BCS (Biopharmaceutics Classification System)
How does the BCS Classification aid your Drug Development Program?
The “Waiver of In-vivoBioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System” is an FDA guidance document, which allows pharmaceutical companies to forego clinical bioequivalence studies, if their drug product meets the specification detailed in the guidance (http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm128219.htm).
The principles of the BCS classification system can be applied to NDA and ANDA approvals as well as to scale-up and post approval changes in drug manufacturing. A waiver of In-vivo Bioavailability and Biioequivalence studies based on the BCS classification can therefore save pharmaceutical companies a significant amount of development time and reduce development costs.
The BCS classification system is based on the scientific rationale that, if the highest dose of a drug candidate is readily soluble in the fluid volume on average present in the stomach (250 ml) and the drug is more than >90% absorbed, then the in vitro drug product dissolution profiles should allow assessment of the equivalence of different drug formulations. Solubility and dissolution can be easily measured in vitro. Extent of absorption has historically been determined by conducting mass balance studies both preclinically and clinically. However, our work and that of our collaborators has demonstrated that the effective intestinal permeability (Peff) of therapeutic agents correlates well with total fraction absorbed in both humans, rats, and to a lesser extent in vitro tissue culture systems (1-5). Based on these studies a drug candidate can fall into one of four BCS categories, with category I, High Permeability and High Solubility, being the subject of the BCS guidance. The WHO has recently recommended biowaivers for Class III and some Class II drugs and AAPS-FDA scientific conferences have recommended biowaivers for Class III compounds as well.
Why TSRL as your Partner for Biopharmaceutical Research and BCS classification?
Therapeutics Research Laboratory (TSRL, Inc.) has been a valued partner to pharmaceutical companies for over 20 years. Our founder and Chairman, Gordon L. Amidon, is internationally recognized as a world leader in oral drug delivery research. In fact, the BCS Classification System was conceived as a consequence of Gordon’s sabbatical research at the FDA. Researchers at TSRL are experts of biopharmaceutical strategies for oral drug delivery with over 100 years of combined experience. Our 7,000 sq.ft. integrated research facility combines in vitro drug product research, tissue culture research, in vivo preclinical ADME/BCS testing, and state-of-the-art analytical capabilities to provide our partners with highest quality data and expert consulting on oral drug delivery issues. It is our mission to be a virtual extension of your drug discovery or development team to aid you in the development of scientifically sound and commercially viable oral drug delivery strategies.
What specific Services does TSRL offer?
Biopharmaceutics Consulting Services:
TSRL senior researchers are available to consult clients on any aspects of oral drug delivery ranging from solubility and dissolution issues to intestinal membrane limitations to oral drug delivery. Based on the nature of the issue, TSRL will provide biopharmaceutical research services to identify the underlying mechanism of poor oral absorption and recommend strategies to overcome those limitations. These strategies may be implemented using client technologies, but could also utilize TSRL’s proprietary drug delivery technologies, which include formulation solutions, prodrug approaches, and controlled release technologies.
Peff Screening and Mechanistic Studies:
Discovery screening studies can be performed with either the in situ perfusion or in Caco-2 studies. At TSRL, we place greater confidence in permeability determinations from the rat in situ perfusion model as it has clearly demonstrated superior correlation to human permeability data compared to tissue culture models. The in situ perfusion studies follow the same protocol as the BCS biowaiver studies described below, but are conducted under non-GLP conditions. The in situ perfusion can be modified to answer specific project questions, i.e. transport mechanism, Pgp-mediated secretion and/or site specific permeability in different sections of the gastrointestinal tract.
BCS Biowaiver Studies:
Permeability determinations for the purpose of biowaiver application are conducted using the in situ single pass perfusion method in rats under GLP conditions. This system underwent in-depth suitability testing with 20 reference compounds2. Permeability is assessed in jejunal segments of the rat intestine at 3 concentrations covering the expected dose range of the drug. Solubility and dissolution will be determined at a number of pH’s spanning the physiological range of the intestine. TSRL assists in report preparation necessary for submission of the data package to the FDA to gain regulatory approval for the biowaiver.
- GL Amidon et al., Pharm Res Vol 12(3): 413-420, 1995
- JS Kim et al., Molecular Pharmaceutics, Vol 3(6): 686-694, 2006
- X Cao et al, Pharm Res Vol 23(8):1675-1686, 2006
- H Lennernas at al., Pharm Res Vol 14(5): 667-671, 1997
- P Artursson and J Karlson, Biochem Biophys Res Comm. Vol175(3): 880-885, 1991
For more information, please contact:
Elke Lipka, PhD, MBA
VP Business Development
540 Avis Drive, Suite A
Ann Arbor, MI 48108
Phone: (734) 663-4233 x236