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The Food and Drug Administration states that cleaning equipment before use is nothing new, so the 1963 GMP regulation (Part 133.4) declares that “equipment shall be kept very clean and orderly.” A similar section for instrumentation cleansing (211.67) was included in the 1978 CGMP rule.
Of course, the principle of requiring clean equipment is to prevent contamination or adulteration of drug products. Historically, the FDA investigated inadequate cleaning and maintenance of equipment and poor dust control systems. Also, historically speaking, the FDA finds product contamination or cross-contamination of drug products with potent steroids or hormones.
Many product recalls have occurred over the past decade due to actual or potential penicillin cross-contamination.
An incident that made the Food and Drug Administration aware of possible cross-contamination, because inadequate procedures were followed. In 1988 a finished drug product, cholestyramine resin USP was withdrawn.
Wanted to make bulk pharmaceutical chemical drugs but was contaminated by the small size of the intermediate. Cross-contamination, in that case, is believed to be due to reuse of recovered solvents. Recovered solvents were contaminated because there was a lack of control over the reuse of solvent drums.
Drums that are used to store recovered solvents from chemical production processes cannot store recovered solvents later used for organic compound production plans. The company did not have controls on these solvent containers, did not adequately test the container solvents, and did not have valid cleaning procedures.
Some chemical shipments can contaminate bulk pharmaceuticals, thereby contaminating the baggage used in the facility’s fluid bed dryers with chemical contamination, consistently leading to large amounts of cross-contamination at sites where no pesticides are normally produced.
The FDA issued an import warning in 1992 on a foreign bulk pharmaceutical manufacturer that manufactured a potent steroid product in addition to a non-steroid product using common equipment.
The firm was a multi-use bulk pharmaceutical facility. The FDA considers the potential for cross-contamination to be significant and pose a serious health risk to the general public.
The firm recently began a cleanliness validation program during testing and was deemed inadequate by the Food and Drug Administration. One explanation that was thought to be insufficient was that the firm was only searching for evidence of the absence of the precursor compound. From the TLC examination of the rinse water, the firm had evidence of the presence of reaction by-products and degradant residues from the previous process.
