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Cited by 150Drug Solubulity and Delivery SystemsAdvanced Drug Delivery SystemsPharmaceutical studies and practices

G.L. Amidon, H. Lennernas, V.P. Shah, and J.R. Crison. A Theoretical Basis for a Biopharmaceutic Drug Classification: The Correlation of In Vitro Drug Product Dissolution and In Vivo Bioavailability, Pharm Res 12, 413–420, 1995—Backstory of BCS

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Shah, Vinod P., Amidon, Gordon L.·2014·The AAPS Journal
DOI 10.1208/s12248-014-9620-9PMC PMC4147045
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Abstract

The Biopharmaceutics Classification System (BCS) has become widely accepted today in the academic, industrial, and regulatory world. While the initial application of the BCS was to regulatory science bioequivalence (BE) issues and related implications, it has come to be utilized widely by the pharmaceutical industry in drug discovery and development as well. This brief manuscript will relate the story of the BCS development. While much of the ground work for the BCS goes back to the pharmacokinetic and drug absorption research by Gordon Amidon (GLA) in the 1970s and 1980s, the realization of the need for a classification or categorization of drug and drug products for setting dissolution standards became apparent to GLA during his 1990-1991 sabbatical year at the FDA. Initiated at the invitation of the then CEDR director, Dr. Carl Peck, to become a visiting scientist at the FDA, the goal was to promote regulatory research at the FDA, in my case, in biopharmaceutics, and to develop a science-based system to simplify regulatory requirements.

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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 [6]

    The Introduction says the FDA published its final BCS guidance in August 2000, and WHO GUIDANCE says the FDA guidance provided biowaivers for highly soluble, highly permeable Class I products. BCS GUIDANCE describes the dissolution criteria, but the paper does not establish that the FDA was the first regulatory agency to publish such guidance; it says only that this was the first guidance with “waiver” in its title. (LLM, conf=0.86)

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  • The Biopharmaceutics Classification System (BCS) is based on aqueous solubility and intestinal permeability and has been widely used since 1995 as a mechanism for waiving in vivo bioavailability and bioequivalence studies.

    “The Biopharmaceutics Classification System (BCS), based on aqueous solubility and intestinal permeability, has enjoyed wide use since 1995 as a mechanism for waiving in vivo bioavailability and bioequivalence studies.”

    From BCS Biowaivers: Similarities and Differences Among EMA, FDA, and WHO Requirements (2016) · cites this paper as [6]

    The BCS Guidance section (page unavailable) defines BCS by aqueous solubility and intestinal permeability and describes biowaivers for eligible products. The copy identifies the original BCS publication as dating to 1995 but cites FDA biowaiver guidance from 2000; it does not establish that BCS was widely used to waive in vivo studies since 1995. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The BCS is now widely established in the academic, industrial, and regulatory world for waiving the regulatory requirements of conducting comparative bioavailability studies to demonstrate in vivo BA/BE of immediate-release solid oral dosage forms containing BCS Class I and Class III drugs.

    “Thus, the BCS is now widely established in the academic, industrial, and regulatory world for waiving the regulatory requirements of conducting comparative bioavailability studies to demonstrate in vivo BA/BE of immediate-release (IR) solid oral dosage forms containing BCS Class I and Class III drugs (5,6).”

    From BCS Biowaivers: Similarities and Differences Among EMA, FDA, and WHO Requirements (2016) · cites this paper as [6]

    The BCS GUIDANCE section says dissolution studies may establish bioequivalence for eligible Class I immediate-release oral products. WHO GUIDANCE says very rapidly dissolving Class III products can also be eligible for biowaivers, but it does not establish that waivers for both classes are already widely adopted across academic, industrial, and regulatory settings. The paper also notes that regulatory acceptance and harmonization will take time. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The 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 [6]

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Research works printed but not linked: 1

  1. [6]6. Knutson L et al. Segmental intestinal perfusion. A "new" t e c h n i q u e f o r h u m a n s t u d i e s . L a k a r t i d n i n e n . 1994;91(19):1941-6.

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Authors
Shah, V. P., & Amidon, G. L.
Affiliations
University of Michigan (US)
Corresponding author
Amidon, Gordon L.
ORCID
Amidon, Gordon L.
Venue
The AAPS Journal
Publisher
Springer Science and Business Media LLC
Published
2014-06-25
Volume
16
Issue
5
Pages
894-898
ISSN
1550-7416 (ISSN-L)
DOI
10.1208/s12248-014-9620-9
PMC
PMC4147045
OpenAlex
W2062596549
Cited by
150
References
20
Citations by year
2026: 6 · 2025: 10 · 2024: 15 · 2023: 20 · 2022: 14 · 2021: 19 · 2020: 17 · 2019: 13 · 2018: 9 · 2017: 6 · 2016: 16 · 2015: 4 · 2014: 1
FWCI
5.29
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • The AAPS Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Keywords
Biopharmaceutics Classification System, dissolution testing, bioavailability, in vitro-in vivo correlation, bioequivalence, regulatory science, FDA regulation
MeSH terms
Animals, Biological Availability, Biopharmaceutics, Drug Administration Routes, Pharmaceutical Preparations, Humans, Models, Biological, Models, Chemical, Terminology as Topic, Pharmacokinetics, Solubility, United States, United States Food and Drug Administration, Drug Approval, History, 20th Century, History, 21st Century

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