The AAPS Journal

, Volume 14, Issue 3, pp 627–638 | Cite as

Summary Workshop Report: Facilitating Oral Product Development and Reducing Regulatory Burden Through Novel Approaches to Assess Bioavailability/Bioequivalence

  • James E. Polli
  • Jack A. Cook
  • Barbara M. Davit
  • Paul A. Dickinson
  • Domenick Argenti
  • Nancy Barbour
  • Alfredo García-Arieta
  • Jean-Marie Geoffroy
  • Kerry Hartauer
  • Shoufeng Li
  • Amitava Mitra
  • Francis X. Muller
  • Vivek Purohit
  • Manuel Sanchez-Felix
  • John W. Skoug
  • Kin Tang
Meeting Report Theme: Facilitating Oral Product Development and Reducing Regulatory Burden through Novel Approaches to Assess Bioavailability/B

Abstract

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 vitroin 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).

Keywords

Area Under Curve Biopharmaceutics Classification System Bioequivalence Study Paliperidone Palmitate Biopharmaceutics Classification System Class 

References

  1. 1.
    Yu LX. Pharmaceutical quality by design: product and process development, understanding, and control. Pharm Res. 2008;25:781–91. doi: 10.1007/s11095-007-9511-1.PubMedCrossRefGoogle Scholar
  2. 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.
  3. 3.
    Rowland M, Peck C, Tucker G. Physiologically-based pharmacokinetics in drug 414 development and regulatory science. Annu Rev Pharmacol Toxicol. 2011;51:45–73.PubMedCrossRefGoogle Scholar
  4. 4.
    Penner N, Xu L, Prakash C. Radiolabeled absorption, distribution, metabolism, and excretion studies in drug development: why, when, and how? Chem Res Toxicol. 2012;25:513–31. doi: 10.1021/tx300050f.PubMedCrossRefGoogle Scholar
  5. 5.
    Ding X, Rose J, Van Gelder J. Developability assessment of clinical drug products with maximum absorbable doses. Int J Pharm. 2012;427:260–9.PubMedCrossRefGoogle Scholar
  6. 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. 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).
  8. 8.
    Rathore AS, Winkle H. Quality by design for biopharmaceuticals. Nat Biotechnol. 2009;27:26–34. doi: 10.1038/nbt0109-26.PubMedCrossRefGoogle Scholar
  9. 9.
    Dubey R. Bioequivalence challenges in development of fixed-dose combination products: looking beyond reformulation. Expert Opin Drug Deliv. 2012;9:325–32. doi: 10.1517/17425247.2012.655723.PubMedCrossRefGoogle Scholar
  10. 10.
    Wolen RL. The application of stable isotopes to studies of drug bioavailability and bioequivalence. Clin Pharmacol. 1986;26:419–24.Google Scholar
  11. 11.
    Cook JA. Development strategies for IVIVC in an industrial environment. Biopharm Drug Dispos. 2012. doi: 10.1002/bdd.1791.
  12. 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. 13.
    Purohit VS. Biopharmaceutic Planning in Pediatric Drug Development. AAPS J. 2012. doi: 10.1208/s12248‐012‐9364‐3.
  14. 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.
  15. 15.
    Dickinson PA, Lee WW, Stott PW, Townsend AI, Smart JP, Ghahramani P, Hammett T, Billett L, Behn S, Gibb RC, Abrahamsson B. Clinical relevance of dissolution testing in quality by design. AAPS J. 2008;10:380–90. doi: 10.1208/s12248-008-9034-7.Google Scholar
  16. 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. 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
  18. 18.
    Qiu Y. In vitroin vivo correlations: fundamentals, development considerations, and applications. In: Qiu Y, Chen Y, Zhang GZ, editors. Developing solid oral dosage forms: pharmaceutical theory and practice. Burlington: Academic; 2009. p. 379–408.CrossRefGoogle Scholar
  19. 19.
    Samtani MN, Gopal S, Gassmann-Mayer C, Alphs L, Palumbo JM. Dosing and switching strategies for paliperidone palmitate based on population pharmacokinetic modelling and clinical trial data. CNS Drugs. 2011;25:829–45.PubMedGoogle Scholar
  20. 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.
  21. 21.
    Davit BM, Conner DP, Fabian-Fritsch B, Haidar SH, Jiang X, et al. Highly variable drugs: observations from bioequivalence data submitted to the FDA for new generic drug applications. AAPS J. 2008;10:148–56.PubMedCrossRefGoogle Scholar
  22. 22.
    Health Canada, Therapeutic Products Directorate. Conduct and analysis of bioavailability and bioequivalence studies—part B: oral modified release formulations. 1996.Google Scholar
  23. 23.
    Endrenyi L, Tothfalusi L. Do regulatory bioequivalence requirements adequately reflect the therapeutic equivalence of modified-release drug products? J Pharm Pharm Sci. 2010;13:107–13.PubMedGoogle Scholar
  24. 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.
  25. 25.
    Chen M-L, Shah VP, Ganes D, Midha KK, Caro J, Nambiar P, et al. Challenges and opportunities in establishing scientific and regulatory standards for assuring therapeutic equivalence of modified-release products: workshop summary report. Eur J Pharm Sci. 2010;40:148–53.PubMedCrossRefGoogle Scholar
  26. 26.
    Gupta E, Barends DM, Yamashita E, Lentz KA, Harmsze AM, Shah VP, Dressman JB, Lipper RA. Review of global regulations concerning biowaivers for immediate release solid oral dosage forms. Eur J Pharm Sci. 2006;29:315–24. doi: 10.1016/j.ejps.2006.05.001.PubMedCrossRefGoogle Scholar
  27. 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
  28. 28.
    Polli JE. In vitro studies are sometimes better than conventional human pharmacokinetic in vivo studies in assessing bioequivalence of immediate-release solid oral dosage forms. AAPS J. 2008;10:289–99. doi: 10.1208/s12248-008-9027-6.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2012

Authors and Affiliations

  • James E. Polli
    • 1
  • Jack A. Cook
    • 2
  • Barbara M. Davit
    • 3
  • Paul A. Dickinson
    • 4
  • Domenick Argenti
    • 5
  • Nancy Barbour
    • 6
  • Alfredo García-Arieta
    • 7
  • Jean-Marie Geoffroy
    • 8
  • Kerry Hartauer
    • 9
  • Shoufeng Li
    • 10
  • Amitava Mitra
    • 11
  • Francis X. Muller
    • 12
  • Vivek Purohit
    • 2
  • Manuel Sanchez-Felix
    • 9
  • John W. Skoug
    • 13
  • Kin Tang
    • 14
  1. 1.University of Maryland School of PharmacyBaltimoreUSA
  2. 2.Pfizer Global Research and DevelopmentNew LondonUSA
  3. 3.Food and Drug AdministrationCenter for Drug EvaluationRockvilleUSA
  4. 4.Clinical Pharmacology and PharmacometricsAstraZeneca R&DMacclesfieldUK
  5. 5.Janssen Pharmaceutical Research and DevelopmentRaritanUSA
  6. 6.Bristol-Myers Squibb CompanyPrincetonUSA
  7. 7.Agencia Española de Medicamentos y Productos SanitariosMadridSpain
  8. 8.Takeda Global Research & Development CenterDeerfieldUSA
  9. 9.Eli Lilly and CompanyIndianapolisUSA
  10. 10.Novartis Pharmaceuticals CorporationEast HanoverUSA
  11. 11.Merck and Company, Inc.West PointUSA
  12. 12.GlaxoSmithKline PharmaceuticalsCollegevilleUSA
  13. 13.Abbott LaboratoriesAbbott ParkUSA
  14. 14.Hoffmann-La Roche Inc.NutleyUSA

Personalised recommendations