Validation of processes for surface preparation is crucial to many industries, including pharmaceuticals, biomedical device and even food preparation. The effectiveness of the methods for surface preparation in these industries should be established, documented and monitored on an on-going basis.
Validation helps ensure that the surface has been cleaned to an acceptable contamination level. This maximum tolerable contamination level may be termed the target level. Sampling and analysis techniques must have the specificity, sensitivity, reliability and robustness to assure that contamination does not exceed the target limit. The areas of surface where contamination is most adherent or where the negative consequences of contamination are greatest must receive special attention. The nature of potential contaminants must also be considered. While much attention is paid to biological debris, microbes, and pyrogens, other organic and inorganic contaminants can potentially impact product quality.
As applied to processes for surface preparation, validation is a quantifiable, structured approach to demonstrate and document process effectiveness and process consistency. The following are suggestions for a comprehensive validation process.
Process efficacy must be evaluated prior to implementing the procedure. The procedure should require re-validation after changes to the processes that may significantly affect the types and amount of contamination left on the surface, or when significant changes are made to the cleaning process and result of re-validation must be documented.
The essence of process validation is documented, scientific proof of consistent successful process performance. Full, detailed documentation is an integral part of the validation process to show that the process consistently performs as expected and yields a result that consistently meets predetermined specifications. Predetermined specifications in this situation refer to the maximum acceptable level of contamination that can be tolerated on the surface. Written procedures must be established detailing the surface preparation processes. Those responsible for performing, approving and documenting the validation study and the acceptance criteria must be included, as should documentation of the frequency of process monitoring. Written procedures on how process changes will be validated and requirements for documentation of validation should also be developed.
Sampling and analysis methods must provide for sample collection and detection of levels of contamination relevant to the target limit. The technique must be suited to the types and the target level of contamination. The detection technique should be reviewed periodically for its effectiveness and relevance to the type and level of contaminants currently encountered. Prior to accepting and implementing a validation procedure, the analytical or surface testing technique itself should be evaluated and successfully replicated at least three times. Where possible, direct surface monitoring is desirable and may be preferred over indirect, extractive methods. Part configuration and test method sensitivity must be considered.
Establishing appropriate target levels of maximum acceptable contamination is a challenge. Generally, the main consideration should be as to how much surface contamination can be tolerated. There are many ways of establishing contamination limits. Cost must be considered in determining the target contamination level. For each level of surface contamination there is an associated cost of achieving that level. In addition, with each level of contamination there is a level of non-conformance or failures. The cost associated with each level of non-conformance must also be considered. The maximum acceptable level (Target Level) is the one where the incremental cost of removing more contamination is not offset by the corresponding reduction in the non-conformance or failure cost. If, however, the cost of non-conformance is a health threatening, or life threatening product failure, then the target contamination level must be adjusted to an appropriately low level.The situation is akin to extrapolating from animal studies to humans using the lowest dose of a drug or chemical at which no adverse effects are seen.The appropriate “safety factor” or risk factor will depend on the nature of the observed problem animals or the anticipated consequence in humans.
Some general considerations in establishing target levels include the effect of different levels of contamination on the success of subsequent operations; the detection capability of the various analytical techniques available; the anticipated end-use and performance requirement of the product; and the economic and social cost of non-conformance or failure.