TechNet-21 - Forum

This forum provides a place for members to ask questions, share experiences, coordinate activities, and discuss recent developments in immunization.
  1. Larry Schlussler
  2. Cold chain equipment
  3. Tuesday, 28 October 2014
  4.  Subscribe via email
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.
Attachments (1)
Larry Schlussler Accepted Answer
0
Votes
Undo
MKT temperature measurements could be displayed for both a 24 hour period and a 30 day span. The 24 hour measurement would alert to immediate problems and the 30 day monitor would give a better indication of how long term variations in storage temperatures are effecting the life of the vaccines. This single reading of the average 30 day MKT temperature would be simpler to interpret than recorded data showing the minute by minute temperature variation for a 30 day period. From my understanding the MKT and VVM give equivalent information, one is analog and one is digital. For example when a vaccine is produced a small MKT thermometer could be attached to a vaccine vial. If, after 30 days, the MKT temperature is 12 deg C at this temperature the Arrhenius graph for a VVM-2 (attached) indicates that the life of the vaccine is 60 days. Since the vaccine was exposed to this MKT temperature for 30 days the percent of life lost would be 50%. This should correspond with percent loss of life obtained by measuring the density of the center circle on a VVM. Twenty four hour MKT temperature could be used in conjunction with a maximum and minimum temperature alarm to indicate equipment problems rather than temperature alarms based on elapsed time and temperature thresholds. MKT temperature readings would give a more accurate indication of thermal stress on a vaccine in an easier to implement form. I just received the new proposed PQS standards for SDD refrigerators. MKT temperature will be used to measure the performance of SDD refrigerators, using MKT thermometers to measure the performance of a refrigerator in the field would be consistent with this standard.
Attachments (1)
  1. more than a month ago
  2. Cold chain equipment
  3. # 1
Joanie Robertson Accepted Answer
0
Votes
Undo
From a technical standpoint, I think the idea of basing alarms on MKT is quite interesting, but there are a couple concerns that I would expect to come up in a broader global consultation. I list them below for your consideration. • What is the right period for measuring the MKT? A longer period MKT makes more sense to me than a 24 hour one, because vaccines will be in refrigerators for much longer than 24 hours, and I would think you would want assurance over the period that your vaccines are stored. Maybe a rolling 30 day MKT or even 60 day? What are the implications to making it longer? • I’m wondering about how broad the applicability could be? Currently WHO sets out a recommendation for temperature alarms based on elapsed time within certain thresholds. I think this is in the 30 day temperature monitor specification on PQS. Could the standard be changed to an MKT measure? Would the 30-day temperature monitors be able to comply? Is it possible/desirable to have parallel standards? These are not questions I can answer but ones that should be debated by the broader community.
  1. more than a month ago
  2. Cold chain equipment
  3. # 2


There are no replies made for this post yet.
However, you are not allowed to reply to this post.