Cold Chain Qualification : 5 Questions You Must Ask When Shipping Biologics

Posted by Praveen Bezawada-Joseph on Aug 14, 2013 11:30:00 AM

“Cold Chain” refers to the uninterrupted series of logistical activities (packaging, shipping, storage, distribution, handling) of products that must be maintained within a given temperature range. And as those of us in the bio-pharmaceutical industry know well, maintaining cold chain is critical to the integrity of biologically derived therapeutic products.

The Centers for Disease Control and Prevention (CDC) has estimated that $300 million worth of vaccines alone are destroyed each year due to improper storage and distribution; the numbers for other bio-therapeutics are unknown. The scary aspect of that figure is that this includes only the product that was known or suspected to be compromised.

Think of the health care implications for administering adulterated medications to patients! The consequences can go well beyond economic losses: failure at some point in the cold chain can potentially have dire consequences.

Most of us in the bio-pharmaceutical industry would agree that patient safety and regulatory compliance are the key drivers within cold chain logistical systems. Organizations recognize the growing need for control of the entire cold chain. The ever changing global scenario requires highly efficient processes as a backbone to accommodate the growing needs of organizations.

Overview: Five Questions You Must Ask When Shipping Biologics

1. Can You Achieve End-To-End Cold Chain Visibility?
2. Has that Biological Therapy Been Handled Properly?
3. What is That Pre-Qualified Shipper Pre-Qualified for?
4. How Does Your Shipping System Stack Up Over the Entire Transit Process?
5. What About Temperature Monitoring?

1. Can You Achieve End-To-End Cold Chain Visibility?

The advent of global commerce has made the distance between countries appear smaller due to the successful amalgamation of science, process and technologies but the physical separation between geographical entities remains. This is where the enhanced focus on process, end-to-end cold chain visibility and efficient trace-ability systems come in to play.

The good news is that cold chain-related technologies are evolving. Tracking systems, temperature monitoring devices, courier capabilities, and regulations are all changing to accommodate both the increasing numbers of bio-therapeutic products moving through the supply chain and the increasingly stringent criteria for temperature compliance.

How can manufacturers provide end-to-end cold chain visibility and thus satisfy both patient safety and regulatory requirements?

Fisher Clinical Services helps clients by answer this question with “solution-oriented engineering.” We qualify the entire shipping process at a temperature range from X°C to Y°C, for Z hours along the transit lanes. Solution-oriented engineering begins with the components used within the cold chain and extends through the entire shipping/transit lane. An assessment of the materials, suppliers, shipping lanes and methods are part of our process mapping. The goal is to develop cost effective solutions that are end-user friendly and also ensure performance, established through documented testing. We recognize that cold chains are complex and work towards reducing this complexity for our clients by incorporating compliance with cold chain requirements into the testing protocols, pack-outs, shipping instructions, quality agreements, and training that we provide.

In short, end to end cold chain visibility is achieved by meshing together the technologies and carrier capabilities currently available in the market by mapping them to the supply chain components.

2. Has that Biological Therapy Been Handled Properly?

Biologically derived therapies have varying temperature requirements, ranging from cryogenic, ultra-low, frozen, and refrigerated. Maintaining refrigerated temperatures may be the most challenging.

The majority of vaccines require storage and distribution under refrigeration (2°C to 8°C), and exposure to both warmer and colder temperatures may affect their potency. The negative effects of warming above 8°C are usually more gradual, predictable, and smaller in magnitude than losses from temperatures that are too cold. However, exposure to freezing temperatures rapidly diminishes the potency of most vaccines, and according to the CDC1, the potency of a dose of vaccine can be reduced even though there are no visible signs of freezing. For this reason, maintenance of correct temperature of vaccines is especially critical, as well as challenging, be it during storage or distribution.

Biologics that must be kept frozen, whether at around -20°C or -80°C, are typically shipped in dry ice, and these shippers and pack-outs are well defined in the industry. The more recent challenge is the shipping and distribution of cell-based therapies at cryogenic temperatures (<-150°C) in liquid nitrogen.

The most challenging issue in the distribution of cold chain materials is the clinical site. For instance, an assessment of 721 primary care physician offices showed that an estimated 17 to 37 percent of the staff members responsible for managing the vaccine had exposed their vaccine inventory to improper conditions2,3 , including refrigerators that were set too warm or too cold, placing vaccine in the refrigerator door, placing food in the same unit, leaving inventory on a table during group vaccination events, and returning unused doses to the refrigerator.

Managing cell-based therapies at the clinical site is especially challenging, as these products must often be thawed and administered using a specific protocol, and clinical site staff must be trained in handling the shipper as well as the therapy.

Fisher Clinical Services has years of experience in qualifying these dry shippers and is also working inside clinical sites to provide the training, infrastructure, and implement best practices in handling bio-therapeutics all the way to the patients’ bedside. Ensuring the correct handling of biological therapies and creating a fully transparent distribution system means extending the cold chain not to the clinical site door, but to the patient.

3. What is That Pre-Qualified Shipper Pre-Qualified for?

The cold chain distribution process is an extension of the good manufacturing practice (GMP) environment that all drugs and biological products are required to adhere to, and is enforced by the Food and Drug Administration (FDA) and other regulatory bodies in the US and overseas.

Most manufacturers and distributors of vaccine and other biological therapeutics turn to pre-qualified shippers, and there many choices available. Fisher Clinical Services does not manufacture shippers, but we test and qualify shippers and pack-outs for our clients, and these units do not always perform as specified. There are a number of reasons why shippers may not perform, and before purchasing a pre-qualified shipper, you need to investigate how the testing was conducted. For instance, shippers can fail because of

• Inadequate stressing: The environmental stressing profile standards typically employed to qualify these shippers come from ISTA (International Safe Transit Association), which are not representative of most transit conditions and should only be used as a starting point for more rigorous and true to life temperature simulations.

• Issues with pre-qualification: We have found instances where the testing profile selected helped to ensure a successful run, either through lack of temperature extremes or prolonging the duration of compliance by alternating the heat and cold stress to keep the package within the targeted temperature range.

4. How Does Your Shipping System Stack Up Over the Entire Transit Process?

Due diligence in cold chain means not simply using a qualified shipper, but qualifying the shipper to perform within the condition of the entire shipping process, whether overnight to the Midwest, or four days to the Far East.

Commissioning a transit study to qualify your shipping system will lower costs in a number of ways. This includes dramatically reducing loss of material and the repetitive testing of suspect material. A transit study will allow you to identify when a more expensive shipper combined with a less expensive transport option, such as two-day ground vs. overnight, is more cost effective than a less expensive shipper, combined with occasional use of a specialized courier service (such as FedEx’ White Glove service).

Choosing the right shipping system begins with:

1) A thorough shipping lane analysis

2) Determining critical control points

3) Performing a transit study—testing the shipper and configuration to the highest degree of performance during transit.

What does shipping lane analysis entail? This is where we identify critical elements such as the package carriers operating within the shipping route and the environmental/ temperature trends affecting the geographical locations along the route. Critical control points include but are not limited to the shipper, coolant, pack-out, size of your payload, the stability and allowable temperature range of the materials, and storage and handling requirements.

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1. Galazka, A.; Milstien, J. & Zaffran, M. (1998). Thermostability of Vaccines. World Health Organization, Global Programme for Vaccines and Immunization, Geneva, Switzerland: Publication No. WHO/GPV/98.07.
2. Gazmararian, J.A.; Oster, N.V.; & Green, D.C. et al. (2002). Vaccine storage practices in primary care physician offices. American Journal of Preventive Medicine, 23(4):246–53.
3. Bell, K.N.; Hogue, C.J.; Manning, C. & Kendal, A.P. (2001). Risk factors for improper vaccine storage and handling in private provider offices. Pediatrics 1:107:E100.
4. European Commission. (2011). Commission Guidelines on Good Distribution Practice of Medicinal Products for Human Use. Brussels, Health and Consumers Directorate-General, 32 pp.
5. World Health Organization. (2005). Good Distribution Practices (GDP) for Pharmaceutical Products. Working Document QAS/04.68/Rev.2, 28 pp.
6. World Health Organization. (2010) WHO Good Distribution Practices for Pharmaceutical Products. World Health Organization, Geneva, WHO Technical Report Series, No. 957, 30 pp.