FDA Continuing to Issue 483’s to Compounding Pharmacies

FDA continues to issue 483s to compounding pharmacies for a lack evidence and cGMP
framework in preventing/mitigating beta-lactam cross-contamination

Warning Letters and significant FDA 483 observations continue to plague the compounding pharmacy industry with over 40% of compounders inspected receiving Warning Letters and nearly 100% receiving critical observations. One of the more common observations cited by the FDA directly relates to the implementation of manufacturing controls to prevent cross-contamination of finished pharmaceuticals and active pharmaceutical ingredients (APIs) with non-penicillin beta-lactam drugs.

In the April 2013 guidance document released by the FDA entitled Non-Penicillin Beta Lactam Drugs: A Current Good Manufacturing Practice cGMP Framework for Preventing Cross-Contamination, the agency goes as far as to say that manufacturers generally should utilize separate facilities for the manufacture of these compounds. Beta-lactam antibiotics include the following four classes:

• cephalosporins (e.g., cephalexin, cefaclor)
• penems (e.g., imipenem, meropenem)
• carbacephems (e.g., loracarbef)
• monobactams (e.g., aztreonam)

As a result, the FDA expects and recommends that manufacturers of these antibiotics 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
(2) The contamination of any other type of product by a non-penicillin beta-lactam.

As a manufacturer, it is critical that you evaluate your manufacturing operations for the possibility of cross-contamination and that you implement appropriate controls to reduce or mitigate the potential for cross-contamination. The FDA will expect direct manufacturing control related to the isolation and separation of intermediate and derivative materials, facilities, equipment, and personnel.
LexaMed has considerable experience and expertise in the testing for and development of control strategies for beta-lactam contamination. We have developed and validated an analytical method for detecting trace amounts of beta-lactam and can coordinate swab testing of manufacturing and storage areas to demonstrate control. We can also advise on facility design and procedural controls to assure compliance with FDA expectations for beta-lactam cross-contamination control and isolation.


For more information on developing appropriate manufacturing controls and further clarity on FDA expectations for non-penicillin beta-lactam drugs, please contact LexaMed.

705 Front Street
Toledo, OH 43605
Office: 419-693-5307
Email: jkoenker@lexamed.net