Cold chain

Cold chain

Antibodies to a virus or bacteria are produced by the body when you get an infection. Thus, our bodies develop immunity to the virus. 

During the first months of life, an infant is protected against many infections by antibodies acquired from the mother. The infant starts developing antibodies on its own, either following each contact with a virus or after immunization. 

All vaccines are sensitive biological substances, which lose their potency with time, but this loss can be accelerated when exposed to temperatures higher or lower than those recommended by storage conditions. When a vaccine is damaged by exposure to higher temperatures, light, or freezing, its potency is lost and can never be restored. The damage is permanent; returning the vaccine to correct storage conditions cannot restore it. It should also be understood that exposure to adverse temperatures has a cumulative effect, i.e. the degree of cumulative damage is defined as the number of times a vaccine has been exposed to an inappropriate temperature and the duration of each case. In this case, due to cumulative damage, the vaccine could lose its potency. 

It should be understood that even when stored at proper temperatures, vaccines retain their potency during the defined period. That is why we always take the shelf life specified on the label into account.  
 
Cold chain 

The cold chain is the system used to maintain appropriate conditions during the storage and transport of immunobiological products from the manufacturer to the person being immunized.

The cold chain consists of several components, all designed to ensure safe storage and transport of immunobiological products to patients, such as personnel that maintains the equipment and provides the health service; equipment for storage and transportation (refrigerated trucks, cold boxes, refrigerators, freezer containers, etc.); procedures to manage control over distribution and use of the vaccines. 

The cold chain has the following levels: 

• 1st level: vaccine manufacturer; 

• 2nd level: wholesale warehouse; 

• 3rd level: regional and urban healthcare facilities; 

• 4th level: vaccination rooms in medical and preventive treatment institutions. 

Different cold chain levels require special storage conditions provided by different refrigerating equipment depending on the vaccine volume, its shelf life and storage temperature. All equipment should meet the requirements for the safe storage of vaccines regardless of fluctuations in outdoor environmental conditions. 
The cold chain must protect the vaccine from heat and light. Also, we should not forget about transportation during the winter period when the air temperature drops far below 0 °C. In this case, measures to prevent vaccines from becoming too cold should be taken. Cold boxes and insulated shipping containers can be used to give the required protection. 

Delivery time is one of the critical steps in the transportation process. An investigation of several events of cold chain breaches during transportation and, as a result, the loss of vaccine quality, has demonstrated that mistakes are made at the stage of shipment date approval. For instance, a vaccine was shipped on Thursday, arrived at a particular airport on Friday at the end of the working day, and was collected only on Monday. To avoid such situations, many European distributors ship products only on the first days of the week. 

The cold chain, ensuring the appropriate storage conditions at all levels and the identification of critical stages of transportation, guarantees the quality of the vaccine delivered to a patient. 

Vaccine freezing 

Most vaccines are often stored in ordinary domestic refrigerators; you can see this in the majority of pharmacies. The temperature in these refrigerators must not be below 0°C. The lower temperature limit of 0°C is very important. Most of the vaccines are freeze-sensitive, including DTP, Td, DT, TBE vaccines. Studies performed by WHO together with the Serum Institute of India demonstrated that freezing of vaccines containing tetanus toxoid caused irreversible loss of their effectiveness. 

However, some vaccines can sustain freezing without any damage, for instance, Mumps, Measles, and OPV. 
Failure to comply with storage and transportation conditions may lead not only to the reduction of the therapeutic properties of vaccines and anatoxins but also to the occurrence of unexpected nonspecific adverse events (The Order of MoH No. 595). 

Failure to comply with storage and transportation conditions may lead not only to the reduction of the therapeutic properties of vaccines and anatoxins but also to the occurrence of unexpected nonspecific adverse events (The Order of MoH No. 595). 
 
Table 1. Sensitivity of vaccines to freezing (according to WHO/EPI/LHIS/98.02) 

Note: all vaccines freeze at temperatures just below zero. 

• BCG and measles vaccines must not be frozen after reconstitution; 

• Diluent for any vaccine must never be frozen. 

According to the WHO, cases of vaccines freezing in the cold chain have been recorded in many countries around the globe. As it turned out, using ice packs to freeze the vaccine in countries with a hot climate is the main threat, and an inspection of doctors' offices showed that the majority of vaccines were stored at a temperature below 2 °C. 

Importance of temperature monitoring  

As a rule, it is impossible to determine visually whether a vaccine was exposed to adverse conditions (temperature, light, etc.). If a vaccine loses some or all of its potency, its outward appearance may be unchanged in most cases. Only a competent laboratory equipped with appropriate equipment can conclude if a vaccine is safe for use. And this brings up the question of how a patient can know whether the storage and transport conditions have been met. 

According to WHO requirements, every vaccine dose delivered to the person being immunized must be accompanied by temperature indicators. While meeting these requirements, every patient will be able to check if storage and transportation temperature requirements have been met and feel safe when getting vaccinated. Temperature indicators should be kept near each batch of a vaccine, anatoxin, or tubercular allergen. Cold chain monitor cards and freeze indicators have to be placed in the lower and upper parts of the shipping container.  

There is an opinion that using such a quantity of indicators will significantly increase the cost of a vaccine. In this situation, it would be helpful to look at the matter the other way round. In the case of failure to ensure temperature requirements during transport of a large vaccine batch, it is possible to check each separate dose and identify the number of doses subject to adverse environmental conditions, thereby reducing financial losses.  

According to experts, in the near future of global practice, each vaccine dose will be equipped with a tiny electronic temperature indicator, which will be included in the package and activated by the manufacturer during the manufacturing stage.