REGULATORY RELIANCE PATHWAYS: OPPORTUNITIES, CHALLENGES AND FUTURE DIRECTIONS

GURRAM GNANESHWARI; KIRAN NAGARAJ; SHAILEE DEWAN; VIGNESH MANOHARAN; PRADEEP MANOHAR MURAGUNDI

doi:10.22159/ijap.2025v17i6.55010

Authors

GURRAM GNANESHWARI Department of Pharmaceutical Regulatory Affairs and Management, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India https://orcid.org/0009-0001-3676-1843
KIRAN NAGARAJ Department of Pharmaceutical Regulatory Affairs and Management, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India https://orcid.org/0009-0001-6530-1141
SHAILEE DEWAN Department of Pharmaceutical Regulatory Affairs and Management, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India https://orcid.org/0009-0000-7383-0134
VIGNESH MANOHARAN Department of Pharmaceutical Regulatory Affairs and Management, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India https://orcid.org/0000-0003-3483-3564
PRADEEP MANOHAR MURAGUNDI Department of Pharmaceutical Regulatory Affairs and Management, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India https://orcid.org/0000-0003-4897-6187

DOI:

https://doi.org/10.22159/ijap.2025v17i6.55010

Keywords:

Reliance, National regulatory authorities, Low and middle income countries, Orbis and the access consortium

Abstract

Regulatory reliance allows national agencies to use assessments from trusted regulators instead of repeating the same work. This accelerates approvals, decreases workload, and allows patients to receive safe and effective medications more quickly. Many countries use different forms of reliance procedures, such as work-sharing, mutual recognition, abridged, and verification. These methods are common in regions like the European Union, the United Kingdom, South Africa, and Latin America. Various programs like Project Orbis and The World Health Organization’s (WHO) Collaborative Registration Procedure have reduced review times through collaboration between countries, thereby minimizing resource use and enabling work-sharing. Project Orbis and the Access Consortium have shown the importance of collaborative efforts and their essentiality when dealing with life-threatening diseases. Numerous countries in the Middle East and Asia have used these reliance methods to streamline regulatory processes particularly in public health emergencies. In South African countries, the impact is a 68% reduction in time with regulatory reliance as compared to regular processes. Additionally, the reliance guidelines of WHO initiated the UK’s International Recognition Procedure. During the COVID-19 pandemic regulatory reliance played a pivotal role and facilitated rapid vaccination approvals through international collaboration. Some challenges exist, such as unclear legislation, concerns about independence and legal limitations. Future research should focus on standardizing legislation, modernizing technology like the use of AI-driven evaluations, and improving collaboration as they help to strengthen global coordination to respond to emergencies more promptly. This article explains the reliance pathway and how regulatory decisions from trusted agencies help low-and middle-income countries.

References

1. Reliance-Based Regulatory Pathways The Key to Smart(Er) Regulation? Global Forum; 2022. Available from: https://globalforum.diaglobal.org/issue./reliance-based-regulatory-pathways-the-key-to-smarter-regulation/. [Last accessed on 24 Feb 2025].

2. COVID-19 Vaccines Safety Surveillance. Geneva: World Health Organization. Available from: https://www.who.int/docs/default-source/covid-19vaccines-safety-surveillance-manual/covid19vaccines_introduction_manual. [Last accessed on 10 Jul 2025].

3. Khadem Broojerdi A, Alfonso C, Ostad Ali Dehaghi R, Refaat M, Sillo HB. Worldwide assessment of low and middle-income countries regulatory preparedness to approve medical products during public health emergencies. Front Med (Lausanne). 2021 Aug 13;8:722872. doi: 10.3389/fmed.2021.722872, PMID 34485350, PMCID PMC8414408.

4. IFPMA. IFPMA Position Paper on Regulatory Reliance. Geneva: International Federation of Pharmaceutical Manufacturers and Associations. Available from: https://www.ifpma.org/publications/ifpma-position-paper-on-regulatory-reliance/. [Last accessed on 26 Feb 2025].

5. Mangia F, Lin YM, Armando J, Dominguez K, Rozhnova V, Ausborn S. Unleashing the power of reliance for post approval changes: a journey with 48 National Regulatory Authorities. Ther Innov Regul Sci. 2024;58(6):997-1005. doi: 10.1007/s43441-024-00677-8, PMID 39048766.

6. Pan American Health Organization (PAHO). Regulatory Reliance Principles: Concept Note and Recommendations. Washington, DC: Pan American Health Organization. Available from: https://prais.paho.org/en/paho-regulatory-reliance-principles-concept-note-and-recommendations/. [Last accessed on 10 Jul 2025].

7. US Food and Drug Administration (FDA). International Regulatory Collaboration: Project Orbis Update. In: Silver Spring, MD: FDA; 2023. Available from: https://www.fda.gov/media. [Last accessed on 02 Mar 2025].

8. Therapeutic Goods Administration (TGA), Australia Canada Singapore, Switzerland United Kingdom (Access) Consortium. Canberra (AU): TGA. Available from: https://www.tga.gov.au/about-tga/international/australia-canada-singapore-switzerland-united-kingdom-access-consortium. [Last accessed on 02 Mar 2025].

9. International Recognition Procedure. London (UK): GOV. UK. UK: Medicines and Healthcare Products Regulatory Agency (MHRA). Available from: https://www.gov.uk/government/publications/international-recognition-procedure/international-recognition-procedure. [Last accessed on 02 Mar 2025].

10. Citeline. Regulatory Reliance Pathways: Challenges and Opportunities Ahead Citeline. Available from: https://.citeline.com/ps149684 /regulatory-reliance-pathwayschallenges-and-opportunities-ahead. [Last accessed on 02 Mar 2025].

11. Center for Innovation in Regulatory Science (CIRS). CIRS RD Briefing 82-Regulatory Reliance Pathways: Opportunities and Barriers. In: London, UK: CIRS; Available from: https://www.cirsci.org/publications/cirs-rd-briefing-82regulatory-reliance-pathways-opportunities-and-barriers. [Last accessed on 02 Mar 2025].

12. International Pharmaceutical Regulators Programme (IPRP). IPRP Questions and Answers on Reliance. Geneva: IPRP; 2023 Jun 13. Available from: https://admin.iprp.global/sites/default/files/2023-06/IPRP_RelianceQ%26As_2023_0613.pdf. [Last accessed on 25 Jun 2025].

13. Saint Raymond A, Valentin M, Nakashima N, Orphanos N, Santos G, Balkamos G. Reliance is key to effective access and oversight of medical products in case of public health emergencies. Expert Rev Clin Pharmacol. 2022 Jul;15(7):805-10. doi: 10.1080/17512433.2022.2088503, PMID 35945703.

14. Org R. Access Consortium A Global Collaborative Pathway. Gand L Scientific; 2023. Available from: https://gandlscientific.s3-assets.com/manan-shah-raps-blog-0723.pdf. [Last accessed on 02 Mar 2025].

15. Access Consortium Promise Pilot Pathway: Benefit and Requirements. DLRC Group. Available from: https://www.dlrcgroup.com/access-consortium-promise-pilot-pathway-benefit-and-requirements. [Last accessed on 04 Mar 2025].

16. Therapeutic Goods Administration (TGA) Project Orbis. Canberra (AU): TGA. Available from: https://www.tga.gov.au/project-orbis.

17. Shum M. Work sharing reliance and other novel approaches to accelerating review approvals and access. Therapeutic Goods Administration (TGA). Available from: https://www.tga.gov.au/sites/default/files/presentation-work-sharing-reliance-approaches-accelerating-review-approvals-access.pdf. [Last accessed on 04 Mar 2025].

18. Project Orbis. U.S. Food and Drug Administration (FDA). Available from: https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis. [Last accessed on 04 Mar 2025].

19. Project Orbis: global collaborative oncology review program–05/13/2021. U.S. Food and Drug Administration (FDA); 2021 May 13. Available from: https://www.fda.gov/science-research/fda-grand-rounds/project-orbisglobal-collaborative-oncology-review-program-05132021-05132021. [Last accessed on 07 Mar 2025].

20. World Health Organization (WHO), translator. 1033-annex 10: Good Reliance Practices in the Regulation of Medical Products. In: Geneva: World Health Organization. Available from: https://www.who.int/publications/m/item/annex-10-trs-1033. [Last accessed on 08 Mar 2025].

21. Vaz A, Roldao Santos M, Gwaza L, Mezquita Gonzalez E, Pajewska Lewandowska M, Azatyan S. WHO collaborative registration procedure using stringent regulatory authorities medicine evaluation: reliance in action? Expert Rev Clin Pharmacol. 2022 Jan;15(1):11-7. doi: 10.1080/17512433.2022.2037419, PMID 35130803.

22. Medicines and Healthcare products Regulatory Agency (MHRA). MHRA Grants First Approval via the New International Recognition Procedure. London, UK: GOV. UK. Available from: https://www.gov.uk/government/news/mhra-grants-first-approval-via-the-new-international-recognition-procedure-in-30-d. [Last accessed on 11 Mar 2025].

23. DLRC Group. A first look: MHRA’s new International Recognition Procedure. DLRC Group. Available from: https://www.dlrcgroup.com/ready-for-january2024-a-first-look-at-mhras-new-international-recognition-procedure-irp. [Last accessed on 12 Mar 2025].

24. Fast Tracking Approval of Medicines–UK Publishes Detailed Guidance. Covington & Burling. LLP. Inside EU Life Sciences; 2023 Sep 11. Available from: https://www.com/2023/09/11/fast-tacking-approval-of-medicines-ukpublishes-detailed-guidance-on-its-new-international-recognition-procedure. [Last accessed on 12 Mar 2025].

25. Pharma Lex. UK’s IRP Paves the Way for Faster Market Access. Pharma Lex; Available from: https://www.pharmalex.com/thoughtleadership/blogs/understanding-the-uksinternational-recognition-procedure. [Last accessed on 14 Mar 2025].

26. Danks L, Semete Makokotlela B, Otwombe K, Parag Y, Walker S, Salek S. Evaluation of the impact of reliance on the regulatory performance in the South African Health Products Regulatory Authority: implications for African regulatory authorities. Front Med (Lausanne). 2023 Oct 23;10:1265058. doi: 10.3389/fmed.2023.1265058, PMID 37937144, PMCID PMC10626996.

27. Keyter A, Salek S, Danks L, Nkambule P, Semete Makokotlela B, Walker S. South African regulatory authority: the impact of reliance on the review process leading to improved patient access. Front Pharmacol. 2021 Jul 23;12:699063. doi: 10.3389/fphar.2021.699063, PMID 34366850, PMCID PMC8342884.

28. South African Health Products Regulatory Authority (SAHPRA). Reliance guideline. Pretoria (ZA): SAHPRA. Available from: https://www.sahpra.org.za/document/reliance-guideline. [Last accessed on 21 Mar 2025].

29. Expediting Access Through Reliance Pathways: Mena Region. Biomapas. Available from: https://www.biomapas.com/expediting-access-through-reliance-pathways-mean-region. [Last accessed on 24 Mar 2025].

30. Regulatory framework for drugs approval. Saudi Food and Drug Authority. In: Riyadh: SFDA. Available from: https://www.sfda.gov.sa/en/regulations/65436. [Last accessed on 24 Mar 2025].

31. Jordan FDA Adopts Reliance Review Model. Global Forum; 2019 Oct. Available from: https://globalforum.diaglobal.org/issue./jordan-fda-adopts-reliance-review-model. [Last accessed on 24 Mar 2025].

32. Pakistan Reliance Guidance for Pharmaceutical Regulatory Processes. Drug Regulatory Authority of Pakistan. 2nd ed. 2023. Islamabad: DRAP. Available from: https://www.dra.gov.pk/wp-content/uploads.2023/01relaince-mechansim-in-regulatory-processess.pdf. [Last accessed on 31 Mar 2025].

33. National Pharmaceutical Regulatory Agency (NPRA). Guideline on facilitated registration pathway: abbreviated and verification review. In: Ministry of Health Malaysia. Kuala Lumpur (MY), NPRA; 2019 Mar. Available from: https://www.npra.gov.my/easyarticles/images/users/1051/facilitatedregistration-pathway-guideline_final.pdf. [Last accessed on 31 Mar 2025].

34. Van Der Zee IT, Vreman RA, Liberti L, Garza MA. Regulatory reliance pathways during health emergencies: enabling timely authorizations for COVID-19 vaccines in Latin America. Rev Panam Salud Publica. 2022 Aug 30;46:e115. doi: 10.26633/RPSP.2022.115, PMID 36060200, PMCID PMC9426952.

35. Pavithra GM, Maanvizhi S. Fast track USA regulatory approval for drugs to treat emerging infectious diseases. Asian J Pharm Clin Res. 2021 Jul;14(7):1-4. doi: 10.22159/ajpcr.2021.v14i7.41761.

36. COVID-19 vaccines: safety surveillance manual stakeholders. World Health Organization (WHO); 2020. Available from: https://www.who.int/publications/i/item/9789240032781. [Last accessed on 24 Mar 2025].

37. Patel P, Macdonald JC, Boobalan J, Marsden M, Rizzi R, Zenon M. Regulatory agilities impacting review timelines for Pfizer/BioNTech's BNT162b2 mRNA COVID-19 vaccine: a retrospective study. Front Med (Lausanne). 2023 Nov 8;10:1275817. doi: 10.3389/fmed.2023.1275817, PMID 38020129, PMCID PMC10664654.

38. Saint Raymond A, Sato J, Kishioka Y, Teixeira T, Hasslboeck C, Kweder SL. Remdesivir emergency approvals: a comparison of the U.S., Japanese, and EU systems. Expert Rev Clin Pharmacol. 2020;13(10):1095-101. doi: 10.1080/17512433.2020.1821650, PMID 32909843.

39. COVAX Explained. Gavi the Vaccine Alliance; 2021. Available from: https://www.gavi.org/vaccineswork/covax-explained. [Last accessed on 25 Jun 2025].

40. Pfizer Corona Virus Vaccine FDA Emergency Use Authorization. Axios; 2020 Nov 20. Available from: https://www.axios.com/2020/11/20/pfizer-coronavirus-vaccine-fda-emergency-use-authorization. [Last accessed on 02 Aug 2025].

41. Matwadia E. Three ways COVID sped up SA’s medicine approvals process and how it can help the National Health Insurance Scheme. Johannesburg: the Mail and Guardian; 2022 Nov 7. Available from: https://mg.co.za/health/2022-11-07-three-ways-covid-sped-up-sas-medicine-approvals-process-and-how-it-can-help-the-national-health-insurance-scheme. [Last accessed on 02 Aug 2025].

42. South African Health Products Regulatory Authority. SAHPRA annual report 2021/22. Available from: https://www.sahpra.org.za/wp-content/uploads/2022/10/202122sahpra-annual-report.pdf. [Last accessed on 02 Aug 2025].

43. Gavi, the Vaccine Alliance. COVAX timeline. Available from: https://www.gavi.org/covax/timeline?utm. [Last accessed on 02 Aug 2025].

44. Mao W, Zimmerman A, Urli Hodges E, Ortiz E, Dods G, Taylor A. Comparing research and development launch and scale up timelines of 18 vaccines: lessons learnt from COVID-19 and implications for other infectious diseases. BMJ Glob Health. 2023;8(9):e012855. doi: 10.1136/bmjgh-2023-012855, PMID 37696544.

45. Xu M, Zhang L, Feng X, Zhang Z, Huang Y. Regulatory reliance for convergence and harmonisation in the medical device space in Asia-Pacific. BMJ Glob Health. 2022;7(8):e009798. doi: 10.1136/bmjgh-2022-009798, PMID 35985696.

46. Mukonzo JK, Ndagije HB, Sabblah GT, Mathenge W, Price DA, Grasela TH. Expanding regulatory science: regulatory complementarity and reliance. Clin Transl Sci. 2024 Jan 1;17(1):e13683. doi: 10.1111/cts.13683, PMID 37957894.

47. Sok Bee L. Benefits and challenges of reliance pathways; 2019. Available from: https://apac-asia/images/achievements/pdf/8th/5_ra/12_benefits% 20and%20challenges%20of%20reliance%20pathways.pdf. [Last accessed on 24 Mar 2025].

48. De Lucia ML, Comesana C, Rodriguez H, Dangy Caye A. Impact assessment of divergence on post approval changes classifications of Latin America region with Europe and the United States, and propositions to harmonize classification based on risk as a path to build the trust between national regulatory agencies. Clin Ther. 2024 Feb;46(2):164-72. doi: 10.1016/j.clinthera.2023.11.005, PMID 38092583.

49. Geraci G, Bernat J, Rodier C, Acha V, Acquah J, Beakes Read G. Medicinal product development and regulatory agilities implemented during the early phases of the COVID-19 Pandemic: experiences and implications for the future an industry view. Ther Innov Regul Sci. 2023 Sep;57(5):940-51. doi: 10.1007/s43441-023-00536-y, PMID 37266868, PMCID PMC10237066.

50. Dehaghi RO, Khadem Broojerdi A, Paganini L, Sillo HB. Collaborative training of regulators as an approach for strengthening regulatory systems in LMICs: experiences of the WHO and Swissmedic. Front Med (Lausanne). 2023 May 18;10:1173291. doi: 10.3389/fmed.2023.1173291, PMID 37275356, PMCID PMC10233123.

51. Doerr P, Valentin M, Nakashima N, Orphanos N, Santos G, Balkamos G. Reliance: a smarter way of regulating medical products the IPRP survey. Expert Rev Clin Pharmacol. 2021 Feb;14(2):173-7. doi: 10.1080/17512433.2021.1865798, PMID 33355025.

52. Importance of Reliance to Support Strengthening Latin American and Caribbean Regulatory Systems. Available from: https://pharmaboardroom.com/articles/importance-of-reliance-to-support-strengthening-latin-american-caribbean-regulatory-systems. [Last accessed on 24 Mar 2025].