Introduction

This guidance describes the importance of implementing manufacturing controls to prevent cross-contamination of finished pharmaceuticals and active pharmaceutical ingredients (APIs) with non-penicillin beta-lactam drugs. This guidance also provides information regarding the relative health risk of, and the potential for, cross-reactivity in the classes of sensitizing beta- lactams (including both penicillins and non-penicillin beta-lactams). Finally, this guidance clarifies that manufacturers generally should utilize separate facilities for the manufacture of non-penicillin beta-lactams because those compounds pose health risks associated with cross- reactivity.
Drug cross-contamination is the contamination of one drug with one or more different drugs. Penicillin can be a sensitizing agent that triggers a hypersensitive exaggerated allergic immune response in some people. Accordingly, implementing methods for preventing cross- contamination of other drugs with penicillin is a key element of manufacturing penicillin and current good manufacturing practice (CGMP) regulations require the use of such methods. Non-penicillin beta-lactam drugs also may be sensitizing agents and cross-contamination with non-penicillin beta-lactam drugs can initiate the same types of drug-induced hypersensitivity reactions that penicillins can trigger, including life-threatening allergic reactions. Therefore, manufacturers of non- penicillin beta-lactam drugs should employ similar control strategies to prevent cross- contamination, thereby reducing the potential for drug-induced, life-threatening allergic reactions.
The information in this guidance is intended for manufacturers of finished pharmaceuticals and APIs, including re-packagers. Other establishments that handle drugs, such as pharmacy compounders, may find this information useful. FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidance documents describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in FDA guidance means that something is suggested or recommended, but not required.