Pharmaceutical Testing

The cleaning validation is primarily applicable to the cleaning of process manufacturing equipment in the pharmaceutical industry. It refers to the removal of residues and contaminants, such as detergents, sanitizers, or degradation products resulting from the cleaning process itself.

Cleaning validation is documented evidence with a high degree of assurance that one can consistently clean a system or a piece of equipment to predetermined and acceptable standards. The FDA requires this documentation to ensure that no risks are associated with cross contamination of active ingredients, detergents or sanitizers.

Carry-over of product residues should meet defined criteria, for example the most stringent of the following three criteria:

• No more than 0.1% (1/1000th) of the normal therapeutic dose of any product will appear in the maximum daily dose of the following product.
• No more than 10 ppm of any product will appear in another product
• No quantity of residue should be visible on the equipment after cleaning procedures are performed.
  

The process validation of pilot lots or scale-ups actually refers to testing two aspects of the manufacturing process: the manufacturing time intervals as well as manufacturing volumes.

In manufacturing time intervals, process validation ensures that the product remains consistent within an acceptable range in each step of the manufacturing process by testing samples taken from the beginning, middle and end of the products’ development. For example, if manufacturing 2% salicylic acid, the samples taken from the beginning, middle and end of the process should have within 1.8 – 2.2% specific range.

In the situation where the developing product is held in holding or mixing tanks, process validation engages in testing manufacturing volumes. The validation process uses samples from the top, center, and bottom of the tank to ensure homogeneity in the entire mixture. In the blending of solid, liquid or semi-solid raw materials, manufacturers must make certain that the entire batch is thoroughly mixed.