Environmental validation program

Environmental validation programs are tests performed to verify adequate workmanship in the construction of a test item. It is often necessary to impose stresses beyond those predicted for the mission in order to uncover defects. Thus, random vibration tests are conducted specifically to detect bad solder joints, loose or missing fasteners, improperly mounted parts, and so on. Cycling between temperature extremes during thermal-vacuum testing and the presence of EMI during EMC testing can also reveal the lack of proper construction and adequate workmanship. 

Full acceptance of HPLC/MS methods by the US EPA OPP as enforcement methods occurred between 1998 and 2001. For example, in 1998, the EPA OPP accepted HPLC/MS (without MS/MS) methods as primary enforcement methods, and high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) only was suitable for confirmatory methods. However, in 2001, HPLC/MS/MS methods also became acceptable for primary enforcement. Table 4 summarizes the types of methods that were validated by the EPA OPP method validation program, for both food tolerance enforcement methods and environmental chemistry methods. 

The major source of microbial contamination of controlled environments is personnel. Since the major threat of contamination of product being aseptically processed comes from the operating personnel, the control of microbial contamination associated with these personnel is one of the most important elements of the environmental control program. Personnel training should be conducted before the qualification and validation practice [13]. 

It should be noted that not all parameters that are critical to the manufacturing process are critical with regard to product quality some parameters may be designated critical for process performance, safety, health, or environmental reasons. Because of the nature and importance of these other critical parameters, it is usual for pharmaceutical manufacturers to consider them under the validation program. 

The quotations are to be formally evaluated by the pharmaceutical manufacturer with the purpose of selecting the proposal that best meets requirements and fully supports the pharmaceutical manufacturer s validation program. Quotation evaluation should involve the user representation necessary to ensure that quality, validation, GMP risk, production, technical, maintenance, commercial, and safety and environmental requirements are properly addressed. 

The CCT program involves a number of projects that achieve reduction of SO, NO, and particulate emissions in a single processing unit. The technologies described arc uniquely combined to achieve project goals and, at the same time, to provide commercial-scale validation of technologies for utilities to consider in order to meet environmental standards. 

In 1994, only 15% of EPA method validations (tolerance method validation and environmental chemistry method validations) that involved GC were carried out using GC/MS. In 2002, this number is reversed in that 85% of the GC methods that were validated by both programs used GC/MS. Many of the compounds investigated in these method trials were polar compounds, and hence these compounds required derivatization in order to be amenable to GC. One common methylating agent is (trimethylsilyl)diazomethane, which is used, for example, to methylate the sulfonamide flumetsulam. As opposed to HPLC/MS, where derivatization is often not necessary, the GC/MS procedure involves an extra step to methylate this compound, under dry conditions, prior to determination by GC/MS. 

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