Many pharmaceutical products, including vaccines, can require special cold chain handling during manufacturing and distribution. In particular, biologics such as monoclonal antibodies (maBs), vaccines, and personalized medicine therapeutics require controlled storage at very low temperature conditions to be distributed in a manner that ensures their quality will not be adversely affected.

Cold chain refers to a subset of the total supply chain involving the production, storage and distribution of products that require some level of temperature control in the lower range to retain their potency, healing characteristics and associated benefits.

In 2018 alone, transportation of supply chain products in temperature-controlled environments exceeded $15 billion and this industry is expected to grow at a projected rate of 12.7%YoY.

Generic biologics have recently been introduced in the world of medicine and have rapidly increased in patient use. Apart from excelling in their treatment capability, biologics have placed additional demands on the pharmaceutical supply chain as most of the products require both temperature and time-controlled distribution. Apart from biologics, newer breakthroughs in precision medicine therapies have emerged such as cellular therapies, biomarker testing, and regenerative medicine in the form of stem cells.

Currently, there are 76 COVID-19 vaccines candidates for the coronavirus pandemic, five of which are in clinical trials. If the eventual COVID-19 vaccines are not thermally stable, to distribute them to billions of people worldwide will require a herculean effort of distribution and shipment logistics. Given that it takes a minimum of five years to spin up a new manufacturing and distribution facility; manufacturers are retrofitting their existing plants and warehouses to ramp up production.

From a regulatory standpoint, the Food and Drug Administration (FDA) guidance on stability for the industry notes that adverse shipping and/or environmental conditions may have detrimental effect on the product quality. In recent years, the FDA has increasingly advocated that responsibility for cold chain management ultimately resides with the manufacturer.

The key concepts within the Cold Chain Supply Strategy include:

1.      Defining, maintaining and ensuring temperature specification during shipment

2.      Shipping within and maintaining temperature specifications

3.      Assurance that temperature and humidity controls are monitored during transportation

4.      Establishment of Acceptance criteria for storage and movement of material between sites

5.      Shipping Validation studies

6.      Standard operating procedures, records and documentation available to ensure robust conditions

Supply challenges related to transportation, infrastructure and other issues require early planning and coordination to ensure that the products are adequately handled and maintained at the correct temperature. Securing the cold chain requires innovation, collaboration and communication, ensuring that each of the critical links in the chain satisfy product storage and handling requirements. Advanced technologies, including data loggers, sensors, RFID tags, wireless and wired networks are all potential components of a future forward model that will ensure an ongoing ‘portable record’ of each product throughout its lifecycle.

Deficiencies in good distribution practices with specific focus on temperature control and monitoring during shipment have been recently cited by the FDA. Examples include operational processes lacking acceptance criteria for storage and movement of material between two sites, bulk material intended for refrigerated storage is left at ambient conditions for several days before shipping and shipping validation studies are inadequate.

In order to adhere to the global regulatory requirements and trends, a fully functional quality management system (QMS) and risk management process becomes imperative. Factors to be considered for the QMS may include but are not limited to the: Organization, management, policies, overall roles and responsibilities, process flow, trained resources, implementation plan, compliance, change control, on-time delivery of right product, quality metrics, continuous enhancements and monitoring customer satisfaction.

Complementing the QMS implementation for good distribution practices is an ongoing risk management process comprising of risk identification, assessment, control and monitoring. Areas to be assessed include compliance with ongoing regulations, product profile characteristics, physical and chemical stability programs, environmental factors (temperature mapping, temperature control, temperature and humidity monitoring), modes of transportation (ground, air, sea), shipment destination (domestic, export), package (primary, secondary and tertiary), people (standard operating procedure, training, communication, documentation, correcting adverse events and change controls).

Global regulatory requirements for the handling, storage, and distribution of thermally labile pharmaceutical products have emphasized the importance of assuring that product quality and integrity are not compromised in the distribution channel. Due to the presence of multiple uncontrolled variables in the distribution process, developing an appropriate monitoring program is essential and this should include entities relevant to the cold chain management across the supply chain including manufacturers, distributors, transporters and wholesalers.

Co-author Devashish Pal.