Bishara (2006) summarizes the key regulatory and industry guidelines for pharmaceutical cold chain as follows:
The World Health Organization’s (WHO) working document QAS/04.068 on Good Distribution Practices (GDP) is applicable to all persons and companies involved in the distribution of pharmaceutical products including the: “manufacturers of intermediate and/or finished products, brokers, suppliers, distributors, wholesalers, traders, transport companies, forwarding agents, processors, etc.” This WHO document indicates that the distribution process has generally been “neglected” regarding the: “establishment, development, maintenance and control over the activities involved.” Further, because the distribution segment of the pharmaceutical supply chain involves multiple parties, the risks involved become complex. As stated in the (WHO) working document QAS/04.068: “In order to maintain the original quality, every activity in the distribution of pharmaceutical products should be carried out accordingto the principals of GMP, Good Storage Practice (GSP) and Good Distribution Practice (GDP).” The (WHO) working document QAS/04.068 states: “where special storage conditions (e.g. temperature and relative humidity) are required during transit, these should be provided, checked, monitored and recorded.” It goes on to state: “Temperature mapping of vehicles (where applicable)should support uniformity of the temperature across the vehicle. Recordedtemperature monitoring data should be available for review.” The overall objective of these guidelines is to: “ensure the quality and integrity of pharmaceutical products during all aspects of the distribution process.”
The International Conference on Harmonization document (ICH Q1A (R2)) states: “a drug product should be evaluated under storage conditions (with appropriate tolerances) that test the thermal stability and, if applicable, its sensitivity to moisture or potential for solvent loss. The storage conditions and the lengths of studies chosen should be sufficient to cover storage, shipment, and subsequent use.” Furthermore,“data from the accelerated storage condition and, if appropriate, from the intermediate storage condition may be used to evaluate the effect of short term temperature excursions outside the label storage conditions (such as might occur during shipping).”
The Food and Drug Administration (FDA) Guidance on Stability for the industry notes that adverse shipping and/or environmental conditions may affect the product quality. Deficiencies in good distribution practices with specific focus on temperature control and monitoring during shipment have been cited by the FDA. Several studies by the United States Pharmacopeia (USP) demonstrated temperature and humidity variations during shipping of drugs and vaccines. Time and temperature recording devices documented values as high as 60°C.
The USP standards are cited in <1079> Good Storage and Shipping Practices. USP <1079> describes procedures to maintain proper storage environments for individual articles and ensure the preparation’s integrity until it reaches the user. Risks associated with distribution routes include exposure to temperature excursions, humidity, light and oxygen.Pertinent sections include: “Storage in Warehouses, Pharmacies, Trucks,Shipping Docks, and Other Locations”, “Controlled Room Temperature”,“Personnel Training”, “Qualification of “Cold” Equipment or Stores”,“Distribution and Shipment of Pharmacopeial Articles”, “Qualification Protocol”, “Temperature Challenges”, “Receipt of Pharmaceutical Articles”, “Distribution or Shipping Vehicles”, “Vehicle Qualification”,“Pharmaceutical Delivery Staff”, “Shipment from Manufacturer to Wholesaler”, “Shipment from Manufacturer or Wholesaler to Pharmacy”,“Shipment from Pharmacy to Patient or Customer”, and “Storage of Physician Samples Handled by Sales Representative in Automobiles”.
Recently, Health Canada has published guidelines that place greater responsibility on members of the supply chain including manufacturers,distributors, transporters and retailers to ensure that the drug products will reach the customer uncompromised.The key concepts presented in the European Union Guidance on Good Distribution Practices include: “The quality system operated by distributors (wholesalers) of medicinal products should ensure that storage conditions are observed at all times, including during transportation” and “products requiring controlled temperature storage should also be transportedby appropriately specialized means.”
Source: Bishara, R. 2006. Cold Chain Management - An Essential Component of the Global Pharmaceutical Supply Chain. American Pharmaceutical Review, January/February.