Qualification and validation processes

In this chapter we guide quality assurance (QA) managers, lab managers, IT personnel, and users of equipment hardware and software through the entire qualification and validation process, from writing specifications and vendor qualification to installation and initial and ongoing operation. The following points are covered ... 

If the pharmaceutical industry adopted the lessons learned in other branches (e.g., aircraft industry, automotive industry) it could realize an increased efficiency in the qualification and validation processes. To this end effort should be made to investigate statistical process control (SPC), house of quality, Deming circuits, and so on. 

The results of any risk analysis should be well documented as they become the key input into the qualification and validation process. They are the basis for defining tests in the IQ, OQ, and PQ phases. It is often impossible to say prior to a risk analysis what steps of qualification need to be performed. It depends on the risks and measurements defined during the risk analysis. Equally important, this procedure increases the efficiency of the qualification process. In the past, the decision on which qualification tests to perform was outlined by writing qualification protocols. These usually prompted long and expensive discus-... 

Ensure validations are carried out Oversee whole qualification and validation process ... 

The Quality Unit must be independent of those parts of the organization responsible for testing and production and has a critical role in overseeing the whole qualification and validation process. It is expected to ... 

Custom-built control cabinets are provided for various types of pharmaceutical equipment, usually by the equipment manufacturer. These control cabinets should be UL listed or labeled, otherwise all of the wire and electrical equipment in them are subject to the requirements of the NEC. The functions controlled by these control cabinets and sometimes the equipment within the control cabinets and all of its control circuits should be part of the qualification and validation process. 

Obviously, GMP requirements, especially extensive personnel training, calibration, qualification and validation, enhanced documentation, extensive cleaning and sanitation, and sharpened in-process control must considerably influence process organization and output. All these GMP-related activities are costly and time consuming, and will result in decreased productivity and increased production costs. On the other hand, a quality assurance system contributes to consistent production with a lower number of rejected batches and complaints. 

Retrospective validation involves using the accumulated in-process production and final product testing and control (numerical) data to establish that the product and its manufacturing process are in a state of control. Valid in-process results should be consistent with the drug products final specifications and should be derived from previous acceptable process average and process variability estimates, where possible, and determined by the application of suitable statistical procedures, that is, quality control charting, where appropriate. The retrospective validation option is selected when manufacturing processes for established products are considered to be stable and when, on the basis of economic considerations and resource limitations, prospective qualification and validation experimentation cannot be justified. 

The categories listed above require qualification and validation documentation. It is advisable that process automation and companion computer-integrated manufacturing operations not be initiated until sufficient prospective and concurrent validation studies have been completed. 

Thus, it is through careful design (qualification) and validation of both the process and its control systems that a high degree of confidence can be established that all individual manufactured units of a given batch or succession of batches that meet specifications will be acceptable. 

Qualification and validation of the manufacturing process through appropriate means... 

Optimization techniques are used to find either the best possible quantitative formula for a product or the best possible set of experimental conditions (input values) needed to run the process. Optimization techniques may be employed in the laboratory stage to develop the most stable, least sensitive formula, or in the qualification and validation stages of scale-up in order to develop the most sta-... 

I. Other Sterile Process Systems Requiring Qualification and Validation... 

The effort spent in qualification and validation of the utilities, equipment, and processes that make up a sterile product manufacturing operation is wasted unless the manufacturing environment is maintained under control at all times during production. 

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 must be stressed that a good engineering and project process is the best basis for proper qualification and validation work. It is the current opinion on qualification in the pharmaceutical industry that the later steps in the qualification process need more time and attention than the earlier steps. This may be totally different in other industry branches they tend to spend more effort during the earlier stages to save time and money later on. 

The invention of new terminology that was at odds with commonly accepted practice e.g., demonstration of suitability for equipment and processes instead of qualification and validation... 

---