The work of compounding pharmacies and the possible risks of violating the exclusive rights to original medicines

The revival of production pharmacies in Russia began in 2022. To effectively use the capabilities of compounding pharmacies, it is necessary to take into account the importance of eliminating the risk of infringement of intellectual property rights.

The aim. The study of the foreign practice of compounding pharmacies in terms of infringement of exclusive rights, as well as the position of foreign patent offices and the World Intellectual Property Organization (WIPO).

Materials and methods. A key aspect of the research was the study of the foreign practice of violating the exclusive rights to original medicines. An information search was conducted for publications related to the activities of compounding pharmacies in the world, as well as issues related to the regulation of the relationship between their activities and legislation in the field of intellectual property.

Results. The article analyzes foreign judicial practices and positions of patent offices, summarized by WIPO, on this issue. The results and discussion are based on the consideration of foreign court cases and legislative norms related to the production of patented drugs in compounding pharmacies. The examples of court cases that raise issues of violations of exclusive rights are given.

Conclusion. In Russia, the possibility of one-time compounding of drugs using the invention in pharmacies according to doctors’ prescriptions is fixed at the legislative level. However, this permission only applies to a “specific recipe”. One possible way to reduce the severity of the problem may be to directly allow pharmacies to use contractors to fulfill a specific request. The concept of “one-time compounding” also requires disclosure, which may expand the capabilities of pharmacies. The results obtained can be used in the framework of legislative regulation of the compounding of medicines in a pharmacy.

1. Polak Y, Jacobs BAW, van den Berg S, Colen-de Koning JCA, Hollak CEM, Kemper EM. Medicine compounding in the pharmacy. Ned Tijdschr Geneeskd. 2023;167:D6806.

2. Buurma H, de Smet PA, van den Hoff OP, Sysling H, Storimans M, Egberts AC. Frequency, nature and determinants of pharmacy compounded medicines in Dutch community pharmacies. Pharm World Sci. 2003;25(6):280–287. DOI: 10.1023/b:phar.0000006521.41736.db

3. Mamedov DD, Yurochkin DS, Leshkevich AA, Erdni-Garyaev SE, Golant ZM, Narkevich IA. Compounding pharmacy regulations: experience of the North American pharmaceutical market. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2023;16(1):80–86. DOI: 10.17749/2070-4909/farmakoekonomika.2022.155

4. Fisenko VS, Farrakhov AZ, Solomatina TV, Alekhin AV, Yurochkin DS, Erdni-Garyaev SE, Mamedov DD, Golant ZM. Monitoring of compounding pharmacies in the Russian Federation. Vestnik Roszdravnadzora. 2023;3:22–33. EDN: XZJIJT

5. Malchenkova SS, Golyak NS. Current status of extemporal manufacturing in compounding pharmacies in Minsk. Pharmacoeconomics: theory and practice. 2023;11(2):36. DOI: 10.30809/phe.2.2023.21

6. Farrakhov AZ. Compounding pharmacy restoration as a current healthcare priority. Regulatory Research and Medicine Evaluation. 2024;14(4):380–385. DOI: 10.30895/1991-2919-2024-14-4-380-385

7. Minghetti P, Pantano D, Gennari CG, Casiraghi A. Regulatory framework of pharmaceutical compounding and actual developments of legislation in Europe. Health Policy. 2014;117(3):328–33. DOI: 10.1016/j.healthpol.2014.07.010

8. Brion F, Nunn AJ, Rieutord A. Extemporaneous (magistral) preparation of oral medicines for children in European hospitals. Acta Paediatr. 2003;92(4):486–490. DOI: 10.1111/j.1651-2227.2003.tb00583.x

9. Minghetti P, Pantano D, Gennari CG, Casiraghi A. Regulatory framework of pharmaceutical compounding and actual developments of legislation in Europe. Health Policy. 2014;117(3):328–333. DOI: 10.1016/j.healthpol.2014.07.010

10. Watson CJ, Whitledge JD, Siani AM, Burns MM. Pharmaceutical Compounding: a History, Regulatory Overview, and Systematic Review of Compounding Errors. J Med Toxicol. 2021;17(2):197–217. DOI: 10.1007/s13181-020-00814-3

11. Belousova V, Meteleva LP. Pharmacy: history and modernity. Biology. 2010;(4):22–25. Russian

12. Belyatskaya AV, Krasnyuk II, Krasnyuk II, Stepanova OI, Korol LA, Rastopchina OV. Usage of finished dosage forms in the manufacture of extemporaneous powders. Drug Development & Registration. 2017;(1):82–85. EDN: YKPHDP

13. Moroz TL, Ryzhova OA. Problems in drug provision for prevention and treatment facilities due to a reduction of intra-pharmacy preparation of medicines. Remedium. 2015;(1–2):43–46. EDN: TJZSXZ

14. Vatanskaya OA, Zhidkova UU, Enikeeva RA. Practical importance of extemporal recipe in modern pharmaceutical practice. Russian Military Medical Academy Reports. 2020;39(S3-4):23–27. EDN: QERILV

15. Gudeman J, Jozwiakowski M, Chollet J, Randell M. Potential risks of pharmacy compounding. Drugs R D. 2013;13(1):1–8. DOI: 10.1007/s40268-013-0005-9

16. Guharoy R, Noviasky J, Haydar Z, Fakih MG., Hartman C. Compounding pharmacy conundrum: "we cannot live without them but we cannot live with them" according to the present paradigm. Chest. 2013;143(4):896–900. DOI: 10.1378/chest.13-0212

17. Mohiuddin AK. Extemporaneous Compounding: Selective Pharmacists with Separate Skill. Innov Pharm. – 2019;10(4):10.24926/iip.v10i4.1660. DOI: 10.24926/iip.v10i4.1660. Retraction in: Innov Pharm. 2020;11:1. DOI: 10.24926/iip.v11i1.3942

18. Yuliani SH, Putri DCA, Virginia DM, Gani MR, Riswanto FDO. Prevalence, Risk, and Challenges of Extemporaneous Preparation for Pediatric Patients in Developing Nations: A Review. Pharmaceutics. 2023;15(3):840. DOI: 10.3390/pharmaceutics15030840

19. Foehr ED. Compounding pharmacies: how to navigate the new regulatory and business environment and ensure high quality, safe products, which are cost effective. Pharm Pharmacol Int J. 2014;1(1):17–19. DOI: 10.15406/ppij.2014.01.00005

20. Shepherd J. Regulatory Gaps in Drug Compounding: Implications for Patient Safety, Innovation, and Fraud. DePaul L Rev. 2019;68(Issue 2):12.

21. Timko RJ, Crooker PE. Pharmaceutical compounding or pharmaceutical manufacturing? A regulatory perspective. Int J Pharm Compd. 2014;18(2):101–111.

22. Fernanda FF, Hilinski EG, Martins VAP, Vieira EA, Trujillo LM. Divergências nas exigências regulatórias para preparações magistrais e medicamentos industrializados. Infarma – Ciências Farmacêuticas. 2020;32(2):128. DOI:10.14450/2318-9312.v32.e2.a2020.pp128-136

23. Haider S, Thomas RE, Reed ED, Panja S. 8752 The Ethical Concerns of Improper Semaglutide Administration After Acquisition from a Compounded Pharmacy. Journal of the Endocrine Society. 2024;8(Issue 1):A499–A500. DOI: 10.1210/jendso/bvae163.959

24. Egorova SN, Kondakov SE, Gordeev VV, Belezky SO, Hayatov AR, Ikhalaynen ES. Recent problems of children pharmaceutical dosage formulation in Russian Federation. Vestnik of the Smolensk State Medical Academy. 2019;18(4):220–228. EDN: FLQJCB

25. Korol LA, Egorova SN, Kudlay DA, Krasnyuk II, Sologova SS, Korol VA, Smolyarchuk EA, Sadkovskii IA, Mandrik MA. Modern extemporaneous formulations in the geriatric care management: current opportunities and future challenges. A review. Terapevticheskii Arkhiv. 2022;94(8):1020–1027. DOI: 10.26442/00403660.2022.08.201805

26. Kalyatin V. Storing the product in digital form as a method of its use. Bulletin of Economic Justice. 2017;(1):70–81. EDN: YFPUJV

27. Farrakhov A.Z., Solomatina T.V., Mamedov D.D, Yurochkin D.S., Golant Z.M., Narkevich I.A. Fundamentals of forming a strategy for the development of the segment of manufacturing and dispensing of medicines in the Russian Federation // Vestnik Roszdravnadzora. 2023;6:6–17. EDN: NAHOAC

28. Boodoo J.M. Compounding problems and compounding confusion: federal regulation of compounded drug products and the FDAMA circuit split. Am J Law Med. 2010;36(1):220–247.

29. Petrov AYu, Airo IN, Berezhnaya ES, Kinev MYu, Goncharova YuM. PROBLEMS OF EXTEMPORAL MANUFACTURE OF DOSAGE FORMS IN PHARMACY ORGANIZATIONS AS A FORM OF PERSONALIZED PHARMACY IN THE RUSSIAN FEDERATION AND ABROAD. Medicine. Sociology. Philosophy. Applied research. 2022;(6):77–84. EDN: JUHZVI

30. Narkevich IA, Golant ZM, Yurochkin DS, Leshkevich AA, Erdni-Garyaev SE. Development of proposals for improving the processes of circulation of extemporal drugs and regulation of prescription and production activities of pharmaceutical organizations in the Russian Federation. Remedium. 2021;(4):14–29. DOI: 10.32687/1561-5936-2021-25-4-14-29

31. Rosenberg N, van den Berg S, Stolwijk NN, Jacobs BAW, Post HC, Pasmooij AMG, de Visser SJ, Hollak CEM. Access to medicines for rare diseases: A European regulatory roadmap for academia. Front Pharmacol. 2023;14:1142351. DOI: 10.3389/ fphar.2023.1142351

32. Mamedov DD, Yurochkin DS, Golant ZM, Fisenko VS, Alekhin AV, Narkevich IA. Past, current and future of legal regulation of drugs compounding in the Russian Federation. Pharmacy & Pharmacology. 2023;11(3):176–192. DOI: 10.19163/2307-9266-2023-11-3-176-192

33. Chikina IV, Onegin SV, Parfenov AA, Trubnikov AA. Modern extemporaneous pharmaceutical manufacturing: problems and prospects. Patient-Oriented Medicine and Pharmacy. 2024;2(2):43–50. DOI: 10.37489/2949-1924-0049

34. Soldatenko DM. Healthcare and the IP Multilateral Systems: Current Challenges. Russian Foreign Economic Journal. 2022;(10): 79–90. DOI: 10.24412/2072-8042-2022-10-79-90

35. Abashidze AKh, Malichenko VS. Expanding access to medicines in frame of the right to enjoy the benefits of scientific progress and its applications. Eurasian Law Journal. 2017;5(108):23–38. EDN: YTSUPD

36. Grabowski HG, DiMasi JA, Long G. The roles of patents and research and development incentives in biopharmaceutical innovation. Health Aff (Millwood). 2015;34(2):302–310. DOI: 10.1377/hlthaff.2014.1047

37. Kyle MK. Incentives for pharmaceutical innovation: What’s working, what’s lacking. Incentives for pharmaceutical innovation: What’s working, what’s lacking. Int J Ind Org. 2022;84:102850. DOI: 10.1016/j.ijindorg.2022.102850

38. Mian P, Maurer JM, Touw DJ, Vos MJ, Rottier BL. Pharmacy compounded pilocarpine: An adequate solution to overcome shortage of pilogel® discs for sweat testing in patients with cystic fibrosis. J Cyst Fibros. 2024;23(1):126–131. DOI: 10.1016/j.jcf.2023.09.014

39. Hendrickx K, Dooms M. Orphan Drugs, Compounded Medication and Pharmaceutical Commons. Front Pharmacol. 2021;12:738458. DOI: 10.3389/fphar.2021.738458

40. Dooms M, Carvalho M. Compounded medication for patients with rare diseases. Orphanet J Rare Dis. 2018;13(1):1. DOI: 10.1186/s13023-017-0741-y

41. Picavet E, Dooms M, Cassiman D, Simoens S. Drugs for rare diseases: influence of orphan designation status on price. Appl Health Econ Health Policy. 2011;9(4):275–279. DOI: 10.2165/11590170-000000000-00000

42. Minn M. Development of Orphan Drugs under European Regulatory Incentives and Patent Protection. Eur J Health Law. 2017;24:239–263.

43. Oronsky B, Caroen S, Brinkhaus F, Reid T, Stirn M, Kumar R. Patent and Marketing Exclusivities 101 for Drug Developers. Recent Pat Biotechnol. 2023;17(3):257–270. DOI: 10.2174/1872208317666230111105223

44. Collier R. Drug patents: innovation v. accessibility. CMAJ. 2013;185(9):E379–80. DOI: 10.1503/cmaj.109-4465

45. Maggs P.B. Medical intellectual property: questions of life and death. Works on Intellectual Property. – 2024;50(3):70–73. DOI: 10.17323/tis.2024.22300

46. Alekhin AV, Erivantseva TN, Ryazhenov VV, Lyskov NN, Alekhina NA, Kuznetsova MM. New role of extemporaneous manufacturing in regulating drug products access onto the market. Pharmacy & Pharmacology. 2023;11(2):161–172. DOI: 10.19163/2307-9266-2023-11-2-161-172

47. Malchenkova SS, Golyak NS. Current status of extemporal production of medicines in the Federal Republic of Germany. Vestnik Farmacii. 2022;(3(97)):44–56. DOI: 10.52540/2074-9457.2022.3.44

48. Saito J, Akabane M, Ishikawa Y, Iwahashi K, Nakamura H, Yamatani A. Retrospective survey of compounded medications for children in Japan. Eur J Pharm Biopharm. 2020;155:122–127. DOI: 10.1016/j.ejpb.2020.08.016