Part 2: Recent Findings on the Potential for Temperature Damage During Shipping and Handling in the United States
 

By Nick Puro, President, Temptime Corporation

Many medical products can be damaged and lose effectiveness if they are exposed to heat or are frozen. This is particularly true of products that require refrigerated storage. If there is a temperature event such as heat exposure outside the recommended range (usually 2°C to 8°C/36°F to 46°F) followed by refrigeration or a freeze event followed by a thaw, damage to the product can go unnoticed.

This article focuses on the recent research done on the impact of temperature damage, or perceived temperature damage, during shipping and handling in the United States.  Vaccines are the subject of the following studies and the target of the WHO and CDC requirements because they are broadly distributed and affect a large percentage of the population, but it is important to note that it is equally important to manage, control and monitor the distribution of other temperature sensitive medical products, biologicals, drugs and medical devices. 

The inconsistencies of the storage and handling of vaccines in the United States have been the focus of recent studies: two conducted by the Association of Immunization Managers (AIM) and one by the California Department of Public Health. AIM is a non-profit organization created in 1999 in a cooperative agreement with the US Center for Disease Control (CDC). Its members include all 64 state, city and territorial National Center for Immunization and Respiratory Diseases (NCIRD) immunization grantees that work together to effectively prevent and control vaccine preventable disease and improve coverage in the United States and its territories.

1) AIM Study: Problems Associated with Vaccine Storage & Handling Policies
A study conducted by AIM examined the problems associated with vaccine storage and handling policies among the immunization programs in the United States. Every day, immunization program managers must make difficult decisions concerning the course of action when storage failures occur.  The critical questions are whether or not vaccines have been exposed to heat or freeze events, have these vaccines been damaged, and should they be discarded.  If the vaccine has lost enough potency, it will not effectively protect patients against communicable diseases.  In the absence of definitive information, providers and AIM program managers make the most conservative decisions that support patient safety to avoid the need to revaccinate.  As such, in many instances good product is discarded, reducing supply unnecessarily. A major finding of this study was that little or no evidence-based guidance is available to help immunization program managers make these important decisions. As a result, there is considerable inconsistency in how these decisions are made across states.

2) AIM Study: Understanding and Characterizing Wasted Vaccine
Another AIM study was conducted among the United States immunization programs to understand and characterize vaccine waste resulting from storage failures in an eight (8 week) period. Common events affecting the vaccine were vaccine left outside of refrigeration that was exposed to ambient temperature, or vaccine in poorly controlled refrigerators that was exposed to freezing. The study found that one (1) in five (5) events related to vaccine left out of refrigeration with the vast majority being an exposure to ±72°F for up to 72 hours, perhaps resulting in heat damage to the vaccine which could render the vaccine ineffective. The other events were caused by transportation methods and refrigerated storage practices that resulted in freezing and loss of vaccine potency. Much of the cost associated with damaged or potentially damaged vaccine can be avoided with a strong national policy on qualified storage equipment and monitoring practices.  When temperature abuse is suspected, without any way to verify (or quantify) the abuse, vaccines are discarded.

3) California Department of Health Study: Importance of Storage and Handling
A study performed by the California Department of Public Health, Immunization Branch, examined the importance of storage and handling and the need for policies and recommendations that are better aligned with available science. Study data indicated that many millions of dollars of vaccine are wasted each year due to poor handling and storage practices that result in the freezing of vaccine which irreversibly reduces vaccine potency. In one clinic the refrigerator repeatedly dropped below freezing over a 17-month period without being noticed. The study found:

·         Many refrigerators are over-stocked limiting air circulation which may cause some vaccine to freeze while other vaccine is too warm.

·         Dorm style refrigerators do not have long-term storage capabilities

·         Combined refrigerator/freezer units with a single door do not maintain appropriate temperatures and, are problematic because of the method of cool air flow creates hot spots and frozen zones and dripping condensation can damage vaccine packaging.  

·         Medical specialty equipment while expensive performs best, but the study indicated that some less expensive single purpose units for home use may be acceptable.

WHO Case Study

The World Health Organization (WHO) has actively participated in the storage and transportation of the vaccine that is used in its worldwide expanded program on immunization (EPI) vaccination campaigns. The WHO is currently considering a “two-temperature” cold chain:

1) Freeze-sensitive vaccine transported with chilled water packs and/or at ambient temperature and a vaccine vial monitor (VVM) on each unit of vaccine.

2) Heat-sensitive vaccine (that is not freeze sensitive) transported with frozen ice packs and a VVM on each unit of vaccine.

The WHO has been using VVM on each vial of vaccine in EPI vaccination campaigns since 1996.

Vaccines for Children Case Study

In the US the CDC requires its distributor of vaccine for the Vaccines for Children (VFC) Program to insert a cold chain monitor (CCM) in each box of vaccine for the transportation from the distributor to the distributor’s point of delivery. There are three basic types of CCMs:

1) Those that indicate whether packages have reached temperatures that are too warm

2) Those that indicate whether packages have reached temperatures that are too cold

3) Those that continuously record the temperature.

These types of monitors are designed to be irreversible indicators of inappropriate temperature exposures.

Currently, McKesson is distributing the vaccine to VFC providers using two (2) indicators in each box of vaccine shipped: a FREEZEmarker^® that changes color to show a freeze event at 0°C and a MonitorMark™^® set to signal at 10°C in 48 hours to 7 days. This “first leg” of the distribution chain is monitored, but there is no requirement or standard for continued monitoring of the vaccine after that. Even without a requirement from the CDC, some local immunization programs have recognized the storage related dangers and have taken steps to continue the monitoring until the vaccine is administered.

Significant progress toward establishing a secure distribution chain of temperature sensitive medical products, reducing risk, and protecting patients can be accomplished with the adoption of policies and requirements for cold chain management, including:

• Adoption of standards for equipment used in storage and handling of temperature sensitive medical products, and
• Requiring monitoring of the cold chain, from beginning to end, so that potentially damaged products can be identified and
  • Removed from the supply if adulterated by temperature damage, or
  • Used if their efficacy has not been materially affected.