I. PURPOSE OF VALIDATION
High-quality water and air are essential for the manufacture of pharmaceuticals. Water is the most commonly used raw material in pharmaceutical manufacturing; it is indirectly used in the manufacture of all dosage forms for cleaning manufacturing equipment, and is also used as a major component which constitutes injectable products. It is the one raw material that is usually processed by the pharmaceutical manufacturer prior to use because it cannot be used as supplied by the vendor. Water should be regarded as one of major raw materials for the manufacture of pharmaceuticals whether or not it remains as a component of the finished dosage form or is eliminated during the manufacturing process. Water is thus an important raw material in GMP and in validating the manufacturing process.
Air supplied to the pharmaceutical manufacturing area or the air in the environment of the pharmaceutical manufacturing area always contacts with pharmaceuticals, and the quality of air influences the quality of the pharmaceuticals manufactured, particularly in their cleanliness, particulates, and microbial quality. Temperature and humidity in the manufacturing environment also influence the quality of the pharmaceuticals manufactured. The importance of air quality and air handling system are described in CFR 211-46 as part of GMP.
The USP identifies several grades of water that are acceptable for use in pharmaceuticals, and also defines the quality of the environment or the quality of air for the manufacturing of pharmaceuticals according to its criticality. Water and the environment must be periodically monitored for these quality attributes, and in some instances the results are not available for days after the sample is obtained. Meanwhile, the water would have been used to manufacture a great number of pharmaceutical products or else the products would have already been exposed to the environment. Water treatment and air handling systems are highly dynamic, and careful attention has to be paid to their operation, even though this may sometimes be somewhat unreliable. Consequently, they must be validated and then closely monitored and controlled.
The purpose of validation is to demonstrate the capability of the water treatment and air handling system to continuously supply the required quantity of water and air with the specified quality attributes. “Documented” means to provide documented “evidence.” Validation provides the system owner with the means of assessing when a water treatment and/or air handling system is operating outside established control parameter limits and provides a means for bringing the system back into a state of control. It results in written operating and maintenance procedures for personnel to follow, which in turn helps ensure
consistent system performance.
