From Smart Tags to Brilliant Tags: Advances in Drug Stability Monitoring

Nov 01, 2005
Volume 18, Issue 11

Envision some logical problems? What happens if the drug is stored at 9°C for one minute? Will the drug deteriorate into a less potent or even harmful form? What happens after one day at room temperature?

Present drug storage stability labeling has two types of problems. The first is that the labeling ignores well-known laws of chemical reactions such as the Arrhenius equation, and instead will typically take thermodynamically unrealistic positions (e.g., that 9°C is greatly different than 8° C). The second problem is that the labeling totally ignores human factors considerations. Clearly it is not possible for a health-care practitioner to take a drug from 2 to 8°C and instantly inject it into a patient. Rather, the drug will typically be removed from refrigeration, warmed to room temperature for some time, and then injected.

What if the drug is expensive and someone has left it out by mistake for an hour? Should it be thrown away or returned to the refrigerator? The attending healthcare worker usually makes decisions like this on an ad-hoc basis. But how can this be done on a rational or consistent basis? The nurse or physician isn't a stability expert, the detailed drug stability information is almost never published, and usually there is no precise record of how long the drug was left at an improper temperature.

One key aspect of the second human-factor problem is that the burden of making important drug stability decisions has been passed from organizations with a high knowledge of the drug's stability (e.g., the manufacturer) to healthcare workers with less knowledge of drug stability. The consequence of violating the labeling, which happens constantly because of unrealistic labeling, is guesswork concerning a drug's viability. Will the drug be only slightly less potent? Will the drug deteriorate into a harmful form? Is there a safety margin? Are busy health-care workers who have little information really the best people to make this decision?

In this instance, the third-world is actually somewhat more advanced than the first-world. Tropical medicine experts are well aware that present drug labeling is inadequate when drugs are stored under tropical conditions. As a result, they conduct their own independent stability testing and publish supplemental storage guidelines for tropical conditions.

The WHO mandate that all vaccines must incorporate chemical time-temperature labels that let users know if the vaccine has been damaged by heat suggests an interesting possibility. What if it was possible to put a stability-indicating time-temperature label on all drugs with marginal stability?

Unfortunately present chemical time-temperature indicators (cTTI) are not precise enough for these applications. cTTIs usually require users to do some sort of color matching comparison, which can be interpreted differently by different people. cTTIs have the additional problem that they cannot accommodate complex degradation kinetics such as when damage occurs at both low and high temperatures. In spite of these drawbacks, cTTIs are a step in the right direction.

In addition to cTTIs, many different time-temperature loggers are commercially available.5 Although highly accurate and capable of storing large amounts of temperature data, such loggers are not easy to use. The logger data must be downloaded, transmitted to a remote site where the data can be analyzed, and the results then transmitted to the user. Although well suited for monitoring shipments of bulk quantities of drugs, this is a cumbersome process not well suited for most everyday health-care applications.

The basic cTTI concept of an "instant stability assessment" is nearly ideal, but the flexibility and accuracy of this approach needs to be upgraded to meet the high accuracy demanded by therapeutic proteins and other modern drugs. Is there a way to utilize modern electronics to perfect this concept? Are more precise electronic time-temperature indicators (eTTI) feasible?

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