The 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. It 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). The 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.
FDA recommends similar manufacturing controls for the manufacture of non-penicillin beta lactam drugs, although a separate building is not necessary. Primarily, the manufacturer should focus on separate air handling systems, validated cleaning procedures and validated methods for detection of residual active, production campaigns, and personnel training.
The document applies to the manufacture of drug products, API synthesis and to repackagers. We have seen an increase in the number of inspections related to repackagers, because inadequate cross contamination controls existed at many drug repackagers.