The usability of STAMP in drug development

05/03/2023All rights reserved. For republishing contact [email protected]

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The usability of STAMP in drug developmentArete-Zoe in cooperation with Stuttgart University Study authors: Veronika Valdova, Ronald L Sheckler, Asim Abdulkhaleq and Stefan Wagner (Jonathan Fishbein)Presentation of synopsis: Veronika ValdovaPresented at STAMP team meeting, PSCI, ACRES on February 26, 2016


2Abstract

• This paper explores the usability and applicability of STAMP (System-Theoretic Accident Model and Processes) in managing risks associated with the development of new drugs.

• STAMP is used in the context of other existing but non-standardly implemented risk management approaches and tools.

• The STAMP accident model uses system theory and treats safety as a control problem rather than a failure problem.

• This paper uses the well-publicized TGN1412 incident where human volunteers suffered severe adverse reaction to trial therapy doses.

• Utilizing STAMP could have identified control vulnerabilities reducing ambiguity and potential risk to trial subjects.


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TGN1412, March 2006

Crystal structure of human CD28 in complex with the Fab fragment of a mitogenic antibody. Structure solved by the T-cell biology group at the University of Oxford, in collaboration with TeGenero who provided the antibody, and published in the March 2005 edition of Nature Immunology. Animated gif created by Wikimedia Commons user Deglr6328 from Protein Data Bank information.

Graphics intended for publication are not part of this presentation


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Current practices in risk management in drug development

This guideline provides principles and examples of tools for quality risk management that can be applied to different aspects of pharmaceutical quality. These aspects include development, manufacturing, distribution, and the inspection and submission/review processes throughout the product lifecycle.

GOOD CLINICAL PRACTICE

As implemented in national legislation


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Systemic vulnerability: transition from animal to human studies

Pre-clinical • Project owner • R&R • Jurisdiction (DE)• Process vulnerabilities • Assumptions made• Consequences

First-in-Man• Multiple stakeholders• R&R (coordination)• Jurisdiction (UK)• Process vulnerabilities • Information flow • Consequences

CONTROLLED TRANSITION


6Controls, constraints, enforcement

• Tool used: STPA (hazard/vulnerability analysis)

• Looking for: • uncoordinated or absent controls • lack of constraints • ineffective enforcement of constraints during transition

• Allocation of responsibility • R&R: legislation vs. functional relationships• Accountability and consequence

• Jurisdictional differences (coordination of controls)

• Coordination of activities between stakeholders, same process

• Uncorrected assumptions (review and approval)

• Information flow (missing, inconsistent, incomplete)


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Safe and hazardous states: Regulatory review and approval

• Identification of assumptions made in earlier stages

• Detection of limiting clinically relevant vulnerabilities

• Definition of safe range

• Imposing controls (detectable, providing enough time to give opportunity to decide)

• Enforce(ability of) controls

• Outcome: correct/incorrect approval and rejection

Health & Medicine

The usability of STAMP in drug development