Procedure Reasoning

• Instances of pharmaceuticals contaminated due to improperly cleaned equipment led the FDA to develop swab cleaning validation procedures. Specifically, in 1988, the pharmaceutical Cholestyramine Resin USP went to market contaminated with solvents used in the manufacture of pesticides. Upon investigation of the contamination, the FDA found that drums previously used to store pesticide-related chemicals were subsequently used to store pharmaceutical chemicals without thorough cleaning.
  
  

Cleaning Requirements

• All pharmaceutical manufacturing firms must compose their own cleaning protocol for each piece of equipment and for all variations, such as cleaning equipment between batches versus cleaning equipment for new drug production. Some manufacturers decide to dedicate certain equipment to the manufacture of one particular drug, which avoids cross-contamination altogether. In addition to cleaning equipment free of materials used in production, manufacturers must also ensure that no remnants of any cleaning compounds remain.
  
  

Validation Requirements

• The FDA similarly requires pharmaceutical manufacturers to validate their cleaning procedures and to compose written protocol delimiting all aspects of validation. Drug firms must state when validation must take place, who performs the validation and particular validation methods and procedures used. Two validation procedures exist: direct surface sampling (swabbing) and rinsing. The FDA recommends swab validation but acknowledges that rinsing allows manufacturers to test large surface areas and to test the insides of equipment that are difficult to disassemble.
  
  

Swabbing Procedure

• Swab cleaning validation provides a sample from a direct and limited area and can lift insoluble residues through contact. Testers dip a swab in a solvent liquid that does not interfere with sampling outcome. Testers then rub the swab on the sample area horizontally and vertically. Finally, swab cleaning validation testers place the sample in a centrifuge, extract any residue and analyze the sample to ensure the equipment is thoroughly clean.