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.

V. Trial Methods and the Clinical Evaluation

55. A trial shall include a definite number of observations to guarantee the scientific validity of the clinical evaluation and conclusions.

56. The procedures used in the trial shall be appropriate to the relevant medical device.

57. The trial shall be conducted in circumstances similar to the normal conditions of use of the medical device.

58. All the features of the relevant medical device, including those related to the safety of operation and design of the medical device and effects thereof, as well as the action of the medical device on the patients and trial subjects, shall be examined when conducting a trial.

59. The manufacturer shall update constantly the clinical data of the technical documentation of the medical device manufacturing, based on the information obtained within the scope of the post-market surveillance of the mass-produced medical device. If the clinical evaluation of the medical device is not performed within the scope of the post-market surveillance of the device, it shall be duly justified and documented.

60. The manufacturer shall provide the investigator with access to the required technical and clinical data regarding the relevant medical device.

VI. Protection of a Trial Subject

61. An investigator shall be liable for ensuring healthcare of the trial subject and for all the activities related to the trial. If necessary, the manufacturer shall ensure additional training of the investigator.

62. Prior to commencing a trial, an investigator shall provide the trial subject with written information regarding:

62.1. the objective of the trial and the methods to be used;

62.2. the expected benefit and potential risks;

62.3. the planned duration of the trial;

62.4. the compensation related to participation in the trial (if any);

62.5. the civil liability insurance of the investigator, containing the provisions regarding compensation to be granted to the trial subject in the event of harm caused thereto, and the procedures for covering the medical treatment expenses of the trial subject associated with the harm caused in the clinical trial;

62.6. the option of discontinuing participation in the trial at any time, without giving explanation for the reasons of such action;

62.7. the measures planned in order to protect the health and safety of the trial subject and not to allow adverse impact of the trial on the health of the trial subject; and

62.8. the use of the data obtained during the trial, which are related to the state of health of the trial subject and the quality of the trial, in the trial assessment procedures.

63. An investigator shall provide the information referred to in Paragraph 62 of this Regulation in a manner comprehensible to a trial subject, by completing the form drawn up by the investigator regarding the voluntary consent of the trial subject for participation in the trial of the relevant medical device.

64. The form referred to in Paragraph 63 of this Regulation shall be drawn up in two copies, and it shall be signed and dated by the trial subject or his or her guardian or trustee, and the investigator. One copy of the form shall be kept by the investigator, while the second copy shall be issued to the trial subject or his or her guardian or trustee.

65. It is prohibited to perform a clinical trial on a pregnant woman and a nursing mother, except in cases when the clinical trial cannot be otherwise conducted, and the risk from conducting the clinical trial is reasonably balanced with the expected benefit for the embryo, foetus or the suckling infant.

66. Persons needing active medical treatment of a disease shall not be included in a trial control group.

67. In order to ensure the protection of the data of a trial subject, the investigator shall assign to each trial subject an identification code, which shall substitute the given name and surname of the trial subject when providing information to the manufacturer, the Agency and the Ethics Committee.

68. If during a trial an investigator obtains information concerning the circumstances which can pose a threat to the life or health of the trial subject, he or she shall immediately inform the trial subject thereof in writing.

69. In the case referred to in Paragraph 68 of this Regulation, an investigator has a duty to receive a written voluntary consent of the trial subject concerning the further participation in the trial.

70. If a trial is discontinued or completed before the term anticipated in the trial plan, the investigator shall inform the trial subject thereof and ensure further observation, examination and medical treatment of the trial subject within the scope of the relevant medical treatment episode during which the medical device had been used, as well as in case if harm has been caused to the trial subject in the trial.

71. The manufacturer shall not be liable for harm caused to the health of a trial subject, which has been intentionally (on purpose) done by the investigator or sub-investigator or which has arisen due to gross negligence or wrongful intent of the investigator.

VII. Monitoring of a Trial and Submission of Reports

72. In order to monitor the course of a trial and ensure its conformity to the requirements of this Regulation, the Agency shall:

72.1. register, assess and, in co-operation with the manufacturer of the medical device, analyse serious adverse events and unexpected occurrences caused by the medical device by acting in an unexpected way on the trial subject, especially in the case if there are risks that have not been notified by the manufacturer, but which can endanger the life of the trial subject and cause serious health impairments;

72.2. maintain an electronic database of the investigation section of the medical device register LATMED;

72.3. develop and publish the guidelines on the clinical evaluation of medical devices, recommendations and other information exchange documents;

72.4. if necessary, request to make changes in the trial plan or suspend the trial process, taking into account the interests of the public health protection and aspects of the prevention of the risk to the safety of the trial subject. In this case, the Agency shall, indicating the justification of the action, inform the European Union Member States by using the Databank; and

72.5. provide the Health Inspectorate (hereinafter - Inspectorate) with information concerning the decisions taken in connection with the trial permits.

73. In order to ensure the conformity of implementation of the trial plan with the trial objective, the Inspectorate, according to the competence thereof, is entitled to carry out an inspection of the trial. The Inspectorate shall notify the Agency regarding the results of the inspection.

74. In order to ensure monitoring and appropriate quality control, the duty of persons involved in a trial shall be to provide the Agency and the Inspectorate with direct access to the documents at all the sites related to the trial.

75. If necessary, the Agency shall involve in the evaluation of the trial course experts with the appropriate qualification and experience.

76. If there is information at the disposal of the Agency attesting that the manufacturer or investigator has not observed the requirements set out in this Regulation, the Agency shall inform the manufacturer and investigator thereof without delay, by specifying measures for eliminating infringements and execution terms thereof.

77. During the course of a trial the manufacturer shall submit, once a year, to the Agency and the Ethics Committee the following documents:

77.1. the trial progress report (if duration of the trial exceeds 18 months); and

77.2. the review regarding the serious adverse events and unexpected occurrences detected.

78. The manufacturer shall, within 90 days after the end of the trial, submit to the Agency and the Ethics Committee a final report of the trial. The report shall include the following information:

78.1. stability of the parameters and performance and the medical device under normal conditions of use, and conformity with the essential requirements of the medical device;

78.2. the clinical evaluation of serious adverse events and unexpected occurrences;

78.3. the effect of the medical device on the trial subject and the evaluation thereof; and

78.4. the summary of the previously conducted trials or copies of scientific publications related to the trial of the relevant medical device.

79. If a trial is discontinued or completed before the term anticipated in the trial plan, the manufacturer shall submit to the Agency a written report containing information regarding the reasons for discontinuation or completion or the trial and clinical evaluation of all the data obtained in the trial. If the life or health of the trial subject has been endangered, the referred to report shall be sent to the European Commission and European Union Member States, by using the Databank.

80. The manufacturer shall ensure documentation of all the serious adverse events and unexpected occurrences related to the performance of the medical devices belonging to Class I, IIa, IIb and III, and shall, within three days after a serious adverse event or unexpected occurrence being determined, notify the Agency thereof, indicating the circumstances and description of the adverse event.

81. A serious adverse event is any adverse event which has caused death of a trial subject or medical practitioner or which endangers the life or health of a trial subject or medical practitioner, and in the result of which medical treatment of a trial subject or medical practitioner in an outpatient institution is necessary or the duration of the medical treatment in an outpatient institution is prolonged or which causes permanent or serious health impairments (impairment of the anatomic organisation or functions of a human being, the elimination of which requires invasive treatment, causes permanent work disability, congenital defects, pathology of pregnancy).

82. An unexpected occurrence is any occurrence which, due to its nature and severity degree, does not conform to the information provided by the manufacturer previously in respect of the planned effect of the medical device.

83. The manufacturer shall ensure documentation of changes in clinical symptoms and laboratory data of the trial subject detected during the performance of the medical devices irrespective of whether such serious adverse events and unexpected occurrences were or were not caused by the relevant medical device.

VIII. Storage of Trial Data

84. The lists of identification codes of trial subjects shall be stored for at least 15 years, while the standard operating procedures, investigator's brochure, data registration documents of each trial subject, reports on the trial and opinions regarding the trial plan and the course of the implementation thereof - for at least 10 years after the end of the trial.

85. The manufacturer shall be liable for the storage of the documents referred to in Paragraph 84 of this Regulation.

IX. Closing Provision

86. Paragraphs 32 and 39, Sub-paragraph 72.4 and Paragraph 79 of this Regulation shall come into force on 1 May 2011.

Informative Reference to European Union Directives

This Regulation contains legal norms arising from:

1) Council Directive 90/385/EEC of 20 June 1999 on the approximation of the laws of the Member States relating to active implantable medical devices;

2) Council Directive 93/42/EEC of 14 June 1993 concerning medical devices; and

3) Directive 2007/47/EC of the European Parliament and of the Council of 5 September 2007 amending Council Directive 90/385/EEC on the approximation of the laws of the Member States relating to active implantable medical devices, Council Directive 93/42/EEC concerning medical devices and Directive 98/8/EC concerning the placing of biocidal products on the market.

Prime Minister V. Dombrovskis

Minister for Health D. Gavars

 

Annex
Cabinet Regulation No. 891
21 September 2010

Medicīniskās ierīces klīniskās izpētes iesniegums
Application for Clinical Trial of a Medical Device

I. Vispārīgā informācija General information

1. Klīniskā pētījuma nosaukums Name of clinical trial

2. Klīniskās izpētes plāna kods (versijas numurs vai datums) Clinical trial plan code (version number or date)

3. Ierīces ražotājs vai pilnvarotais pārstāvis (nosaukums, adrese, tālrunis, fakss, e-pasta adrese) Device manufacturer or authorised representative (name, address, phone, fax, e-mail)

4. Ierīces ražotāja pārstāvis (vārds, uzvārds, adrese, tālrunis, fakss, e-pasta adrese) Representative of the manufacturer (name, surname, address, phone, fax, e-mail)

5. Izpētes centrs (nosaukums, adrese, tālrunis, fakss, e-pasta adrese) Trial centre (name, address, phone, fax, e-mail)

6. Izpētes centra pārstāvis (vārds, uzvārds, adrese, tālrunis, fakss, e-pasta adrese) Representative of the trial centre (name, surname, address, phone, fax, e-mail)

7. Atbildīgais par klīniskās izpētes uzraudzību Latvijā (vārds, uzvārds, adrese, tālrunis, fakss, e-pasta adrese) Person responsible for clinic trial monitoring in Latvia (name, surname, address, phone, fax, e-mail)

II. Medicīniskā ierīce, kas paredzēta klīniskajai izpētei Medical device intended for clinical trial

8. Medicīniskās ierīces nosaukums vai kodēts nosaukums (šifrs), modelis vai tipa numurs Name or code (cipher), model or type number of medical device

9. Medicīniskās ierīces grupa Group of medical device

10. Medicīniskās ierīces klase Class of medical device

11. Medicīniskās ierīces lietošanas veids Mode of use of medical device

12. Medicīniskās ierīces sastāvā esošo bioloģiski aktīvo vielu vai to vielu nosaukums, kas atrodas saskarē ar audiem Name of biologically active substances contained in medical device or name of substances which are in contact with tissues

III. Medicīniskās ierīces lietošanas mērķis Intended use of medical device 13. Klīniskā izpēte attiecas uz: Clinical trial refers to

13.1. invazīvām medicīniskām ierīcēm Invasive medical devices

13.2. neinvazīvām medicīniskām ierīcēm Non-invasive medical devices

13.3. substanci, materiālu Substance, material

13.4. medicīniskām ierīcēm, kas paredzētas slimību diagnostikai Diagnostic medical devices

13.5. medicīniskām ierīcēm, kas paredzētas slimību profilaksei Medical devices intended for disease prevention

13.6. medicīniskām ierīcēm, kas paredzētas dzimstības kontrolei Medical devices intended for birth control

13.7. medicīniskām ierīcēm, kas paredzētas traumu un sakropļojumu diagnostikai Medical devices intended for diagnosis of traumas and mutilations

13.8. medicīniskām ierīcēm, kas paredzētas slimību ārstēšanai vai atvieglošanai Medical devices intended for disease healing or relieving

13.9. medicīniskām ierīcēm, kas paredzētas cilvēka anatomijas vai fizioloģisko procesu pētīšanai, aizstāšanai vai pārveidošanai Medical devices intended for research, substitution or transformation of human anatomy or physiological processes

13.10. medicīniskām ierīcēm, kas paredzētas cilvēka anatomisko vai fizioloģisko trūkumu atvieglošanai vai kompensēšanai Medical devices intended to relieve and compensate anatomical and physiological defects

13.11. medicīniskām ierīcēm, kas paredzētas traumu un fizisku trūkumu atvieglošanai un ārstēšanai Medical devices intended to heal and relieve traumas and bodily defects

13.12. medicīniskām ierīcēm, kas paredzētas slimību novērošanai Medical devices intended for disease observing

13.13. medicīniskām ierīcēm, kas paredzētas fizisku trūkumu monitorēšanai Medical devices intended for monitoring bodily defects

13.14. medicīniskām ierīcēm, kas paredzētas traumu un fizisku trūkumu ārstēšanai Medical devices intended to heal traumas and bodily defects

13.15. citu ierīci (lūdzu norādīt) Other kind of device (please specify)

14. Medicīniskās ierīces reģistrācijas numurs medicīnisko ierīču reģistrā LATMED (ja ierīce ir reģistrēta) Registration number of medical device in register of medical devices LATMED (if registered)

15. Medicīniskās ierīces reģistrācija ražotājvalstī, Eiropas Savienības dalībvalstī vai citā valstī (ja ierīce ir reģistrēta) Registration of medical device in the manufacturing country, EU Member State or other country (if registered) _________________________________________________________________________________________

IV. Medicīniskā ierīce reģistrēta Medical device is registered

Valsts Country

Reģistrācijas Nr. Registration No.

Nosaukums Name

V. Medicīniskā ierīce pieteikta reģistrācijai Medical device has been applied for registration

Valsts Country

Datums Date

Nosaukums Name

16. Salīdzinājuma medicīniskā ierīce vai citas klīniskajā izpētē papildus izmantojamās ierīces (ja iespējams, norādīt nosaukumu, reģistrācijas numuru, ražotāju un ražotājvalsti) Comparator medical device or other additional medical devices used in the clinical trial (if possible, specify name, registration number, manufacturer and manufacturing country)

VI. Klīniskās izpētes projekts Clinical trial project

17. Klīniskās izpētes mērķis Objective of clinical trial

18. Klīniskās izpētes tips Type of clinical trial

19. Ekvivalences izpēte Research of equivalence

20. Jauna kombinācija New combination

21. Jauna indikācija New indication

22. Pētāmo personu skaita palielināšana Increasing the number of research involving persons

23. Analizējamās pētāmās personas Research involving persons to be analyzed

24. Cits tips (lūdzu norādīt) Other type (please specify)

VII. Klīniskās izpētes veids Type of clinical trial

Salīdzinošs Comparative

Randomizēts Randomised

Krustots Cross over

Atklāts Open

Paralēlu grupu Parallel group

Placebo kontrolēts Placebo controlled

Akls Single blind

Dubultakls Double blind

Trīskāršakls Triple blind

Cits veids Other kind

(lūdzu norādīt) (please specify)

VIII. Klīniskās izpētes nozare Sphere of clinical trial

Kardioloģija Cardiology

Onkoloģija Oncology

Kosmetoloģija Cosmetology

Infektoloģija Infectology

Traumatoloģija Traumatology

Dietoloģija Dietics

Dermatoloģija Dermatology

Ķirurģija Surgery

Zobārstniecība Dentistry

Ortopēdija Orthopaedy

Radioloģija Roentgenology

Cita joma Other sphere

IX. Klīniskā izpēte ir Clinical trial is

starptautiska un multicentriska International and multicentral

monocentriska Latvijā Monocentral in Latvia

multicentriska Latvijā Multicentral in Latvia

izpētes centru skaits Latvijā Number of trial centres in Latvia

X. Paredzētais pētāmo personu skaits Latvijā Number of planned research involving persons in Latvia

25. Paredzētais pētāmo personu kopējais skaits (ja klīniskā izpēte ir starptautiska) Total number of planned research involving persons (if clinical research is multinational)

XI. Klīniskās izpētes laika grafiks Timetable of clinical trial

26. Klīnisko izpēti plānots sākt (datums) Clinical trial will start (date)

27. Klīnisko izpēti plānots beigt (datums) Clinical trial will end (date)

28. Medicīniskās ierīces lietošanas ilgums un biežums Length and frequency of medical device usage

29. Klīniskās izpētes ilgums un biežums pētāmajai personai Length and frequency of clinical trial for research involving person

XII. Klīniski pētāmās personas Clinical trial involving persons

Veseli brīvprātīgie Healthy volunteers

Pacienti Patients

Grūtnieces Pregnant women

Bērni Children

Citas personas Other persons

XIII. Izpētes centri Latvijā Trial centres in Latvia

30. Atbildīgais pētnieks (minēt pirmo) un pētnieki Responsible researcher (please, mention as the first) and researchers

31. Pētnieka palīgi Researcher's assistants

32. Klīniskās izpētes koordinators (vārds, uzvārds, adrese, tālrunis, fakss, e-pasta adrese) Coordinator of a clinical trial (name, surname, address, phone, fax, e-mail)

33. Valstis, kurās tiek veikta konkrētās medicīniskās ierīces klīniskā izpēte Countries where the clinical trial of a particular medical device is performed

XIV. Pielikumā Annex

34. Dokumentācija par medicīniskajām ierīcēm Documentation concerning medical devices

35. Apstiprinājums, ka ražotājam vai pētniekam ir spēkā esoša civiltiesiskās atbildības apdrošināšana, kas ietver nosacījumus par atlīdzību pētāmajai personai, ja viņai ir nodarīts kaitējums vai iestājusies pētāmās personas nāve, ko izraisījusi izpēte Confirmation that a manufacturer or a researcher has a valid civil liability insurance which contains compensation conditions for the research involving person if harm or death is caused by the trial

36. Medicīniskās ierīces un kontroles ierīces kvalitāti apliecinošo dokumentu kopijas (ražotāja atbilstības deklarācija, produkta sertifikāts, ražošanas kvalitātes sistēmas sertifikāts, atbilstības deklarācija par produkta kvalitātes nodrošināšanu, atbilstības deklarācija par pilnīgu kvalitātes nodrošināšanu, pārbaudes apliecība) Copies of the documents proving the quality of a medical device and control equipment (conformity declaration of a manufacturer, certificate of the product, certificate of production quality system, conformity declaration about products quality provision, conformity declaration about total quality provision, certificate of control)

37. Klīniskās izpētes uzraudzības un kontroles metodes apraksts Description of the initiated surveillance and control method of clinical trial

38. Pētnieka un pētnieka palīgu pieredzes un kvalifikācijas apraksts (pievienots dzīvesgaitas apraksts (Curriculum Vitae)) Description of the qualification and experience of a researcher and researcher's assistants (Curriculum Vitae attached)

39. Klīniskajā izpētē iegūto datu reģistrācijas dokumenta paraugs (versijas numurs un datums) An example of a register form for data obtained through clinical trial (version number and date)

40. Pētnieka un pētnieka palīgu rakstisks apliecinājums, ka klīniskā izpēte tiks veikta atbilstoši izpētes plānam un normatīvajiem aktiem par cilvēkiem paredzēto medicīnisko ierīču klīniskās izpētes kārtību Written statement by a researcher and researcher's assistants that the clinical trial will be performed according to the trial plan and in compliance with requirements set out in the regulatory enactments regulating the procedure of clinical trial of medical devices for human subjects

41. Izpētes centra vadības rakstiska piekrišana par klīniskās izpētes veikšanu izpētes centrā Written consent by the head of the trial centre for trial performance in the trial centre

42. Pētāmās personas identificēšanas pasākumu apraksts Description of identification measures for the research involving person

43. Ražotāja izstrādāta pētāmo personu brīvprātīgas piekrišanas dokumenta veidlapa (paraugs) Form of a voluntary consent document (sample) of research involving persons drafted by the manufacturer

44. Ražotāja izsniegta pilnvara (ja dokumentus iesniedz ražotāja pilnvarotais pārstāvis) Letter of authorisation from a manufacturer (if documents are submitted by a representative of the manufacturer)

45. Medicīniskās ierīces darbības parametri, ierīces darbības traucējumi un ar to novēršanu saistīto plānoto pasākumu kontrole  Operational parameters of a medical device, malfunctions of the device and control of the measures related to elimination of malfunctions

46. Informācija, kurā norādīts, vai ierīces neatņemama sastāvdaļa ir zāles, cilvēka asins atvasinājumi vai cilvēka izcelsmes šūnu un audu rūpnieciski ražoti produkti Statement indicating whether the device incorporates, as an integral part, medicine, human blood derivatives or products manufactured from human cells and tissues

47. Informācija, kurā norādīts, vai ierīce ir ražota, izmantojot dzīvnieku izcelsmes audus Statement indicating whether the device is manufactured utilising tissues of animal origin

48. Neatkarīgu ekspertu sniegtais pētījuma novērtējums Assessment of clinical trial by independent experts

49. Veidlapa par pētāmās personas brīvprātīgu piekrišanu dalībai konkrētas medicīniskās ierīces izpētē Form of a voluntarily consent of the research involving person on participation in a trial of a concrete medical device

50. Cita informācija, kas saistīta ar klīnisko izpēti un paredzēta pētāmajai personai (versijas numurs un datums) Other information which is related with and intended for the research involving person (version number and date)

51. Ražotāja iesniegtie dokumenti ētikas komitejā (datums) Documents submitted by the manufacturer to the Ethics Committee (date) ____.____.___________

52. Citi dokumenti (lūdzu norādīt) Other documents (please specify)

53. Persona, kuru ražotājs vai viņa pilnvarotais pārstāvis pilnvarojis sadarbībai ar Zāļu valsts aģentūru Person who is authorised by the manufacturer or representative of the manufacturer for the cooperation with State Agency of Medicines

53.1. vārds, uzvārds Name, surname

53.2. amats Position

53.3. adrese Address

53.4. tālruņa numurs Phone

53.5. faksa numurs Fax

53.6. e-pasta adrese E-mail

XV. Ražotāja apliecinājums Statement by a manufacturer Esmu iepazinies ar medicīnisko ierīču klīniskās izpētes noteikumiem Latvijas Republikā. Apliecinu, ka iesniegumā un tam pievienotajos dokumentos sniegtā informācija ir pareiza, aktuāla un pilnīga un ka nav slēpti būtiski dati, kas varētu ietekmēt pētāmo personu drošību un izpētes rezultātu ticamību. I am familiar with the rules of clinical trial of medical devices within the Republic of Latvia. I guarantee that the information in the attachment and submitted documents is correct, actual and complete. There are no any hidden data which can influence the safety of the research involving persons and the credibility of research results.

 

Ražotājs Manufacturer		Datums
	(vārds, uzvārds un paraksts*) (name, surname and signature*)	Date

 

Piezīme. * Dokumenta rekvizītu "paraksts" neaizpilda, ja elektroniskais dokuments ir sagatavots atbilstoši normatīvajiem aktiem par elektronisko dokumentu noformēšanu.

Note. *Document property "signature" is not filed out if the electronic document is formatted in compliance with regulatory enactments on formatting of electronic documents.

Minister for Health D. Gavars

 

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Translation © 2011 Valsts valodas centrs (State Language Centre)