlined on the Clinical Studies Sweden website. This only covers the main applications. You may need to contact other entities in your local county council (i.e. hospitals, local priority advice, pharmacy).

COMPETENT AUTHORITY

To develop a clinical trial authorisation (CTA), an EudraCT number must first be created. The European clinical trials database (EudraCT) is a database of all clinical trials initiated in the EU from May 2004 onwards. AnEudraCT number is a unique identifier for the clinical trial. The application form can be completed and downloaded from the EudraCT website once the EudraCT number has been created. Detailed information on the CTA procedures (in Swedish) is available on the Läkemedelsverket website.

ETHICAL REVIEW BOARD(S) (ETIKPRÖVNINGSMYNDIGHETEN)

Detailed information on the application procedures for ethical review of clinical trials in Sweden is available on the Etikprövningsmyndighetens website.

BIOBANK

According to the Swedish Biobank Act (SFS 2002:297) (in Swedish),human biological specimens collected and/or stored within the healthcare system may be used for research purposes provided that the patient/donor has given his/her consent. The collection and/or use of human samples for research purposes requires approval by the ethical review board for each specific research project/clinical trial. A biobank application is needed for all samples collected specifically for a clinical trial (including routine samples that are collected outside clinical practice), even when the samples are analysed and directly destroyed. For more information, read Biobank Sweden

RADIATION PROTECTION COMMITTEE

In the case of clinical trials where the participants are exposed to radiation, these trials shall be approved by a radiation protection committee. An application must be sent in with ethical application in Prisma, Radiation safety application (in Swedish).