Impact of Discordance Among Regulations for Biopharmaceutics Classification System-Based Waivers of Clinical Bioequivalence Studies
Open accessAbstract
Approximately 10 years ago, the FDA issued a guidance whereby dissolution could be used to establish bioequivalence for highly soluble and highly permeable immediate-release products.This pathway has advantages in lower costs for pharmaceutical companies and avoids unnecessary exposure of human subjects who would derive no medical benefit from participating in bioequivalence studies.Subsequently, other agencies have also adopted similar guidances.However, there are differences among agency guidances that significantly impact the number of compounds eligible for BCS-based biowaivers across all regulatory agencies.These include differences in BCS Classes for which biowaivers are considered, differences in the definition of highly permeable, and differences in the definition of highly soluble.The currently low rate of biowaiver submissions may in part be due to these differences.
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In 2000, the US-FDA was the first regulatory agency to publish guidance for industry describing criteria for requesting a waiver of in vivo bioavailability and bioequivalence studies for highly soluble, highly permeable (BCS Class I) drugs.
“In 2000, the US-FDA was the first regulatory agency to publish guidance for industry describing how to meet criteria for requesting a waiver of in vivo bioavailability and bioequivalence studies for highly soluble, highly permeable (BCS Class I) drugs.”
From BCS Biowaivers: Similarities and Differences Among EMA, FDA, and WHO Requirements (2016) · cites this paper as [11]
The Abstract describes FDA guidance for highly soluble, highly permeable immediate-release products, and References entry 2 dates the FDA’s BCS-based waiver guidance to 2000. However, the Introduction explicitly says the FDA published the first such regulatory guidance in 2005. The paper therefore supports the guidance’s purpose but gives conflicting dates for the claim’s key year. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe low rate of BCS-biowaiver submissions from 2000 to 2015 may have been due in part to these differences.
“The low rate of BCS-biowaiver submissions from 2000 to 2015 may have been due in part to these differences (11); for example, from 2000 to 2015, the number of BCS biowaiver requests submitted to the US-FDA averaged approximately two per year (Mehta M. Applicability of BCS-Based Biowaiver: Requirements and Conditions -US-FDA Perspective.European Federation for Pharmaceutical Sciences Global Bioequ”
From BCS Biowaivers: Similarities and Differences Among EMA, FDA, and WHO Requirements (2016) · cites this paper as [11]
The Conclusions (page not available) say that differences among agency guidances may partly explain the currently low rate of biowaiver submissions. The paper does not establish that this explanation applies specifically to the stated 2000–2015 period. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe first regulatory guidances encouraging the use of the BCS for biowaivers of Class I immediate-release solid oral dosage forms were issued by the US-FDA in 2000 and by the EMA in 2001.
“The first regulatory guidances encouraging the use of the BCS for biowaivers of Class I immediate-release (IR) solid oral dosage forms were issued by the US Food and Drug Administration (US-FDA) in 2000 (6,11) and by the European Medicines Agency (EMA) in 2001 (12).”
From BCS Biowaivers: Similarities and Differences Among EMA, FDA, and WHO Requirements (2016) · cites this paper as [11]
The References list the FDA’s BCS-based guidance for immediate-release solid oral dosage forms as issued in 2000. However, the Introduction says the FDA first published that guidance in 2005, and the copy does not give 2001 as the date of the EMA’s first guidance; its cited EMA guideline is dated 2010. The source therefore does not support the full chronology claimed. (LLM, conf=0.83)
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Cites
Amidon, G. L., Lennernäs, H., Shah, V. P., & Crison, J. R. (1995) · Pharmaceutical Research · doi:10.1023/a:1016212804288 · Cited by 5,430 · see citing works
Lindenberg, M., Kopp, S., & Dressman, J. (2004) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2004.03.001 · Cited by 866 · see citing works
Molecular Properties of WHO Essential Drugs and Provisional Biopharmaceutical Classification
Kasim, N. A., Whitehouse, M., Ramachandran, C., Bermejo, M., Lennernäs, H., Hussain, A. S., Junginger, H. E., Stavchansky, S. A., Midha, K. K., Shah, V. P., et al. (2003) · Molecular Pharmaceutics · doi:10.1021/mp034006h · Cited by 849 · see citing works
Takagi, T., Ramachandran, C., Bermejo, M., Yamashita, S., Yu, L. X., & Amidon, G. L. (2006) · Molecular Pharmaceutics · doi:10.1021/mp0600182 · Cited by 607 · see citing works
WHO Expert Committee on Specifications for Pharmaceutical Preparations.
Yin, H., Hetzke, J., Kozarewicz, P., et al. (1969) · PubMed · Cited by 262 · see citing works
Blume, H. H., & Schug, B. S. (1999) · European Journal of Pharmaceutical Sciences · doi:10.1016/s0928-0987(99)00076-7 · Cited by 150 · see citing works
Davit, B. M., Braddy, A. C., Conner, D. P., & Yu, L. X. (2013) · The AAPS Journal · doi:10.1208/s12248-013-9499-x · Cited by 119 · see citing works
The BCS, BDDCS, and Regulatory Guidances
Chen, M.-L., Amidon, G. L., Benet, L. Z., Lennernas, H., & Yu, L. X. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0438-1 · Cited by 93 · see citing works
Tsume, Y., & Amidon, G. L. (2010) · Molecular Pharmaceutics · doi:10.1021/mp100053q · Cited by 92 · see citing works
Impact of Biopharmaceutics Classification System-Based Biowaivers
Cook, J., Davit, B. M., & Polli, J. E. (2010) · Molecular Pharmaceutics · doi:10.1021/mp1001747 · Cited by 53 · see citing works
Self-citationYu, L. X., Ellison, C. D., Conner, D. P., et al. (2001) · AAPS PharmSci · doi:10.1208/ps030324 · Cited by 24 · see citing works
Sediq, A. S., Kubbinga, M., Langguth, P., et al. (2013) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.23769 · Cited by 18 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [4]4. Guideline on the Investigation of Bioequivalence. CPMP/ EWP/QWP/1401/98 Rev. 1/ Corr; Committee for Medicinal Products for Human Use (CHMP), European Medicines Agency: London, 2010. http://www.ema. europa.eu/docs/en_GB/document_library/Scientific_ guideline/2010/01/WC500070039.pdf (accessed April 6, 2015).
- [15]15. Chen, M.-L.; Amidon, G. L.; Benet, L. Z.; Lennernas, H.; Yu, L. X. The BCS, BDDCS, and Regulatory Guidances. Pharm. Res. 2011, 28 (7), 1774-1778. DOI: 10.1007/ s11095-011-0438-1.
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BCS Biowaivers: Similarities and Differences Among EMA, FDA, and WHO Requirements
Davit, B. M., Kanfer, I., Tsang, Y. C., & Cardot, J.-M. (2016) · The AAPS Journal · doi:10.1208/s12248-016-9877-2 · Cited by 92 · see citing works
- Authors
- Cook, J.
- Affiliations
- Pfizer (United States) (US)
- Corresponding author
- Cook, Jack
- ORCID
- Cook, Jack
- Venue
- Dissolution Technologies
- Publisher
- Dissolution Technologies
- Published
- 2015
- Volume
- 22
- Issue
- 2
- Pages
- 6-10
- ISSN
- 1521-298X (ISSN-L)
- OpenAlex
- W2605091467
- Cited by
- 8
- References
- 13
- Citations by year
- 2024: 1 · 2021: 1 · 2019: 1 · 2017: 3 · 2016: 2
- FWCI
- 0.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Dissolution Technologies (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
- Keywords
- Biopharmaceutics Classification System, dissolution testing, immediate-release formulation, FDA guidance, international regulatory harmonization
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