Steve Plogsted, a pharmacist at Nationwide Children’s Hospital in Columbus, Ohio, is an expert on gluten in medications. His website, glutenfreedrugs.com, is widely recognized as the most reliable source of information on gluten-free prescription and over-the-counter drugs. Have a question about gluten and medications? Send it to [email protected]
Q: What steps are taken to minimize or prevent cross-contamination in a pharmaceutical manufacturing facility?
A: There are numerous requirements and precautions employed by any pharmaceutical manufacturer who plans to sell their product in the U.S. market. This includes plants in other countries that manufacture for a U.S. distributor. They must maintain the same standards and are required to undergo examination by a U.S. Food and Drug Administration (FDA) inspector. People who work with the drug products wear suits similar to what you might see in an operating room. All facilities and production procedures must be approved by the FDA. Here are excerpts from the FDA manual on manufacturing practices:
“All utilities that could affect product quality (e.g., steam, gas, compressed air, heating, ventilation and air conditioning) should be qualified and appropriately monitored and action should be taken when limits are exceeded. Drawings for these utility systems should be available. Adequate ventilation, air filtration and exhaust systems should be provided, where appropriate. These systems should be designed and constructed to minimize risks of contamination and cross-contamination and should include equipment for control of air pressure, microorganisms (if appropriate), dust humidity and temperature, as appropriate to the stage of manufacture.
“Particular attention should be given to areas where APIs [active pharmaceutical ingredients] are exposed to the environment. If air is recirculated to production areas, appropriate measures should be taken to control risks of contamination and cross-contamination. Permanently installed pipework should be appropriately identified. This can be accomplished by identifying individual lines, documentation, computer control systems or alternative means.
“Pipework should be located to avoid risks of contamination of the intermediate or API. Drains should be of adequate size and should be provided with an air break or a suitable device to prevent back-siphonage, when appropriate. Equipment should be constructed so that surfaces that contact raw materials do not alter quality of the intermediates and APIs beyond the official or other established specifications. Closed or contained equipment should be used whenever appropriate. Where open equipment is used, or equipment is opened, appropriate precautions should be taken to minimize the risk of contamination.”
The manufacturers predominantly use materials that are easy to clean and sterilize, such as stainless steel, and employ specific cleaning processes. I spoke with a generic drug manufacturer and learned that a precise cleaning and sterilization procedure is used in a production room where a single drug product is manufactured. If more than one type of drug product is produced in that room, additional cleaning steps are employed, and the room is quarantined until the results are thoroughly evaluated. The cleanliness and sterility of these facilities is a crucial point of emphasis.