KLH-20 version 5

Application for authorisation/notification of clinical trials  

This guideline supersedes guideline KLH-20, version 4  as of  January 1st 2013.

You can use guideline KLH-20 version 4 or version 5 duringtransition period till January 1st 2013.

Submission of Application for Authorisation/ Notification of a Clinical Trial in the Czech Republic.

Types of application and time periods:

A)  
An application for clinical trial authorisation shall be submitted for each clinical trial (hereinafter referred to as CT) which uses investigational medicinal products (hereinafter IMPs)( i.e. tested or comparator) and is required even for non-investigational medicinal products provided by the sponsor, e.g. obligatory rescue medications established and ordered by the protocol (hereinafter non-IMPs) obtained by biotechnology or containing substances of human or animal origin which are not authorised in the Czech Republic or in other EU Member States, regardless of whether they are authorised in a third country. SÚKL shall provide its opinion on the application within 60 days. Where advanced therapy IMPs are concerned (i.e. medicinal products of the nature of gene therapy, somatic cell therapy, or containing genetically modified organisms, including IMPs for tissue engineering) the period shall be extended by further 30 days, i.e. SÚKL shall provide its opinion within the period of 90 days. In justified cases the period for assessment of an advanced therapy MP may be extended by another 90 days. The time period for assessment of an application for authorisation of a clinical trial involving a xenogenic cell therapy shall not be limited.

B) 
Notification of a clinical trial, for which SÚKL shall provide its opinion within 60 days, shall be obligatory for any clinical trial using investigational IMPs (i.e. tested or comparator)  and is required even for non-IMPs provided by the sponsor (e.g. obligatory rescue medications established and ordered by the protocol):

a) obtained by biotechnology or containing substances of human or animal origin authorised in the Czech Republic or in other EU Member States (authorised by national, decentralised, mutual recognition or centralised procedure), which, however, are not used in accordance with the terms of marketing authorisation.

b) any other medicinal products (mostly of chemical origin) which:

  • §  are not authorised in the Czech Republic,
  • §  are or are not authorised in EU Member States,
  • §  are or are not authorised in a third country,
  • §  are authorised in the Czech Republic, but are used out of the terms of marketing authorisation.

C)  
Notification of a clinical trial on which SÚKL shall provide its opinion within 30 days, shall be obligatory for each intervention clinical trial involving investigational medicinal products (i.e. tested or comparator) and is required even for non-IMPs provided by the sponsor (e.g. obligatory rescue medications established and ordered by the protocol) authorised in the Czech Republic either by a decision issued by SÚKL or by the European Commission (in a centralised procedure), and used in accordance with the terms of marketing authorisation, i.e. in compliance with the approved summary of the product characteristics (the same indications, population defined, dosage).

Important note: MP (medicinal product) used in the study must be identical to the MP placed on the market in the Czech Republic; it is not acceptable to state in the application a marketing authorisation number of a medicinal product authorised in the Czech Republic and to import the product to be used in the clinical trial from another country. 

Guidance for Applicants:

  1. The application shall be accompanied by a cover letter, as specified below, and a completed SUKL Questionnaire (Annex No. 1).
  2. The application may be submitted with a completed form “Certificate of authorisation/notification of clinical trial for customs procedure” which will be sent to the specified address once the decision on the conduct of the clinical trial has been adopted.
  3. The clinical application form (hereinafter referred to as CTA) is available from the European Medicines Agency (EMA) website https://eudract.ema.europa.eu under “Access to EudraCT” The completed CTA shall be submitted in hard copy (signed) and electronically in the XML format on a CD ROM or DVD. Detailed instructions for completing the CTA can be found at the above mentioned website (under “Help”).  
  4. The CTA shall be completed in the English language, only the study name shall be bilingual, i.e. also in Czech and the address of clinical trial sites shall be completed only in Czech language. This is because the data are entered into the European clinical trials database (EudraCT database) in the same form as received by SUKL in electronic format. 
  5. Each application for authorisation/notification of a clinical trial must contain the EudraCT identification number, which may be obtained from https://eudract.ema.europa.eu/ choosing “Access to EudraCT” followed by “Create” and the “EudraCT number” on the upper bar, see below. Where the EudraCT number is allocated via e-mail it is necessary to print out the e-mail or save it in pdf. format and to attach it as a proof of allocation of the European identification number. The EudraCT number must be thereafter shown on all documents pertaining to the clinical trial concerned (e.g. when amendments to clinical trial, suspected unexpected serious adverse reaction reports (SUSARs), etc. are submitted).
    How to obtain a EudraCT number:
    https://eudract.ema.europa.eu/ð Access to EudraCT Application ð in the upper bar open Create ð choose EudraCT number (fill in).
  6. Pursuant to Section 112 of Act No 378/2007 Coll., on Pharmaceuticals and on Amendments to Some Related Acts (the Act on Pharmaceuticals), as amended (hereinafter referred to as the Act), prior to submission of the application the applicant shall be obliged to pay the fee covering  the costs of expert activities conducted in respect of the assessment of the application for clinical trial authorisation or in respect of the assessment of a notified clinical trial on pharmaceuticals. The fee to be paid and the payment procedure are specified in the current version of SÚKL guideline UST-29. The above-mentioned provision of the Act, moreover, stipulates that SÚKL may waive or decrease the fee under certain conditions – relevant details are provided in the current version of SÚKL guideline UST-24.
  7. Pursuant to Section 13 paragraph 1 of Decree No 226/2008 Coll. on Good Clinical Practice and Detailed Conditions of Clinical Trials on Medicinal Products (hereinafter referred to as the Decree ) the application for authorisation/notification of clinical trials shall be submitted to SÚKL by the sponsor or by a person authorised thereby. Where the application for authorisation/notification of a clinical trial is submitted by a person other than the sponsor, the sponsor's authorisation issued for this person shall be attached to each application or notification. The authorisation must be submitted in the original or in an authenticated copy of the original. A template for the letter of authorisation is provided in Annex 4. The application must be signed by the same person who is mentioned in section C.1 (Request for the Competent Authority)

    Pursuant to Section 51, paragraph 2 (d) of the Act, the sponsor may be only a person residing or established within the territory of the Czech Republic or any of the EU Member States, or EEA (European Economic Area, i.e. EU + Iceland, Norway, Lichtenstein) or, where applicable, a person who has appointed an authorised representative satisfying this condition.

    Where the application or notification is submitted by a sponsor residing outside the territory of the Czech Republic or the EU, he/she shall be obliged to submit the power of attorney for the person (natural or legal) whose registered office or address of residence is within the territory of the Czech Republic or the EU/EEA (legal representative) together with the application. The registered office of an organisational unit (branch) of a sponsor from a third country in the Czech Republic or in the EU/EEA cannot be considered the sponsor's registered office; in this case the sponsor must appoint its legal representative as stipulated by Section 51, paragraph 2 (d) of the Act, see Annex 3 and 4.
  8. In the case of clinical trials submitted by health professionals or by scientific societies (grant studies, academic research), the above specified requirements must be also observed; however, to simplify the procedure, the department of Clinical Trials provides free consultations to assist with the completion of applications and submission of required documentation.

Documents required for authorisation/notification of clinical trials

The requirements described below are based on the provisions of the Act on Pharmaceuticals No 378/2007 Coll., as amended, and Decree No 226/2008 Coll., on Good Clinical Practice and Detailed Conditions of Clinical Trials on Medicinal Products, and the Commission Communication - Detailed guidance on the request to the competent authorities for authorisation of a clinical trial on a medicinal product for human use, the notification of substantial amendments and the declaration of the end of the trial (KLH-1). Documents are to be submitted in the Czech, Slovak or English language, in the electronic form in CTD format on a CD ROM or DVD and in hard copies as indicated in the table below to SÚKL mail room, or sent to the following address: State Institute for Drug Control, Clinical Trials dept., Šrobárova 48, 100 41 Praha 10.

List of documents to be submitted together with the European Application form to regulatory authorities of Member States and to ethics committees, indicating the documents which must be submitted together with the SÚKL application

Document

Electronic format or hard copy as required by SÚKL

EudraCT certificate

Electronic format

Cover letter

1x hard copy, signed

SUKL questionnaire (Annex 1)

Electronic format

Application Form for Authorisation/Notification of a Clinical Trial in hard copy

1x hard copy, signed + electronic format

Disk with the EudraCT application form in XML format

Electronic xml. format

Protocol and all effective amendments thereto (KLH-8 refers)

1x hard copy + electronic format

Investigator's Brochure – preclinical and clinical data   - KLH-9 refers

1x hard copy + electronic format

Case Report Forms

Electronic format

Investigational medicinal product dossier (IMPD) – scope of information to correspond to the requirements specified in the updated version of KLH-19 (for all investigational medicinal products, i.e. the tested medicinal product, comparator, placebo and non-IMPs rescue or relief medication, if strictly required by the protocol)

CTD electronic format

Simplified investigational medicinal product dossier for known products as per the requirements specified in  the updated version of KLH-19

CTD electronic format

Summary of the Product Characteristics (SPC; REG-74 refers) for products authorised in the Czech Republic (via national or centralised procedure in the EU) and used in compliance with the marketing authorisation

Electronic format

List of regulatory authorities to whom the application has been submitted, and  decision details

Electronic format

A copy of the opinion of the Ethics Committee, if available

Electronic format

Where the applicant is not the sponsor, an authorisation issued for the applicant to act on behalf of the sponsor

Original or an authenticated copy

A copy of the licence to use or release genetically modified organisms (if applicable and available)

Electronic format

Informed Consent Form in the Czech language and its amendments, if applicable

1x hard copy + electronic format

Information for trial subjects in the Czech language

1x hard copy + electronic format

Subject recruitment organisation

-

Protocol summary in the Czech language –Annex 1 refers

1x hard copy + electronic format word

An overview of all active clinical trials with the same tested medicinal product

Electronic format

Peer review for the clinical trial, if available

-

Ethical assessment carried out by the principal investigator or  coordinating investigator

-

Viral safety study

Electronic format

Labelling study medication (IMP and non-IMP, which will be supplied by sponsor)

Electronic format

Relevant authorisations issued for the trial or products of special nature (if available), such as GMO, radiopharmaceuticals

Electronic format

TSE certificate, if applicable

Electronic format

Declaration of GMP status of  an active substance of biological origin

Electronic format

A copy of the manufacturing authorisation pursuant to Article 13.1 of the Directive, stipulating the scope of this authorisation, if the investigational medicinal product is manufactured in the EU and has not been authorised in any EU Member State

Electronic format

Declaration of the qualified person of importer from third countries stating that the manufacturing site complies with GMP requirements (if applicable)

Electronic format

A copy of the manufacturing authorisation for importers from third countries as referred to in Article 13.1 of the Directive. For importers from third countries, manufacturing authorisation is required.

Electronic format

A representative certificate of analysis for the tested product.

Electronic format

Planned trial sites (incl. the full name and title of the investigator)

Electronic format

CV of the coordinating investigator in the concerned Member State for multicentric CTs

-

CV of each investigator responsible for the conduct of the CT in  individual sites in the Member State (principal investigator)

-

Information about auxiliary personnel

-

Information about the contact person referred to in Art. 3.4 of the Directive (specified in Patient Information)

Electronic format

Insurance coverage or provision of compensations for injuries to health or death due to participation in the CT

-

Liability insurance concluded for the investigator and sponsor

-

Compensation for the investigator

-

Compensation for trial subjects

-

Agreement concluded by the sponsor and trial sites

-

Certificate of agreement concluded by the sponsor and the investigator, unless provided in the protocol

-

Agreement concluded by the investigators and trial sites

-

Note: For bioequivalence study applications the Investigator`s Brochure (IB) of the tested products may be replaced by the Summary of Products Characteristics (SmPC) of the comparator (original). In case of differences between IB (proposed SmPC) of the tested product and SmPC of the original product the differences must be listed in the summary of changes. 

The Cover Letter must be duly signed and contain the following information:

  • List of all documents, incl. no. of version and date of version
  • When the clinical trial is submitted within VHP procedure, national phase 3, this fact should be stated in the Cover Letter together with the VHP number.
  • For cover letters related to re-submitted applications, the applicant should point out all changes against the previous submission. Unchanged documentation should not be re-submitted, only referred to.
  • For Integrated Protocol Design (protocol covering two separate parts of a clinical trial where different subjects will be enrolled in part I a part II), indicate whether both parts will be conducted in the Czech Republic. If only one part is to be conducted in the Czech Republic, state which one and also where the other part will be/was conducted.
  • When a medical device provided by the sponsor is used within a CT, its CE mark, manufacturer´s declaration of conformity and instructions for use in the Czech language must be submitted (e.g. glucometers, thermometers). This applies to all medical devices which are not taken from the Czech market. When a simultaneous clinical trial of a medicinal product and clinical trial of a medical device is concerned, this fact has to be stated in the cover letter. In such case an application for authorisation/notification of a clinical trial including documentation listed in this guidance has to be submitted to the SUKL Clinical Trials Unit and at the same time submit a notification of the intention to conduct a clinical trial on medical devices to SUKL, Adverse incidents and clinical evaluation of medical devices . Notification of the intention to conduct a clinical trial on a medical device shall be submitted on form in Annex 16 of Government Regulation No. 336/2004 coll., with documentation listed under point 2.2. of annex 8 of the above mentioned Regulation.
  • The Cover Letter must be signed; the applicant´s signature confirms that the sponsor has ensured that the provided information is complete, submitted documents contain all available information, clinical trial will be conducted in compliance with the protocol, suspected unexpected serious adverse reactions and information related to results will be reported in compliance with applicable legal regulations.  

Other documentation - requirements:

  • When the written information for investigators are replaced by the summary of products characteristics (for authorised MPs) it is necessary to submit together with the SmPC, provided that the terms of use in the clinical trial differ from the approved terms of use, also an overview of relevant clinical and non-clinical data supporting the use of investigational medicinal product in the clinical trial.   
  • When the investigational medicinal products is specified in the protocol only by its active substance the sponsor should choose one summary of products characteristics as equivalent to the investigator´s brochure for all medicinal products containing the active substance and used in any trial site.
  • For applications for authorisation/notification of a CT preceded by administration of the MP to humans, summary of all available information from previous clinical trials and experience from use in man with the proposed investigational medicinal products have to be submitted. All studies should be conducted in compliance with the principles of good clinical practice. Therefore, the sponsor´s/ applicant´s is required to submit a declaration of compliance of the stated clinical trials with good clinical practice. In particular, when clinical trials have been conducted in a third country, this fact should be explicitly declared.  
  • The submitted documentation should also contain a short and comprehensive summary providing a critical analysis of non-clinical and clinical data in relation to potential risks and benefits of the proposed trial unless this information is already provided in the protocol. If this information is part of the protocol the applicant should refer to the appropriate part of the protocol. If any clinical trial has been terminated prematurely appropriate statement indicating reasons for early termination shall be included.

Documentation required for medical devices used within a CT:

  • List of used medical devices provided by the sponsor for use within a CT.
  • CE certificate  and EU Declaration of Conformity for each medical device
  • When the medical device is to be used by the trial subject, instructions for use in the Czech language shall be submitted.

List of Annexes:

Annex 1 SÚKL Questionnaire.docx, soubor typu docx, (87.19 kB)

Annex 2 Protocol Summary Template in the Czech language.docx

Annex 3 Guidance on Power of Attorney.doc, soubor typu doc, (52.5 kB)

Annex 4 Power of Attorney_Letter of Authorisation templates.docx

Annex 5 Requirements for submission of pharmaceutical data for investigational medicinal products already assessed by SÚKL.docx