Cleaning Validation in Pharmaceuticals

The manufacturing process of an active pharmaceutical industry typically consists of various chemical reactions and purification steps followed by physical changes. Early steps generally undergo further processing and purification and so potential carryover of the previous product would be removed. It is very necessary to note that cleaning validation in pharmaceuticals offers more than one way to validate a process. As a result validation processes are tested to show whether scientific data shows that the system continuously does as expected and produces a result that meets the predestined specifications.

Firms are required to have written procedures detailing the cleaning process used for various equipment. In the event that a firm has one cleaning process for cleaning different batches of the same product and use different process for cleaning between product changes it is expected to have written procedures addressing the scenarios. Bulk pharmaceutical firms may decide to dedicate certain manufacturing processes that produce gummy residues that are difficult to remove from the equipment. Another example of an equipment that is difficult to clean is the fluid bed dryer bags and is often dedicated to a specific product,

Evaluation of cleaning validation

The first step in validation process is focusing on the objective of the process to be used for cleaning validation in pharmaceuticals. Often companies end up using extensive sampling and testing programs without an evaluation of the steps used in cleaning the equipment. Some of the questions that need to be addressed when evaluating the cleaning process are at what point does the equipment/system become clean and whether it has to be scrubbed by hand? Answers to these questions are important in inspection and evaluation of the cleaning process.

Equipment design

It is of greater essence to examine the design of the equipment especially in large systems during cleaning validation in pharmaceuticals. Operators should have knowledge of these systems and the level of training and experience in cleaning the same systems. It also important to check the written and validated cleaning process to determine whether these systems have been clearly identified and validated. It is advisable to always check the validation of an often critical element in the documentation of the cleaning process; identifying and controlling the time length between the end processing and each step in cleaning. This is normally important for tropical suspensions and bulk drug operators. In addition to the cleaning process, equipment may be subjected to sterilization procedures where the equipment is used for sterile processing.

Procedure and documentation

It is essential to examine the detail and specificity of the procedure for cleaning being validated and amount of documentation that is required. Some processes have log sheet systems that requires some type of specific documentation for performing each documentation step. Depending on the system’s complexity and cleaning process, the level of documentation that is necessary for performing various cleaning steps vary. It is essential for one to document the cleaning steps when complex cleaning procedures are required. Other factors like the history of cleaning residue levels found after cleaning and variability of test results may also dictate the amount of documents required.

Analytical methods

Determine the sensitivity and specificity of the analytical method used to detect the contaminants. Advances in analytical technology have made it possible to detect residues from manufacturing and cleaning processes at low levels. Firms should challenge the analytical method in combination with the sampling methods to show that contaminants can be determined at any level.

Sampling

There are two sampling methods in cleaning validation that are acceptable. The direct surface sampling and the use of rinse samples. Direct sampling is advantageous in that it evaluates areas that are hard to clean and reasonably inaccessible. Also residues that are insoluble can be sampled by physical removal. Rinse samples allow larger surface areas to be sampled.

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