As bio-pharmaceutical manufacturers are aware, the industry is facing a unique combination of circumstances. Not least, in the wake of the Coronavirus pandemic and ongoing vaccine research, the increasing development of cell and gene therapy (CGT) treatments have led to a rise in medicinal and medical shipments.
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Logistically, the pharmaceutical sector’s characteristically high standards represent a challenge. To ensure the safety and quality of deep-frozen and super-chilled cryogenic deliveries, they have to check the correct qualification of cryotanks. At the same time, logistics and transport company management must respond to the intrinsic immediacy or urgency of the consignments.
For the above reasons, qualification of cryotanks and physical conditions is essential in shipments of cryogenic and deep-frozen material.
Pharma industry standards require adequate documentation to comply with regulations and verify quality for corporate customers and patients alike.
Against the backdrop mentioned above of CGT (a.k.a. vein-to-vein treatments), COVID-19, and flu vaccine distribution, in tandem with ongoing research, industry commentators describe today’s demands on supply and delivery cold chains as unprecedented. They add that first-class support is vital for proactive logistics planning, efficient communication, and the qualification of cryotanks and cryogenic containers.
Below, you will find more on the simple qualification of cryogenic containers. We also discuss the implications for transportation fleets within the current regulatory environment.
Simple vs. Fleet Qualification of Cryogenic Containers
Simple qualification involves verifying that a pressure vessel and the vehicle transporting it comply with technical conditions and regulations. Conversely, fleet qualification refers to standards generically applied to a wider inventory of vehicles, such as in a logistics or delivery company.
Good distribution practices (GDP) require manufacturers of medicinal products to control and supervise the supply chain, including transport companies. Specifically, each manufacturer must have a qualified person (QP) who is responsible for managing standards.
In addition, the organization concerned should prepare a written procedure with instructions for controlling seasonal temperature variations and ensuring correct delivery procedures. Documenting the necessary precautions and corrective actions and making staff aware of their requirements will help reduce error and the incidence of mishaps.
Guidelines recommend GDP for distributing medicines and similar products for human use within the European Union. As you might expect, the recommendations align with corrective actions and preventive actions (CAPA) principles.
Wholesale distributors are responsible for ensuring that vehicles and equipment used to distribute, store, or handle medicinal products are suitable. Specifically, chapters 3.2.1, 5.5, and 9 of the European guidelines refer to temperature and environmental control in storage and transit. Significantly, chapter 9 also covers the correct labeling of packages.
Temperature-sensitive medicines and deep-frozen or cryogenic products require conditions that will not compromise their quality and integrity. There should be written procedures for operating and maintaining all vehicles and equipment involved in the distribution process, including cleaning and safety precautions.
In temperature-controlled vehicles, typically the case in this type of delivery, temperature monitoring equipment is subject to regulation. The sensors and measuring devices ought to undergo routine maintenance and regular calibration. Probes and equipment units require checks, tests, and calibration at least once a year—or more frequently if their serviceability or reliability comes into question.
Ideally, the handling of bio-pharmaceutical products or medicines calls for the use of dedicated vehicles and equipment. However, if transported in a non-dedicated van, adequate procedures and precautions must be in force to prevent damage, degradation, or other quality issues.
Furthermore, technicians should carry out temperature mapping under representative conditions, taking seasonal variations into account.
Delivery route planners should follow the principles of risk assessment when choosing delivery routes. When assessing potential hazards and likely conditions during the journey, they are to consider the necessity for controlling ambient conditions inside the delivery vehicle(s) concerned.
Notably, the EU published guides in GDP that recommend minimizing delays and temporary storage during transportation. In their standard operating procedure (SOP) documentation, companies should specify any foreseeable problem(s), such as when consignments await the next leg of their transportation route. Moreover, long pauses in deliveries should be subject to risk assessment.
DOT Regulations: Qualification of Cryotanks
In the US, the Department of Transportation (DoT) regulates motor vehicle movement of hazardous materials. Nonetheless, the regulations have some exceptions, one of which is Materials of Trade (MOT). This exclusion provides relief from several DoT rules, as long as employees receive awareness training and follow set requirements.
Material of Trade
Under DoT regulations, the term materials of trade means hazardous materials—other than waste—carried on or in a motor vehicle by a private carrier. The latter term includes delivery companies and couriers.
Significantly, the consignment and journey must be in direct support of a bona fide business activity. Deliveries between laboratories and hospitals or clinics, for instance, would fall within this category.
Cryogenic materials, including liquid nitrogen and helium, are regulated as DoT hazard class 2.2 since their outer transport container remains dry. Thus, they benefit from the MOT exemption.
Suppose you use your own car or van in a delivery. In that case, it is your responsibility to have adequate personal insurance coverage for yourself, the vehicle, and any damage that arises due to hazardous materials.
Requirements for MoT Exemptions
- Maximum weight of any single liquid nitrogen container (including contents): 220 lb or 100 kg.
- Maximum weight per vehicle: 440 lb (200 kg).
- Must be securely packaged, with closures held in place.
- Not pressurized above 25.3 PSI.
- Cylinders must meet full DoT requirements and bear the recommended marking(s).
- Package labeling is to include the common and proper substance names.
- Outer containers are to be the manufacturer's original or an approved equivalent type.
- The outer box or package is to be secure and protected against shifting inside the transport vehicle during the journey.
Exemptions from DoT regulations
Small liquid nitrogen containers are exempt from DoT regulations, providing they meet the following conditions:
- Less than one liter in volume.
- Inner vessel includes a double glass wall insulated construction and is not pressurized.
- Sturdy outer packaging, i.e., cushioned box.
- Clearly labeled with a common name.
- Not transported in a closed vehicle.
Making sure that all cryogenic containers are duly qualified and comply with the regulations is mandatory. It can either be done by a simple qualification where each cryogenic container is qualified on its own or by performing a fleet qualification. A fleet qualification is recommended, if you want to make sure that you comply with the regulations within the whole transport chain. Doing this on your own mind sounds difficult, but ELPRO, as a leader in temperature monitoring solutions, has in- depth knowledge of the requirements and is happy to assist you any time.