Revisiting Cold Chain Trend Predictions
Forecasting is fun business—if you’re not held to your predictions. I wrote these predictions at the start of 2016 and never expected to see them again. However, the team at Pharma Logistics IQ asked me to revisit them and discuss if they provided any insight. Obviously, I declined to make any predictions for 2017 now that I know I will be held to such scrutiny. Here goes:
Specialized packaging and network designs for specific drugs
Stable and better characterized drugs with an exemplary safety record were expected to migrate to deferred shipping lanes, new transport modes including ocean freight, and an increased allowable range in shipping temperatures. In our practice, we have been helping clients address a wider range of shipping temperatures, but the focus was on new drugs, not commercialized drugs with solid stability data and a proven record of safety. I overestimated the perceived risk in discussing (with regulatory agencies) a wider shipping temperature range and the unintended consequences, and I underestimated the cost pressures to innovate within the supply chain. The search for lower-cost cold chain logistics has grown lower-margin products (e.g. insulin) and was a driving force in biosimilars development in 2016.
Greater characterization of more fragile platforms like monoclonal antibodies (for not only for temperature hazards, but a full range of environmental hazards including shock, vibration, temperature and humidity) were expected to drive these platforms to more specialized logistics needs. The characterization of these synthesized human proteins in solution has shown a remarkable robustness that has not required the extensive modifications of existing cold chain networks.
Tighter controls on clinical trial operations in extreme environments
Tighter controls in clinical trial operations were predicted, especially in vaccine trials, to be seen in 2016. These controls were expected to extend beyond just standard temperature monitoring to a top-to-bottom review of processes, procedures, and packaging to ensure end-to-end control of the cold chain in extreme environments. We predicted end-to-end monitoring of clinical trials in the most challenging of logistical environment, and we have seen this trend continue. Not only do trials use visual controls on individual doses, but we have seen a renewed emphasis on clinical trial operational design, freezer qualification, and on-going facility process and procedure audits on in-country operations. All these trends led to greater control in some of the harshest environmental conditions.
Greater scrutiny on BLA submission for cold chain products
Greater regulatory scrutiny on the cold chain management processes by regulators as part of the biosimilar approval process was accelerated in 2016. The trend to confirm that all the elements of your cold chain management processes—characterization, qualification/validation, and tech transfer/implementation—are fully integrated and well-documented in your quality system prior to submission were expected. Manufacturers who planned for a similar level of review as a novel therapy were surprised. The FDA has implemented their proposed “stepwise” approach to demonstrating biosimilarity. The scope of drug product characterization and associated controls has depended upon the uncertainty level about the biosimilarity.
Primary container and drug product interactions were seen as a patient safety risk. Questions focused on including data from studies for the worst-case anticipated shipping route and assessing of product quality pre- and post-shipment for all shipping configurations. Assessment of product quality followed real-time shipment and/or data from studies that simulate the worst-case conditions that the product would encounter based on the shipping route and method(s) of transport, including shaking, vibration and shock, pressure, and temperature excursions. Each of these worst-case conditions was requested for assessment.
Simulation studies were requested for biosimilars to ensure full range testing of environmental hazards. Applicants were expected to present data and draw conclusions on risks to exposures outside of labeled storage conditions in marketing applications to show understanding of the impact of all environmental hazards.
Biosimilars definitely required a different approach in 2016. Applicants were asked to clearly define all their risks up front and understand environmental hazard challenges other than temperature, including the interactions between multiple hazards: temperature and shock/vibration to particulate formation, shock/vibration and pressure to CCI and sterility, etc.
Agencies were requesting applicants to consider using simulation studies to conduct operational qualification on drug product because of the benefit of a controlled (the ability to conduct full-range testing hazards in your ‘design space’) versus uncontrolled environment. And very importantly, your strategy was expected to be written down in a Validation Master Plan!
2016 was an exciting year, and I fully expect greater challenges in 2017. But I’m not ready to make any more predictions this year!
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