Sağlık Bakanlığı’nın SAK Denetimi ile ilgili Gereklilikleri

Hilal İlbars, SAKDER ve UCROF tarafından düzenlenen “Türkiye’de Klinik Araştırmalar – Perspectives 2012” konferansında “Sağlık Bakanlığı’nın SAK Denetimi ile ilgili Gereklilikleri” konulu bir sunum gerçekleştirdi.

Hilal İlbars, SAKDER ve UCROF tarafından düzenlenen “Türkiye’de Klinik Araştırmalar – Perspectives 2012” konferansında “Sağlık Bakanlığı’nın SAK Denetimi ile ilgili Gereklilikleri” konulu bir sunum gerçekleştirdi.

Sunum olarak görmek için tıklayın…

Current Legal Regulations that should be specifically known with respect to Clinical Trials in Turkey and Statistical Data Related with Clinical Drug Investigations

Author:  Hilal Ilbars, Doctor of Pharmacy

The Ministry of Health of Turkey, the General Directorate of Pharmaceuticals and Pharmacy

Clinical Trials and Drug Safety Department

Abstract

This manuscript refers to relevant articles of the legal regulations on clinical researches entered into force effective from 2011, which require awareness at the minimum. It would be beneficial to have knowledge of current legal regulations before planning clinical research on volunteers in Turkey. Consent of guardian must not be neglected if a clinical research is planned to be carried out on disabled and children, and relevant parts of the regulations must be taken into consideration. Along with the details of current regulations relating to clinical researches, studies that require approval from Ethics Committee as well as approval from the Ministry of Health have been specified in the manuscript. In the final section of the manuscript, distribution of clinical drug investigations which were carried out in our country from 1997 until the end of 2011 are given based on the data from General Directorate of Pharmaceuticals and Pharmacy of the Ministry of Health of Turkey.

The objective of this article is to refer to relevant items of the legal regulations, which require awareness at the minimum, instead of giving details of current legal regulations on clinical researches in effect in Turkey as from 2011. The details of the legislation specified in the article can be accessed to both through the Official Gazette and the corporate websites.

It will be beneficial to be informed on legal regulations given below under main headings before planning a clinical trial on subjects in Turkey.

The second chapter of 1982 Constitution of the Turkish Republic on the rights and duties of individuals clearly specifies, under Article 17 in Section 1 related to the privacy, tangible and intangible existence, that no clinical trials can be conducted in the absence of the consent of the individual.

Article 70 of the Law for Method of Performance of the Medical Profession and the Branches Thereof No. 1219 stipulates that no clinical trials may be performed in the absence of the consent of the individual and consent of guardian must not be neglected if a clinical research is planned to be carried out on disabled and children.

Moreover, additional Article 10 of the Basic Health Services Law no. 3359 must be known.

In addition, the conditions specified in subparagraph 2 of Article 90 captioned “Tests On Humans” of the Turkish Criminal Law no. 5237 must be known by people intended to perform research for not being subject to penal liability for scientific trials conducted on humans based on consent. Otherwise, as specified in the first subparagraph of Article 90, “Any person performing scientific experiments on humans shall be penalized with imprisonment from one to three years.”

If a clinical trial is planned on children, the “amended Article 31/3/2005-5328/7” of the Turkish Criminal Law should be known. According to this Article, if the scientific data obtained as the result of research conducted necessitates performance of these researches also on children in order to achieve the intended target, requires obtaining the assent of the child who is capable of giving the assent himself/herself in addition to written consent of the parents or the guardian of the child and a specialist of child health and diseases must attend at the authorized committees which will give authorization for the research.

If clinical trial is planned on special groups (such as disabled, children, etc.), being informed on Articles 9-13 of the Turkish Civil Law in terms of competency of action, Articles 14-16 in terms of incompetency of action, Article 23 in terms of protection of personality, Articles 404-410 in terms of conditions requiring custody, Articles 411-412 in terms authorization for procedures of custody, Articles 413-416 in terms of appointment of custodian, Articles 417-418 conditions preventing to be appointed as custodian will be beneficial particularly at the stage of explaining and having informed consent.

The current version of the Helsinki Declaration (last version date. 2008) must be taken into due consideration when performing a clinical trial on subjects.

Agreement for Protection of Human Rights and Human Dignity as to Biological and Medical Practice (Oviedo Agreement): Section V of The Law Confirming the Approval of Human Rights and Biomedicine Agreement refers to scientific research and needs to be reviewed.

For assignments (particularly in assignment of pharmacists) due consideration must be given to Public Servants Law No. 657 and the Pharmacists and Pharmacies Law No. 6197.

Articles 10 and 11 of the Medical Deontology Regulation emphasize that the procedure performed must be defined as research and the procedure in question should be tested on animals in advance.

Regulations, guides and standard operating procedures to be known when performing clinical trials on subjects in Turkey are listed in the following:

Regulations:

1. 1. Regulation on Clinical Trials published in the Official Gazette No. 28030 dated 19 August 2011 must be known in detail.
2. 2. Item (ğ) of subparagraph 9 of Article 6 of the Regulation for Promotional Activities for Human Medicinal Products published in the Official Gazette no. 28037 on 26 August 2011 specifies that license/authorization holders may grant human medicinal products, laboratory kits and similar donations for use in clinical trials directly to the principal investigator. Paragraph 4 of Article 7 specifies that investigator meetings of national and international multi-center clinical trials supported by license/authorization holders held in and outside of Turkey shall not be considered as participation in congresses or symposiums and the nature of the meeting and the meeting is held for this purpose must be clearly specified in applications to the Ministry for authorization. Subparagraph (g) of paragraph 1 of Article 9 clearly specifies that promotional samples cannot be used as investigational product in clinical trials.
3. 3. The Regulation on Assessment of Bioavailability and Bioequivalence (BA/BE) of Pharmaceutical Products published in the Official Gazette no. 21942 dated 27 May 1994 is particularly important for assessment of BA/BE studies.
4. 4. For researches to be conducted using medical devices, information should be obtained on the Medical Devices Regulation, the Regulation for Implantable Active Medical Devices published in the Official Gazette no. 27957 on 07 June 2011 and the Regulation for In Vitro Medical Diagnostic Devices published in the Official Gazette no. 26398 dated 09 January 2007 as well as the related regulations of the Turkish Standards Institute (TSE).
5. 5. It will be beneficial to review the sections of the Patient Rights Regulation, related to clinical trials, published in the Official Gazette no. 23420 on 01 August 1998.

Guides:

1. 1. Good Clinical Practice Guide
2. 2. Good Manufacturing Practice Guide, the section related to investigational products
3. 3. Guide Related To Ethical Approach To Clinical Trials Conducted in Pediatric Population
4. 4. Guide On Insurance Cover in Clinical Trials
5. 5. Guide Related to the Form of Application to the Ministry for Clinical Trials
6. 6. Guide Related to the Form of Application to the Ethics Committee for Clinical Trials
7. 7. Guide On Collection, Verification and Submission of Reports on Adverse Events/Reactions occuring during Clinical Drug Trials
8. 8. Guide On Independent Data Monitoring Committees
9. 9. Guide On The Principles of Site Organization Management In Assignment of Site Coordinator during clinical drug trials

10. Guide On Principles of Archiving in Clinical Trials

11. Guide On Storage and Distribution of Investigational Products Used In Clinical Trials prepared for guidance regarding storage under appropriate conditions and distribution of investigational products to be used in clinical trials

12. Guide on Human Medicinal Products with Fixed Combination

13. Guide on Biosimilar Medicinal Products

14. Guide on Principles and Procedures of Good Clinical Practice of Advanced Therapeutic Medical Products

15. Guide On Preparation of Good Clinical Practice Audit Reports

16. Guide on Conductance of Good Clinical Practice Audits Related to laboratories participating Clinical Drug Investigations

17. Guide On Conductance of Good Clinical Practice Audits Related to the Sponsor and the Contract Research Organization

18. Guide On Conductance of Good Clinical Practice Audits Related to Pharmacokinetic and Statistical Analysis of Bioanalysis Part of Bioequivalence Studies

19. Guide on Conductance of Good Clinical Practice Audits Related to Phase I Units

20. Guide on Observational Studies Conducted With Drugs

21. The Section titled ‘Prohibitions’ of Non-indicated Drug Use Guide for publications

22. Early Access to Medicine for Humanistic Purpose Guide for the purpose of free of charge supply of any drug not licensed in Turkey but licensed or not licensed in other countries, by the developer/supplier of the drug for humanistic purposes, to patients with a serious and emergent, life threatening disease, the treatment of which has failed with existing medicinal products licensed by the Ministry and available in Turkey

Principles of the Standard Operation Method:

1. 1. Principles of Standard Operating Method of Ethics Committees

In the light of all legal regulations mentioned above, the authorizations of both the Ethics Committee and of the Ministry of Health is necessary for certain studies, which are listed below:

ü  Clinical trials to be performed using drugs and compositions thereof even if licensed or authorized

ü  Clinical trials to be performed using advance therapeutic medicinal products

ü  Observational drug studies

ü  Clinical trials to be conducted using traditional herbal medicinal products

ü  Observational medical device studies

ü  Clinical trials to be performed using medical devices

ü  Clinical trials to be performed using cosmetic ingredients or products

ü  Clinical trials to be performed using all other ingredients and products that may be tested on humans

ü  Bioavailability and bioequivalence (BA/BE) studies

ü  Comparability studies for biosimilar products

ü  Clinical trials to be conducted using industrial advanced medical products

ü  Clinical trials to be conducted using non-industrial advanced medical products

ü  Stem cell transplant researches on humans

ü  Organ and tissue transplant researches

ü  Surgical researches

ü  Gene treatment researches

According to data provided by the Ministry of Health General Directorate of Pharmaceuticals and Pharmacy, the distribution of clinical drug investigations performed in Turkey between 01.01.1997 and 31.12.2011 in line with the legal regulations in our country is as follows.

Table 1. Distribution of clinical trials on annual basis

*BA/BE: Bioavailability/Bioequivalence studies
**ODS: Observational Drug Studies

The distribution of clinical trials on annual basis according to figures given in the Table is given in Figure 1-5.

Figure 1. Distribution of clinical trials on annual basis

Figure 2. Distribution of phase studies, BA/BE studies and ODS studies on annual basis

Figure 3. Phase studies, BA/BE studies and ODS studies on annual basis

Figure 4. Distribution of phase clinical studies on annual basis

Figure 5. Distribution of BA/BE and ODS studies on annual basis

Caution must be taken to conduct clinical trials in compliance with internationally accepted scientific and ethical standards, to follow legal regulations in order to protect the rights, welfare and health of subjects and to present qualified and reliable data as the result of the studies.