title: The biopharmaceutics risk assessment roadmap for optimizing clinical drug product performance.
abstract: The biopharmaceutics risk assessment roadmap (BioRAM) optimizes drug product development and performance by using therapy-driven target drug delivery profiles as a framework to achieve the desired therapeutic outcome. Hence, clinical relevance is directly built into early formulation development. Biopharmaceutics tools are used to identify and address potential challenges to optimize the drug product for patient benefit. For illustration, BioRAM is applied to four relatively common therapy-driven drug delivery scenarios: rapid therapeutic onset, multiphasic delivery, delayed therapeutic onset, and maintenance of target exposure. BioRAM considers the therapeutic target with the drug substance characteristics and enables collection of critical knowledge for development of a dosage form that can perform consistently for meeting the patient's needs. Accordingly, the key factors are identified and in vitro, in vivo, and in silico modeling and simulation techniques are used to elucidate the optimal drug delivery rate and pattern. BioRAM enables (1) feasibility assessment for the dosage form, (2) development and conduct of appropriate "learning and confirming" studies, (3) transparency in decision-making, (4) assurance of drug product quality during lifecycle management, and (5) development of robust linkages between the desired clinical outcome and the necessary product quality attributes for inclusion in the quality target product profile.
authors.affiliation: Office of New Drug Quality Assessment, US Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, Maryland. Electronic address: arzu.selen@fda.hhs.gov.
authors.forename: Arzu
authors.initials: A
authors.lastname: Selen
authors.affiliation: Quantitative Clinical Pharmacology, AstraZeneca, Macclesfield, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Dickinson
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
authors.affiliation: Bristol-Myers Squibb, New Brunswick, New Jersey.
authors.forename: John R
authors.initials: JR
authors.lastname: Crison
authors.affiliation: Physiomics PLC, Oxford, UK.
authors.forename: Hitesh B
authors.initials: HB
authors.lastname: Mistry
authors.affiliation: Merck & Company, West Point, Pennsylvania.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Cruañes
authors.affiliation: US FDA/CVM, Rockville, Maryland.
authors.forename: Marilyn N
authors.initials: MN
authors.lastname: Martinez
authors.affiliation: Department of Pharmacy, University of Uppsala, Uppsala, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Lennernäs
authors.affiliation: Child Development Center, University of California, Irvine, California.
authors.forename: Tim L
authors.initials: TL
authors.lastname: Wigal
authors.affiliation: iRND3, Mountain View, California.
authors.forename: David C
authors.initials: DC
authors.lastname: Swinney
authors.affiliation: School of Pharmacy, University of Maryland, Baltimore, Maryland.
authors.forename: James E
authors.initials: JE
authors.lastname: Polli
authors.affiliation: College of Pharmacy and Health Sciences, St. John's University, Queens, New York.
authors.forename: Abu T M
authors.initials: ATM
authors.lastname: Serajuddin
authors.affiliation: Pfizer Inc., Groton, Connecticut.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Cook
authors.affiliation: Institute of Pharmaceutical Technology Biocenter, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Dressman
mesh_terms: D000818:Animals; D001702:Biopharmaceutics / Q000592:standards; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D055808:Drug Discovery / Q000379:methods* / Q000592:standards; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D010599:Pharmacokinetics; D011786:Quality Control; D018570:Risk Assessment; D012307:Risk Factors; D018675:Toxicity Tests
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004364:Pharmaceutical Preparations
keywords: Quality by Design (QbD); bioavailability; biopharmaceutics classification system (BCS); clinical trial simulations; controlled delivery; in silico modeling; in vitro models; in vitro/in vivo correlations (IVIVC); oral drug delivery; pharmacodynamics; pharmacokinetics