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54 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2018 P h a r mTe c h . c o m Quality 20% should be devoted to performing the study. This optimizes the chances of success. Often, how- ever, the reverse percentages are employed, result- ing in wasted resources and yielding validation reports that do little to support the effectiveness of the processes they were intended to validate. A process consists of inputs operating through a processing system resulting in outputs. The inputs, outputs, and the processing system, are influenced by people, materials, equipment, procedures, and the environment in which the process operates. All of these things must be considered and evalu- ated before developing the validation strategy and writing the validation protocol. Each process is unique, and no validation approach is universally applicable. Validation of a purification process for monoclonal antibodies differs substantially from validation of a steam-sterilization process for a drug product in its final container. Terminal ster- ilization does not work as a model for validation of a pharmaceutical water system. Commercial production processes must be ro- bust and reliable to ensure consistent product qual- ity, maximize efficiency, and minimize cost. A few simple guidelines will help to simplify vali- dation planning and execution: • Define the inputs, the processing system, and the expected outputs. • Don't get bogged down in terminology. • Define critical and non-critical process attri- butes and parameters. • Use common sense. • Demonstrate a state of control. The following provides a generalized example in- tended to show how a validation plan might be de- veloped to support a process unrelated to biophar- maceutical manufacture, but which demonstrates various points to consider related to the inputs, the processing system, and the outputs that can be ap- plied to biopharmaceutical processes and systems. An example Let's say one is about to open a coffee shop and wants to ensure its success. The process to be vali- dated is coffee-brewing. The goal is to consistently produce good tasting coffee. For the sake of sim- plicity, no specialty coffee (e.g., latte, cappuccino) is considered and no cream, sugar, or f lavoring is added to the brewed coffee. The process is de- scribed as the following: • Inputs include water and coffee. • The processing system is the coffee brewer and the coffee grinder. • The outputs are brewed coffee and process waste: coffee grounds and used filters. The process seems simple enough, but to begin with the end in mind, it is important to define good-tasting coffee. A controlled, double-blind study should be conducted to determine which coffee the majority of tasters prefer to obtain a def- inition of "good-tasting coffee." To have a mean- ingful result, the brewed coffee used in the study must be produced in some standardized way not only to achieve reproducible tasting results but to enable the ultimately chosen brewing process to be validated and to produce coffee equivalent to that used in the tasting study. The obvious analogy is a clinical trial followed by subsequent commercial- scale production of a biopharmaceutical product. The process inputs are water and coffee; but what type of coffee is selected and how is it roasted and ground? Should the coffee be a blend, or should it be a single type? If a blend is desired, what types should be used and in what proportion? Should