Procedures for the Clinical Trial of Medical Devices Intended for Human Use




Yüklə 178.31 Kb.
səhifə1/3
tarix14.04.2016
ölçüsü178.31 Kb.
  1   2   3


Republic of Latvia
Cabinet

Regulation No. 891

Adopted 21 September 2010

Procedures for the Clinical Trial
of Medical Devices Intended for Human Use


Issued pursuant to

Section 34, Paragraph two of the Medical Treatment Law


I. General Provisions
1. This Regulation prescribes the procedures for the clinical trial of medical devices intended for human use.
2. Clinical trial of a medical device (hereinafter – trial) is any planned, lawful and systematic activity performed within the framework of the trial, in order to evaluate the conformity of effect of the medical device subject to the trial with the aims of the trial objectively in the trial centre.
3. A trial centre is a medical treatment institution or scientific institution complying with the mandatory requirements set out in the regulatory enactments in respect of medical treatment institutions, which, for the duration of a trial, is provided with the resources necessary for conducting the trial, including certified medical practitioners and other persons needed for conducting the trial.
4. A person participating in a trial (hereinafter – trial subject) is a clinically healthy natural person or patient voluntarily involved in the trial process of the manufacturer of medical devices or an authorised representative thereof (hereinafter – manufacturer). A trial subject shall be involved in a trial in order to analyse the effect of a medical device on the relevant subject or to investigate the samples derived from his or her body, including tissues and blood drawn. The trial subject may be a member of a control group. A control group is trial subjects involved in a trial, who use comparator medical devices with or without a therapeutic effect, in order to compare the results of the trial.
5. A medical device intended for trial (hereinafter – medical device) is a device created by the manufacturer for use in healthcare according to the latest achievements in mechanical engineering and engineering science, and which a trial subject can commence using in an adequate clinical environment within the framework of the particular trial under the supervision of a qualified medical practitioner.
6. An investigator is a medical practitioner who has a certificate of medical practitioner attesting to the professional background and competence of the relevant person in the sector related to the field of the medical device trial. An investigator shall be selected according to his or her qualification and experience by the manufacturer who shall take responsibility for the commencement and implementation of the trial, as well as for ensuring compensation to the trial subject in the event of unexpected risk.
7. A sub-investigator is a person involved in a trial, who works under the supervision of the investigator.
8. Purposes of a trial shall be the following:

8.1. to ensure and obtain proof that the performance of a medical device under normal conditions of use meets the essential requirements specified for it, and it has a previously expected effect on the trial subject;

8.2. to identify undesirable events or serious accidents likely to happen under normal conditions of use, and to assess whether they pose a risk for the health of the trial subject and user, so that, as the result of the performance of the medical device, the expected therapeutic benefit outweighs the potential risk posed for the trial subject; and

8.3. to obtain proof for the evaluation of the potential risk and therapeutic benefit ratio.


9. Clinical data is information regarding the safety and performance of a medical device sourced from:

9.1. the clinical trial of the device concerned; and



9.2. the trials reported in the scientific literature, of a similar device for which equivalence to the device in question can be demonstrated.
II. Opinion of the Ethics Committee
10. Prior to commencement of a clinical trial, the Ethics Committee shall provide an opinion regarding any issue related to the trial and of concern to the public, in order to ensure the rights, safety and well-being of a trial subject, as well as to convince the public that the trial subject is protected. The Ethics Committee is an independent organisation operating in a medical treatment institution or separately from a medical treatment institution.
11. The Ethics Committee shall be composed of persons having the appropriate qualification and experience, who can carry out a professional evaluation of ethical and scientific aspects of the relevant trial.
12. The Ethics Committee shall be composed of at least nine members. At least two persons not having medical education, as well as at least two independent persons who are not associated with the trial centre (the site where activities related to the clinical trial take place) shall be included in the Ethics Committee. The Ethics Committee shall comprise representatives of both genders.
13. The Ethics Committee has the right to invite experts without voting rights.
14. Activities of the Ethics Committee shall take place according to the by-law approved by the Chairperson of the Ethics Committee. The by-law shall be developed in accordance with this Regulation, recommendations of good clinical practice and the regulatory enactments regarding the data protection of natural persons.
15. The Ethics Committee shall have a quorum, if more than a half of the members of the Ethics Committee participates in the meeting.
16. An opinion of the Ethics Committee shall be issued by majority vote, by open voting of the members of the Committee.
17. Meetings of the Ethics Committee shall be minuted, and decisions of a meeting shall be recorded in the minutes. A member of the Committee whose opinion differs from the final decision of the Committee is entitled to express his or her opinion in an Annex to the minutes.
18. Only the Committee members independent from the investigator concerned may vote and express an opinion regarding the issues related to a particular clinical trial.
19. The Ethics Committee shall store all documents for five years after termination of the relevant clinical trial, except the cases where a longer period for the storage of documents has been set out in the regulatory enactments regarding the procedures for the record-keeping of medical documentation.
20. Information regarding the personnel of the Ethics Committee and qualification of the members, as well as the by-law of the Ethics Committee, shall be available upon the request to the investigator, the State Agency of Medicines (hereinafter – Agency) and the Ministry of Health.
21. The Ethics Committee shall submit to the Ministry of Health information regarding the personnel of the Committee, indicating the contact information, as well as information regarding the field of expert-examination and payment for the examination of a clinical trial submission. The Ministry of Health shall insert this information on the Internet home page thereof.
22. An applicant has the right to contest a decision of the Ethics Committee in the Central Medical Ethics Committee. The decision of the Central Medical Ethics Committee may not be appealed.
23. In order to receive an opinion of the Ethics Committee, a manufacturer shall submit the following documents to the Ethics Committee:

23.1. the trial plan;

23.2. the description of measures for involvement of the trial subjects;

23.3. the form referred to in Paragraph 63 of this Regulation;

23.4. the documentation specifying whether compensation related to the participation in the trial is anticipated for the trial subject;

23.5. the statement regarding conformity with the ethical aspects of the trial plan; and

23.6. the authorisation issued by the manufacturer, if the documents are submitted by the authorised representative thereof. The manufacturer shall ensure that the authorised representative thereof is registered in a European Union Member State or European Economic Area State.
24. The Ethics Committee shall assess the conformity of the documents referred to in Paragraph 23 of this Regulation with the ethical norms as concerns the protection of human rights and human dignity in a trial, and shall, within 30 days after receipt of the documents referred to in Paragraph 23 of this Regulation, provide the manufacturer with a written opinion regarding the trial plan. A copy of the opinion shall be submitted to the Agency.
25. Every year the Ethics Committee shall draw up and until 1 February submit to the Agency a list of all the trial submissions examined and decisions taken in the preceding year.
III. Issue of Permits for Conducting a Trial
26. The manufacturer shall receive a permit of the Agency for conducting a trial.
27. In order to receive a permit of the Agency for conducting a trial (hereinafter – trial permit), the manufacturer shall, 30 days prior to the commencement of the trial, submit the following documents to the Agency:

27.1. an application for receiving the trial permit (Annex);

27.2. the form referred to in Paragraph 63 of this Regulation; and

27.3. a receipt attesting to the manufacturer’s payment for the services referred to in Paragraph 28 of this Regulation.


28. The manufacturer shall cover the expenditure related to the examination of an application for receiving the trial permit. If the manufacturer is refused the trial permit, the paid expenditure shall not be repaid.
29. The Agency shall:

29.1. accept the manufacturer’s application for receiving the trial permit and the documents appended thereto;

29.2. evaluate an opinion provided by independent experts in respect of the medical device; and

29.3. assess the adequacy of the trial centre resources (medical practitioners and medical treatment support persons, appropriate medical technologies) and the number of patients of the relevant type for conducting the trial, as well as the ability to evaluate the clinical data obtained.


30. Pursuant to the procedure set out in the Administrative Procedure Law, the Agency, after receipt of the documents referred to in Paragraph 27 of this Regulation, shall take a decision regarding the issue of the trial permit, if the following conditions are fulfilled:

30.1. all the documents referred to in Paragraph 27 of this Regulation have been submitted, and they conform to the requirements set out in this Regulation;

30.2. an opinion of the Ethics Committee has been received, where a positive evaluation of the trial plan is provided, and no objections are made or no substantial corrections are proposed concerning the trial plan;

30.3. the trial is expected to be conducted in compliance with the requirements of this Regulation; and

30.4. the trial centre resources (professional qualification and experience of the medical practitioners and medical treatment support persons, medical technologies), the number of patients of the relevant type and the possibilities for evaluating the clinical data obtained conform to the requirements set out for conducting the trial.
31. The Agency shall, within five working days after taking of the decision referred to in Paragraph 30 of this Regulation, inform the manufacturer in writing regarding the decision taken.
32. The Agency shall enter information concerning the decisions taken, which are referred to in Paragraph 30 of this Regulation, into the European Databank on Medical Devices Euramed (hereinafter – Databank). The following information shall be included into the Databank:

32.1. the name of the manufacturer;

32.2. the name of the medical device;

32.3. the title of the trial;

32.4. the version number of the trial plan;

32.5. the primary objective of the trial;

32.6. the given name, surname of the contact person of the Agency;

32.7. the decisions taken in relation to suspension of the operation of the trial permit or withdrawal of the trial permit (the date of and justification for taking the decision); and

32.8. information concerning suspension or termination of the trial before the term anticipated in the trial plan, if the life or health of the trial subject is endangered (the date of and justification for taking the decision).
33. The Agency shall issue a trial permit to the manufacturer for the period of trial set out in the trial plan.
34. The manufacturer is entitled to commence a trial of medical devices belonging to Class III, implantable medical devices and long-term use invasive medical devices belonging to Class IIa or IIb within 30 days after submission of the documents referred to in Paragraph 27 of this Regulation, unless the Agency has taken a decision regarding the refusal to issue the trial permit.
35. The manufacturer is entitled to commence the trial of medical devices bearing the CE marking, if in the opinion of the Ethics Committee a positive evaluation of the trial is provided, no objections are made or no corrections are proposed concerning the trial plan, and the Agency, within 30 days after receipt of the information referred to in Paragraph 48 of this Regulation, has not taken a decision regarding the refusal to issue the trial permit due to the non-compliance with the requirements referred to in this Regulation (except the case if the objective of the trial is to obtain proof that the medical device acts on the trial subject in a way that has not been expected when assessing the device in the conformity assessment procedure).
36. The Agency shall temporarily suspend the operation of a trial permit, if the Agency has the following information at the disposal thereof:

36.1. concerning the risk not studied and analysed by the manufacturer and due to which the life or health of the trial subject or medical practitioner is endangered; or

36.2. concerning the non-conformity of the trial with the trial plan.
37. The Agency shall renew the operation of a trial permit after rectification of the risks and non-conformities referred to in Paragraph 36 of this Regulation.
38. The Agency shall withdraw a trial permit, if the following information is at the disposal thereof:

38.1. the medical device is dangerous and causes or has the potential to cause direct threat to the life or health of the trial subject or medical practitioner;

38.2. the documents referred to in Paragraph 27 of this Regulation have contained false or misleading information; or

38.3. the infringements referred to in Paragraph 76 of this Regulation have not been eliminated within the time period specified.


39. The Agency shall inform the European Commission and the European Union Member States regarding the decision taken in connection with the suspension of operation of a trial permit or withdrawal of a trial permit by using the Databank.
40. The manufacturer is entitled to amend a trial plan, informing the Agency thereof. In order to continue a trial, a new opinion of the Ethics Committee and a new trial permit shall be received pursuant to the procedures set out in this Regulation, except the cases when the harm caused to the health of the trial subject should be eliminated without delay.
41. The manufacturer has the right to contest a decision taken by the Agency in the Ministry of Health. A decision of the Ministry of Health may be appealed to a court by the manufacturer in accordance with the procedures set out in the Administrative Procedure Law.
IV. Requirements for a Trial and Medical Devices
42. The manufacturer shall prepare documentation concerning each medical device, including the following information:

42.1. the data allowing identification of the medical device in question;

42.2. the trial plan;

42.3. the opinion of the Ethics Committee;

42.4. the given name and surname of the doctor responsible for the trial or of another authorised person, and the name of the institution responsible for the trial;

42.5. the planned trial site, the date of commencement and the planned term;

42.6. the statement concerning the conformity of the medical device in question with the essential requirements, except the aspects related to the objectives of the trial, and that in respect of these aspects everything is being done for the protection of the health and safety of the patient;

42.7. the confirmation that the manufacturer or investigator has a valid civil liability insurance containing the provisions regarding compensation to be granted to the trial subject in the event of harm caused thereto or death of the trial subject caused by the trial;

42.8. the form referred to in Paragraph 63 of this Regulation;

42.9. the investigator’s brochure;

42.10. the document specifying whether the device incorporates, as an integral part, a medicinal product, human blood, a human blood component, or manufactured products derived from human cells and tissues; and

42.11. the document specifying whether the device has been manufactured by using tissues of animal origin.


43. A trial plan is a document containing the following information:

43.1. the objective of the trial;

43.2. the justification for the scientific, technical and medical necessity of the trial;

43.3. the parties involved in the trial and responsibility thereof;

43.4. the assessment of impact on the state of health of the trial subject and the expected benefits for the trial subject;

43.5. the methods for selection of the trial subjects (conditions for inclusion or non-inclusion) and the planned number of the trial subjects;

43.6. the evaluation of potential risks related to the use of the medical device, and measures for the prevention thereof;

43.7. the planned duration of the trial, and planned trial measures;

43.8. the number of the medical devices intended to be used in the trial;

43.9. the methodology for processing data obtained in the trial, monitoring and management of the processing;

43.10. the conditions for the evaluation, protection and storage of the data obtained in the trial; and

43.11. the procedures for publishing the results of the trial.


44. The manufacturer shall ensure, for the needs of the Agency, storage of the following information regarding medical devices:

44.1. the general description of the medical device and expected method of use thereof;

44.2. the design drawings, planned manufacturing methods (in particular as regards sterilisation), as well as diagrams of components, sub-assemblies, circuits, etc.;

44.3. the descriptions and explanations of the documentation referred to in Sub-paragraph 44.2 of this Regulation;

44.4. the results of the risk analysis and list of standards applied in full or in part, as well as solutions for ensuring compliance with the essential requirements, if the referred to standards are not applied in full;

44.5. the results of the design calculations, tests and technical tests; and

44.6. the data concerning the tests conducted, which are required for assessment of the safety, quality and usefulness of the medical devices, taking into account the intended purpose of use of the relevant device, if the device incorporates, as an integral part, a medicinal product, human blood, a human blood component, derivatives of cells or tissues.
45. The manufacturer shall store the information included in the documentation referred to in Paragraphs 42 and 44 of this Regulation for at least five years, while the information concerning the active implantable devices – for at least 15 years.
46. The manufacturer shall ensure that in the manufacturing process such medical devices are produced which conform to the conditions referred to in Sub-paragraphs 44.1 and 44.2 of this Regulation and the requirements set out in the regulatory enactments regarding the registration, conformity assessment, distribution, operation and technical supervision of medical devices.
47. The requirements referred to in Paragraphs 34, 42, 44, 45 and Sub-paragraphs 49.1 and 49.2 of this Regulation shall not be applicable to medical devices bearing the CE marking, except the cases if the objective of the trial is to obtain proof that the medical device acts on the trial subject in a way that has not been expected when assessing the device in the conformity assessment procedure.
48. Prior to commencing the trial of the medical devices referred to in Paragraph 47 of this Regulation, the manufacturer shall provide the following information to the Agency:

48.1. the name of the medical device or codified name of the medical device, its type and manufacturing (batch) number;

48.2. the number of the medical devices intended to be used in the trial;

48.3. the objective of the trial and justification for necessity of the trial (also conditions for inclusion and non-inclusion of the trial subjects and methods to be used for data analysis);

48.4. the parties involved in the trial:

48.4.1. the given name, surname and profession (speciality) of the investigator and sub-investigators;

48.4.2. the planned trial site;

48.4.3. the planned number of the trial subjects;

48.5. the planned date of commencement of the trial and the planned term;

48.6. the form referred to in Paragraph 63 of this Regulation;

48.7. the form of the registration document of the data obtained during the trial; and

48.8. the opinion of the Ethics Committee.


49. The manufacturer shall ensure supply of medical devices, as well as comparator devices, if they are used in the trial, to the trial centre free of charge. A medical device shall be accompanied by the following:

49.1. the documentation regarding a medical device referred to in Paragraph 42 of this Regulation;

49.2. the trial permit;

49.3. the general description of the medical device and the intended use thereof;

49.4. the detailed description of the medical device, including information regarding the qualitative and quantitative composition of the device and features characteristic of the device, or the design drawings of the medical device, as well as information regarding the methods of manufacture, also regarding the components of the device, sub-assemblies, circuits and sterilisation methods, containing the descriptions and explanations required; and

49.5. design calculations, the results of testing and technical trials performed.


50. The following information shall be indicated on the packaging of a medical device:

50.1. the name of the medical device or codified name of the medical device;

50.2. the type and manufacturing (batch) number of the medical device;

50.3. the data of the manufacturer (name, address);

50.4. the identification number of the trial;

50.5. the methods of use and routes of administration of the medical device;

50.6. the identification code of the trial subject (if the medical device is intended for one trial subject);

50.7. the given name, surname of the investigator;

50.8. the conditions for storage of the medical device;

50.9. the date of expiry of the medical device, indicating the year and month before which the medical device may be used safely, if the medical device has a limited use period (or the life cycle of the device, if the medical device has a limited life cycle);

50.10. the indication whether the device incorporates human blood, a human blood component, derivatives of human cells or tissues; and

50.11. the indication “Vienīgi klīniskajai izpētei” [For clinical trial only].


51. The labelling of a medical device shall contain at least the information referred to in Sub-paragraphs 50.2, 50.3 and 50.6 of this Regulation.
52. The manufacturer shall be liable for the safety, quality, supply of a medical device to the trial centre, conditions for storage, duration of use and provision of the record-keeping system.
53. The manufacturer shall provide all the persons involved in the trial with information concerning the safety, quality, conditions for storage, duration of use of a medical device and the provision of the record-keeping of the use thereof. The persons involved in a trial have a duty to strictly comply with all the conditions specified by the manufacturer in respect of the storage and operation of the medical device.
54. An investigator shall be liable for the storage of a medical device in the trial centre.
  1   2   3


Verilənlər bazası müəlliflik hüququ ilə müdafiə olunur ©azrefs.org 2016
rəhbərliyinə müraciət

    Ana səhifə