SPECIFIC ASPECTS OF BENEFIT-RISK EVALUATION OF HERBAL MEDICINAL PRODUCTS: ANALYSIS OF REGISTRATION DOSSIERS

The use of medicinal plants for therapeutic purposes (herbal medicine) is still popular nowadays. The aim of the present paper was to analyse registration dossiers for herbal medicines submitted for expert evaluation in accordance with the current national legal requirements for dossier compilation and methodological approaches to the examination of the benefit-risk ratio of herbal medicinal products. The article describes specific features of the preclinical and clinical sections of the common technical document for herbal medicinal products. The article also considers current national requirements for safety and efficacy evaluation of herbal medicinal products. It analyses specific aspects of preclinical (toxicological, pharmacokinetic and pharmacological) and clinical trials of medicines. Based on the results of the analysis the authors elucidate the main mistakes in the preparation of the necessary documents for registration dossiers for herbal medicinal products, namely: lack of complete information on the preclinical toxicological study of the product; inconsistencies in the product composition as specified in different documents; lack of statistical analysis of the results of studies; errors in draft patient information leaflets for herbal medicinal products. The materials presented in the article are high on the agenda and will help applicants properly compile registration dossiers for herbal medicinal products.

1. Grigoryan ER. Methodical Approach to Optimization of Assortment of the Medicinal Plant Preparations Used in the Conditions of Sanatorium and Resort Rehabilitation Complex of the Caucasian Mineral Waters. Сand. Pharm. Sci. [dissertation]. Pyatigorsk; 2015 (In Russ.)

2. Mironov AN, Sakaeva IV, Sakanyan EI, Korsun LV, Mochikina OA. Current Approaches to Standartization of Herbal Substances. The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products 2013;(2):52–6 (In Russ.)

3. Federal Law of the Russian Federation, April 12, 2010, No. 61-FZ «On Circulation of Medicines» (In Russ.)

4. Order of the Ministry of Health and Social Development of the Russian Federation, August 24, 2017, No. 558n «On Approval of Rules of Carrying out Examination of Medicines for Medical Use and Features of Examination of Separate Types of Medicinal Preparations for Medical Application (Reference Medicinal Preparations, the Reproduced Medicinal Preparations, Biological Medicinal Preparations, Bioanalogue (Biosimilar) Medicinal Preparations (Bioanalogues), Homeopathic Medicinal Preparations, Medicinal Vegetable Preparations, Combinations of Medicinal Preparations) of forms of the conclusions of the commission of experts» (In Russ.)]

5. Guidelines for Preclinical Study of Drugs Derived from Natural Raw Materials. In: Guideline on Preclinical Evaluation of Medicines. Part 1. Moscow: Grif i K; 2012. P. 829–33 (In Russ.)

6. Planning Preclinical and Clinical Trials of Drugs of Plant Origin. In: Guideline on Examination of Medicines. V. 3. Moscow: Poligraf-Plus; 2014. P. 179–216 (In Russ.)

7. Interstate Standard GOST 33044–2014. Principles of Good Laboratory Practice. Moscow: Standartinform; 2014 (In Russ.)

8. The Order of the Ministry of Health of the Russian Federation, April 1, 2016, No. 199n «On the Approval of the Rules of Good Laboratory Practice» (In Russ.)

9. General Monograph 1.4.1.0018.15 Infusions and Broths. The State Pharmacopoeia of the Russian Federation. 13th ed. V. 2. Moscow; 2015 (In Russ.) Available from: http://www.femb.ru/feml

10. Krepkova LV, Bortnikova VV, Sokolskaya TA. Some Aspects of Toxicological Study of Medicinal Preparations Based on Medicinal Plants. Fundamental Research 2013;(9–2):256–8 (In Russ.)

11. Supplement No. 1. The Recommended Amount of the Study of Pharmacological Activity and Toxicological Properties of Drugs of Natural Origin, Depending on the Innovation. Guidelines on Preclinical Evaluation of Medicines. Part 1. Moscow: Grif i K; 2012. P. 834–7 (In Russ.)

12. Supplement No. 2. Features of Preclinical Study of a New Dosage Form, Developed From Medicinal Plant Raw Materials, Raw Vegetable Powder in Filter Bags. Guidelines on Preclinical Evaluation of Medicines. Part 1. Moscow: Grif i K; 2012. P. 838–41 (In Russ.)

13. State Standard R 52379–2005. Good Clinical Practice. Moscow: Standartinform; 2005 (In Russ.)

14. The Order of the Ministry of Health of the Russian Federation, April 1, 2016, No. 200n «On Approval of the Rules of Good Clinical Practice» (In Russ.)

15. Order of the Ministry of Health of the Russian Federation, July 12, 2017, No. 409n «On Approval of Procedure of Formation of the Registration Dossier of the Medicinal Product and Document Requirements into it Requirements for the Amount of Information Provided as Part of the Registration Dossier, for Certain Types of Medicines for Medical Application and Submission of Documents From which it is Generated the Registration Dossier of the Medicinal Product for Medical Use for its State Registration» (In Russ.)

16. Order of the Ministry of Health of the Russian Federation, September 21, 2016, No. 724n «On Approval of Requirements to Instructions for Medical Use of Drugs» (In Russ.)

17. Lyakina MN, Kovaleva EL, Nikolaeva OB, Krutikova NM, Olenina NG, Kolganov LA. Group Names for Herbal Remedies: the Need for Introduction and Rationale for Establishing. The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products 2016;(3):9–11 (In Russ.)