Comparing a Statistical Model and Bayesian Approach to Establish the Design Space for the Coating of Ciprofloxacin HCl Beads at Different Scales of Production.

The primary objective of this study was to compare two methods for establishing a design space for critical process parameters that affect ethylcellulose film coating of multiparticulate beads and assess this design space validity across manufacturing scales. While there are many factors that can affect film coating, this study will focus on the effects processing conditions have on the quality and extent of film formation, as evaluated by their impact coating yield and drug release. Ciprofloxacin HCl layered beads were utilized as an active substrate core, ethylcellulose aqueous dispersion as a controlled release polymer, and triethyl citrate as a plasticizer.

A Systematic Approach of Employing Quality by Design Principles: Risk Assessment and Design of Experiments to Demonstrate Process Understanding and Identify the Critical Process Parameters for Coating of the Ethylcellulose Pseudolatex Dispersion Using Non-Conventional Fluid Bed Process.

The goal of this study was to utilize risk assessment techniques and statistical design of experiments (DoE) to gain process understanding and to identify critical process parameters for the manufacture of controlled release multiparticulate beads using a novel disk-jet fluid bed technology. The material attributes and process parameters were systematically assessed using the Ishikawa fish bone diagram and failure mode and effect analysis (FMEA) risk assessment methods. The high risk attributes identified by the FMEA analysis were further explored using resolution V fractional factorial design.

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

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.

Quality-by-design III: application of near-infrared spectroscopy to monitor roller compaction in-process and product quality attributes of immediate release tablets.

The objective of this study is to use near-infrared spectroscopy (NIRS) coupled with multivariate chemometric models to monitor granule and tablet quality attributes in the formulation development and manufacturing of ciprofloxacin hydrochloride (CIP) immediate release tablets. Critical roller compaction process parameters, compression force (CFt), and formulation variables identified from our earlier studies were evaluated in more detail. Multivariate principal component analysis (PCA) and partial least square (PLS) models were developed during the development stage and used as a control tool to predict the quality of granules and tablets.

The reliability-quality relationship for quality systems and quality risk management.

Unlabelled: Engineering reliability typically refers to the probability that a system, or any of its components, will perform a required function for a stated period of time and under specified operating conditions. As such, reliability is inextricably linked with time-dependent quality concepts, such as maintaining a state of control and predicting the chances of losses from failures for quality risk management. Two popular current good manufacturing practice (cGMP) and quality risk management tools, failure mode and effects analysis (FMEA) and root cause analysis (RCA) are examples of engineering reliability evaluations that link reliability with quality and risk.

Quality by design I: Application of failure mode effect analysis (FMEA) and Plackett-Burman design of experiments in the identification of "main factors" in the formulation and process design space for roller-compacted ciprofloxacin hydrochloride immediate-release tablets.

As outlined in the ICH Q8(R2) guidance, identifying the critical quality attributes (CQA) is a crucial part of dosage form development; however, the number of possible formulation and processing factors that could influence the manufacturing of a pharmaceutical dosage form is enormous obviating formal study of all possible parameters and their interactions. Thus, the objective of this study is to examine how quality risk management can be used to prioritize the number of experiments needed to identify the CQA, while still maintaining an acceptable product risk profile. To conduct the study, immediate-release ciprofloxacin tablets manufactured via roller compaction were used as a prototype system.

Probability concepts in quality risk management.

Unlabelled: Essentially any concept of risk is built on fundamental concepts of chance, likelihood, or probability. Although risk is generally a probability of loss of something of value, given that a risk-generating event will occur or has occurred, it is ironic that the quality risk management literature and guidelines on quality risk management tools are relatively silent on the meaning and uses of "probability." The probability concept is typically applied by risk managers as a combination of frequency-based calculation and a "degree of belief" meaning of probability.

Rapid benefit-risk assessments: no escape from expert judgments in risk management.

The "human health impacts assessment" described by Cox and Popken (this issue) is intended to be a benefit-risk tool that avoids pitfalls of using expert judgments for policy analysis or during strict application of the precautionary principle in risk management. The proposed benefit-risk calculation uses numerous assumptions and suppositions to calculate a ratio of quality-adjusted life years (QALYs) lost for the number of human illness days prevented by the use of a food-animal antimicrobial drug, to the number of human illness days caused by the use of the antimicrobial drug. Assumptions about data--e.

Antimicrobial resistance risk assessment in food safety.

Microbiological risk assessments generally focus on estimating adverse human health risks from exposures to human pathogenic microbes. The assessment of potential human health risks posed by pathogens that have acquired resistance to antimicrobial drugs is a new application of risk assessment that is closely related to microbiological risk assessment. Antimicrobial resistance risk assessment is a risk analyticalprocess that focuses on resistance determinants as hazardous agents that might lead to drug-resistant microbial infections in humans exposed to bacteria carrying the determinants.

Clinical pharmacology of topiramate versus lamotrigine versus phenobarbital: comparison of efficacy and side effects using odds ratios.

Clinical pharmacologists, neurologists, internists, and all health care givers must consider the efficacy, safety, and side effect profile of a given antiepileptic drug (AED) when determining which drug is best for a given patient. The first purpose of this paper is to address whether the "new" AEDs have advantages over the "old" drugs. The second purpose is to teach those interested in clinical pharmacology about the use of Web-based information access to answer a neurology/clinical pharmacology problem: to compare the efficacy and side effects of topiramate versus lamotrigine versus phenobarbital using odds ratios.