The Flat Earth Theory in Cold Chain Supply

I remember the terrestrial globe at home and the story about Christopher Columbus' voyage to find a new trading route to the Indies but he instead arrived to a new continent. I was too little to be concerned about trading routes or a new continent so my attention went to another part of the story, the common belief that the earth was flat with an abyss at the edge where monsters awaited for the sailors who dared to go that far. I looked at the terrestrial globe again and asked why some people believed that flat earth theory? How did men prove that our planet was a sphere? I was pleasantly surprised to learn that men in different times and at different places had demonstrated the roundness of the earth through observation and science centuries before Columbus’ voyage. I learned that Columbus had read other people's work (Greek and Arab astronomy) and knew that the earth was not flat so he took a calculated risk with the information available at that time. Today the idea of a spherical-shape earth is not only well known but also accepted by everyone.

One common misconception in cold chain supply is perhaps that product storage and distribution temperatures are the same. The idea that the products’ long-term storage temperature is not the same as the distribution temperature can be easily forgotten. I often use the example of how milk and ice cream are handled from the store to the home kitchens. We store (long-term) ice-cream in frozen conditions but we certainly expose it to warmer conditions for transportation purposes for short periods (i.e. from the store freezer shelves to our home refrigerator). Cold chain products will be exposed in the same manner to warmer (or colder too) conditions as it moves downstream the supply chain. Customers may not be fully aware that the ice cream or milk they purchased has been exposed to warmer temperatures for short periods of time because the effect to product quality is negligent. The containers are taken out of the target refrigeration temperature range for a short period and later placed back to the proper conditions without compromising the product quality. In the biotech and pharmaceutical industries, we find that the stability studies are mandatory by health authorities and these studies are performed following a strict and standardized method outlined by the International Committee of Harmonization (ICH). In most companies, the Quality Stability group performs these studies and the Regulatory group uses the results to establish storage temperature and product shelf life, to file the drug product registrations and to answer questions from regulatory bodies. Stability studies are lengthy and expensive and are specific to the primary container and the manufacturing site so changes to an approved stability study are not easy and may require new submissions, inspections and possible questions from the regulatory bodies. The stability data shows how stable the product is when stored at the ICH conditions and is used to establish the product shelf life (i.e. expiration date). On the other hand, a standardized method to define the distribution temperature has not been available. Therefore it is common to find that many companies only performed the long-term stability studies and established storage temperatures. Companies with only storage temperature have the flat-earth view because they assumed that distribution temperature must be the same as the storage temperature. This flat-earth view creates many supply chain inefficiencies because of the need of extra protection due to the fear of the unknown (i.e. conditions outside the ICH long-term stability studies). There are other companies that have ventured out to find the distribution temperatures and devised many tests such as accelerated stability, temperature cycling and freeze-thaw cycles. These accelerated studies conditions are also defined by ICH but the temperature cycling and the freeze-thaw cycles represent a wide variety of testing conditions. The lack of a standardized method has created a plethora of conditions that are product specific or company specific. Earlier this year, the Parenteral Drug Association (PDA) published a report that aims to standardize the testing conditions for these cycling and freeze-thaw studies. The PDA technical report is the first step in an effort to harmonize the method to calculate the allowable temperature range to support distribution. One drawback of this technical report is that proposed conditions are called "examples" with a disclaimer that these conditions need to be evaluated on a case by case. The technical report resembles the educated risks that Columbus took and I suspect that as more companies adopt these cycling and freeze thaw studies, the need to standardize the conditions will trigger collaboration among industry, regulatory bodies and organizations such as PDA. Why is it important to define the temperature for distribution? Again taking an educated risk will provide companies the distribution stability needed to assemble a stability budget. Therefore, even though fluctuations in temperatures exist during the distribution process it can be managed. Only a few companies have taken the initiative to generate the stability data for distribution and today this stability data for distribution still remains unclear. I believe the PDA technical report is a good step toward the standardization. Companies that do not adopt the stability studies to support distribution will be forced to over design in the shipping containers, freight services, warehousing, and other manufacturing operations because the storage stability provides a smaller range of conditions to operate. I leave you with few questions: Does your company have a stability budget? Has your stability group performed accelerated stability studies? freeze-thaw studies? cycling studies? Are you collaborating with the stability group to start the accelerated, freeze-thaw, and cycling studies at the same time as the ICH product stability studies? I look forward to your comments and will continue talking about the stability budget and the impact of those studies in managing the cold supply chain. Until the next post....