Biologics require refrigeration or ultra-low temperature (ULT) storage, meaning that pharmaceutical laboratories must have cold-chain, temperature-controlled logistics in place to ensure quality in production, storage, and distribution. Moreover, the preceding development process—from concept through screening, validation, and multiple rounds of clinical trials—requires proper management and movement of biological samples, human specimens, reagents, and materials from individual laboratories to and among various GLP and GMP facilities.
In one sense, biologics are the most contemporary and advanced medicines, based on revolutionary understandings of antigen presentation and acquired immunity, coupled with the technological capabilities to generate recombinant proteins, and raise and purify antibodies at industrial scale. However, a biologic is any pharmaceutical product generated in an animal or cell-based system that, because of its biological activity and liquid composition, requires special storage and distribution parameters to mitigate loss or re-treatment of affected patients. The original biologic is the vaccine, regulation of which predates official establishment of the FDA itself. The Biologics Control Act of 1902, passed in the wake of children’s deaths from contaminated diphtheria vaccines, codified a series of standards ensuring vaccine purity and integrity. Iterations of control over ensuing years established guidelines for cold storage, and most recently coalesced around the NSF/ANSI 456 standard.
When vaccines were the only biologics, their storage largely required temperatures in the 2-8° C range, something a simple household or laboratory refrigerator can usually handle. However, refrigerator design propagates temperature fluctuations and hot/cold zones near walls, fans, and combined -20° C frost-free freezer elements. These geographical variables can prove disastrous, causing obligate liquid samples to freeze and become worthless both in economic and medical terms. Mapping airflow and placing items accordingly and sparingly, or placing glass bottles full of water inside doors, can mitigate these shortcomings to an extent. But the best solution is to use purpose-built pharmaceutical-grade refrigeration, with the following considerations and features:
- Appropriate size and type (compact, under-counter, upright) to comfortably hold the maximum quantity/volume that will be stored at the busiest time of production
- Temperature range and controls, with measurement at set intervals
- Digital data logging for temperature readings and fluctuations/excursions, using a buffered probe rather than a thermometer
- Compliance with NSF/ANSI and CDC standards and guidelines
- Strict SOPs that include plans for equilibrating initial temperature, unit placement, movement, and an action plan for power failure
Beyond refrigeration, the worldwide COVID-19 pandemic drastically changed cold storage requirements and put unprecedented pressures on supply chains with the advent of RNA vaccines. The lability of RNA requires constant ULT storage (-70°C) and avoidance of temperature fluctuations or freeze/thaw cycles before use. Cell therapies such as CAR-T necessitate even colder temperatures in the range of liquid nitrogen (-140° C), to maintain long-term viability of precious genetically edited cell cultures. With any ULT storage system, there are additional needs to have duplicate units and adequate floor space for sample/product transfers when frost builds up over time, and to incorporate unit oil management into SOPs. Automated data logging and remote alarms can lessen much of the hands-on management of ULT systems.