Shippers and distributors are to follow the proper storage and shipping requirements as indicated by the manufacturer. For particular cases, such as shipment of vaccines or other special care products, manufacturers may require special shipping and storage conditions generally referred to as cold-chain management. For example, manufacturers may attach temperature-monitoring devices and/or ship under specified controlled conditions to ensure that the desired temperature is maintained during distribution (see Monitoring DevicesTime, Temperature, and Humidity 1118
). Validated, available temperature- and/or humidity-monitoring technologies can be used to monitor the overall environmental effect on compendial articles during shipment and distribution. In these cases, the shipping conditions of the package are recorded. In general, extreme temperature conditions (i.e., excessive heat, freezing) should be avoided. Distribution systems chosen to deliver pharmaceutical products from the manufacturer to the consumer should take into account basic operational parameters, including timeliness and accountability. The manufacturer's FDA-approved storage conditions, printed in the labeling of the product, should be observed carefully at each destination of the distribution chain (see Figure 1
), unless specifically instructed otherwise in the immediate label of a shipping container. This may be the case for certain pallet-sized shipping containers where the amount of refrigerant contained (e.g., dry ice, gel packs) is based on an anticipated exterior condition approximating controlled room temperature. In such cases, placing the shipping container in a refrigerator could lead to the product inside freezing, potentially affecting its quality. Items requiring special handling conditions will have those conditions clearly indicated in the labeling for the product. The Prescription Drug Marketing Act of 1987 and the ensuing regulations in 21 CFR Part 203, Prescription Drug Marketing, and Part 205, Guidelines for State Licensing of Wholesale Prescription Drug Distributors, provide the necessary regulations and guidance for several legs of the distribution chain for the prescription drug. The manufacturers and distributors should work together to establish proper distribution and product-handling requirements for the purpose of ensuring appropriate product maintenance in transit. Pharmacists and physicians should educate patients regarding proper storage of products to ensure product integrity at the patient level. Information that may be considered in determining the ability of pharmaceutical articles to maintain their Pharmacopeial requirements of identity, strength, quality, and purity through the distribution channel may include, but is not limited to the following: ICH stability studies, temperature cycling studies, stability shipping studies, ongoing regulatory stability commitment studies, market experience portfolio (i.e., product complaint files, historical product performance data, product development data), and product labeling commitments.