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AAPS PharmSciTech. 2016 Apr;17(2):233-44. doi: 10.1208/s12249-015-0349-2. Epub 2015 Jul 23.

Quality-by-Design II: Application of Quantitative Risk Analysis to the Formulation of Ciprofloxacin Tablets.

Author information

1
Office of Compliance, FDA Center for Drug Evaluation and Research, Silver Spring, MD, USA.
2
Office of New Animal Drug Evaluation, Food and Drug Administration, Rockville, MD, USA.
3
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA.
4
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA. shoag@rx.umaryland.edu.

Abstract

Qualitative risk assessment methods are often used as the first step to determining design space boundaries; however, quantitative assessments of risk with respect to the design space, i.e., calculating the probability of failure for a given severity, are needed to fully characterize design space boundaries. Quantitative risk assessment methods in design and operational spaces are a significant aid to evaluating proposed design space boundaries. The goal of this paper is to demonstrate a relatively simple strategy for design space definition using a simplified Bayesian Monte Carlo simulation. This paper builds on a previous paper that used failure mode and effects analysis (FMEA) qualitative risk assessment and Plackett-Burman design of experiments to identity the critical quality attributes. The results show that the sequential use of qualitative and quantitative risk assessments can focus the design of experiments on a reduced set of critical material and process parameters that determine a robust design space under conditions of limited laboratory experimentation. This approach provides a strategy by which the degree of risk associated with each known parameter can be calculated and allocates resources in a manner that manages risk to an acceptable level.

KEYWORDS:

Bayesian Monte Carlo simulation; ciprofloxacin and granulation; ciprofloxacin hydrochloride; qualitative risk assessment; quality-by-design (QbD); roller compaction

PMID:
26202064
PMCID:
PMC4984889
DOI:
10.1208/s12249-015-0349-2
[Indexed for MEDLINE]
Free PMC Article

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