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Your Current Monitoring May Not Be Good Enough For COVID-19 Vaccines

Introduction

The Vaccines for Children Program (VFC) is a federally funded program in the United States, providing vaccines to children who lack health insurance or who otherwise cannot afford the cost of the vaccination. In this program, the vaccine is provided at no cost to the states, and the states must develop the capability to administer it. Every state has a VFC program. The government has recently announced that the VFC infrastructure will serve as a key delivery mechanism for the COVID-19 vaccines.

Specific storage conditions are required to maintain the viability of vaccines–most must be stored at refrigeration temperatures (3C-8C). A critical but flawed aspect of the VFC program is the CDC defined standards for assuring this is done.

CDC guidance calls for the use of digital data loggers (DDL), sampling rates of 15 to 30 minutes, twice daily check-in (during business hours), and the use of a temperature buffer. In reviewing global standards we find they are all very similar to this.

Beginning with an audit by the Office of Inspector General in 2012, followed by numerous independent studies, one of which was conducted by one of the authors and published in a peer-reviewed journal in 2016 these practices have been shown repeatedly to allow a substantial portion (30% or more) of the vaccine inventory to be compromised without the vaccine manager necessarily being aware of it.

While this is clearly a problem for measles and chickenpox, it would be a disaster for a COVID-19 vaccine.  Fortunately, current technology provides a solution to this problem that can absolutely assure the efficacy of the vaccine, and notify the vaccine manager immediately if it is in danger of being compromised. This paper describes the features of a “no compromise” state-of-the-art solution available with today’s technology.

Overview

In the US, the Center for Disease Control and Prevention (CDC) has provided guidance for vaccine storage and handling, and in conjunction with the National Institute of Standards and Technology (NIST), has developed the standards for monitoring storage conditions that are used within the VFC program. These specifications have become the basis for much of the standards in pharmaceutical monitoring. In summary, they involve

  • use of a digital data logger to establish a record of the storage temperature
  • twice daily check-ins to record the temperature during normal business hours
  • inserting the temperature probe in a “buffer” vial to approximate the temperature of the stored product, not the air.

The CDC readily admits that these standards were developed to allow for the capabilities of the least sophisticated vaccine administrators in the nation. The “holes” in this protocol are obvious:

  1. The sample rate of the data logger is not adequate and can be as long as 30 minutes
  2. Twice daily check-in of the current temperature will not notice temperature excursions that occur in between check-ins and then remediate themselves.
  3. The size and geometry of the vial used as a temperature buffer is not specified and may not correspond to the size and geometry of the drug vials. There may also be vials of different sizes in the same storage unit, all of which can not be accurately represented by a single buffer vial. Consequently, the temperature read in the buffer vial may not represent the experience of the actual vaccines.

While the CDC guidance has been updated every year, they still do not fully exploit the capabilities of the most current technology, and continue to allow risks to the stored product. As mentioned above, this is by design in order to define a set of practices that can be followed reliably by everyone in the country. While this may be the appropriate trade-off for less critical vaccines, it is wholly inappropriate for the COVID-19 vaccine. If someone is unknowingly given a compromised measles vaccine, there is a high probability they won’t get measles anyway because of the herd immunity in most parts of the US. If that occurs with the COVID-19 vaccine, there is a very good chance people will get sick and some will die. It would be an improvement if the monitoring protocols were “smart” enough to notify the vaccine manager that the product has been compromised, but that would still result in a reduction in the available supply of what will almost certainly be a seriously constrained supply system.

Given the higher value of the stored good today (e.g., oncology drugs, bio-similars, human tissue, etc.), more advanced methods using some version of continuous monitoring are already widely deployed. The rest of this paper will describe the features of the only kind of monitoring system that would be suitable for use with the COVID-19 vaccine—absolutely foolproof.

Real-Time Monitoring

The most fundamental requirement for a COVID monitoring system is real-time monitoring, with sample times of 5 minutes or less. The aforementioned OIG audit stated the following regarding the effectiveness of periodic checks during the workday:

“Although the majority of storage temperatures we independently measured during a two week period were within the required ranges, VFC vaccines stored by 76% of the 45 selected providers were exposed to inappropriate temperatures for at least five (5) cumulative hours during that period” (Office of Inspector General, 2012)

Real-Time Data Analysis

The recommended sampling rate also allows for prompt trend analysis to identify developing problems before they jeopardize the inventory. The data not only needs to be reported in real-time but analyzed in real-time. A 15-minute sampling rate could take 3 times as long to identify a trend.

Real-Time notification of problems

These capabilities would have much less value without prompt notification to the vaccine manager. Real-time notification via text message, email, or phone call is essential to preventing problems rather than just finding them. The “alerting” function should be delivered in a form that reaches out to the designated manager via phone call, text message, and/or email to ensure it’s receipt, and should require an active acknowledgment.

Support for all necessary sensors

The system should support all the temperature sensors required for every vaccine environment, from 8C to -80C at a minimum, and possibly  -192C.

Selection of an appropriate temperature buffer

The CDC requires the use of a temperature buffer to simulate the experience of the stored product and not respond to transient changes in air temperature. The correct selection of a buffer that matches the size and geometry of the vaccine vials is of critical importance. When poorly chosen, this can be a source of significant misinformation about the vaccine environment. More problematic are situations in which the vaccine may be in different size containers in the same storage. While this situation can not be accurately simulated physically, there are mathematical solutions that can do so (Rusnack, 2020)

Ability to be deployed rapidly and operate in any situation

Everyone agrees that the existing vaccine distribution infrastructure, including the people,  will not be enough for the volume of COVID-19 vaccines. The rapid expansion of infrastructure will require a monitoring system that can be quickly deployed, can work anywhere from a hospital hallway to a school parking lot, and can be easily used by anyone with a half-hour training or less. The system features that support this are:

A cloud-based system. This eliminates the need for hardware to store the data and is instantly available and scalable.

  • Cellular communications. The other options are wired or WiFi. A wired system, if not already in place, would be expensive, time-consuming, and not applicable to all possible situations. WiFi is a definite improvement over wired, but requires a technical infrastructure of routers and often significant networking expertise to manage. Cell-based communications do not need any of this, and can operate anywhere there is cell service.
  • A phone-based app to use the system. While the system may also be accessible with a laptop or iPad, a phone would provide a single, consistent interface with a system that would work anywhere.
  • Clear, intuitive data presentation when needed. Ideally, a system user would never need to look at any of the data detail. They would only have to respond to alerts. Unfortunately, there are situations that will require access to detailed data. One is the CDC requirement that vaccine managers in the VFC program actually look at the data twice a day, and document that they have done so. This is completely superfluous, but the requirement exists. The best solution is a system that makes this as easy as possible. The other situation occurs when it might be necessary to diagnose the underlying reason for a temperature excursion. In this case, the necessary data should be accessible on the mobile app, and available in graphic form to identify patterns and trends.
 

Reliability

Finally, since no monitoring system helps when it is not operational, vaccine managers should look for a demonstrated minimum of 99.999% uptime. This level of reliability is available today, and is primarily a result of two things:

Self Monitoring Capability – The system should not only notify vaccine managers of problems with the drug storage conditions, but also of any problems with the monitoring system itself. These conditions should include:

  • Low battery
  • No AC power (when operating on wall power)
  • Immediate notification of any problem with the temperature sensor causing loss of connection
  • Probe disconnection
 

System Architecture – The system should be designed with as few single points of failure as possible. The use of cloud-based services can eliminate many of those potential failure points, such as specific servers. This use of multiple servers for data storage should be transparent, seamless, and spread across different regions. In addition, the system should have an automatic failover to battery in the event of loss of wall power (when operating on AC), and the ability of the sensor to store data locally in the event of loss of connectivity.

Conclusion

This paper outlines the ideal system for monitoring the efficacy of COVID-19 vaccines during storage and transport. A system with all of these capabilities will necessarily be more expensive than the most basic, data-logger based systems, but usually not high-cost in the context of other associated expenses. If there was ever a case for investing in such a system, this is it.

By Ray Sasso, CEO

 

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CDC. n.d. “Historical Vaccine Safety Concerns.” Vaccine Safety. https://www.cdc.gov/vaccinesafety/concerns/concerns-history.html.

 

—. 2020. “Vaccine Storage and Handling – Chapter 5.” Epidemiology and Prevention of Vaccine Preventable Diseases. July. https://www.cdc.gov/vaccines/pubs/pinkbook/vac-storage.html.

 

—. 2020. “Vaccine Storage and Handling Toolkit.” January.

 

Office of Inspector General. (2012, June 5). Vaccines for Children Program: Vulnerabilities in Vaccine Management. U.S. Department of Health and Human Services.https://oig.hhs.gov/oei/reports/oei-04-10-00430.asp

 

Rusnack, Michael. 2020. “Virtual Temperature Buffering.” https://community.ameri-pharma.com/2020/02/20/virtual-temperature-buffering/

 

 

Real-Time RT-PCR Panel for Detection 2019-Novel Coronavirus

Purpose: This document describes the use of real-time RT PCR (rRT-PCR) assays for the in vitro qualitative detection of 2019-Novel Coronavirus (2019-nCoV) in respiratory specimens and sera. The 2019-nCoV primer and probe sets are designed for the universal detection of SARS-like coronaviruses (N3 assay) and for specific detection of 2019-nCoV (N1 and N2 assays).

Protocol Use Limitations: The rRT-PCR assays described here have not been validated for platforms or chemistries other than those described in this document.

 

Below is a list of necessary equipment, supplies and reagents with links to the products that Southern Labware can provide for you.

 

Reagents and Supplies

Equipment