Decree No. 226 / 2008 Coll.
Ordonnance on good clinical practice and closer conditions of clinical trial of medicinal products
Valid
Order
Effective from 01.07.2008
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226
DECLARATION
of 23 June 2008
on good clinical practice and closer conditions for the clinical trial of medicinal products
The Ministry of Health and the Ministry of Agriculture shall determine, pursuant to § 114 (2) and in order to implement § 51 (2) (h), § 52 (6), § 53 (1), (8), (12) and (13), § 54 (1), § 55 (7) to (9), § 56 (1) (a), § 56 (7), § 57 (2), § 58 (8), § 59 (1), § 60 (2), (4) and (9), § 61 (2) (a) and (b) (1) (6), § 61 (2) (c) and § 61 (4) (e) of Law No 378 / 2007 Coll.
COMMON PROVISIONS
Preliminary provisions
(1) This Decree implements the relevant provisions of the European Communities (1) and regulates the rules of good clinical practice and the detailed conditions for clinical evaluation of medicinal products (hereinafter referred to as "clinical trials").
(2) For the purposes of this decree:
(a) the opening of a clinical trial of a medicinal product for human use at the moment when the first subject of the evaluation under § 51 (2) (g) of the Medicines Act or its legal representative signs an informed consent to participate in the clinical trial in the Czech Republic; in acute situations under Section 52 (9) of the Drug Act, the initiation of a clinical trial is the moment at which the investigator decides to include the first subject of the trial in the clinical trial in accordance with the protocol and makes a written record of this in the dossier;
(c) the conclusion of the clinical trial at the time when the last act of the clinical trial protocol is carried out in the Czech Republic in relation to subjects; However, follow-up of the evaluation body shall not be considered as such; if the clinical trial protocol provides for the termination of the clinical trial differently, the time set by the protocol shall be deemed to be the end of the clinical trial;
(e) records of the evaluation bodies of documents in paper, image or electronic form intended to record all information which, under the clinical trial protocol, is transmitted by the sponsor to each evaluation body;
(f) by a contractual research organisation, a natural or legal person in a contractual relationship with a contracting entity which ensures that one or more of the activities or functions of the contracting entity relating to the clinical trial are carried out;
(g) quality assurance of all planned and systematic procedures to ensure that clinical trials are conducted and clinical trial data are obtained, recorded and reported in accordance with good clinical practice and related legislation;
(h) quality management of procedures and activities to ensure, within the framework of the quality assurance system, compliance with the quality requirements of all activities relating to the clinical trial;
(i) by standard working procedures, detailed written methods of carrying out individual operations in the framework of a clinical trial aimed at achieving uniform implementation of those operations;
(j) an unique identifier assigned by the investigator to each subject in order to prevent disclosure of the identity of the subject of the evaluation;
(k) blindness in a clinical trial means the procedure whereby the subject of the trial, or, where appropriate, the investigator or other persons involved in the clinical trial, does not have access to information on the assignment of the investigational medicinal product to individual subjects;
(l) a significant change in the clinical trial protocol which is likely to affect the safety of subjects or alter the scientific hypothesis of the clinical trial.
(3) In carrying out the clinical trial of radiopharmaceuticals, the provisions of this decree are without prejudice to the atomic law and legislation issued for its implementation (2).
General principles of good clinical practice
The clinical trial shall be carried out in accordance with the clinical trial protocol set out in Annex 1 to this Regulation (hereinafter referred to as the "Protocol ') and the Appendices to the Protocol.
CLINICAL EVALUATION OF HUMAN MEDICINAL PRODUCTS
THE ETIC COMMISSION,
Establishment, composition and activity of the Ethics Commission
(1) The establishment of an Ethics Commission under Section 53 (1) of the Drug Act means the appointment in writing of the members of the Ethics Commission. The Ethics Committee shall consist of at least 5 members of the appropriate qualifications and shall have experience in assessing and evaluating the submitted clinical trials from a scientific, medical and ethical point of view. Prior to the appointment of members of the Ethics Commission, the Health Facility or the Ministry of Health (hereinafter referred to as "the person"), which is established by the Ethics Commission, shall seek their written consent to membership of the Ethics Commission and to respect the conditions set out in § 53 (2) (a) to (c) of the Drug Act.
(2) The appointment of new members of the Ethics Commission after that commission has already been established shall be treated mutatis mutandis in accordance with paragraph 1.
(3) The Institute publishes a list of ethical committees in the Czech Republic, indicating in particular the contact address of the Ethics Committee, the expertise of its members, the dates of establishment or, where appropriate, the demise, and whether it is an ethical committee for multicentre clinical trials and what opinions were issued on the proposed clinical trials by that Ethics Committee.
(4) If the Ethics Committee is to carry out the activities of the Ethics Committee on Multi-Centre Evaluation, the Ministry of Health shall apply for this designation while providing the Institute with a copy of the application together with the documentation provided for the Ethics Committee's activities by the Law on Medicines and this Decree. The Institute shall verify within 60 days whether the Ethics Committee fulfils the conditions laid down and forward its opinion to the Ministry of Health. The Ministry of Health shall decide within 30 days of receipt of the opinion of the Institute whether the Ethics Committee may be designated as the Ethics Committee for Multicentre Evaluation. This designation shall be notified by the Ministry of Health to the Ethics Commission, the medical institution which established it, and the Institute.
(5) Where a clinical trial has been carried out in a health institution for which approval has been given by the Ethics Committee established by the healthcare establishment, the head of the healthcare establishment shall create the conditions for that Ethics Committee to carry out its activities throughout the duration of the clinical trial in that health establishment and where changes in its composition occur to ensure the continuity of its activities and its rights and obligations.
(1) The Ethics Commission shall issue its opinions at meetings which it shall announce in advance in the manner described in the written working procedures of the Ethics Committee referred to in paragraph 2. Only those members of the Ethics Commission who participate in and are familiar with the clinical trial shall express their opinion. The opinion of the Ethics Committee may be adopted only if the Ethics Committee is capable of quorum. At least five members of the Ethics Commission, among whom a non-medical education or professional scientific qualification is present, and a non-employment member, similar employment relationship or dependent status to the healthcare facility in which the proposed clinical evaluation will take place, shall be required for the adoption of an opinion. The examiners shall not take part in the adoption of the opinion of the Ethics Commission.
(2) The Ethics Committee shall perform its functions in accordance with written working procedures which shall include in particular:
(a) the determination of its composition, specifying, where appropriate, the names and surnames and qualifications of the members and of the health care establishment setting it up;
(b) the manner in which meetings are planned, their notification to members of the Ethics Commission and the conduct of meetings;
(c) examination of requests for the approval of the Ethics Committee to initiate the clinical trial and to carry out ongoing supervision of the clinical trial;
(d) the method of determining the ongoing supervision of clinical trials;
(e) rapid assessment and opinion on administrative changes in ongoing clinical trials;
(f) the definition of the manner in which the Ethics Committee accedes to the reports of investigators, the information obtained from the supervision of the clinical trial or otherwise obtained, and the way in which the Ethics Committee communicates in writing its views on the clinical trial, the reasons for its opinions and, where appropriate, the procedures for reviewing the opinion,
(g) the definition of the manner and time limits by which the Ethics Committee communicates the information required by the Law on Medicines and by this Order to the Examiner or the Applicant, the Constitution and, in the case of the Ethics Committee on Multi-Centre Evaluation, also to the Ethics Committees, where they are established at the clinical trial sites;
(h) working procedures under other legislation3) where the Ethics Committee issues opinions for other fields of biomedical research than for clinical trials.
(3) The records kept by the Ethics Commission must be made available at the request of the authorities which perform the administration under Section 10 of the Law on Medicines and of the foreign supervisory authorities in the field of pharmaceuticals.
(4) Written working procedures, a list of members of the Ethics Commission and a statement that the Ethics Committee has been established and works in accordance with good clinical practice and related legislation, the Ethics Committee shall, upon request, provide the examiner, contracting authority or authorities referred to in paragraph 3.
(5) The minutes of the Ethics Commission's deliberations shall contain the date, hour and place of the hearing, the list of members present, the list of other persons invited, the main points of discussion, the record of the opinion, including the manner in which the opinion was adopted, the record of the notification of the possibility of conflicts of interest and the signature of at least one member of the Commission.
(6) In the event of the disappearance of the Ethics Commission, the person who has set up or designated the Ethics Commission shall notify the Institute whether another Ethics Commission is taking over the activities of the Ethics Committee, shall also communicate the list of ongoing clinical trials to which the Ethics Committee has been supervised and how the retention or transmission of the documentation of the Ethics Committee is ensured.
Adopting an opinion on the conduct of a clinical trial
(1) The Ethics Committee shall express its opinion on the conduct of the clinical trial on the basis of a written request and after examination of the documentation submitted. A request for an opinion on the conduct of a clinical trial shall be submitted to the relevant Ethics Committee by the investigator or contracting entity. Documents and documents shall be submitted to the Ethics Commission in the Czech language; The Ethics Committee may allow the submission of documents and supporting documents in another language.
(2) An Ethics Commission shall be submitted:
(a) the Protocol and any amendments thereto;
(b) the text of the informed consent and other written information provided to the evaluation bodies;
(c) procedures for the recruitment of evaluation bodies, in particular advertisements;
(d) a set of information for the examiner containing available data on the safety of the investigational medicinal product;
(e) detailed information on compensation for expenditure and remuneration for evaluation bodies;
(f) a CV of the examiner or other documents certifying his qualifications;
(g) a draft insurance contract or insurance contract providing insurance for the investigator and the sponsor pursuant to Article 52 (3) (f) of the Drug Act;
(h) other documents requested by the Ethics Commission.
(3) When assessing compensation, insurance and remuneration, the Ethics Committee always assesses whether:
(a) compensation or compensation to the subject in the event of death or damage to health as a result of his participation in the clinical trial shall be provided by an insurance contract;
(b) the insurance of liability for the investigator and the contracting entity shall be ensured by an insurance contract or, where appropriate, by insurance of liability of the investigator or contracting entity, not being part of their employment relationships;
(c) the compensation does not exceed the costs incurred by the evaluation body or by the examiner in connection with his participation in the clinical trial, and also whether the fee for the examiner is known and fixed in advance and whether the contracting authority has submitted a written communication, together with the request, of the amount of such remuneration;
(d) the level of remuneration for the subjects is consistent with the nature of the clinical trial, in particular in relation to those research activities from which the subject does not benefit directly.
(4) In the case of clinical trials where it is not possible to obtain its informed consent before the subject is included in the clinical trial, the Ethics Panel shall assess how and within what time limits the protocol provides for the request of the informed consent of the legal representative of the subject or the subject to the evaluation itself, and shall consider whether it is not appropriate to make the inclusion of each individual subject subject subject subject subject subject subject subject subject subject subject subject subject subject subject subject subject subject subject subject subject subject subject subject subject subject subject to its consent conditional.
(5) The Ethics Commission will provide its opinion to the contracting authority and the Constitution within the time limit laid down in Article 53 (9) and (10) of the Drug Act.
(6) If it is a multi-centre clinical trial, the Ethics Committee for Multi-Centre Evaluation shall forward its opinion to the local Ethics Committees for each clinical trial site specified in the application, the contracting entity and the Institute within the time limit laid down in Sections 53 (9) and 53 (10) of the Medicines Act. Local Ethics Committees shall also provide their opinion to the contracting authorities, the relevant Ethics Committee for Multicentre Evaluation and the Institute in accordance with Sections 53 (9) and (10) of the Drug Act.
(7) The opinion of the Ethics Committee contains:
(a) the identification data on the assessed clinical trial, in particular the name of the clinical trial, the indication of the contracting entity and the place of evaluation, the protocol number and, where appropriate, the European database Eudract identification number (hereinafter referred to as "the European database"), the date of receipt of the application and the list of clinical trial sites on which the Ethics Committee has expressed its views and overseen;
(b) a list of the documents evaluated;
(c) the operative part and its justification;
(d) the date of delivery of the opinion and the signature of at least one member of the Ethics Commission who is entitled to do so by written procedure as provided for in Article 4 (2);
(e) in cases of clinical trials where it is not possible to obtain its informed consent prior to inclusion in the clinical trial, the Ethics Committee shall expressly state whether it agrees to the procedure for the inclusion of the subjects of the trial in the protocol and shall indicate whether it makes the inclusion of each individual subject subject subject subject subject subject subject subject to its consent; where the classification of each individual body makes the evaluation conditional on its agreement, it shall also indicate the manner in which the examiner requests such consent and how the Ethics Committee will provide the relevant observations without delay;
(f) where the opinion is issued by the Ethics Panel on Multi-Centre Evaluation, this shall be indicated, together with a list of clinical trial sites on which it has expressed its views and overseen.
Changes in clinical trial conditions
(1) The notification of significant amendments to the Protocol pursuant to Article 56 (1) (a) of the Drug Act shall be made in writing with the justification and proposal of the revised relevant part of the dossier to which such amendment and amendment to the Protocol apply. Where there is an amendment to the Protocol of an administrative or organisational nature, or where there is a change in the data, such as telephone, fax, e-mail address, necessary to ensure the interaction of the Ethics Committees and the Constitution with the contracting authority, the contracting authority shall immediately inform the Institute and the Ethics Committees which have expressed their opinion on the clinical evaluation. Such an amendment shall not be considered as a significant amendment to the Protocol.
(2) The Ethics Committee shall act mutatis mutandis in assessing the Appendix to the Protocol and issuing an opinion on it in accordance with Article 5.
(3) The withdrawal of the opinion of the Ethics Commission pursuant to Article 53 (13) of the Law on Medicines shall be notified without delay by the Ethics Committee to the investigator, the sponsor and the Constitution in writing. Except where the safety of the subjects of the evaluation is compromised, the Ethics Committee shall seek the opinion of the contracting authority or, where appropriate, the examiner before taking a decision. Before taking a decision, the Ethics Committee on Multicentre Evaluation shall also seek the opinions of local Ethics Committees at individual clinical trial sites.
(4) Withdrawal of the Ethics Commission's consent contains:
(a) the identification details of the clinical trial, in particular its name, indication of the contracting entity and the places of the clinical trial for which the consent is withdrawn, the protocol number and, where appropriate, the European database identification number;
(b) justification for the withdrawal of consent;
(c) measures to end the clinical trial, in particular the transfer of the subject to another treatment, where the consent has been withdrawn because of a threat to the safety of the subjects of the trial and is not already included in the protocol;
(d) the date of revocation of the consent and the signature of at least one member of the Ethics Commission who is authorised to do so by written procedure of the Ethics Commission.
TESTING
Basic activities examining4)
(1) Before starting a clinical trial, examiners shall be familiar with the correct use and properties of the investigational medicinal product, as described in the protocol and its additions, in the investigator's information file and in other information material provided by the sponsor.
(2) The investigator shall obtain the written informed consent of the subject or his legal representative before each subject is included in the study; in cases of clinical trials where such consent cannot be obtained before the subject is included in the clinical trial, the procedure laid down in Section 52 (9) of the Drug Act and in Section 5 (4) shall be followed.
(3) The investigator, which is dependent on the healthcare operator (5), will obtain the operator's consent to its implementation before commencing the clinical trial.
(4) Examiners in good clinical practice
(a) ensure that all persons cooperating in carrying out clinical trials at the site are sufficiently experienced and adequately qualified and are duly informed of the protocol and its additions, of the investigational medicinal products and of their tasks in connection with the clinical evaluation;
(b) keep a written record of the persons it has entrusted with carrying out the tasks relevant to the conduct of the clinical trial;
(c) ensure that adequate medical care is provided to the subject in the event of an adverse event, including a clinically significant deviation of laboratory values from the normal values associated with the participation of the subject in the clinical trial;
(d) if he or she is informed of the subject's disease in progress, he or she shall inform the subject of the evaluation of that fact;
(e) in the event of the consent of the subject, inform the investigator of his or her participation in the clinical trial;
(f) make reasonable efforts to establish the reasons for the early withdrawal of the subject from the clinical trial, without prejudice to the rights of the subject.
(5) The applicant or the authorised person shall keep records of the delivery of the investigational medicinal product to the place of clinical trial, the state of stocks of the investigational medicinal product at the clinical trial site, the use of each of the subjects and the return of the unused investigational medicinal product to the sponsor or any other means of disposal of the investigational medicinal product. These records shall include the date, quantity, lot, shelf life and code numbers assigned to the investigational medicinal product and to the subjects of the evaluation. The examiner shall keep records showing that the evaluation bodies have been provided with the benefits of the investigational medicinal product listed in the Protocol and reporting the treatment of all investigational medicinal products taken from the sponsor.
(6) The investigator shall ensure that the investigational medicinal product is used exclusively in accordance with the approved protocol, shall further ensure that each assessment body is informed of the correct use of the investigational medicinal product and shall check, at intervals appropriate for the clinical trial, whether each evaluation body follows the instructions.
(7) Where a random selection of subjects is carried out in a clinical trial, the investigator shall ensure that the identification code is only disclosed in accordance with the protocol.
(8) If the clinical trial is blinded, the investigator shall immediately inform the contracting entity of any premature unblinding of the investigational medicinal product and document this.
Lessons and informed consent of the evaluation body
(1) The details of the training of the evaluation body and the informed consent are set out in Annex 2 to this Decree. In obtaining informed consent, the assessment body shall not be unduly affected to participate or continue the clinical trial.
(2) In order to obtain informed consent to participate in a clinical trial, the investigator shall only use and transmit to the subjects information material approved by the sponsor and approved by the relevant Ethics Commission or the Institute. Such information material shall be updated, agreed and approved whenever new information relevant to the evaluation bodies is available.
(3) The examiner or the person authorised by him before obtaining informed consent shall provide the subject with the opportunity, where appropriate, of his legal representative to evaluate the information for decision and to raise questions concerning the clinical trial; these questions shall be answered.
(4) The examiner or the person authorised by him shall provide the evaluation body or its legal representative with a copy signed and the date of informed consent, as well as a copy of the written information on the clinical trial intended for the subjects of the evaluation, including, where appropriate, any amendments and additions. In the event that the informed consent is provided in addition to the legal representative, the evaluation body shall receive a copy of that consent and the evaluation body.
(5) In the case of clinical trials in minors
(a) the investigator obtains informed consent under § 52 (6) (a) of the Drug Act;
(b) the examiner or the person authorised by him who has experience in the work of minors shall provide the minor, within the limits of his or her intended capacity to understand, with true information on the clinical trial, in particular its risks and benefits, possible discomfort and potential difficulties, as well as the right to withdraw from the clinical trial at any time;
(c) where the capacity of a minor so permits, the examiner or the person authorised by him shall provide him with written information on the clinical trial to the extent appropriate to his or her degree of development and shall respect his or her wish to participate in the clinical trial;
(d) the Ethics Committee shall supervise at least half-yearly intervals; where the Ethics Committee has no experience in the field of pediatric medicine, it shall ensure the participation of an expert qualified in the field of pediatric medicine in the exercise of supervision.
Records and reports
(1) Before commencing a clinical trial at the medical institution where the clinical trial is conducted, the documents listed in Section I. of Annex 3 to this Decree must be available to the persons involved in the clinical trial. This Annex also sets out in Sections II and III the documentation to be kept during and after the completion of the clinical trial. These documents must be available to persons participating in a clinical trial unless otherwise specified in the clinical trial authorisation.
(2) The investigator shall ensure accurate, complete, legible and timely recording of data in the records of the evaluation bodies and in all reports. The records of the investigator in the records of the evaluation bodies shall be in accordance with the source documents; any irregularities must be justified.
(3) Any amendment or correction to the records of the evaluation bodies shall be indicated by the date, the signature of the person who made the change and, where appropriate, by an explanation; the change or correction shall be added to the original entry. Changes or repairs shall be carried out by the examiner, his or her co-workers, by the authority to carry out the changes or repairs, or by the contracting entity of the entrusted person in accordance with the written working procedures of the contracting authority; such a change or repair shall be confirmed by the signature of the person who made the change or repair.
(4) The clinical trial records at the clinical trial site shall be accessible to the contracting authorities, the members of the Ethics Commission and the authorised persons of the supervisory authorities referred to in Article 4 (3).
(5) The examiner, at the request of the contracting authority, the person referred to in Article 21 (3) or Article 22 (2), the Ethics Commission or the Audit Offices, will give direct access to all required clinical evaluation records.
(6) The investigator shall immediately inform the contracting authority, the relevant Ethics Commission and the Health Facility of any changes significantly affecting the conduct of the clinical trial, or, where appropriate, increasing the risk of the subjects.
(7) The documentation of the clinical trial shall be kept by the investigator in such a way as to ensure the protection of data on the subject's person under another legislation (6). After completion of the clinical trial, the investigator shall ensure that the source documents are kept in accordance with the provisions for the retention of medical documents7) and in accordance with Section 56 (7) of the Drug Act; the assessment bodies' identification codes shall be kept for at least 15 years.
Notification of serious adverse events
(1) The notification of a serious adverse event to the contracting authority pursuant to Article 58 (1) of the Law on Medicines shall contain an indication of the place of evaluation, the name or name of the sponsor, the name of the clinical trial and the number of the protocol, the identification of the assessment body, the description of the event, the name of the medicinal product causing the serious adverse event, including the dose administered and the route of administration. If the report is not made in writing, it shall be confirmed without delay by a detailed written report. In immediate and subsequent written reports, the evaluation bodies shall be identified preferably by an identification code.
(2) Adverse events, including laboratory deviations, listed in the protocol as critical of the safety assessment are reported in accordance with reporting requirements and within the time limits specified by the contracting authority in the protocol.
Discontinuation of the clinical trial and its termination before any acts provided for in the protocol are implemented
(1) If the clinical trial is interrupted or terminated before any of the operations provided for in the Protocol, the investigator shall immediately inform the subjects of the evaluation and ensure that they are further treated and monitored.
(2) Where the clinical trial is interrupted or terminated under the conditions referred to in paragraph 1, the clinical trial shall:
(a) the examiner, without prior consent of the contracting authority, the investigator, shall immediately inform the Institute, the contracting authority and the Ethics Commission, or the Ethics Commission, which have expressed their views on the clinical trial; the contracting authority and the Ethics Commission or Ethics Committees which have expressed their views on the clinical trial shall provide a detailed written explanation,
(b) by the contracting authority or the Institute, the investigator shall immediately inform the Ethics Commission or, where appropriate, the Ethics Committee which has expressed their views on the clinical trial, providing a detailed written explanation.
(3) If the clinical trial is interrupted or terminated prematurely as a result of a permanent or temporary withdrawal of the approval of the Ethics Commission, the investigator shall immediately inform the medical institution thereof.
ENTERTAINMENT
Basic activities of the contracting authority
(1) The contracting authority shall ensure the establishment and maintenance of quality assurance and management systems and the use of written standard working procedures ensuring that clinical trials, including the conduct of laboratory tests and data handling, are carried out and data are collected, documented, processed, evaluated and reported in accordance with the Protocol, the principles of good clinical practice and other legislation8) in order to ensure their reliability and correctness. Where a contractual research organisation or other body participates in the conduct of a clinical trial, they shall have in place a quality assurance and management system similar to that of the contracting entity.
(2) The contracting authority shall designate the investigator, taking into account his qualifications, the nature of the clinical trial and the equipment of the medical establishment in which the clinical trial is to be conducted. The contracting authority shall agree with the investigator, health care institution or other persons involved in the clinical trial by a written contract, which may also be annexed to the Protocol, the conditions for carrying out the clinical trial, including its financing and reimbursement of the costs of treatment in the event of injury to the subject's health in connection with his participation in the evaluation, the responsibility for dealing with the Ethics Commission or the Institute, the retention of documentation and reporting and information. Prior to the conclusion of a clinical trial contract, the sponsor shall provide the examiner or health care establishment with a protocol and an updated set of information for the investigator to acquaint himself with these documents and other information provided.
(3) The contracting authority shall ensure that the examiner:
(a) conduct clinical trials in accordance with good clinical practice, relevant legislation, protocol agreed by the contracting authority and opinion of the Ethics Commission;
(b) comply with the procedures for recording and reporting data.
(4) In addition, the contracting authority shall ensure that the investigator ensures that:
(a) the basic documents relating to the clinical trial shall be kept until the contracting authority has notified the examiner or the medical institution that they are no longer necessary;
(b) access to medical facilities carrying out clinical trials, source documents and reports for monitoring, audits, inspections of the Institute or foreign inspection offices shall be granted.
(5) In addition, the contracting authority shall ensure, by written contract, a clear definition of the obligations, functions and activities it transmits to the contractual research organisation where such organisation participates in carrying out the clinical trial; However, the responsibility for the accuracy and completeness of the data obtained by the contracting authority shall remain unaffected.
(6) Before commencing a clinical trial, the sponsor shall define, establish and distribute all obligations and functions relating to the clinical trial and shall ensure that only sufficiently qualified and experienced persons participate in all activities related to the preparation, implementation, evaluation, monitoring and auditing of the clinical trial, so that such persons are informed of their rights, duties and, where appropriate, functions and that their qualifications are documented.
(7) A procuring entity shall establish for the bodies of the evaluation or their legal representative a suitably qualified and readily available physician to provide consultations on health problems and issues arising from the clinical evaluation.
(8) The protocol, the choice of dosage form, the duration and route of administration of the investigational medicinal product should be supported by sufficient data on safety and efficacy from non-clinical studies or clinical trials, as appropriate.
(9) If the sponsor finds that there is a breach of the study protocol, standard working procedures, principles of good clinical practice, legislation or requirements of the Institute to examiners, medical establishments or other persons involved in the clinical trial, he shall without delay take action to ensure that deficiencies are remedied. If the monitoring or audit has revealed a serious or permanent breach as per the previous sentence on the part of the examiner or medical institution, the sponsor shall terminate the investigator's participation in the clinical trial or terminate the clinical trial at that point.
(10) Where the contracting authority is also an examiner, the provisions applicable to the examiner shall apply to it, with the exception of paragraph 4.
(11) In the case of a clinical trial which takes place in several locations, the contracting authority shall ensure that:
(a) prior to the initiation of the clinical trial, the responsibilities of the coordinating investigator, if any, and other participating examiners shall be documented;
(b) all examiners shall obtain guidance on compliance with the protocol, a single set of standards for the assessment of clinical and laboratory results and for the completion of the records of the evaluation bodies;
(c) communication between examiners is allowed;
(d) examiners are informed of the serious unexpected adverse reactions of investigational medicinal products occurring at other clinical trial sites;
(e) in the event of a change to a clinical trial or of a supplement to a request on the basis of an unfavourable opinion of the Ethics Committee for Multicentre Evaluation for that evaluation, a new application shall be submitted to the same Ethical Committee for Multicentre Evaluation.
(12) The contracting authority shall ensure that each evaluation body has given its written consent to direct access to its initial medical documentation for the purpose of monitoring, auditing, Ethics Commission inspections and inspection of the supervisory authority in connection with the clinical evaluation.
Application for authorisation and notification of a clinical trial by the Institute
(1) An application for authorisation of a clinical trial or for notification of a clinical trial pursuant to Article 55 (2) of the Medicines Act is submitted by the contracting authority to the Institute. Where an application or notification is made by a person other than the contracting entity, the application or notification of the mandate of the contracting entity shall be submitted to that person. Individual parts of the documentation shall be presented separately, with continuously numbered pages, indicating the content. The application shall be accompanied by proof of reimbursement of the expenditure of the examination of the application or of the declaration.
(2) The following documentation shall be submitted in duplicate with a request for authorisation of a clinical trial or a report of a clinical trial:
(a) a list of the documentation submitted,
(b) the Protocol and any additions thereto containing the particulars listed in Annex 1 to this Decree;
(c) written information to the investigator, either in the form of a set of information for the examiner, which contains the information referred to in Annex 4 to this Regulation, or in the form of a summary of product characteristics;
(d) written informed consent of the subject or his legal representative in the Czech language with any additions;
(e) written information addressed to the subjects of the evaluation, including the instruction of the subject or his legal representative in the Czech language;
(f) the records of the evaluation bodies;
(g) whether the clinical trial has already been issued by an ethics commission or by a foreign supervisory authority;
(h) pharmaceutical data on investigational medicinal products as listed in Annex 5 to this Decree;
(i) in the case of a multi-centre clinical trial, information on which Ethical Committee for Multi-Centre Assessment has been submitted for an opinion;
(j) a summary of the study in the Czech language.
Where clinical trials are not aimed at obtaining documentation for the marketing authorisation or the development of a medicinal product and in which neither the manufacturers nor the persons involved are involved, the scope of such documentation, as well as its management and storage, may, after consultation with the Institute, be adapted to the appropriate nature of the clinical trial, for example as regards the documentation referred to in point (h).
(3) If the clinical trial subject to the authorisation and the investigational medicinal product is a genetically modified organism9), proof of the registration of the genetically modified organism in the List of genetically modified organisms and products approved for circulation in the Czech Republic under the GMO and genetic product management law shall be submitted together with the application, where appropriate before the authorisation is granted. The application shall be accompanied by a risk assessment under another legislation10).
(4) Upon request by the Institute, the contracting authority shall submit the additional supporting documents necessary for the assessment of the clinical trial, such as the information requested by the State Office for Nuclear Safety in the case of clinical trials with radiopharmaceuticals. The Institute may notify the various parts of the required documentation referred to in paragraph 2, the procedure characterising the different types of clinical trial and the relevant requirements and supporting documents by publication in its information medium.
Clinical trial, data collection and record keeping
(1) In the course of a clinical trial, the contracting authority shall continuously evaluate the clinical trial procedure, the safety of the investigational medicinal product, critical efficacy parameters, where appropriate, and, on the basis of the findings, take appropriate measures, including changes to or termination of the clinical trial.
(2) When using an electronic or remote management system for clinical trial data, the contracting authority shall:
(a) ensure and demonstrate that these electronic systems meet the criteria for completeness, accuracy, reliability and are suitable for the purpose;
(b) maintain standard operating procedures for the use of such systems;
(c) ensure that the proposed systems allow data changes in such a way that they are documented and the input data are not deleted;
(d) maintain a security system preventing unauthorised access to data;
(e) keep a list of persons authorised to make changes to the data;
(f) ensure adequate data backup;
(g) ensure the blindness of data if the clinical trial is blinded for the duration of the blind clinical trial.
(3) Where data or observations obtained during a clinical trial are further processed, comparison of original data and observations with processed data shall be possible.
(4) The contracting authority shall use the unique identifier of the evaluation bodies to identify all the monitoring data of each evaluation body.
(5) The contracting authority shall ensure that the documentation referred to in Annex 3 to this Regulation is drawn up and maintained before and during the clinical trial. Any change in ownership of the data obtained from the clinical trial and any interruption of the clinical development of the investigational medicinal product shall be notified by the sponsor to the Institute.
(6) After completion of the clinical trial, the contracting authority shall keep the documents listed in Annex 3 to this Regulation.
(7) The contracting authority shall draw up written procedures to ensure that changes made by representatives of the contracting authority in the records of the evaluation bodies are necessary, documented and agreed by the investigator. In the event of such changes, the representative of the contracting authority shall provide the examiner with a record of changes and repairs.
(8) Where a clinical trial is a sponsor, a medical institution, a university or a State through its organisational component, and where neither a manufacturer of medicinal products nor a person commercially linked to it is involved and has been agreed between the sponsor and the Institute, it shall ensure that data on suspected serious unexpected adverse effects of the investigational medicinal product are entered in the European database of the Institute.
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Regulation Information
| Citation | Decree No. 226 / 2008 Coll., on Good Clinical Practice and Closer Conditions of Clinical Evaluation of Medicinal Products |
|---|---|
| Regulation Type | Order |
| Author | - |
| Collection | Code of Laws |
| Date of Promulgation | 30.06.2008 |
|---|---|
| Effective from | 01.07.2008 |
| Effective until | - |
| Status | Valid |
The regulation text is for informational purposes only.
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