Biosimilar development and review process in the BRICS-TM countries: Proposal for a standardized model to improve regulatory performance

ABSTRACT

Objectives

The current study is aimed at proposing a standardized regulatory model for biosimilar development and approval for adoption by BRICS-TM agencies, based on evaluation of regulatory guidelines and potential solutions to challenges.

Methods

An established validated questionnaire was used and the recommendations were collated. Propositions deemed critical for improving the regulatory pathway for biosimilar development were synthesized to design a new regulatory model.

Results

The key areas for improvement in BRICS-TM countries were: effective implementation of a step-wise approach; adoption of science-based regulatory evaluation for clinical efficacy studies and acceptance of analytical comparability studies in lieu of confirmatory clinical trials; a streamlined biosimilar development program for RBP sourcing; regulatory reliance for joint or shared review of the applications; and enhanced transparency and communication between the regulatory agencies and biosimilar developers. Based on these identified critical aspects, a simplified and standard regulatory model was developed to enable standardization of biosimilar guidelines across BRICS-TM countries for a common development program.

Conclusions

Effective implementation of the proposed standardized model for biosimilar development and approval processes across the BRICS-TM agencies will eliminate unwarranted studies, reduce the development costs, and enhance process efficiency thereby expediting patients’ access to new affordable biosimilar medicines.

Plain language summary

The studies presented in this article have identified key areas for improvement in biosimilar development and approval pathways in BRICS-TM countries, which have formed the basis for development of a model to standardize requirements for biosimilar development and the approval process, with a view to improve regulatory performance. Implementation of the proposed model by the BRICS-TM regulatory agencies with consideration of a stepwise approach and science-based evaluation of analytical data could reduce the duplication and unnecessary conduct of non-clinical studies, thereby reducing the development cost and review timelines. Data assessment based on reliance as considered in the proposed model would strengthen reliance networks and improve the process efficiency among the BRICS-TM regulatory agencies. Flexibility in regulatory requirements by the BRICS-TM agencies for the use of Reference Biologic Product (RBP) from other emerging economies and their interaction with the developers would enhance transparency and ease the challenges in sourcing RBP from different jurisdictions. This would further help in expediting a common biosimilar development process. Good Manufacturing Practice (GMP) inspection of the biosimilar manufacturing facilities by desktop audit or off-site audit and acceptance of GMP certifications from other reference agencies would improve the overall regulatory performance and reduce overall review timelines, leading to faster availability of biosimilar medicines for patient access.

KEYWORDS:

• Biosimilar development
• BRICS-TM
• emerging market
• model
• regulatory agency

Acknowledgments

The authors wish to acknowledge the invaluable contribution of Klein Agnes (BRDD, Canada), Adriana Hernández-Trejo (Mexico), Lawrence Liberti (CIRS), Magda Bujar (CIRS), Zoher Sihorwala (Wockhardt, India) and Andrea Keyter (South Africa) for their help and advice with data collection and review of the entire manuscript. In addition, the authors would like to thank Shobhna Aanand (Metina PharmConsulting) for her editorial contribution to the draft manuscript.

ABBREVIATIONS

ACSS: Australia, Canada, Singapore, Switzerland; ADCC: Antibody Dependent Cellular Cytotoxicity; AMANC: Asociación Mexicana de Ayuda a Niños con Cáncer; AMCP: Academy of Managed Care Pharmacy; ANVISA: Agência Nacional de Vigilância Sanitária; AusPAR: Australian Public Assessment Reports; BDEA: Biosimilar Development, Evaluation and Authorization; BDSR: Biosimilar Development, Submission and Review; BLA: Biologic License Application; BPCIA: Biologics Price Competition and Innovation Act; BPQ: Biosimilar Physician Questionnaire; BPAQ: Biosimilar Patients’ Access Questionnaire; BRDD: Biologic and Radiopharmaceutical Drugs Directorate; BRIC: Brazil, Russia, India, China; BRICS-TM: Brazil, Russia, India, China, South Africa, Turkey, Mexico; BSSO: Brazilian Society of Surgical Oncology; CACA: China Anti-Cancer Association; CANSA: Cancer Association of South Africa; CDC: Complement Dependent Cytotoxicity; CDR: Complementarity Determining Region; CDSCO: Central Drugs Standard Control Organization; CHOC: Childhood Cancer Foundation South Africa; COFEPRIS: Comisión Federal para la Protección contra Riesgos Sanitarios; CORD: Chinese Organisation for Rare Disorders; COVID-19: Corona Virus Disease; EAFO: Eurasian Federation of Oncology; EMA: European Medicines Agency; EPAR: European Public Assessment Report; EU: European Union; FDA: Food and Drug Administration; GBT: Global Benchmarking Tool; GMP: Good Manufacturing Practice; HCOs: Healthcare Organisations; HSA: Health Sciences Authority; IGBA: International Generic and Biosimilar Medicines Association; LMICs: Low-to-Middle-Income Countries; mAbs: Monoclonal Antibodies; MOU: Memorandum of Understanding; MRA: Mutual Recognition Agreement; NDA: New Drug Application; NHP: Non-Human Primates; NMPA: National Medical Products Administration; NMRAs: National Medical Regulatory Agencies; NRA: National Regulatory Authorities; MHRA: Medicines and Healthcare products Regulatory Agency; PAR: Public Assessment Report; PARE: People with Arthritis and Rheumatism; PD: Pharmacodynamics; PIC/S: Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme; PK: Pharmacokinetics; RBP: Reference Biologic Product; SAGES: South Africa Gastroenterology Society; SBP: Similar Biotherapeutics Product; SPSS: Statistical Product and Service Solutions; SAHPRA: South African Health Products Regulatory Authority; SwissPAR: Swiss Public Assessment Report; TACRC: Turkish Association for Cancer Research and Control; ToE: Totality-of-the-Evidence; TGA: Therapeutic Goods Administration; TITCK: Türkiye İlaç ve Tıbbi Cihaz Kurumu; TUSPA: Turkish Scientists And Physicians Association; UK: United Kingdom; US: United States; USFDA: United States Food and Drug Administration; WHA: World Health Assembly; WHO: World Health Organization; WHOPAR: WHO Public Assessment Report; ZaZiBoNa: Zambia, Zimbabawe, Botswana, Namibia.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Author contributions

H Rahalkar contributed to the design of the research methodology, questionnaire development, the study sample selection, online interviews, data collection, interpretation and writing of the first draft of the manuscript. A Sheppard contributed to the review of the questionnaire, support in identifying appropriate participants for the study and review of the first draft of the manuscript. S Salek contributed to the development of the concept, supervision of the study, review of the questionnaire, research coordination, interpretation of the results and review of the first and final draft of the manuscript.

Disclaimers

The views, analysis, and interpretation presented in this article do not represent that of any biopharmaceutical industries, physicians, regulatory agencies. The views are purely based on data collated from individual representatives of biopharmaceutical industries, physicians, regulatory agencies and experts closely associated with the agencies based on their understanding of the existent regulatory norms during the study period. The article does not purport to represent the actual regulations/ guidelines across BRICS-TM agencies.

Additional information

Funding

This paper was not funded.