Is there any restriction to manufacture Meropenem products in cephalosporin facility? If yes, would anybody please share the respective guideline link.
Beta-lactam antibiotics, including penicillins and the non-penicillin classes, share a basic
chemical structure that includes a three-carbon, one-nitrogen cyclic amine structure known as the beta-lactam ring. The side chain associated with the beta-lactam ring is a variable group attached to the core structure by a peptide bond; the side chain variability contributes to antibacterial activity. As of the date of this publication, the USFDA has approved over 34 beta-lactam compounds as active ingredients in drugs for human use.
Beta-lactam antibiotics include the following five classes:
• penicillins (e.g., ampicillin, oxacillin)
• cephalosporins (e.g., cephalexin, cefaclor)
• penems (e.g., imipenem, meropenem)
• carbacephems (e.g., loracarbef)
• monobactams (e.g., aztreonam)
Allergic reactions associated with penicillins and non-penicillin beta-lactams range from rashes
to life-threatening anaphylaxis.
All non-penicillin beta-lactams also have the potential to sensitize individuals, and subsequent
exposure to penicillin may result in severe allergic reactions in some patients. Regardless of the rate of cross-reactivity between beta-lactam drugs or the mechanism of action by which such cross-reactivity may occur, the potential health risk to patients indicates that drug manufacturers should take steps to control for the risk of cross-contamination for all beta-lactam
products.
Because of the potential health risks associated with cross-reactivity (cross-sensitivity) of betalactams, manufacturers should assess and establish stringent controls (including appropriate
facility design provisions assuring separation) to prevent cross-contamination. Just as FDA
considers the separation of production facilities for penicillins to be current good manufacturing
practice, FDA expects manufacturers to treat sensitizing non-penicillin beta-lactam-based
products similarly. Specifically, FDA recommends that manufacturers establish appropriate
separation and control systems designed to prevent two types of contamination:
(1) the contamination of a non-penicillin beta-lactam by any other non-penicillin beta-lactam, and (2) the contamination of any other type of product by a non-penicillin beta-lactam.
Accordingly, USFDA recommends that the area in which any class of sensitizing beta-lactam is manufactured be separated from areas in which any other products are manufactured, and have an independent air handling system.
As with penicillin, the section of a facility dedicated to manufacturing a sensitizing nonpenicillin beta-lactam should be isolated (i.e., completely and comprehensively separated) from
areas in the facility in which other products are manufactured. This control applies to each of the
five classes of sensitizing beta-lactams; the area in which any class of sensitizing beta-lactam is
manufactured should be separated from areas in which any other products are manufactured,
including any other class of sensitizing beta-lactam.
Therefore, it is apparent that the manufacture of Meropenem products must be done in a separate facility than that of Cephalosporin products, as recommended by the USFDA.
Reference- Guidance for Industry by USFDA, April 2013
Non-Penicillin Beta-Lactam
Drugs: A CGMP Framework for Preventing Cross Contamination