Introduction
What is Cold Chain
This is the maintenance of ideal conditions of vaccines from the place of manufacture to when it is administered. The manner of storage, transportation and handling of these vaccines is critical to preservation of a cold chain and must be done properly.
Why maintain Cold Chain
A breach in cold chain can occur if the vaccines are exposed to light or unsafe temperatures arising from power outages, human errors, and equipment failure. To appreciate the importance of maintaining a cold chain, a good understanding of the nature of vaccines is important. For example, inactivated vaccines when subjected to extreme temperature (high or low) variations can adversely affect the quality of such vaccines and consequently will not offer protection to the individual to be immunized. mRNA vaccines unlike vaccines that are protein-based can be destroyed very easily because of the very numerous enzymes contained in them. No wonder the two leading vaccines against COVID-19, Moderna’s and Pfizer vaccines is a concern for many countries of the world including rich countries as they require a storage temperature of -20℃ and -70℃ respectively.
Unfortunately, countries who are still developing have inadequate temperature-controlled storage for an immunization campaign to control COVID-19 and this could result in the poor being unable have access to these vaccines and remain unprotected against the deadly virus.
When vaccines are effective due to maintenance of cold chain, it leads to high level of public confidence in their usage. A high level of acceptability of vaccines will prevent hundreds of thousands if not millions from vaccine preventable diseases and less people would visit the clinics thereby saving cost.
How to determine a broken cold chain
Shake test and Vaccine Vial Monitor (VVM) can be used to check if a vaccine is safe to use or not.
- Vaccine Vial Monitor (VVM)
Vaccine vial monitor is a white and small square label in coloured circle placed on a vial containing vaccine which is sensitive to temperature rise above a specified temperature range and changes colour when exposed to temperatures too high for a period.
It is a temperature sensitive label placed on vaccine vials which shows if the vaccine has been preserved at a temperature which preserves its quality. VVM is present at every process from distribution to administration of the vaccine showing if the vaccine has been exposed to immoderate temperature over time and whether it is possible to have been damaged. By observing a VVM, health workers are easily able to check whether or not a vaccine have been exposed to unsafe temperatures and the extent of damage to a vaccine.
The idea of VVM was gotten from a related method used to label and guard food which are refrigerated during transport. This system was simple but effective. The idea seemed easy but reality was difficult. Till date, only Temptime, has been able to make the technology in such a way that it can work on vaccines.
However, it took more than three decades to turn this idea into a common practice once the technology was perfected. In developing countries where even a little increment in vaccine price was a burden they hesitated to bear. Though the vial monitors was not so expensive but still it was an increase in price which became a burden to overcome.
Interventions from Organizations like the World Health Organization (WHO), (Programme for Appropriate Technology in Health) (PATH), the United States Agency for International Development (USAID), the Global Alliance for Vaccines and Immunization (GAVI), United Nations Children’s Fund (UNICEF), and the Centers for Disease Control and Prevention among others, helped to prevent VVM pricing problem.
According to UNICEF and WHO, the global health community saves $14 million and more each year by preventing the discard of undamaged vaccines since the start of the use of VVMs on basic vaccines.
VVM prevent good vaccine from being wasted. Vaccine vial monitors ensure that children use only efficacious and safe vaccine. It helps health workers to ascertain if the vaccine has been protected from heat sufficiently to be used. Previously, it was impossible to check the level of heat exposure of vaccines.
Vaccinators as well as storekeepers can determine the level of exposure of vaccine vials to heat in order to know which vials have experienced more heat exposure than the others. Vials with higher level of heat exposure should be used before vials with lower heat exposure. In this way, health workers and storekeepers can minimize the number of vials which have to be rejected. This will also decrease vaccine wastage.
Figure 1: Vaccine Vial Monitor indicating no heat exposure. (WHO, 2002)
It is structured as a circle which has a small square inside it as shown above. It can be printed on the label of the product. It can also be attached to the vaccine vial cap or to an ampoule neck.
How the VVM works
VVM is a small coloured circle printed on the label of vaccine vials. It changes colour on continuous exposure to heat. If it is kept cool after it leaves the factory, the monitor changes colour slowly, it changes colour faster as the level of heat exposure increases. When the vaccine has been exposed to a significant amount of heat, the monitor signals that the level of heat exposure is already at maximum level and cannot be used anymore. In this case, the vial should be discarded. It is important to note that VVM cannot be used to determine the potency of the vaccine but it provides information about the most important factor that affects vaccine potency which is the level of heat the vaccine has been exposed to overtime.
Figure 2: How to read and interpret the VVM (WHO, 2002)
The heat sensitivity of vaccines is used to classify them into four types and are VVM2, VVM7, VVM14 and VVM30. The VVM number is derived by observing the time measured in days it takes for the square inside the square to reach the color indicated at discard point on continuous exposure of the vial to a constant temperature of 37℃.
Table 1: VVM reaction rates by category of heat stability
| Category | No. of days to end point at +37oC | No. of days to end point at +25oC | Time to end point at +25oC |
| VVM 30High stability | 30 | 193 | > 4 years |
| VVM 14Medium stability | 14 | 90 | > 3 years |
| VVM 7Moderate stability | 7 | 45 | > 2 years |
| VVM 2Least Stability | 2 | NA | 225 days |
The reactions of VVM to which vaccines are assigned are dependent on the category of the vaccine. The most sensitive vaccine OPV is assigned VVM2, which takes 48 hours at 370C to reach its end-point. VVM 30 is assigned to Hepatitis B vaccine as it takes 30 days to reach its end-point at 370C, it is one of the most heat stable vaccines. Vaccines manufactured by different manufacturers may have different heat stability characteristics and may therefore be assigned to different categories by WHO. Manufacturer A’s Polio vaccine might use a VVM 30 while manufacturer B’s Polio needs a VVM 10.
The color on VVMs can be used to determine which vaccines to be used first. When there are vaccines in which the square in the VVM is darker but are lighter in colour compared to the outer circle should be used first.
- ii) Shake Test
Freezing of some vaccines can destroy them which makes them lose potency and potency once lost cannot be regained. The aim of performing shake test is check if an adsorbed vaccines have been frozen anytime in the past. T Series vaccines (DPT, DT and TT) Typhoid and hepatitis B vaccines can be damaged due to freezing. it is not to be performed for OPV, measles and BCG vaccines.
Procedure of a shake test:
- Take the vial which is suspected to have been damaged due to freezing.
- Take another vaccine vial of same batch and manufacturer and label properly as ‘control’.
- Freeze the control and thaw at room temperature.
- Shake both vials rigorously
- Place both vials against a source of light and place them on a flat surface side by side. Compare both vials by observing their sedimentation rates.
- If frozen vial sediments faster than test vial then use your test vial.
- If both vials have similar sedimentation rates. Discard it.
What makes an effective cold chain
For a cold chain to be effective, three key factors are considered and these are i) People, ii) Cold chain equipment iii) policies, procedures and protocols.
- People: The key factor for a cold chain to be effective is well trained personnel who is aware of his or her roles and responsibilities in the cold chain. Health care professionals are trained in carrying out handling and storage of vaccines with a good knowledge on the nature of vaccines and requirements for storage of different vaccines. This is important because vaccines are delicate in nature to avoid wastage and loss.
Proper use of digital thermometers and data loggers, cold boxes, vaccine carriers, cold chain equipment maintenance and repair, inventory management, transportation of vaccines, response to handling, storage and disposal of vaccines require highly trained personnel to maintain a cold chain which is effective.
- Cold chain equipment
They are designed to transport or store diluents and vaccines within ideal temperature range. The capacity required determines the cold chain equipment that will be used. Larger stores generally use cold rooms or rooms whose temperature ranges from 0oC and below whereas smaller stores use vaccine refrigerators and freezers. For transporting vaccines between stores, larger shipment requires refrigerated trucks. Cold boxes kept in insulated vans are used for smaller shipments.
Two main types of cold chain equipment are refrigerators and passive containers which includes vaccine carriers and cold boxes.
Cold boxes are containers lined with ice packs to maintain cold chain of diluents and vaccines during temporary storage and transportation.
Ice packs are required to maintain temperature in cold boxes or insulated carriers. Some commercial ice packs containing chemical products are capable of maintaining temperatures below freezing temperature standing for longer hours than water-filled icepacks.
A digital, electronic or mercury/maximum thermometer and chart for recording daily temperature reading is essential for monitoring of cold chain during storage or transportation of vaccines.
Environmental parameters can be automatically monitored and recorded over a period of time electronically with the use of data loggers. Such parameters include temperature and humidity. It allows the conditions to be validated, analyzed, documented and measured. It contains a sensitive sensor which collects and a computerized chip to store it. Temperatures can be monitored over a 24-hour period or more especially when shipping vaccines from overseas with the data logger.
It cannot be overemphasized the need for trained personnel in handling cold chain equipment.
- Policies, Procedures and Protocols
For a cold chain management to be effective, there must be clearly written policies and protocols by government which must be followed. Health workers must adhere strictly to laid down procedures on temperature monitoring, equipment maintenance and repair, vaccine storage, response to handling and storage issues, disposal, inventory management and so on.
The National Agency for Food and Drug Administration and Control (NAFDAC), have guidelines for good cold chain management for vaccines and other biopharmaceutical products on their website (www.nafdac.gov.ng).
Conclusion
Cold chain management helps to keep vaccines in perfect condition as prescribed by the manufacturer. With this, it helps to ascertain that the vaccines are of safe and good quality for use. Cold chain management also prevent unnecessary loss of vaccines.
Adekunle-Segun.O., Omosimua Shedrack.O., Ajayi Toluwani
