Commonwealth of independent states

The Commonwealth of Independent States is a regional intergovernmental organisation, formed in 1991

1. Department of Pharmaceutical Sciences, Maharshi Dayanand University Guided By… Prof. (Dr.) Arun Nanda Professor (Pharmaceutics ) Presented By… Garima Saini M.Pharm. DRA(SEM-II ) Commonwealth of Independent States (CIS)

2. Commonwealth of Independent States

3. Background The Commonwealth of Independent States is a regional intergovernmental organisation formed in 1991, and currently composed of Azerbaijan, Armenia, Belarus, Georgia, Kazakhstan , Kyrgyzstan, Moldova, Russia , Tajikistan, Turkmenistan, Uzbekistan, and Ukraine . The aim of the organisation is to facilitate and strengthen cooperation among its member states in the political, economic, ecological, humanitarian, cultural, and other fields.

4. https://cdn.britannica.com/s:1500x700,q:85/46/108246-004-92D4DA73/Commonwealth-of-Independent-States-creation-1991.jpg

5. RUSSIA In Russia, medicinal products were regulated for more than one decade by the "old" Federal law "on medicines" of 22 June 1998. During this period this law was revised and amended at least 8 times. It was therefore abolished and replaced in 2010 by completely new legislation The Russian Federal law No. 61-FZ “on the regulation of the medicines" was introduced on 12 April 2010. On 15 June 2018,  Federal Law No. 140-FZ “On Amendments to the Federal Law ‘On the Circulation of Medicines’” * (the “ Law ”) came into force. It simplifies the registration of foreign medicines, enhances the opportunities for contract manufacturing in Russia and introduces new grounds for suspending the use of medicines

6. The Russian Ministry of Health (MOH) is responsible for drug regulatory issues in Russia. This includes the following responsibilities:- Registration and control of pharmaceutical products, medical equipment and devices; Approval of state reference specifications for pharmaceuticals; Certification and control of the quality of medicinal products; and Certificates of manufacturers and distributors of drugs and medical equipment.

7. Registration Procedure in Russia Roszdravnadzor , an executive body responsible for control and supervision of health care and social development, is in charge of medicines' registration and maintenance of the register . Registration stages : 1. Preclinical trial of a medicine 2. Applying for state registration of a medicine 3. Document expertise for obtainment of permission to carry out clinical trial 4. Ethic expertise 5. Clinical trial 6. Medicine's quality expertise and expertise of medicine's benefit/risk ratio . If the creator of a medicine properly fulfills its obligation on each stage and achieves positive results in trials, Roszdravnadzor registers the medicine.(time period no more than 210 days (from submitting an application to registration of medicines ))

8. Preclinical trial of a medicine organized in scientific research organizations, educational institutions possessing necessary equipment and skilled staff . organized in accordance with the Good Clinical Practice, internationally recognized rules for clinical trials .

9. Submitting an application for state registration of a medicine All proceedings take place after submitting an for its state registration coupled with supplements as required by New Law. After consideration of documents provided Roszdravnadzor within 5 days issues requests addressed to the expert organizations whereby asks them to conduct the following expertises : Document expertise for obtainment of permission to carry out clinical trial; Quality expertise. If the applicant submits the document improperly, Roszdravnadzor refuses to issue expertise request.

10. Document expertise for obtainment of permission to carry out clinical trial carried out by the authorized state budget institution. exempted those medicines which have been allowed to be applied in Russian more than 20 years ago and with respect of which it is impossible to organize bioequivalence research those which have been checked in multi-central clinical trials (including trials in Russia).

11. Ethic expertise(expertise of possibility to organize clinical testing) conducted by the ethic council to be established at Roszdravnadzor. Currently another institution - the ethic committee – functions at Roszdravnadzor. It established in accordance with Law No. 86 and performs duties similar to those to be performed by the ethic council as stipulated by New Law.

12. Clinical trial of the medicine applicant shall submit the results of document expertise and ethic expertise to Roszdravnadzor. The latter considers them and decides on possibility or impossibility to issue permission for clinical trial. It must notify the applicant on the decision made.

13. Medicine's quality expertise and expertise of medicine's benefit/risk ratio After clinical trials the new medicines shall go through the following expertises : Medicine's quality expertise Expertise of medicine's benefit/risk ratio The overall period for conducting both expertises shall not exceed 110 days Roszdravnadzor examines the results of the expertise’s and check compliance with requests. Then it decides on registration or refuse to register the new medicine. The reasons for refusal may be conclusion of Roszdravnadzor on one of the following: Results of prior tests and trials do not confirm effectiveness of the medicine Risk of damage to health exceeds effectiveness from use.

14. Working procedure Submission the dossier to MOH Within 5 working days MOH considers dossier and gives the decision regarding carrying out of expertise Applicant submit the POA(Power of Attorney) to FGBU(Federal Governmental Budget Unit) with request to calculate of samples quantity Laboratory calculates the samples during 2 weeks (as maximum) and applicant can see the calculation in regmed.ru Within 15 working days after receiving the letter for assignment to pharmaceutical examination on hands applicant submit the samples, reference standards and columns to the laboratory. Pharmaceutical examination should be finished after 110 working days from the moment of samples submission. After that MOH give conclusion about registration of product or rejection .

15. Regulatory process flow chart for Russia

16. Pharmacovigilance Art . 64 to 66 of the Russian law and Decree No. 757n of the MOH of Russia describe a national pharmacovigilance system. According to Decree No. 757n, the MAH has to submit the PSURs within the following timeframe beginning from the first marketing authorization in the world Every six months during the first two years after the first authorization Once a year for the following two years (third and fourth years) Thereafter (beginning from the fifth year) at three-yearly intervals. The PSURs have to be submitted not later than 30 days after the data lock point of the report .

17. UKRAINE all ex-Soviet Union Republics, the Ukraine started to develop its own regulatory legislation in the early 1990s after gaining independence. first Ukrainian Drug Law came into force in 1996 Ukraine began to harmonize its regulatory legislation with the European laws: procedures for MAAs, non-clinical and clinical trial authorizations, format of the dossiers for initial applications and for variations, pharmacovigilance and Good Manufacturing Practice (GMP) rules have been adopted to a great extent in line with ICH/EU Guidelines and European legislation. currently valid procedures for MAAs were passed by the Cabinet of Ministers of Ukraine in the form of the Decree No. 376 . Decree No. 426, along with the Decree No. 376 and the Ukrainian Drug Law (all three as amended) are what mainly determine regulatory activities in the Ukraine

18. Registration Procedure for Ukraine The Ministry of Health ( MoH ) is the responsible body for regulating and approving the import, manufacture, sale and marketing of medicinal products in Ukraine. State registration is carried out on basis of application and respective document package submitted to the State Drug Inspectorate by the applicant liable for manufacturing, safety and efficacy of medical products. The State Drug Inspectorate shall examine submitted documents within max. 90 days. In order to conduct necessary expert examinations and testing of medical products the State Drug Inspectorate shall engage expert institutions and give the applicant respective referrals . The applicant shall choose expert institutions taking into account profile of the expert institution and the list comprised and approved by the State Drug Inspectorate. Results of the expert examination conducted by the expert institution shall be stated in a protocol (report, conclusion) which shall be sent to the State Drug Inspectorate or handed over directly to the applicant .

19. Registration Procedure for Ukraine Based on consideration of expert examination (testing) report and recommendation of the advisory body the State Drug Inspectorate shall make a decision on registration of or refusal in registration, Within 10 days the State Drug Inspectorate shall inform the applicant in writing. Based on decision on state registration medical products shall be included to the State Register of Medical Equipment and Medical Products kept by the State Drug Inspectorate, and the applicant shall receive a certificate on state registration of a medical product. The certificate is valid for up to 5 years, after expiration of its term import to Ukraine, sale and use of medicinal products is possible only after its re-registration.

20. Regulatory Flow Chat for Ukraine

21. Post-marketing commitments and pharmacovigilance obligations A manufacturer/applicant must submit information to the SE Centre about the medicinal product's adverse effects under MOH Order on the Approval of the Procedure for Monitoring of Side Effects of Medicinal Products Permitted for Medical Use No. 898, 27 December 2006.A manufacturer/applicant must also submit regular updated safety reports to the SE Centre.

22. KAZAKHSTAN The Ministry of Health and Social Development of the Republic of Kazakhstan provides marketing authorization (state registration) of finished medicinal products and active pharmaceutical ingredients, medical devices and medical equipment based on expert examination carried out by the  National Center for Expert Evaluation of Medicinal Products, Medical devices and Medical Equipment

23. Registration Procedure for Kazakhstan Submission of the Application on registration of pharmaceutical products with enclosed confirmation of payment of state registration fee to the Committee of Pharmaceutical Control. The Applicant concludes the contract with NCE for carrying out expert examination The specialist of expert department accepts the Application for state registration, checks the availability of contract for expert examination. After check the registration dossier, samples and standards of pharmaceutical products validity of samples, standards and storage mode all these goes to small achieve. The certificates of analyze is require for the given standards and samples. (In case of failure to submit the all necessary document within 30 day the company must inform in written form about the term to NCE, otherwise the given pharmaceutical product will get a refusal in state registration.

24. Registration Procedure for Kazakhstan Primary expertise of documents and materials carry out within 20 days for registration of pharmaceutical product and 10 days in case of re-registration from the day of money in payment to the account of NCE. In case of positive finding of primary expertise the product sends for analytic expertise. Analytic expertise conducts out within 50 days, immune biological products - 70 days. Special pharmaceutical expertise conducts by Pharmacopoeia Center (including expertise of technological normative document on control of quality and security, 40 days) within 90 days. Special pharmacological expertise conducts by Pharmacological Center within 90 days after getting the positive decision of pharmaceutical expertise.

25. Registration Procedure for Kazakhstan After passing of complete cycle of expert’s work the conclusion on safety, efficiency and quality of pharmaceutical product prepares within 20 days if registration, 10 days if re-registration On the bases of the order of Chairman of Committee of Pharmaceutical Control the registration card issues. The applicant receives following: Registration card with term within the given pharmaceutical product is allowed for medical usage on the territory of the Republic of Kazakhstan. Confirmed technical limitation document on control of quality and safety of the product. Confirmed guidance for medical usage of pharmaceutical product in Russian and Kazakh languages. Confirmed package and labels design Second exemplar of registration dossier Timelines: 12 Months

26. State marketing authorization procedure followed in Kazakhstan

27. Pharmacovigilance The fundamentals of pharmacovigilance system in the Republic of Kazakhstan are established by Article 85 of the Code of the Republic of Kazakhstan “On the Public Health and the Health Care System”. Marketing Authorization Holders as well as health care and pharmaceutical professionals are obliged to submit information on identified adverse reactions, in the order determined by the Ministry of Health of the Republic of Kazakhstan.

28. Pharmacovigilance Manufacturing authorisation holders should submit the following information to the competent authority: About location of master file of pharmacovigilance system. About specialist responsible for pharmacovigilance activities in the territory of Kazakhstan. About any prohibitions or restrictions in use implemented in other countries related to medicinal product registered in Kazakhstan. About all cases of adverse reactions identified in the territory of the Republic of Kazakhstan. About cases of serious unexpected adverse reactions identified in other countries.

29. REFERENCES https:// dig.watch/actors/commonwealth-independent-states https://uk.practicallaw.thomsonreuters.com/4-501-0563?transitionType=Default&contextData=% 28sc.Default%29 https:// ldv-group.ru/en/services/drug-registration/ Handoo , S., Arora, V., Khera, D., Nandi, P. K., & Sahu, S. K. (2012). A comprehensive study on regulatory requirements for development and filing of generic drugs globally.  International journal of pharmaceutical investigation ,  2 (3), 99 . https:// cratia.ua/en/registration-medical-products-countries-former-soviet-union-cis-and-middle-asia/kazakhstan.html