In a general sense, to "validate" means to give official sanction to, approve or confirm. Accordingly, "validation" can be applied to a very wide range of procedures, products or circumstances.
In the area of cold chain distribution - where it is critical to maintain a stable environment during the shipping of temperature-sensitive cargo - validation is a vital part of the quality control process; assuring that active or passive insulate shippers are thoroughly tested and able to meet specific hold time requirements.
Vaccines and pharmaceuticals are particularly sensitive materials which, if not manufactured and shipped under stringent controls, can become ineffective or even hazardous to the consumer. To that end, in the 1970s the Food and Drug Administration (FDA) began to develop specific guidelines to test and evaluate biologic and pharmaceutical products before they could be released to the public.
Validation procedures started to take shape and were applied to the pharmaceutical and vaccine approval process. Eventually, validation methods and guidelines were developed for the cold chain delivery system as well, with the goal of providing temperature assurance during the manufacturing, storage, shipping and delivery of medicines. Specifically, the Parenteral Drug Administration's (PDA) Technical Report #39 outlines validation strategies for the cold chain.
The Cold Chain Validation Process
With some exceptions, the temperature standard during the manufacturing, storage and shipping of pharmaceuticals and vaccines is between 2 to 8 degrees Celsius. Because of the critical nature of this cargo, rigorous testing must be performed on the equipment and materials responsible for its effective delivery to ensure that it meets established standards. The target temperature must be maintained under the adverse conditions that insulated shipping containers might be exposed to. These conditions are at first simulated and then tested "in the field." Results from these tests are documented in great detail.
With new cold chain solutions in place, the pharmaceutical supply chain is more stable and reliable than ever before. Data logging and reporting technology has taken a step forward and is more meticulous. The technology surrounding insulated shippers is more advanced as well.
Of course with this progression comes an increased number of qualifications for cold chain equipment to meet and surpass as part of the validation process.
Though they vary slightly according to each unique situation, some of the fundamental procedures within a cold chain validation testing process are:
• All testing equipment, from thermal test chambers to vibration tables, is subjected to a full validation process. This ensures that equipment is installed properly and functions as intended. Temperature monitoring devices are calibrated to ensure that data is accurately documented.
• All elements of the cold chain packaging system to be validated are inspected to ensure that they meet specification. This ranges from insulated shipping containers and refrigerant packs to active heating and cooling systems.
• In a lab environment, the cold chain packaging system is subjected to a simulation of worst case transit conditions. This includes thermal testing against hot and cold ambient temperature profiles and physical hazards such as drops, vibration, and compression. Equipment and data are carefully monitored and all observations and findings are well-documented.
• The cold chain packaging system is then monitored in a live field test to demonstrate that performance seen in the lab environment translates to "real world" conditions.
If there are any inconsistencies or problems with the process or equipment during testing, there will be no validation. Validation will not occur until issues are resolved and the hold time capability has demonstrated stability under further rigorous testing.
Cold chain validation does not stop upon successful testing. The monitoring, analysis and documentation of the system will continue even after initial validation testing is done. The importance of consistent and reliable temperature control in situations where life-saving products are involved cannot be emphasized enough. And to those who manage cold chain distribution operations, the validation process offers insurance.