Rarely, if ever, do new products and processes work perfectly and as designed “right out of the box.” Consider a new aircraft that will be put into service and expected to transport passengers from place to place. If you knew the aircraft was a completely new model and had never been proven or demonstrated to be able to sustain flight, would you...
Monitoring is an important aspect of maintaining validation
Monitoring includes information collection over time, reviewing and analyzing the information, and defining warning limits
Monitoring is applicable to process parameters, raw material quality, utility performance, product characteristics, and other important considerations
The 2008 US...
The following key points are discussed in this article:
Lyophilization, or freeze-drying, is used to remove moisture by sublimation
Products are lyophilized to increase shelf life
Freeze-dried products are reconstituted with water at time of use
Lyophilization processes are based on the physical properties of water, as described by the phase...
Analysis of variance (ANOVA) is an extremely important method in exploratory and confirmatory data analysis. Unfortunately, in some complex problems it is not always easy to set up an appropriate ANOVA. ANOVA is classified as one-way ANOVA and two-way ANOVA (1). This paper shows how easily one-way ANOVA can be used to determine whether there is a...
Physical properties of pharmaceutical solids such as particle size, particle shape, and particle surface characteristics
Physical properties may have significant effects on pharmaceutical manufacturing
Particle size is the primary parameter monitored in pharmaceutical manufacturing
Particle shape and particle surface area including porosity...
A validation master plan (VMP) is the primary tool for validation planning
There is typically a hierarchical structure to VMPs that may include breakdowns by sites and processes
A VMP is not a stand-alone document; it is usually intertwined with other quality systems and objectives including other VMPs
A VMP has three main planning focuses in...
Recovery is a set of unit operations in a biotech process that remove target molecules from the production environment (i.e., microbial or mammalian cells and/or medium) and into a state that is ready for purification (i.e., properly folded, solubilized, pH adjusted, etc.)
Centrifugation is generally defined as a process by which product streams...
This article is intended for system validation and continuous improvement practitioners supporting maintenance of validated systems. This article was written with the assumption that the reader has some background in Lean Six Sigma tools and define, measure, analyze, improve, control (DMAIC) methodology. The methods discussed in this article are...
Scientific inference requires both deductive and inductive inference
Three main approaches to inductive inference are used
Fisherian induction uses the P-value as a measure of evidence against the null hypothesis
Neyman-Pearson induction controls the long-run decision risk over repeated experiments
Bayesian induction obtains direct...
The US Food and Drug Administration issued a new Draft Guidance for Industry Process Validation: General Principles and Practices in November 2008
The guidance applies to manufacturing of human and animal drug products including biological and biotech products, active pharmaceutical ingredients (API), and the drug component of medical device...
Setting limits for the active in biotechnology-based manufacture of bulk actives has been problematic in that conventional dose-based carryover (maximum allowable carryover) calculations don’t fit well with the nature of the manufacturing processes. This is partly based on the fact that if a carryover calculation is performed considering the...
