Regulatory agencies have become increasingly rigorous with regards to the detection, identification and quantification of extractable and leachable compounds in pharmaceuticals, drug delivery systems and biomedical devices. This increased scrutiny is the result of several well-documented incidents of contaminants leaching from containers and packaging, resulting in a potential or real risk to humans.
During the 1990s, the FDA became aware that some of the seals in metered-dose inhalers (MDIs) used for inhalation delivery were leaching polycyclic aromatic hydrocarbons (PAHs) into the formulation in trace amounts. PAH compounds had been identified as a primary cause of high cancer rates among chimney sweeps in the 18th century from their exposure to coal tar, and are a primary risk factor for cardiovascular disease among smokers. This discovery of PAHs in MDIs was recognized as a potential risk to human health by the FDA, resulting in further investigation and subsequent regulation.
Perhaps the most recent publicly recognized incident was in 2010, when McNeil Consumer Healthcare voluntarily recalled more than 500 lots of Tylenol, Motrin, Benadryl and Zyrtec. This was in response to consumer complaints about a “musty” odor in the drug products. The cause of the musty odor was eventually determined to be caused by an antifungal chemical used to treat the shipping pallets, 2, 4, 6-tribromoanisole, a suspected carcinogen, which had leached from the pallet, through the outer packaging, and into the drug containers. The recall cost the manufacturer an estimated $900 million in lost sales.
Regulatory agencies, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA), continue to increase their scrutiny on potential extractables and leachables in drug product container and closure systems. Proving that pharmaceutical packaging is safe and will not leach undesired chemicals into drug product is the responsibility of the drug manufacturer.