VVM’s and MKT are equivalent methods of measuring the effect of temperature variations on vaccines. VVM’s & MKT measurements can be used in a complimentary manner, the VVM’s give information on the life of individual vaccine vials. MKT measurements can be used to effectively measure the performance of equipment and the effect of short temperature excursions. The MKT is defined as “A single derived temperature that, if maintained over a defined period of time, afford the same thermal challenge to a drug substance or drug product as would be experienced over a range of both higher and lower temperatures for an equivalent defined period. The mean kinetic temperature is higher than the arithmetic mean temperature and takes into account the Arrhenius equation“(Seevers, Robert H., Ph.D. "The Use of Mean Kinetic Temperature (MKT) in the Handling, Storage, and Distribution of Temperature Sensitive Pharmaceuticals. “Pharmaceutical Outsourcing (2009): 30-35. Web. 9 Oct. 2014.) The paper was referenced in the PQS type-testing protocol for solar powered refrigerators with rechargeable batteries (E03/RF04-VP.2). The attached Arrhenius graph for a sensitive VVM-2 vaccine shows the relationships between temperature and vaccine life. The graphs are generated for vaccines of different sensitivities. If the vaccine is exposed to changing temperatures the MKT can be used in conjunction with the Arrhenius graph to determine the life of the vaccine. For example, if a temperature sensitive vaccine, VVM-2, spent half its life at 5 C and half at 20 C its average temperature would be 12.5 C and the MKT would be 15.4 C. Under these conditions the Arrhenius graph could be used to determine the life of a newly produced vaccine is 40 days. Direct Reading MKT Thermometer for Alarm Control: With modern electronics a small device could be built to directly measure MKT. For example, the performance of a refrigerator in a clinic could be monitored to assure it is performing properly. The MKT could be measured for a 24 hour period. To obtain 24 hours of data a data point is recorded every 10 minutes. The data is updated every 10 minutes by measuring the current temperature and deleting the reading taken 24 hours and 10 minutes ago. The MKT would then be recalculated and displayed. This method would give a clear picture of the impact of temperature excursions, eliminating false alarms. If, for example, a refrigerator typically storing vaccines at 4 C experienced a 1 hour temperature excursion to 20 C the MKT temperature for that day would be 5.5 C and the excursion would not impact the life of the vaccines. In this case there would be no need to set an alarm off. If the vaccines are exposed to a 20 C temperature 2.5 hours the MKT temperature will reach 8 C. An alarm could then be set off. This technique would work equally well if the temperature varied during the temperature excursion. In a recent comment Oz Mansoor pointed out that a short temperature excursion can be of no importance and the inadvertent alarm should be avoided. The MKT temperature is an easy to interpret analytic method to determine if there is a potential storage problem. There could also be a button on the device to display the MKT temperature for the past 30 days, so that performance could be evaluated for a longer period of time. An additional built-in alarm could indicate if the refrigerator temperature varied beyond some extreme high or low setting. MKT Temperature and Vaccine Carriers: Measuring the MKT temperature for a short trip would be helpful in evaluating the performance of a vaccine carrier and the impact of temperature excursions on the vaccines on an actual trip. For example, for a 6 day trip if the temperature in the carrier increased linearly from 4 C to 27 C the MKT temperature over 6 days would be 18 C. From the Arrhenius graph for a VVM-2 vaccine in stage 1 the vaccine should have a life of 28 days when stored at 18C. The trip should then not have a significant effect on vaccine effectiveness. The use of an MKT thermometer would also be of value for the controlled temperature chain (CTC). MKT Temperature for Testing Refrigerators: The MKT temperature is currently being used for PQS testing to a limited degree. For solar powered refrigerators with battery storage it is used to measure the temperature of the refrigerator compartment during the day/night temperature test. Extending the use of the MKT to other tests such as the stable run test would have numerous advantages without sacrificing the efficacy of vaccines. Suppose a refrigerator manufacturer is having a chest SDD refrigerator tested, and during the stable run test the temperature at the top of the storage area climbs from 4 C to 12 each night. To maintain the storage areas in the 2 C to 8 C temperature range they may opt to add a fan and ancillary battery to eliminate stratification. They may also opt to reduce the daytime running temperature to close to 2C to minimize the night time temperature excursions above 8 C. With the minimum temperature reduced it is more likely that under atypical conditions freezing conditions could be reached. Assuming that each night the temperature increases linearly from 4 C to 12 C for 12 hours the 24 hour MKT would be 7 C. The performance of the refrigerator would then be the same as a refrigerator kept at an accepted constant storage temperature of 7 C. The additional proposed modifications (fans, ancillary batter, etc) would be unnecessary. The consequence of not using the MKT temperature can be a more complex expensive and less sustainable product. Extending the use of the MKT temperature to other PQS tests would result in superior less expensive products without sacrificing performance or vaccine safety. Sun Frost Larry Schlussler, Ph.D.
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