U.S. Food and Drug Administration Agency (US FDA) is announcing the availability of a draft guidance for industry titled Non-Penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross-Contamination. This guidance revises the final guidance issued on April 17th, 2013 and expands the scope of the guidance to include all compounds containing a beta-lactam ring in their structure. All beta-lactam compounds, including non-penicillin beta-lactam antibacterial drugs as well as non-antibacterial beta-lactam compounds (including intermediates and derivatives), have the potential to cause allergic reactions and represent a life-threatening risk to certain patients.
The draft guidance:
- describes methods, facility design elements, and controls that are important in preventing drugs from being cross-contaminated with non-penicillin beta-lactam antibacterial drugs or non-antibacterial beta-lactam compounds and makes recommendations for how manufacturers can be compliant with current GMP requirements for preventing cross-contamination;
- provides information regarding the relative health risk of, and the potential for, allergic reactions due to cross-reactivity in the classes of non-penicillin beta-lactam antibacterial drugs and non-antibacterial beta-lactam compounds;
- recommends manufacturers to have complete and comprehensive separation between non-penicillin beta-lactam antibacterial drugs and manufacturing operations of other drugs;
- provides recommendations on cross-contamination prevention strategies, including examples of relevant design features and control approaches for those seeking to justify a cross-contamination prevention strategy other than complete and comprehensive separation, when appropriate.
Significant changes from previous version include:
- clarifying that the scope of the guidance also includes all compounds, including intermediates or derivatives, that are not a penicillin, have a chemical structure that includes one or more beta-lactam rings, and have a mechanism of action other than an antibacterial mechanism of action;
- providing US FDA’s interpretation of terms, such as allergic reaction, cross-reactivity, and complete and comprehensive separation, used in this guidance;
- clarifying the distinction between non-penicillin beta-lactam antibacterial drug(s) and non-antibacterial beta-lactam compound(s)–in terms of the cross-contamination and patient exposure risks and the control strategies appropriate for manufacturing operations involving each category;
- providing recommendations for drug manufacturers that seek to justify alternative cross-contamination prevention strategies for non-antibacterial beta-lactam compounds.