|
ANMAT, Argentina |
MFDS, Republic of Korea |
| ANVISA, Brazil | MHLW/PMDA, Japan |
| COFEPRIS, Mexico | MHRA, UK |
| CPED, Israel | NAFDAC, Nigeria |
| EC, Europe | SAHPRA, South Africa |
| EDA, Egypt | SFDA, Saudi Arabia |
| FDA, United States | Swissmedic, Switzerland – co-Chair |
| Health Canada, Canada | TFDA, Chinese Taipei |
| HSA, Singapore – co-Chair | TGA, Australia |
| INVIMA, Colombia | TITCK, Türkiye |
| JFDA, Jordan | WHO (Observer) |
| Medsafe, New Zealand |
The scope of the BEWGG is aligned with the scope of activities as outlined in the IPRP Terms of Reference. It covers the implementation and interpretation of bioequivalence requirements, procedures and tools for the assessment of bioequivalence in generic drug products.
The BEWGG’s areas of work will complement and not duplicate established international initiatives and developments that are in progress.
The BEWGG identifies opportunities for regulatory convergence and harmonisation by surveying and collating information from each member agency/organisation regarding issues of common interest related to the bioequivalence assessment of generic drug products. Where appropriate, the BEWGG also develops tools to aid in the assessment of bioequivalence in generic drug products applications.
Objective 1: Facilitate regulatory convergence and identify opportunities for harmonisation in the area of bioequivalence supporting generic drug applications
To identify areas of commonalities and differences in existing technical and regulatory requirements concerning bioequivalence (and biowaivers) in order to highlight opportunities for regulatory convergence and harmonisation.
Objective 2: Support bioequivalence assessment of generic drug applications
To engage in information sharing to highlight best practices, international regulatory requirements and sharing of technical issues of interest encountered in day to day work.
Acceptance of foreign comparator products in bioequivalence studies
The differing requirements on the acceptability of foreign comparator products in bioequivalence studies submitted to various regulatory authorities is an important reason for the need to repeat such studies for global filings by generic companies.
The BEWGG originally published an article in the Journal of Pharmacy and Pharmaceutical Sciences on 27 December 2018 which compared the acceptance and requirements for foreign comparator products among the participating regulators and organisations. Since then, the BEWGG’s membership has grown and some members have also changed their requirements/recommendations to facilitate generic submissions. An updated manuscript is currently under preparation and publication is anticipated by early 2026.
Biowaivers for various dosage forms
Excluding solid oral dosage forms, many dosage forms are eligible for biowaivers subject to certain criteria being met. However, many regulatory authorities do not have published guidelines that clearly state the biowaiver criteria for each dosage form. This may cause ambiguity regarding the need for in vivo bioequivalence studies to support generic submissions in multiple jurisdictions.
The BEWGG has published the requirements for oral and injectable dosage forms among the participating regulators and organisations in the Journal of Pharmacy and Pharmaceutical Sciences on 15 March 2021. This article is accompanied by dosage form-specific assessment report templates.
The BEWGG is currently preparing a similar manuscript and assessment report templates for topical, otic/ophthalmic, rectal and vaginal dosage forms and publication is anticipated by March 2025.
A third manuscript and set of assessment report templates for nasal and inhaled products is expected to follow in 2026.
Support for ICH harmonization
The BEWGG is in a unique position to support the harmonization of standards for generic drugs by ICH in the area of bioequivalence and biowaivers due to the critical mass of regulators in its membership, technical focus and established practices for information sharing.
To date, IPRP work products have supported the development of the ICH M9, M13A and M13B guidelines, as well as their subsequent implementation. The BEWGG is currently assessing further work areas to support the upcoming ICH M13C guideline as well as future ICH topics on bioequivalence.
Data integrity issues in bioequivalence studies
In recent years, there have been several incidents of contract research organisations (CROs) which have submitted manipulated data in support of generic submissions across multiple jurisdictions. The BEWGG regularly discusses this area of concern as part of its working scope and objectives.
The following work products have been completed.
BCS-based biowaivers
Regulatory Authorities participating in the IPRP Bioequivalence Working Group for Generics were surveyed for their requirements for biowaivers based on the Biopharmaceutics Classification System (BCS). The results of the comparison of criteria for BCS biowaivers among the participating regulators and organisations were published in the Journal of Pharmacy and Pharmaceutical Sciences on 25 January 2018.
To ensure that the relevant information for a BCS biowaiver is consistently taken into account during assessment, a template for a BCS Biowaiver Assessment Report was developed for use by Members. The Members of the Working Group envisage that this BCS Biowaiver Assessment Report template will also be of benefit to applicants and the broader regulatory community and have decided to make the BCS Biowaiver Assessment Report template available on the IPRP website. The template was updated in November 2024 in accordance with the ICH M9 guideline.
Non-IPRP member regulators may implement the template within their own responsibility. IPRP is not responsible for any contents of these documents implemented by non-IPRP member authorities.
BCS Biowaiver Assessment Report template
Acceptance of foreign comparator products in bioequivalence studies
Regulatory Authorities participating in the IPRP Bioequivalence Working Group for Generics have differing requirements on the acceptability of bioequivalence studies conducted using foreign comparator product of oral dosage forms. The results of a survey conducted to compare the acceptance and requirements for foreign comparator products among the participating regulators and organisations were published in the Journal of Pharmacy and Pharmaceutical Sciences on 27 December 2018.
An abstract to this article was also published in the GaBI Journal on 30 April 2019.
Additional strength biowaivers (immediate- and modified-release solid oral dosage forms)
The members of the Bioequivalence Working Group for Generics commonly grant biowaivers for non-study strengths (‘additional strengths’) under certain circumstances when bioequivalence has been demonstrated for one or two other strengths.
Surveys were conducted on the requirements for additional strength biowaivers for immediate-release and modified-release oral solid dosage forms among the member organisations and the results of the comparison of criteria were published in the Journal of Pharmacy and Pharmaceutical Sciences on 29 September 2019 and 25 October 2021, respectively.
To ensure that the relevant information for additional strength biowaivers is consistently taken into account during assessment, a template for Biowaiver Assessment Report for Additional Strength(s) of Systemically Acting Immediate Release Oral Dosage Forms was developed for use by Members. The Members of the Working Group envisage that this template will also be of benefit to applicants and the broader regulatory community and have decided to make it available on the IPRP website.
The Word version available on this webpage is provided in addition to the PDF version. Non-IPRP member regulators may implement these documents within their own responsibility. IPRP is not responsible for any contents of these documents implemented by non-IPRP member authorities.
BEWGG - Additional Strength Report_Template, dated 4 February 2019 (Word Version)
BEWGG - Additional Strength Report_Template, dated 4 February 2019 (PDF Version)
Biowaivers for various dosage forms
The members of the Bioequivalence Working Group for Generics commonly grant biowaivers for certain dosage forms subject to certain criteria.
A survey was conducted on the requirements for biowaivers for oral and injectable dosage forms among the member organisations and the results of the comparison of criteria were published in the Journal of Pharmacy and Pharmaceutical Sciences on 15 March 2021.
An abstract to this article was also published in the GaBI Journal on 10 June 2021.
To ensure that the relevant information for a dosage form biowaiver is consistently taken into account during assessment, assessment report templates for the various dosage forms are being developed by the Working Group. The Members envisage that they would be of benefit to applicants and the broader regulatory community, hence they are made freely available via the IPRP website.
In November 2024, the first set of templates were released and pertain to oral and injectable dosage forms.
Non-IPRP member regulators may implement the templates within their own responsibility. IPRP is not responsible for any contents of these documents implemented by non-IPRP member authorities.
Biowaiver assessment report templates - Set 1: Oral and injectable products
Alternative comparator product policies
When an established comparator product (usually the innovator product) is no longer available in the local market, an alternative comparator product needs to be identified for new bioequivalence studies in support of incoming generic products. This is a complex topic for which harmonisation is not expected but the sharing of practices among global regulators may be useful for the pharmaceutical industry when preparing for filings to different markets.
A survey was conducted on the selection criteria for alternative comparator products among the BEWGG member organisations and the results of the comparison of criteria were published in the Journal of Pharmacy and Pharmaceutical Sciences on 8 October 2022.
Bioequivalence study designs
Bioequivalence studies are commonly considered to be the gold standard for demonstrating that the in vivo performance of a test product is sufficiently similar to that of its comparator. While global regulators share many similarities in the broad requirements for how such studies should be conducted, differences exist on the more detailed aspects.
A survey was conducted on the bioequivalence study design requirements for immediate-release solid oral dosage forms among the BEWGG member organisations. The survey results were shared with the ICH M13 Expert Working Group and used to identify and analyse gaps during the harmonisation process. The results of the comparison of criteria were published in the Journal of Pharmacy and Pharmaceutical Sciences on 21 March 2024.