With the advent of Coronavirus (COVID-19) disease as a public health emergency, and the development of novel vaccine candidates, addressing the challenges of cold chain management for storage and distribution will be critical. While vaccines typically require similar transport and storage controls, some of the innovative technologies for a COVID-19 vaccine will present additional cold storage and shipping challenges to maintain product stability, some to require ultra-low storage temperatures [e.g., -80 to -70 degrees Celsius].
Drug product holding and distribution standards are currently promulgated as a legal requirement under 21 CFR part 211 Finished Pharmaceuticals Current Good Manufacturing Practice [CGMP] regulations. As addressed by regulation, holding and distribution controls should ensure that drug products are stored under appropriate conditions to include but not limited to temperature controls so that the identity, strength, quality, and purity of the drug product is not affected.
Storage and distribution of COVID-19 vaccines may present unique challenges for product shipment around the world. Good storage and distribution practices as promulgated in regulation via cGMPs will be critical to maintaining the integrity of COVID-19 vaccines during storage and distribution.
Quality Risk Management [ICH Q9] principles will need be applied to storage and shipping controls as it will relate to COVID-19 vaccine pharmaceutical quality.
Points to be considered with advances in the development of COVID-19 novel vaccines are as follows:
- A transport validation study should qualify packaging for transport throughout the supply chain.
- Failure to validate shipping poses the risk of administration of a dosage potentially harmful to patients or may result in loss of potency, thus failing to induce protective immunity.
- Study design should include both upper and lower temperature control limits, noting that product may not only be impacted by high temperature ranges but may also be impacted/damaged if stored at ultra-low temperatures.
- A well-designed transport study should validate the packaging configuration in use and include environmental conditions that may be encountered during shipment to include environmental temperature challenges.
- Environmental tests challenges should be conducted under laboratory conditions in advance of real-time product shipment.
- Simulating transport in the laboratory will assist with the knowledge based / lessons learned in advance of design and controls established for real-time product shipment qualification studies.
- Environmental challenges that may potentially be experienced during drug product transport and storage should be evaluated.
- Targeted packaging and packaging configuration(s) to include worst case locations for placement of temperature monitoring devices to support continuous environmental control in transport and storage should be addressed.
- Packaging attributes should be assessed to include study data to support confidence that packaged product will consistently be unaffected by environmental conditions to be experienced in shipment and storage.
- All elements of product transport, local shipment, worldwide shipment, modes of transport (via vehicle, train, sea and/or air), and handovers (U.S. Customs hold, etc.) should be represented in shipping assessments.
- Compliance with tamper-evident packaging regulations relevant to shipping methods that may require package opening and re-icing [e.g., product transport in dry ice shippers] in transit.
- Industry recognized guidance for the design of a transport validation study (e.g., compliance with United States Pharmacopeia (USP) General Chapter <1079 > [Good Storage and Distribution Practices for Drug Products], Parenteral Drug Association (PDA) Technical Report (TR) 53 [Guidance for Industry Stability Testing to Support Distribution of New Drug Product], World Health Organization (WHO) Technical Report Series, No. 957, 2010 Annex 5 [WHO good distribution practices for pharmaceuticals] and European Union Good Distribution Practice for Medicinal Products for Human Use (2013/C 68/01)] should be referenced as a guide.
- An up-front investment in product storage and shipping controls is critical. Failure to develop and execute a well thought out transportation plan risk loss of product or potential risk to product quality and patient safety.