Summary Workshop Report: Facilitating Oral Product Development and Reducing Regulatory Burden Through Novel Approaches to Assess Bioavailability/Bioequivalence
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This summary workshop report highlights presentations and over-arching themes from an October 2011 workshop. Discussions focused on best practices in the application of biopharmaceutics in oral drug product development and evolving bioequivalence approaches. Best practices leverage biopharmaceutic data and other drug, formulation, and patient/disease data to identify drug development challenges in yielding a successfully performing product. Quality by design and product developability paradigms were discussed. Development tools include early development strategies to identify critical absorption factors and oral absorption modeling. An ongoing theme was the desire to comprehensively and systematically assess risk of product failure via the quality target product profile and root cause and risk analysis. However, a parallel need is reduced timelines and fewer resources. Several presentations discussed applying Biopharmaceutics Classification System (BCS) and in vitro–in vivo correlations in development and in post-development and discussed both resource savings and best scientific practices. The workshop also focused on evolving bioequivalence approaches, with emphasis on highly variable products (HVDP), as well as specialized modified-release products. In USA, two bioequivalence approaches for HVDP are the reference-scaled average bioequivalence approach and the two-stage group-sequential design. An adaptive sequential design approach is also acceptable in Canada. In European Union, two approaches for HVDP are a two-stage design and an approach to widen C max acceptance limits. For some specialized modified-release products, FDA now requests partial area under the curve. Rationale and limitations of such metrics were discussed (e.g., zolpidem and methylphenidate). A common theme was the benefit of the scientific and regulatory community developing, validating, and harmonizing newer bioequivalence methodologies (e.g., BCS-based waivers and HVDP trial designs).
KeywordsArea Under Curve Biopharmaceutics Classification System Bioequivalence Study Paliperidone Palmitate Biopharmaceutics Classification System Class
- 2.Wilson W, Peng Y, Augsburger LL. Generalization of a prototype intelligent hybrid system for hard gelatin capsule formulation development. AAPS PharmSciTech. 2005. doi: 10.1208/pt060356.
- 6.Dickinson PA, Abu Rmaileh R, Ashworth L, Barker RA, Burke WM, Patterson CM, Stainforth N, Yasin M. An investigation into the utility of a multi-compartmental, dynamic, system of the upper gastrointestinal tract to support formulation development and establish bioequivalence of poorly soluble drugs. AAPS J. 2012;14:196–205. doi: 10.1208/s12248-012-9333-x.
- 7.CDER/FDA. Guidance for Industry, Q8(R2) Pharmaceutical development. November 2009. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM073507.pdf. Accessed 30 Apr 2012).
- 10.Wolen RL. The application of stable isotopes to studies of drug bioavailability and bioequivalence. Clin Pharmacol. 1986;26:419–24.Google Scholar
- 11.Cook JA. Development strategies for IVIVC in an industrial environment. Biopharm Drug Dispos. 2012. doi: 10.1002/bdd.1791.
- 12.Japan Institute of Health Sciences, Division of Drugs. Guideline for bioequivalence studies for formulation changes of oral solid dosage forms. December 2006. http://www.nihs.go.jp/drug/be-guide(e)/form-change2006e.pdf. Accessed 30 Apr 2012.
- 13.Purohit VS. Biopharmaceutic Planning in Pediatric Drug Development. AAPS J. 2012. doi: 10.1208/s12248‐012‐9364‐3.
- 14.CDER/FDA. Guidance for Industry, waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a Biopharmaceutics Classification System. August 2000. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070246.pdf. Accessed 30 Apr 2012.
- 16.Cardot J-M, Davit BM. In vitro-in vivo correlations: tricks and traps. AAPS J. 2012. doi: 10.1208/s12248-012-9359-0.
- 17.Farrell C, Hayes S. IVIVC for oral drug delivery: immediate release and extended release dosage forms. In: Chilukuri DM, Sunkara G, Young D, editors. Pharmaceutical product development: in vitro-in vivo correlation. New York: Informa Healthcare; 2007. p. 125–40.Google Scholar
- 20.Committee for Medicinal Products for Human Use (CHMP), European Medicines Agency (EMA). Guideline on the investigation of bioequivalence. January 20, 2010. http://www.emea.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070039.pdf. Accessed 30 Apr 2012.
- 22.Health Canada, Therapeutic Products Directorate. Conduct and analysis of bioavailability and bioequivalence studies—part B: oral modified release formulations. 1996.Google Scholar
- 24.CDER/FDA. Briefing Information for the April 13, 2010 Meeting of the Pharmaceutical Science and Clinical Pharmacology Advisory Committee. http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AdvisoryCommitteeforPharmaceuticalScienceandClinicalPharmacology/ucm207954.htm. Accessed 30 Apr 2012.
- 27.Selen A, Cruañes MT, Müllertz A, Dickinson PA, Cook JA, Polli JE, Kesisoglou F, Crison J, Johnson KC, Muirhead GT, Schofield T, Tsong Y. Meeting report: applied biopharmaceutics and quality by design for dissolution/release specification setting: product quality for patient benefit. AAPS J. 2010;12:465–72. doi: 10.1208/s12248-010-9206-0.PubMedCrossRefGoogle Scholar