Evaluation of the Regulatory Requirements for Development and Approval of Biosimilar Medicines in the BRICS-TM Countries: Improving Patients' Access

Biosimilars are affordable medicines of the original innovator biologic products that has the potential to improve access and create valuable savings for patients and the overall healthcare systems. Biosimilars are expected to emerge as a rapidly growing segment in emerging economies, as the treatment rates with biologics are low in these economies combined with constraints on affordability. However, unlike small molecule generics, biosimilars are complex molecules and have high associated cost of development. The biosimilar industry faces multiple challenges and obstacles in developing and marketing these complex products. While a common regulatory framework has been proposed by World Health Organisation (WHO), countries have only partially adopted them. Regulatory principles governing biosimilars in emerging economies like BRICS-TM (Brazil, Russia, India, China, South Africa, Turkey, Mexico) are still in an evolving stage. There is differing regulatory guidelines for biosimilar development and registration in these countries; hence there remains scope for improving transparency in the national regulatory frameworks and aligning regulatory standards among these countries. Standardisation of regulatory requirements would assist in the common biosimilar development process across these economies. Comparisons of the regulatory requirements with mature regulatory agencies of countries such as Australia, Canada, Singapore and Switzerland (ACSS consortium) will facilitate benchmarking best practices leading to convergence of regulatory processes in BRICS-TM countries. This would impact the overall review and approval process as well as enabling a common development programme across these countries. Also, biosimilars are similar but not identical to the innovator product and therefore prescribers are sometimes unsure about the safety and efficacy profile of these medicines. Due to such roadblocks, the healthcare system and patients are yet to realize the full benefits of biosimilars. The aim of the research study was to explore, identify and evaluate the biosimilar regulatory framework in terms of resources in biosimilar domain, biosimilar development criteria i.e., biosimilarity principle, comparative studies including physicochemical characterisation, non-clinical studies, clinical studies and biosimilar marketing authorisation approval pathway, of regulatory agencies in BRICS-TM (Brazil, Russia, India, China, South Africa, Turkey, Mexico) countries. This was achieved by identifying and comparing the regulatory requirements of the selected emerging economies with those of mature agencies to understand the differing regulatory expectations for biosimilar development and approval process. The study also focused on understanding the perspectives of different stakeholders like industry, regulators, physicians and patients on the challenges for the development and uptake of biosimilars in these emerging economies. The outcome from the assessment of the challenges faced by the stakeholders, biosimilar development criteria, content of the marketing authorization application and approval pathway were likely to form the basis of a proposed standardized model for the BRICS-TM countries. The research programme considered various methodologies for determining the appropriate study design including a combination of self-administered questionnaires and interviews to achieve the study objectives. A semi-quantitative questionnaire was developed covering the different criteria used in biosimilar development and registration process. Eleven regulatory agencies from BRICS-TM and ACSS countries were invited to take part in the study. Similarly, another semi-quantitative questionnaire was designed based on secondary research for the representatives from biopharmaceutical industry specifically to understand the perceptions of industry on the barriers faced by them in terms of complexity, costs for biosimilar development and time-to-market of biosimilar product. Following completion of the questionnaires, interviews were carried out and recorded verbatim to exclude any misinterpretations. Another set of questionnaires were prepared for the physicians and patients to identify challenges to the uptake of biosimilar medicines by physicians and patients in the developing countries. The results indicated that the perspectives of the BRICS-TM regulatory agencies varied on a number of aspects relating to the review criteria for biosimilar development and licensing process. The most prevalent model for data assessment was the ‘full review’ of a marketing authorisation application and absence or partial reliance approach across most of these economies. The biggest hurdles in the development of biosimilar product were the sourcing of the reference biological product (RBP); there was lack of a standard approach or flexibility in the regulatory standards across the BRICS-TM agencies on sourcing of the reference biological product and hence posed as key concern for facilitating cost-effective development of biosimilar products. Despite alignment over biosimilarity, the mandate for in vivo non-clinical studies and additional local clinical studies in some of the BRICS-TM countries illustrated a lack of effective implementation of a step-wise approach. Most agencies limited interaction with biosimilar developers and any scientific advice was non-binding. The marketing authorisation approval was dependent on scientific assessment of the dossier, sample analysis and GMP certification. The BRICS-TM agencies except ANVISA (Brazil), did not issue any public assessment report specifying the summary basis of biosimilar approval. The results also revealed that physicians have significant knowledge gaps in the area of biosimilar medicines. While they understand the importance of improving patients’ access to biological therapies, they expect to gain complete confidence in the quality, efficacy, safety, and immunogenicity of these medicines to underpin their decision to prescribe them. For the patients, access to affordable biosimilar medicines was the single biggest factor that greatly influenced their wider adoption. The findings from this study indicated the scale of the challenges that could exist across the emerging economies (i.e. BRICS-TM), the need for fresh perspectives in guidelines and policies facilitating wider adoption of biosimilars as well as improved patients’ access. The outcomes from these studies formed the basis of a proposed standardized model for the BRICS-TM countries. This proposed regulatory model is likely to simplify new biosimilar development programmes and pave the way for patients’ access to quality and affordable biosimilar medicines. It is hoped that the outcomes of this study will help in streamlining of the regulatory standards in these countries, leading to improved patient access to affordable medicines without compromising their quality, safety, or efficacy.

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