Both penicillin and non-penicillin beta-lactam drugs can initiate drug-induced hypersensitivity reactions in some patients which can be life-threatening. Therefore the US Food and Drug Administration (FDA) has issued a series of recommendations to antibiotic manufacturers in order to minimise the risk of cross-contamination at plants that produce multiple products.
The guidance - Non-Penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross-Contamination, finalised last week - draws on current Good Manufacturing Process (cGMP) regulations which state that “operations relating to the manufacture, processing, and packing of penicillin shall be performed in facilities separate from those used for other drug products.”
Such regulations have been stretched to cover non-penicillin beta-lactam (the active ingredient of antibiotics), 34 of which have been identified by the FDA, as the agency acknowledges that contamination within this category of antibiotic can also be a health hazard to a user.
However, the FDA did clarify “that separate buildings may not be necessary, provided that the section of the manufacturing facility dedicated to manufacturing penicillin is isolated.”
According to the guidance, manufacturers must install appropriate separation and control systems designed to prevent contamination of a non-penicillin beta-lactam by any other non-penicillin beta-lactam or, indeed, any other type of product.
The guidance says: “As with penicillin, the section of a facility dedicated to manufacturing a sensitizing nonpenicillin beta-lactam should be isolated” though “manufacturing that is restricted to a specific class of beta-lactam compound generally would not mandate separate facilities and air handling systems, and could permit production campaigning and cleaning as sufficient control.”
The cGMP regulations do not strictly cover API (active pharmaceutical ingredient) production yet the FDA has stretched the guidance “because some APIs are sensitizing compounds that may cause anaphylactic shock” and thus it is as important to prevent cross-contamination with APIs as it is with finished products.