Validation of equipment

The production of the API and finished dosage form is required to comply with GMP regulations discussed in Chapter 9 and Section 10.2. The quality system, quality control, and validation of equipment and processes have to be developed and adhered to in the manufacturing process. Proper records and documentation are required to be kept in the forms of batch records. 

The calibration and validation of equipment have been addressed extensively but, equipment that can be shown as fit for use, within the GLP environment is generally acceptable to most regulatory inspectors. (For additional information on the GLP requirements for equipment, see Principles, Section II, 4, p. 22.)... 

Lack of documentation of installation and/or validation of equipment, computers, and software. 

The objective of cleaning validation of equipment and utensils is to reduce the residues of one product below established limits so that the residue of the previous product does not affect the quality and safety of the subsequent product manufactured in the same equipment. 

The inspection should cover the evaluation and assessment of the documentation, premises, equipment, utilities and materials. It should also cover verification of data and documentation such as results, batch records, compliance with SOP and information submitted on the manufacturing method, equipment and aspects including (but not limited to) validation of the manufacturing process, validation of utilities and support systems, and validation of equipment. 

Chapter 3 continues the themes developed in the first two chapters and applies to changes made to equipment. This is a topic of special interest to the FDA because in the processing of semisolid products, the equipment plays a pivotal role. The mixing of drags within the base media is highly affected by the process and mechanism of mixing used. Also, because of the nature of product manufactured, often the cleaning and validation of equipment become serious issues. 

Validation of equipment performance on installation, is essential. Planned maintenance and frequent checks on performance are also important for critical items of equipment such as sterilisers, air filtration systems, and skills. Checks on steam and hot air sterilisers should include heat distribution and heat penetration studies, niter efficiency tests should be conducted on air supply systems. Details of maintenance operations and performance checks should be recorded. 

Agalloco J. Points to consider in the validation of equipment cleaning procedures. J Parenteral Sci Technol 1992 46(5). 

X-6] VINOGRADOV, O.S., SMIRNOV, I.P., TIGRAEV, I P. Hydrodynamics of fuel assemblies with pebble beds. Annals of TsKTI, issue 145, Studies and Validation of Equipment for NPPs, 107-119, Leningrad (1977, in Russian). 

Clearly, the turboexpander is one of several key components in a process plant and liquid production is related to the performance of all components of the plant, not the turboexpander alone. It has previously been assumed that changes in the normal design conditions of turboexpanders have not adversely affected other equipment in the plant because adverse impact on other equipment, if any, would further reduce liquid production. This simplifies the assumptions, but does not affect the general validity of the findings. 

The standard requires the supplier to assess and document the validity of previous inspection and test results when inspection, measuring, and test equipment is found to be out of calibration. 

Design and validation of special-purpose tools and equipment... 

Figure 3-12 is a schematic of a deflagration suppressant system for process equipment. Each application requires experimental validation of the suppression system design. 

In Table 3.2, a number of factors are listed that were not used as separate levels in the CCPS taxonomy because of assumptions made by the CCPS Subcommittee. The analyst must, wherever possible, try to assess the validity of these assumptions for the particular situation and establish if the equipment represented by the data ... 

In addition, the protocol should specify a sufficient number of process runs to prove consistency of the process, and provide an accurate measure of variability among successive runs. The number of batches should depend on the extent of validation and complexity of the process or importance of any process changes. Furthermore, the protocol should address the quality of materials used in the process from starting materials to new and recovered solvents, and evidence of the performance and reliability of equipment and systems. 

The validation of ne v facilities, systems or equipment is usually accomplished using a four-stage process of design qualification (DQ), installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ). 

Example 62 If a manufacturing process involves two raw materials, each defined by three sets of specification limits, and four pieces of equipment with one control knob, then a complete validation protocol would ask for (Three settings Lo, Target, Hi) (2 materials 3 specs + 4 machines 1 control) = 3 = 59 000 experiments, even without repetitions. This product would never reach the market if one did not employ experience and scientific rationale to simplify development by testing only the presumed critical issues, say a total of three specification points for 3 = 27 experiments. 

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