TY - JOUR

T1 - Integrated Multi-stakeholder Systems Thinking Strategy

T2 - Decision-making with Biopharmaceutics Risk Assessment Roadmap (BioRAM) to Optimize Clinical Performance of Drug Products [incl, correction]

AU - Selen, Arzu

AU - Mullertz, Anette

AU - Kesisoglou, Filippos

AU - Ho, Rodney J. Y.

AU - Cook, Jack A.

AU - Dickinson, Paul A

AU - Flanagan, Talia

N1 - Correction to: Integrated Multi-stakeholder Systems Thinking Strategy: Decision-making with Biopharmaceutics Risk Assessment Roadmap (BioRAM) to Optimize Clinical Performance of Drug Products DOI: 10.1208/s12248-020-00534-0

PY - 2020

Y1 - 2020

N2 - Decision-making in drug development benefits from an integrated systems approach, where the stakeholders identify and address the critical questions for the system through carefully designed and performed studies. Biopharmaceutics Risk Assessment Roadmap (BioRAM) is such a systems approach for application of systems thinking to patient focused and timely decision-making, suitable for all stages of drug discovery and development. We described the BioRAM therapy-driven drug delivery framework, strategic roadmap, and integrated risk assessment instrument (BioRAM Scoring Grid) in previous publications (J Pharm Sci 103:3377-97, 2014; J Pharm Sci 105:3243-55, 2016). Integration of systems thinking with pharmaceutical development, manufacturing, and clinical sciences and health care is unique to BioRAM where the developed strategy identifies the system and enables risk characterization and balancing for the entire system. Successful decision-making process in BioRAM starts with the Blueprint (BP) meetings. Through shared understanding of the system, the program strategy is developed and captured in the program BP. Here, we provide three semi-hypothetical examples for illustrating risk-based decision-making in high and moderate risk settings. In the high-risk setting, which is a rare disease area, two completely alternate development approaches are considered (gene therapy and small molecule). The two moderate-risk examples represent varied knowledge levels and drivers for the programs. In one moderate-risk example, knowledge leveraging opportunities are drawn from the manufacturing knowledge and clinical performance of a similar drug substance. In the other example, knowledge on acute tolerance patterns for a similar mechanistic pathway is utilized for identifying markers to inform the drug release profile from the dosage form with the necessary "flexibility" for dosing. All examples illustrate implementation of the BioRAM strategy for leveraging knowledge and decision-making to optimize the clinical performance of drug products for patient benefit.

AB - Decision-making in drug development benefits from an integrated systems approach, where the stakeholders identify and address the critical questions for the system through carefully designed and performed studies. Biopharmaceutics Risk Assessment Roadmap (BioRAM) is such a systems approach for application of systems thinking to patient focused and timely decision-making, suitable for all stages of drug discovery and development. We described the BioRAM therapy-driven drug delivery framework, strategic roadmap, and integrated risk assessment instrument (BioRAM Scoring Grid) in previous publications (J Pharm Sci 103:3377-97, 2014; J Pharm Sci 105:3243-55, 2016). Integration of systems thinking with pharmaceutical development, manufacturing, and clinical sciences and health care is unique to BioRAM where the developed strategy identifies the system and enables risk characterization and balancing for the entire system. Successful decision-making process in BioRAM starts with the Blueprint (BP) meetings. Through shared understanding of the system, the program strategy is developed and captured in the program BP. Here, we provide three semi-hypothetical examples for illustrating risk-based decision-making in high and moderate risk settings. In the high-risk setting, which is a rare disease area, two completely alternate development approaches are considered (gene therapy and small molecule). The two moderate-risk examples represent varied knowledge levels and drivers for the programs. In one moderate-risk example, knowledge leveraging opportunities are drawn from the manufacturing knowledge and clinical performance of a similar drug substance. In the other example, knowledge on acute tolerance patterns for a similar mechanistic pathway is utilized for identifying markers to inform the drug release profile from the dosage form with the necessary "flexibility" for dosing. All examples illustrate implementation of the BioRAM strategy for leveraging knowledge and decision-making to optimize the clinical performance of drug products for patient benefit.

KW - systems thinking

KW - biopharmaceutics

KW - integrated risk assessment

KW - blueprint meetings

KW - decision-making for the system

KW - RELEVANT DISSOLUTION SPECIFICATIONS

KW - EXTENDED-RELEASE FORMULATIONS

KW - PROCESS TRACING METHODS

KW - UREA CYCLE DISORDERS

KW - IN-VIVO PERFORMANCE

KW - PHARMACEUTICAL-INDUSTRY

KW - MODEL

KW - ABSORPTION

KW - VITRO

KW - DESIGN

UR - https://doi.org/10.1208/s12248-020-00534-0

U2 - 10.1208/s12248-020-00470-z

DO - 10.1208/s12248-020-00470-z

M3 - Journal article

C2 - 32719954

VL - 22

JO - A A P S Journal

JF - A A P S Journal

SN - 1550-7416

IS - 5

M1 - 97

ER -