Comparison of BRICS-TM Countries' Biosimilar Regulatory Frameworks With Australia, Canada and Switzerland: Benchmarking Best Practices

Objectives: The aim of this study was to identify, compare and evaluate regulatory requirements for the biosimilar development and review processes in BRICS-TM (Brazil, Russia, India, China, South Africa, Turkey, Mexico) countries with mature regulatory systems of Australia, Canada, Singapore and Switzerland. It is hoped that this benchmark study provides an opportunity for BRICS-TM agencies to identify the key areas for improvement in their regulatory processes. Materials and Methods: 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 (Australia, Canada, Switzerland and Singapore) countries were invited to take part in this study. Data processing and analysis was carried out using descriptive statistics for quantitative data and content analysis to generate themes for qualitative data. Results and Discussions: Nine of the 11 regulatory agencies recruited for the study completed the questionnaire. China and Singapore did not meet the deadline due to lack of resources. The organisational structure of BRICS-TM agencies revealed support from external assessors by most of these agencies in comparison with ACSS agencies. There was absence of reliance approach and participation in harmonisation activities across most BRICS-TM agencies. Despite alignment over biosimilarity, the mandate for in vivo non-clinical studies and additional local clinical studies in some of the BRICS-TM countries illustrates a lack of effective implementation of a step-wise approach. Adopting flexible regulatory standards in the sourcing of a RBP (Reference Biologic Product) by BRICS-TM similar to ACSS, will facilitate cost-effective development of biosimilar products. Conclusions: Comparative assessment of the biosimilar regulatory framework of BRICS-TM with ACSS agencies reveals the scope for enhancing efficiency of the regulatory approval process. To achieve this, BRICS-TM agencies should consider relying on reference agencies for alternative review mechanisms such as abridged or verification models, streamlined processes for providing scientific advice to developers and for waiving local clinical studies in-lieu of advanced scientific data.Peer reviewedFinal Published versio

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

Challenges Faced by the Biopharmaceutical Industry in the Development and Marketing Authorization of Biosimilar Medicines in BRICS-TM Countries: An Exploratory Study

Abstract: Background: Biosimilars are expected to emerge as a rapidly growing segment of the biopharmaceutical industry. However, the biosimilar industry faces multiple challenges and obstacles in developing and marketing these complex products. Divergent regulatory framework in emerging countries adds to repetitive trials and increased cost of biosimilar development, delaying the approval process. Due to such roadblocks, healthcare systems and patients are yet to realize the full benefits of biosimilars. Objectives: The aim of this exploratory study was to specifically identify the challenges faced by the industry in emerging countries including Brazil, Russia, India, China, South Africa, Turkey and Mexico (BRICS-TM), pertaining to biosimilar development and the regulatory approval process. In particular, this study aims to understand the perceptions of industry on the barriers faced by them in terms of complexity, costs for biosimilar development and time-to-market for biosimilar product. Methods: A semi-quantitative questionnaire was designed based on secondary research. A total of 93 industry personnel and representatives from 14 trade associations from the BRICS-TM countries with 15-year minimum experience were identified and invited to take part in the study and participate in interviews, which were recorded verbatim. Data processing and analysis was carried out; descriptive statistics were used for quantitative data and content analysis was employed to generate themes for qualitative data. Results: Of the 107 biopharmaceutical industry and trade association representatives invited to participate in the study, respondents from 33 biopharmaceutical companies agreed to take part and underwent the interviews. The industry personnel perceived biosimilar guidelines and approval processes as being protracted and in a state of evolution. The absence of an abridged approval pathway limited effectiveness of the regulatory process. The biggest hurdles in the development of biosimilar dossiers were the sourcing of the reference biological product and expectations around confirmatory clinical trials by the agencies. The non-comprehensive implementation of a stepwise approach resulting in unnecessary toxicity studies was also reported as a major challenge. The authors recommend further primary research with BRICS-TM regulatory agencies in order to propose a simplified pathway for development and approval. Conclusions: Lack of standardized biosimilar development criteria and regulatory convergence across BRICS-TM agencies has led to challenges in multi-country development programmes for these medicines, in turn impacting the ability of industry to launch newer and more affordable biosimilars.Peer reviewe

Current Regulatory Requirements for Biosimilars in Six Member Countries of BRICS-TM: Challenges and Opportunities

© 2021 Rahalkar, Sheppard, Santos, Dasgupta, Perez-Tapia, Lopez-Morales and Salek. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/Background: The aim of the study was to identify, interpret, and compare the current perspectives of regulatory agencies in six member countries of BRICS-TM (Brazil, Russia, India, China, South Africa, Turkey, and Mexico) on the different criteria used for biosimilar development and marketing authorisation process. Methods: A semi-quantitative questionnaire was developed covering the organisation of agency, biosimilar development criteria and marketing authorisation process and sent to seven regulatory agencies covering the BRICS-TM countries. All data was kept anonymous and confidential. Data processing and analysis was carried out; descriptive statistics were used for quantitative data and content analysis was employed to generate themes for qualitative data. Results: Out of the seven regulatory agencies included in the study, six representatives provided the responses. The perspectives of these six regulatory agencies varied on a number of aspects relating to the review criteria for biosimilar development and licencing process. The most prevalent model for data assessment is the “full review” of a marketing authorisation application. There is lack of a standard approach across the agencies on sourcing of the reference biological product, in vivo toxicity studies and confirmatory clinical studies. Most agencies restrict interaction with biosimilar developers and any scientific advice is non-binding. The marketing authorisation approval depends on scientific assessment of the dossier, sample analysis and GMP certification. The agencies do not issue any public assessment report specifying the summary basis of biosimilar approval. Conclusion: Regulatory agencies across the six emerging economies are steadily improving the regulatory mechanism in the area of biosimilars. However, there remains scope for increasing the effectiveness and efficiency of the processes by encouraging open and transparent interaction with developers, adopting a flexible approach toward accepting advanced analytical data in lieu of clinical studies and enhancing regulatory reliance amongst agencies. This will help to simplify the new biosimilar development programmes and make them more cost-effective.Peer reviewe

Comparison of BRICS-TM Countries' Biosimilar Regulatory Frameworks With Australia, Canada and Switzerland: Benchmarking Best Practices

Objectives: The aim of this study was to identify, compare and evaluate regulatory requirements for the biosimilar development and review processes in BRICS-TM (Brazil, Russia, India, China, South Africa, Turkey, Mexico) countries with mature regulatory systems of Australia, Canada, Singapore and Switzerland. It is hoped that this benchmark study provides an opportunity for BRICS-TM agencies to identify the key areas for improvement in their regulatory processes.Materials and Methods: 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 (Australia, Canada, Switzerland and Singapore) countries were invited to take part in this study. Data processing and analysis was carried out using descriptive statistics for quantitative data and content analysis to generate themes for qualitative data.Results and Discussions: Nine of the 11 regulatory agencies recruited for the study completed the questionnaire. China and Singapore did not meet the deadline due to lack of resources. The organisational structure of BRICS-TM agencies revealed support from external assessors by most of these agencies in comparison with ACSS agencies. There was absence of reliance approach and participation in harmonisation activities across most BRICS-TM agencies. Despite alignment over biosimilarity, the mandate for in vivo non-clinical studies and additional local clinical studies in some of the BRICS-TM countries illustrates a lack of effective implementation of a step-wise approach. Adopting flexible regulatory standards in the sourcing of a RBP (Reference Biologic Product) by BRICS-TM similar to ACSS, will facilitate cost-effective development of biosimilar products.Conclusions: Comparative assessment of the biosimilar regulatory framework of BRICS-TM with ACSS agencies reveals the scope for enhancing efficiency of the regulatory approval process. To achieve this, BRICS-TM agencies should consider relying on reference agencies for alternative review mechanisms such as abridged or verification models, streamlined processes for providing scientific advice to developers and for waiving local clinical studies in-lieu of advanced scientific data.</jats:p

Current Regulatory Requirements for Biosimilars in Six Member Countries of BRICS-TM: Challenges and Opportunities

Background: The aim of the study was to identify, interpret, and compare the current perspectives of regulatory agencies in six member countries of BRICS-TM (Brazil, Russia, India, China, South Africa, Turkey, and Mexico) on the different criteria used for biosimilar development and marketing authorisation process.Methods: A semi-quantitative questionnaire was developed covering the organisation of agency, biosimilar development criteria and marketing authorisation process and sent to seven regulatory agencies covering the BRICS-TM countries. All data was kept anonymous and confidential. Data processing and analysis was carried out; descriptive statistics were used for quantitative data and content analysis was employed to generate themes for qualitative data.Results: Out of the seven regulatory agencies included in the study, six representatives provided the responses. The perspectives of these six regulatory agencies varied on a number of aspects relating to the review criteria for biosimilar development and licencing process. The most prevalent model for data assessment is the “full review” of a marketing authorisation application. There is lack of a standard approach across the agencies on sourcing of the reference biological product, in vivo toxicity studies and confirmatory clinical studies. Most agencies restrict interaction with biosimilar developers and any scientific advice is non-binding. The marketing authorisation approval depends on scientific assessment of the dossier, sample analysis and GMP certification. The agencies do not issue any public assessment report specifying the summary basis of biosimilar approval.Conclusion: Regulatory agencies across the six emerging economies are steadily improving the regulatory mechanism in the area of biosimilars. However, there remains scope for increasing the effectiveness and efficiency of the processes by encouraging open and transparent interaction with developers, adopting a flexible approach toward accepting advanced analytical data in lieu of clinical studies and enhancing regulatory reliance amongst agencies. This will help to simplify the new biosimilar development programmes and make them more cost-effective.</jats:p

Data_Sheet_1_Current Regulatory Requirements for Biosimilars in Six Member Countries of BRICS-TM: Challenges and Opportunities.PDF

Background: The aim of the study was to identify, interpret, and compare the current perspectives of regulatory agencies in six member countries of BRICS-TM (Brazil, Russia, India, China, South Africa, Turkey, and Mexico) on the different criteria used for biosimilar development and marketing authorisation process.Methods: A semi-quantitative questionnaire was developed covering the organisation of agency, biosimilar development criteria and marketing authorisation process and sent to seven regulatory agencies covering the BRICS-TM countries. All data was kept anonymous and confidential. Data processing and analysis was carried out; descriptive statistics were used for quantitative data and content analysis was employed to generate themes for qualitative data.Results: Out of the seven regulatory agencies included in the study, six representatives provided the responses. The perspectives of these six regulatory agencies varied on a number of aspects relating to the review criteria for biosimilar development and licencing process. The most prevalent model for data assessment is the “full review” of a marketing authorisation application. There is lack of a standard approach across the agencies on sourcing of the reference biological product, in vivo toxicity studies and confirmatory clinical studies. Most agencies restrict interaction with biosimilar developers and any scientific advice is non-binding. The marketing authorisation approval depends on scientific assessment of the dossier, sample analysis and GMP certification. The agencies do not issue any public assessment report specifying the summary basis of biosimilar approval.Conclusion: Regulatory agencies across the six emerging economies are steadily improving the regulatory mechanism in the area of biosimilars. However, there remains scope for increasing the effectiveness and efficiency of the processes by encouraging open and transparent interaction with developers, adopting a flexible approach toward accepting advanced analytical data in lieu of clinical studies and enhancing regulatory reliance amongst agencies. This will help to simplify the new biosimilar development programmes and make them more cost-effective.</p