Regulations On Clinical Trials Of Medicines And The Use Of Observation, The Labelling Of The Investigational Medicinal Product And Procedures Are Evaluated Compliance With Good Clinical Practice Requirements

Original Language Title: Noteikumi par zāļu klīniskās izpētes un lietošanas novērojumu veikšanu, pētāmo zāļu marķēšanu un kārtību, kādā tiek vērtēta atbilstība labas klīniskās prakses prasībām

Read the untranslated law here: https://www.vestnesis.lv/ta/id/130580

Cabinet of Ministers Regulations No. 172 in 2006 (February 28. 29. § 12) the rules on the use of clinical research and observation, the labelling of the investigational medicinal product and procedures are evaluated compliance with good clinical practice requirements Issued in accordance with article 5 of the law on pharmacy, 3, 6, and 15, paragraph i. General questions 1. determine drug (excluding veterinary drug) clinical trials (including multi-centre trials) procedure in accordance with good clinical practice requirements, use the observation procedure the labelling of the investigational medicinal product, order, and the order in which it is assessed compliance with good clinical practice requirements.
2. the investigational medicinal products are pharmaceutical form with or without the active substances that are being studied or used as a reference in a clinical trial, including registered medicinal products usage, shape or packaging, or indications differ from the registered or used to get additional information about the registered type.
3. study of the subject is a person who participates in a clinical trial using investigational medicinal products, or the control group.
4. The investigator is the person for treatment in accordance with the laws governing the treatment have the right to independently deal with treatment and who have practical experience in the sector of treatment associated with the clinical research field.
5. Sponsor means a natural or legal person who assumes responsibility for the clinical trial initiation, management or financing.
6. Protocol (updated version, Protocol amendments) is a document that describes the purpose of the research, design, methodology, statistical considerations and organisation of research, study subjects certainly inclusion and exclusion in the conditions, the research and publication of the results of the monitoring procedure.
7. the multicenter clinical trials according to a single protocol performs several researchers in several places. Trial sites may be located in one or more Member States, or in Member States and third countries.
8. The study subject's rights, safety and well-being is more important than science and the public interest.
9. Each of the clinical trials involved qualifications (education, training and experience) with its tasks.
10. the clinical trial is scientifically sound and in all respects is based on ethical principles.
11. Preclinical and clinical trials information on the investigational medicinal product are sufficient to support the proposed clinical trial.
12. in clinical trials, including bioavailability and bioequivalence studies, shall be designed, conducted and reported in accordance with good clinical practice requirements.
13. Good clinical practice is a set of internationally recognised ethical and scientific quality requirements which observed for designing, conducting and registering clinical trials with human participation in or providing reports on it.
14. The clinical trial information shall be recorded, handled and stored in such a way as to ensure the accurate reporting, interpretation and verification, while providing a trial subject to data protection.
 
 
II. The Sponsor and the investigator responsibility 15. The investigator and the sponsor, launches and clinical trials comply with these provisions, as well as treatment and individual data protection regulatory framework legislation.
16. On the subject of the study on medical care and all related clinical trials with medical decisions responsible is a researcher. The investigator is also responsible for conducting the clinical trial at a trial site. If the clinical trial at a trial site, the investigator is the group that is responsible for this group are referred to as the responsible researcher.
17. The Sponsor selects researchers, taking into account his qualifications and experience. If necessary, the sponsor provides the additional training of researchers.
18. The Sponsor, in whole or in part of its functions may authorize other natural or legal person (hereinafter referred to as the research cooperation). Also in this case, the sponsor shall fully remain responsible for the conduct of clinical trials and research data mining compliance with the requirements of this regulation.
19. The investigator and the sponsor may be one and the same person.
20. The Sponsor provides the conditions for insurance or indemnity to cover the liability of the investigator and sponsor. Sponsor is not responsible for damage caused by the investigator or other person involved in the clinical trial study subject caused intentionally or recklessly.
21. The Sponsor or the sponsor's legal representative is established in the European Union. If the sponsor or the sponsor's representative is a natural person, it is the European Union's declared place of residence.
22. the Sponsor shall provide the necessary clinical trials of investigational medicinal product supply, produced and quality controlled in accordance with the good manufacturing practice requirements.
23. The Sponsor is responsible for the quality of the investigational medicinal product, delivery of a clinical trial venue (Research Center), storage conditions, the duration and, if necessary, the dilution solution and medical equipment the medicine infusion for detection. The said conditions shall be informed of all investigational medicinal product chain involved. This person is obliged to respect the investigational medicinal product storage conditions.
24. On the investigational medicinal product storage and accounting research centre is responsible researcher.
25. the investigational medicinal products, as well as their use for entering the medical device, if they are needed, the sponsor supplied free of charge.
 
III. 26. Researchers the investigator's brochure the brochure is an investigational medicinal product in clinical and non-clinical information summary of drug research that involves people. The information in the investigator's brochure provides a concise, simple, objective, balanced and not advertising to treatment or potential investigator would be able to understand it and make an unbiased planned clinical trial compliance assessments, taking into account the anticipated risks and benefits. These requirements also apply to changes to the investigator's brochure.
27. where investigational medicinal products are established in the Member State of the European Union or the European economic area country, investigator's brochure may be replaced with the summary of product characteristics.
28. The Sponsor will be evaluated and updated investigator's brochure not less frequently than once a year.
 
 
IV. Research subjects protection 29. Clinical trials must be performed just in case: 29.1. the foreseeable risks and inconveniences have been examined in relation to the expected benefits of each trial subject and other present and future patients. Clinical trials may begin only if the Ethics Committee, and the State Agency of medicines has concluded that the estimated therapeutic and public health benefits justify the risks and clinical trials may continue, if compliance with this requirement is continuously monitored;
29.2. the trial subject or, when the person is unable to give consent, its legal representative after due information about the research nature, significance, implications and risks has provided a written, dated and signed, to take part in voluntary consent in clinical research (informed consent). If the person concerned is unable to write, in exceptional cases it can provide oral consent in the presence of at least one witness;
29.3. the trial subject or, when the person is not able to give informed consent, the legal representative has previously had the opportunity in an interview with a researcher or other individual involved in the conduct of clinical trials, clinical research to understand the objectives, risks and inconveniences, as well as the conditions under which it will be carried out, and the trial subject or, when the person is not able to give informed consent, the legal representative is aware of the right at any time to refuse from participation in the research;
29.4. the study subject's rights to physical and mental integrity, to privacy and protection of personal data are secured according to regulations on the physical protection of personal data;
29.5. the subject of the study is provided at any time to discontinue participation in the clinical trial, withdrawing their informed consent, and will have no adverse effect;
18.4. the insurance or reimbursement is provided for terms that cover the liability of the investigator and sponsor.
30. in addition to the provisions of paragraph 29 of the said conditions, clinical trials, in which study subjects are minors, you can do this only if the following conditions are met: 30.1. obtained informed consent provided by at least one of the parents or legal representative. Agreement to represent the minor in the views expressed and can be withdrawn at any time without adverse consequences for the minor party;
30.2. the staff with experience with minors, has informed the minors concerned according to its capacity of understanding about clinical trials, its risks and benefits;
30.3. the investigator or principal investigator is considered minor's express desire to opt out of participation or at any time to discontinue participation in clinical research, if the minor is able to express and justify your opinion and assessing this rule 29.3. information referred to in (a);

18.9. the minor is not encouraged or financially supports, except for compensation for expenses associated with participation in clinical research (for example, transport costs), as well as compensation for damage to health or clinical trials due to intervening death;
5. after clinical trials expected to directly benefit the patient group and, if such research is essential to validate data obtained in clinical trials on persons able to give informed consent or by other research methods. In addition, the studies must be directly linked with the disease suffer from a particular person or minor in nature such that it can only be performed on minors;
30.6. the compliance with the European Medicines Agency's scientific guidance;
19.1. clinical trials are designed to minimise pain, discomfort, fear and any other foreseeable risk in relation to the disease and the degree of development of the child. Both the risk threshold and the degree of suffering is a specially defined and constantly monitored;
19.1. the Ethics Committee, with paediatric expertise (for example, the Member is certified pediatrician) or after the receipt of the expert's clinical, ethical and psychosocial problems in the field of Paediatrics, has endorsed the Protocol;
19.2. the patient's interests prevail over those of science and society.
31. Persons who are not able to give informed consent, subject to all the provisions referred to in paragraph 29 requirements that apply to persons who are able to give such consent. If a clinical trial is a person who is not able to give informed consent and what not to have disclosed or not refused to give informed consent before this ability loss, exploration is allowed if, in addition to those requirements comply with the following conditions: 31.1. legal representative has been obtained informed consent. The consent of the subject of the study reflect the views expressed and can be withdrawn at any time without any adverse effects on the subject of the study;
31.2. a person who is not able to give informed consent has received his/her capacity of understanding relevant information on clinical trials, its risks and benefits;
31.3. the investigator or principal investigator is considered the person's explicit desire to relinquish at any time the membership or stop participating in the clinical trial, which is capable of expressing their views and evaluate the information;
19.5. a person who is not able to give informed consent are not encouraged or stimulated, excluding financial compensation for expenses related to participation in clinical research (for example, transport costs), as well as compensation for damage to health or clinical trials due to intervening death;
31.5. This clinical trial is essential to validate data obtained in clinical trials on persons able to give informed consent or by other research methods and relates directly to a life-threatening or debilitating clinical condition from which the person concerned suffers;
19.6. clinical trials are designed to minimise pain, discomfort, fear and any other foreseeable risk in relation to the understanding of disease and disability. Both the risk threshold and the degree of suffering is a specially defined and constantly monitored;
19.7. the Ethics Committee, with expertise in the relevant disease and the patient population concerned or after receipt of the expert's clinical, ethical and psychosocial problems in the field of the relevant disease and patient population concerned, has endorsed the Protocol;
19.8. the patient's interests prevail over those of science and society;
19.8. There is reason to believe that participation in clinical research will be a benefit to the patient by setting or produce no risk at all.
32. In an emergency, if it is not possible to get the study subject's informed consent and study the subject does not have a legal representative or a legal representative is not available, the subjects of study in clinical research may involve only if the Protocol is a description of the procedure for such involvement, and then agreed to the Ethics Committee, and the State Agency of medicines.
33. the investigator informs the subjects of study for individuals that are not directly subject to the researcher and can provide information on the progress of a clinical trial.
34. Clinical investigations shall be prohibited during pregnancy and her mother, who was breastfeeding, except if otherwise it is not possible to provide a clinical trial and the risk of doing clinical trials is reasonable compared with the expected benefits of the embryo, fetus or infant.
35. the subjects of the study, which requires active disease treatment, control group, in which the entity receives the study comparison without active substances preparation may involve only where compliance with these provisions 29., 30 and 31 and the conditions referred to in the Protocol provides for the involvement of the subject of the study on the scientific and ethical justification.
36. in order to ensure the trial subject's protection of personal data, the researchers will be granted for each trial subject identification code, which replaces the study subject's name and giving messages to the sponsor, the State Agency of medicines and the Ethics Committee. The patient's first and last name of a researcher may decode only at the request of the authorities, in accordance with the law of medical treatment have the right to consult the records of the patient.
37. If in the course of the clinical trial you will get information about the conditions that can cause hazard to the subjects of the study's life or health, the investigator shall immediately inform the subjects of the study. The subject of the study information provided is documented. In such cases, the subjects of the study in accordance with the provisions of paragraph 29, in addition to receiving a voluntary written consent for future participation in clinical research.
38. If the clinical trial is interrupted or completed before the run time specified in the Protocol, researchers shall inform the subjects of the study and determine the further treatment and observation.
 
 
V. 39. The Ethics Committee the Ethics Committee prior to the commencement of the clinical trial provide views on any issue requested to ensure the trial subject rights, safety and well-being, as well as to the public beliefs about this protection. The Ethics Committee is an independent organization, operating in the medical institution or unrelated to treatment.
40. The Ethics Committee is made up of qualified and experienced individuals who can assess the relevant ethical clinical trials and scientific aspects. Personnel of the Ethics Committee for an indeterminate period of time approved by the Minister of health.
41. the Ethics Committee shall be not less than nine members. The Ethics Committee shall include at least two persons who lack medical training, as well as at least two independent parties who are not affiliated with the Research Centre (the location where clinical trials are conducted with related transactions). The Ethics Committee is composed of representatives of both sexes.
42. The Ethics Committee shall have the right to call upon experts without voting rights.
43. the Ethics Committee shall be in accordance with the Ethics Committee approved charters. Charter has been developed according to Health Minister approves, approved these terms, good clinical practice recommendations, regulations on the physical protection of personal data, as well as other laws and regulations.
44. The Ethics Committee shall be valid if the meeting more than half of the members of the Ethics Committee.
45. the Ethics Committee shall be adopted by a simple majority of the members of the ethics committee vote openly.
46. the Ethics Committee meeting and recorded meetings decisions are recorded in the minutes. A member of the Committee whose opinion differs from the final decision of the Committee is entitled to make their views known in the annex to the Protocol.
47. To vote and comment on specific clinical trial issues may be binding only from the investigator and sponsor-independent members of the Commission.
48. The Ethics Committee all documents stored in the five years after the completion of clinical trials, unless the legislation is set for a longer period of storage of documents.
49. information on the composition of the Ethics Committee and members of the Qualifi cations, as well as the Ethics Committee's rules is available on request the researcher, sponsor, the State Agency of medicines and the Health Ministry.
50. The Ethics Committee, along with information on the harmonized personnel shall be submitted to the Ministry of health contact information as well as information on expertise and fee for clinical trial application review. The Ministry of health shall submit this information to the State Agency of medicines, as well as to place it on your website on the internet.
51. Once a year (to February 1) Ethics Committee shall submit to the State Agency of medicines in all the previous year in the clinical trial application and a list of the decisions taken.
52. in order to obtain the opinion of the Ethics Committee, the sponsor or the sponsor's authorized person submitted to the Ethics Committee in the following documents and particulars: 52.1. number the European clinical trials database (eudract);
52.2. the sponsor or the sponsor's authorized person sign the petition, drawn up with the European Commission developed a sample application (available in the State Agency of medicines home page on the internet);

52.3. the sponsor and the investigator shall sign the Protocol and Protocol amendments, if any, do;
52.4. sponsor of the research developed by the consent of the holder of the document in the language of the country. If the clinical trial is planned to involve a person who has knowledge of the national language level, which allows you to understand the consent document, submitted also in writing in a language that the study involved can understand;
52.5. other written information in the language of the country associated with the clinical trial and for the study subject. If the clinical trial is planned to involve a person who has knowledge of the national language level, which allows you to understand the information, it shall also be submitted in the language of the research involved can understand;
52.6. a study subject's involvement in the event description.
52.7. the investigator's brochure or this provision provided for in paragraph 27 of Annex-Summary of product characteristics presented;
52.8. researchers and other persons involved in a clinical trial, which the researchers choose to study centre and working under the supervision of researchers (Assistant researcher), a description of the experience and qualifications (curriculum vitae);
52.9. documents relating to the payment of compensation to the holder of a study of participation in clinical trials, if applicable, as well as the provisions of the policy of insurance or a copy, or a certificate attesting the subject of insurance research clinical trial potential damage as well as liability of the investigator and sponsor;
52.10. treatment services management consent to carry out clinical trials;
52.11. sponsor privileges if the document shall be submitted to the sponsor's authorized person.
53. In considering an application for commencement of a clinical trial and preparing the opinion of the Ethics Committee, particular attention: 53.1. clinical meaning and purpose;
the expected benefits and 53.2. risk assessment according to this rule 29.1. the validity of the findings and to point;
53.3. the Protocol;
53.4. researchers and staff for compliance;
13. the investigator's brochure;
53.6. premises and equipment quality;
53.7. the relevance of the information to be written to a particular clinical trial, the informed consent acquisition procedures, as well as clinical trial support to people who are unable to give informed consent, taking into account the provisions of article 29, 30 and 31, paragraph limits;
53.8. conditions for remuneration or compensation if the clinical trials because of injury to health or death;
is 53.9. any insurance or indemnity to cover the liability of the investigator and sponsor;
53.10. researchers and study the subject of indemnity or compensation provided for and, if necessary, the conditions, as well as between sponsor and the Research Center concluded the contract in which it is determined;
53.11. trial subject recruitment measures.
54. The Ethics Committee shall within 30 days after the registration for such application, which shall include all the information specified in these provisions, shall provide a written opinion for the applicant, stating the grounds for the opinion given in the opinion. A copy of the opinion submitted to the State Agency of medicines.
55. During the examination of the application for an opinion, the Ethics Committee may send a single additional information to the applicant's request. The period laid down in paragraph 54 of these regulations, to additional information.
56. The Ethics Committee extended this provision during the period referred to in paragraph 54, if the clinical trial is planned, which will include medicine gene therapy or somatic cell (any cell of the organism which is not known) for therapy or medicinal products containing genetically modified organisms. In such a case, the provisions referred to in paragraph 54 of the period extended pursuant to the administrative procedure law of the procedures laid down in it, but it is not more than 180 days from the date of registration of the application. Xenogeneic cell (foreign to the human body cells) in the case of the issuance of the opinion of the therapy period restrictions.
57. If a multi-centre clinical trial and all the study centres located in Latvia, the Ethics Committee shall give its opinion on the single of this clinical trial. If the multicenter clinical trial conducted simultaneously in more than one Member State, the Ethics Committee shall give an opinion on a single clinical trial in Latvia.
58. the Ethics Committee shall entitle the applicant to challenge the central medical ethics Committee. Central Medical Ethics Committee decision appeal in accordance with the Administrative Procedure Act.
 
 
Vi. State Agency of medicines authorisation-59. for the State Agency of medicines of the permission to start a clinical trial, the sponsor or the sponsor's authorized person shall submit to the State Agency of medicines in the following documents and particulars: 59.1. number the European clinical trials database (eudract);
59.2. the sponsor or the sponsor's authorized person sign the petition, drawn up with the European Commission developed a sample application (link available in the State Agency of medicines home page on the internet), in paper and electronic format (XML files);
59.3. sponsor and the investigator shall sign the Protocol and Protocol amendments, if any, do;
59.4. Overview of all active trials with investigational medicinal product concerned;
59.5. the use of the investigational medicinal product that summarizes data on the investigational medicinal product, t.sk. the reference for the preparation and the quality of the included placebo pre-clinical and clinical studies carried out previously for results, as well as the efficiency and risk assessment summary that critically analyses the preclinical and clinical data for the planned clinical trials the risks and the benefits, or the simplified search of the investigational medicinal product used, if a government agency of the medicinal product investigational medicinal products evaluated again;
59.6. Summary of product characteristics of the medicinal product in the Member States;
37.1. a list of those Member States in which the application was submitted, as well as the information about these institutions informed decisions, if available;
59.8. manufacturer's license copy, if the investigational medicinal products manufactured in the Member State of the European Union or European economic area Member State;
59.9. finding that the plant complies with the requirements of good manufacturing practice at least equivalent to the European Union good manufacturing practice requirements, as well as the importer's copy of the licence, if the investigational medicinal products manufactured outside the European Union;
59.10. attestation of investigational medicinal products the active substance production compliance with the good manufacturing practice requirements;
59.11. sponsor of the research developed by the consent of the holder of the document in the language of the country. If the clinical trial is planned to involve a person who has knowledge of the national language level, which allows you to understand the document written, submit information in a language that the study involved can understand;
59.12. other written information in the language of the country, related to the clinical trial and for the study of the subject. If the planned clinical trials involve a person who has knowledge of the national language level, which allows you to understand the information, submit information in a language that the study involved can understand;
59.13. insurance rules and a copy of the policy or certificate attesting the subject of insurance research clinical trial potential damage;
59.14. documents certifying that the sponsor and the investigator's liability insurance conditions and;
79. the documents that define the conditions and amount of refund of the study subjects;
59.16. the investigator's brochure or this provision provided for in paragraph 27 of Annex-Summary of product characteristics presented;
59.17. preparations examined a sample of the label of the packaging in the national language;
59.18. researchers the investigator and Assistant experience and qualifications;
59.19. the investigator's written assurance that the clinical trial will be carried out in accordance with the Protocol and regulations, as well as a written assurance that the researcher is trained to conduct the clinical trial in accordance with good clinical practice requirements;
the mandate of the sponsor, 59.20. If documents shall be submitted to the sponsor's authorized person.
60. The applicant, in accordance with the State Agency of medicines of pricing public services shall bear the expenses related to the pharmaceutical clinical trial application. If the clinical trial is denied, the paid expenses are not reimbursed.
61. the State Agency of medicines application (plus all the rules listed in paragraph 59) examines the 45 days after its receipt.
62. During the examination of the application, the State Agency of medicines can be send to the applicant a request for additional information. The period laid down in paragraph 61 of these regulations, to additional information.
63. a National Medicines Agency extended that provision, the period referred to in paragraph 61, if the clinical trial is planned, which will include medicine gene therapy or somatic cell (any cell of the organism which is not known) for therapy or medicinal products containing genetically modified organisms. In this case, the provisions referred to in paragraph 61 of the period extended pursuant to the administrative procedure law of the procedures laid down, but not more than 180 days from the date of registration of the application. Xenogeneic cell therapy in case of issue of term limits.

64. the National Agency for Medicines, this provision and paragraph 61.62. the period referred to in the decision on initiating a clinical trial or on a ban to launch a clinical trial and five working days after the decision shall inform the applicant in writing, stating the grounds for the decision. Permission not granted, pending the provision referred to in paragraph 60. Permit is issued for Protocol clinical trial.
65. A permit is not issued for a gene therapy research, which studies the subject's known to be a genetic identity modificēšano.
66. a clinical trial Authorisation of medicinal products containing genetically modified organisms, is issued in accordance with the laws and regulations on genetically modified organisms in contained use and deliberate release into the environment.
67. The applicant State Agency of medicines has the right to challenge the decisions of the administrative procedure law.
68. If a multi-centre clinical trial and all the study centres located in Latvia, the State Agency of medicines shall adopt a single decision about this clinical trial. If the multicenter clinical trial conducted simultaneously in more than one Member State, the State Agency of medicines shall adopt a decision on a single clinical trial in Latvia.
 
 
VII. Clinical trials started 69. Sponsor initiated clinical trials only after the Ethics Committee has given a favourable opinion and the State Agency of medicines has given permission to start clinical trial. Sponsor shall have the right to submit the application at the same time the Ethics Committee, and the State Agency of medicines.
70. If the Medicines Agency informed the sponsor of the decision to prohibit the commencement of the clinical trial, the sponsor may be only one time to amend this provision in the application referred to in paragraph 59 of the content, in order to take into account the grounds referred to in the decision. If the sponsor does not consider the grounds for the decision, referred to in the application shall be deemed to have been rejected and the clinical trials may not start.
 
 
VIII. Clinical trial of 71. After the commencement of the clinical trial, the sponsor shall have the right to make amendments to the Protocol. If these amendments can dramatically affect the security of the study subject's physical or mental integrity of a study of subject, scientific value, the progress of the study or conduct, the quality of the product of the study or their safety, the sponsor shall provide the national agencies in the application of medicines through the European Commission approved the amendment of the relevant application sample (link available medicines agency website on the internet), as well as in writing inform the Ethics Committee.
72. The Ethics Committee shall give its opinion, and the State Agency of medicines shall decide not later than 30 days after this rule amendment, paragraph 71.
73. If the Ethics Committee has delivered a favourable opinion and the State Agency of medicines has adopted a positive decision, the sponsor continues to perform clinical trials, subject to the amendments to the Protocol.
74. If the opinion of the Ethics Committee or the State agency decision is unfavourable, the sponsor may not introduce amendments to the Protocol before the opinion is not taken into consideration and the reasons for its decision. If a sponsor has not taken note of the opinion or decision referred to in the grounds, the sponsor of the amendments to the Protocol is considered rejected.
75. If clinical trials during the trial or investigational medicinal product research or development related conditions which may affect the safety of the subjects of the study, the sponsor and the investigator shall take appropriate urgent safety measures to protect the subjects of the study. The sponsor shall immediately inform the State Agency of medicines of the circumstances and the measures taken and shall ensure that the well is brought to the Ethics Committee.
76. If the amendments to the Protocol related to administrative matters (for example, change the phone number), the sponsor for them in writing to the Ethics Committee and the State Agency of medicines. The Ethics Committee opinion and national agency for medicinal products authorised in this case is required.
77. within 90 days of the end of a clinical trial the sponsor shall notify the State Agency of medicines and the Ethics Committee that the clinical trial has been completed in the Republic of Latvia. The sponsor shall provide the national agencies in the application of medicines through the European Commission approved the completion of the clinical trial application (link available medicines agency website on the internet). The sponsor shall notify the State Agency of medicines of Latvia patients involved in clinical trials. If the clinical trials are stopped before the end of the research, scheduled for termination of the research sponsor, within 15 days after the termination of a clinical trial shall inform the State Agency of medicines and the Ethics Committee, explaining the reason for termination of a clinical trial.
 
 
IX. the exchange of information 78. State Agency of medicines shall enter in a European clinical trials database information for each territory of Latvia applied clinical trials, including: 78.1. drug submission sponsor the National Agency for permission to request the initiation of the clinical trial;
78.2. any amendments to the application in accordance with the State Agency of medicines and 70 of these rules;
78.3. any amendments to the Protocol after the commencement of the clinical trial in accordance with this provision, 72 and 73 71;
78.4. opinion of the Ethics Committee;
78.5. notification of completion of the clinical trial in the Republic of Latvia;
78.6. information on the monitoring and evaluation of compliance with good clinical practice requirements.
79. at the request of any Member State, or the European Medicines Agency, the European Commission's reasoned request, the State Agency of medicines in addition to the provisions referred to in paragraph 78, the information you provide necessary information.
 
 
X. termination of research and 80. If the State Agency of medicines has reasonable grounds to consider that the provisions referred to in paragraph 59 of the application conditions are not complied with, or it is in possession of information that casts doubt on the safety of clinical trials or scientific validity, the State Agency of medicines has the right to suspend the clinical trials, informed the investigator and sponsor.
81. before the State Agency of medicines shall decide that rule 80. in the case referred to in the paragraph, the sponsor and the investigator so requests a week to provide information on the reasons for non-compliance with the conditions, except where there is a serious risk to the subject of the study.
82. If the State Agency of medicines has reasonable grounds to believe that the sponsor or the investigator or any other clinical trial involving the person does not comply with certain obligations, it shall inform the person concerned and indicate the steps it must take to remedy this situation. The State Agency of medicines shall inform the Ethics Committee, the other competent authorities and the European Commission on the activities undertaken.
83. the State Agency of medicines has the right to prohibit the clinical trial if the clinical trial poses a serious risk to the subject, but the study sponsor and the investigator did not take the necessary measures to ensure the safety of the subjects of the study.
84. Of the decision to suspend or prohibit the clinical trial, as well as the reasons for this decision, the State Agency of medicines shall inform the other competent authorities, the Ethics Committee, the European Medicines Agency and the European Commission.
 
 
XI. the production of investigational medicinal product, import and labelling requirements 85. manufacture of investigational medicinal products and the import of determined by law on the production and control of medicinal products and the importation and distribution of medicinal products.
86. the secondary packaging investigational medicinal product or, if not, the primary language of the country of the packaging indicates the information, in accordance with European Commission recommendations (guidelines), which relate to the production of medicinal products and which is published by the European Commission European Community pharmaceutical legislative framework document inventory (Eudralex).
 
 
XII. The clinical trial set of documents and their storage requirements 87. records of clinical trials is a research framework that supports clinical research and research on the quality evaluation of the data obtained. These documents will show whether the investigator and the sponsor to act in accordance with the principles of good clinical practice and guidelines, as well as the provisions on the registration of the medicinal product.
88. The clinical trial set of documents are the basis for an audit by the sponsor's independent auditors appointed, as well as monitoring and evaluation, conducted by the State Agency of medicines.
89. The basic document content relevant to the clinical trial phase.
90. The Sponsor and the investigator trials master documents shall be kept for at least five years after completion of the study in question, except that rule 91 and 92. documents listed.
91. the investigator is responsible for the trial subject identification code list storage for at least 15 years.
92. The Sponsor is responsible for the Protocol, SOPs, the investigator's brochure, each study subject enrollment data, clinical trial reports, written opinion on the clinical trial protocol and its progress are stored for at least five years after the preparations examined registrations.
93. Master documents stored longer if it's a specific law or between the sponsor and the investigator in the contract concluded.
94. Master documents stored in such a way that after the request of the State Agency, they would be immediately available, except for the ID codes that are only available to the authorities in accordance with the law of medical treatment have the right to consult the records of the patient.

95. Medical records for research subjects stored in accordance with the legislation on medical records filing procedure.
96. the data or a change of ownership of a master document. The new owner assumes responsibility for data storage and archiving in accordance with this rule 91 90, 92, 93, 94,..., and 95 points.
97. The Sponsor shall designate the person responsible for archives (person in charge).
98. access to the archive is only allowed in these regulations 97. persons referred to in point.
99. The master document stored under conditions which ensure the complete and document the requirements of appropriate conservation throughout specific period, as well as their availability at the request of the State Agency of medicines, except that rule 94. identification code referred to in paragraph 1.
100. Any changes to documents are easily traceable by storing the text in which the change was made.
 
 
XIII. The procedure is monitored and evaluated clinical trial compliance with good clinical practice requirements 101. evaluation is an official inspection carried out by the national agency of medicinal products and which time it checks the documents, facilities, records, quality assurance arrangements, and any other resources that the State Agency of medicines shall be deemed related to the clinical trial and Research Centre located in the cooperation of the sponsor or of the study rooms, as well as any other authority that the State Agency of medicines shall deem appropriate for the assessment.
102. in order to monitor and evaluate compliance with good clinical practice requirements, the State Agency of medicines has the right to visit places associated with clinical research, in particular research center and any laboratory used for analyses in the clinical trial.
103. the State Agency of medicines shall comply with the data protection requirements for good clinical practice during the monitoring and evaluation of the information obtained.
104. the monitoring and evaluation may be conducted by a person who has: 104.1. higher education or relevant experience in medicine, pharmacy, pharmacology, toxicology or other appropriate sectors;
104.2. knowledge of the principles and activities related to drug development and clinical trials, as well as knowledge of the European Union and the Republic of Latvia legislation on clinical trials and registration of the medicinal product;
104.3. knowledge of the operations and systems, which require clinical trial data for registration, as well as the health system organization and regulation.
105. the State Agency of medicines shall regularly update the information on the persons who are authorised to monitor and assess compliance with good clinical practice, qualifications, training and experience. The State Agency of medicines shall ensure that individual training, regularly evaluate training needs, as well as take appropriate measures for the persons concerned the maintenance and development of skills.
106. the State Agency of medicines shall ensure that persons referred to in paragraph 105 of the SOPs, as well as the description of the duties, responsibilities and training requirements for detailed descriptions. The State Agency of medicines shall regularly update the description of the SOPs, as well as other rules 105. persons referred to in paragraph 1 for information.
107. the State Agency of medicines that 105 persons mentioned in paragraph provides a document certifying their right to monitor and evaluate clinical trial compliance with good clinical practice requirements.
108. The provisions referred to in paragraph 105 of the person in the starting job, declares in writing of any financial or other relationship with persons or places monitored. The proof of the State Agency of medicines are taken into account in assigning an individual clinical trial, concerned the conduct of monitoring and evaluation.
109. Good clinical practice evaluation can be performed in the following cases: 109.1. prior to the commencement of the clinical trial, the clinical trial, or after its completion;
109.2. a medicinal product registration application.
110. On the evaluation of the State Agency of medicines shall inform the European Medicines Agency. Monitoring and evaluation may be carried out on behalf of the European Union, and the results shall be recognised by the other Member States. The State Agency of medicines has the right to request assistance of another Member State in connection with monitoring and evaluation.
111. After the evaluation, the State Agency of medicines shall draw up an evaluation report. The report is available on the sponsor, providing the necessary data protection. It is available to the other Member States, the Ethics Committee and the European Medicines Agency, if you received a reasoned request.
112. the State Agency of medicines shall be carried out in the clinical evaluation is entitled to participate in the foreign competent authority. To participate in the evaluation, the foreign competent authority 30 days before the evaluation of the medicinal product shall be submitted to the national agency of the application in writing, stating the reasons for the need to participate in the evaluation.
113. in order to ensure the monitoring and evaluation of all clinical research stakeholders are required to ensure the State Agency of medicines, as well as foreign evaluators direct access to all documents related to clinical trials.
114. The clinical trial testing competency may take the national pharmacy Inspectorate and medical care and integrity inspection quality control inspection. The checks referred to in this paragraph results in the inspection report to the State Agency of medicines.
115. If necessary, the State Agency of medicines of the medicines evaluation in clinical trials may involve experts, qualifications and experience of which corresponds to a given clinical trial.
 
 
XIV. The reporting of adverse events 116. researchers will immediately inform the sponsor in writing of any study subject to adverse medical events that occur during the use of the investigational medicinal product, regardless of the causal link with the use of the investigational medicinal product and which does not depend on the dose results in death, is life-threatening, results in the need for hospitalization or extended existing hospitalization, causes permanent or severe forms of disability or incapacity, or is a congenital anomaly or what birth defect (hereinafter referred to as the major adverse event) except for the essential unwanted events that the Protocol or investigator's brochure is not listed among those that require immediate reporting. After the instant message sent to the sponsor, the investigator detailed written report. Instant and future reports to identify the subject of the study used trial subject unique identification assigned to the code.
117. the significant adverse events and laboratory abnormalities that Protocol as essential for the use of the investigational medicinal product security evaluation, researchers will report in writing to the sponsor in accordance with the Protocol specified in the reporting requirements and deadlines.
118. If there was a subject of the study, the researchers provide the sponsor and the Ethics Committee with all of the requested additional information.
119. Sponsor a detailed register of all researchers ziņoto unwanted events and assess their gravity, cause and predictability, as well as, upon request, submit the data to the competent authorities of the Member States that are in a specific clinical trial.
 
 
XV. reporting on significant reactions 120. The Sponsor shall ensure that all relevant clinical trials in the research centers involved in the observed significant adverse and unexpected response to the use of the investigational medicinal product irrespective of the dose used, the nature or severity of which degree does not match the available information on investigational medicinal products (hereinafter referred to as the unexpected serious adverse reactions) that causes the death of the trial subject or a threat to his life, potentially causing investigational medicinal products to be registered. Information about the possible earlier, but not later than seven days after the receipt of such information the sponsor entered the European Medicines Agency, the European supervisory system reactions (EudraVigilance) database clinical trials module (EVCTM). Significant unexpected serious adverse reactions that cause the death of the trial subject or a threat to his life, potentially causing investigational medicinal products and which are observed in clinical trial centres in Latvia, the sponsor shall notify the State Agency of medicines, giving the State Agency of medicines of the EVCTM address, and to the Ethics Committee by providing additional report within eight days after the first message.
121. Significant unexpected serious adverse reactions, causing no death or of the study subjects did not threaten his life, potentially causing investigational medicinal products, the sponsor will enter the European Medicines Agency, the European supervisory system reactions (EudraVigilance) database clinical trials module (EVCTM). On significant unintended side effects, causing no death or of the study subjects did not threaten his life, potentially causing investigational medicinal products and which are observed in clinical trial centres in Latvia, the sponsor shall notify the State Agency of medicines, indicating the medicine EVCTM national agencies, as well as possible before the Ethics Committee, but not later than 15 days after the receipt of the information.
122. the State Agency of medicines shall record information on all reported suspected serious unexpected adverse reactions to an investigational medicinal product.
123. The Sponsor of any significant unintended side effects, which may have given rise to investigational medicinal products, inform all clinical researchers involved in the research.

124. The clinical trial, the sponsor annually no later than 60 days after the Protocol reporting deadline gives the State Agency of medicines and the Ethics Committee report on all security relevant year observed major unintended side effects, which may have given rise to investigational medicinal products, as well as a summary of the study subject's safety during a clinical trial. If clinical trials lasting less than a year, the security report may be submitted together with the notice concerning the completion of the clinical trial.
 
 
XVI. observations of the use of the medicinal product administration 125. observations collects only such data which the operator observations (the doctor) gets the professional activities on the basis of the opinion of the patient's medical condition and treatment. Patients do not perform additional diagnostic and monitoring procedures and the analysis of the data collected using epidemiological methods.
126. the observations of the use of the medicinal product Before the start of the doctor or, if the observation made more doctors, the person in charge (a doctor or a drug company representative responsible for coordination of the observation) (hereinafter applicant) shall submit to the State Agency of medicines and the application of the Ethics Committee. The application specifies the following information: 126.1. name of the medicinal product observation, generic name, pharmaceutical form and strength;
126.2. observation project description (including criteria for patient involvement in the observation and data analysis methods used);
126.3. doctor participating in the observation (name and surname);
126.4. medical establishment participating observation;
126.5. recording of observations;
126.6. planned number of clients involved;
126.7. for the duration of the observations indicating the start and end date.
127. The applicant, in accordance with the State Agency of medicines of pricing public services shall bear the expenses related to the observations of the use of the medicinal product with consideration of the application.
128. the observation of the use of the medicinal product may be launched if the Ethics Committee has delivered a favourable opinion and the State agency within 30 days after the registration of the application is not notified the applicant of the reasons why the Administration should not initiate the observations.
129. observations On the use of the medicinal drug dangers identified adverse reactions physician pursuant to legislation established pharmacovigilance surveillance provisions of all adverse reactions reported to the State Agency of medicines.
130. within 90 days after the end of the doctor or of the observations that rule 126. responsible person referred to in the written report to the State Agency of medicines of the observation end, providing a summary of observations number of patients involved and the perceived drug induced reactions.
131. the observations of the use of the product for compliance with those rules according to the competence of the State Agency of medicines shall monitor and review State Pharmacy Inspectorate and medical care and integrity inspection quality control inspection.
132. the observations of the use of the product will go the tītaj parties are obliged not to disclose patient and clinical data, unless the data in question requires the authorities which, in accordance with the law of medical treatment have the right to consult the records of the patient.
 
 
XVII. Closing questions become 133. unenforceable: 133.1. The Cabinet of Ministers of 12 September 2000, the provisions of no. 312 "drug clinical trials and observations using the order" (Latvian journal, 2000, 323; 2001, 105/324.nr. No; 2003; 2004, nr. 125.98. No.);
133.2. Cabinet of Ministers of 20 august 2002 Regulation No 374 "procedures are assessed compliance with good clinical practice requirements" (Latvian journal, 2002, 119 no).
134. the provisions shall enter into force on the 1 April 2006.
135. The Ethics Committee that operate in these rules, the date of entry into force of this provision, the information referred to in paragraph 50 shall be submitted by 1 May 2006.
 
 
Informative reference to European Union directives, the regulations include provisions resulting from: 1) of the European Parliament and of the Council of 4 April 2001, Directive 2001/20/EC on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use;
2) Commission of 8 April 2005 of Directive 2005/28/EC laying down the good clinical practice principles and detailed guidelines on investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products.
 
Prime Minister a. Halloween Health Minister g. Smith Editorial Note: rules shall enter into force on the 1 April 2006.