In our application notes and articles on validation, we usually stay at the level of principles and best practices because every application is different. The regulations published by the FDA and EMA, as well as other regulatory agencies such as SFDA and PMDA, are written broadly for just this reason: the needs of each product and the parameters of each environment will, more than any other factors, determine how you will apply the practices described in regulations and guidance.
Having said that, along with providing monitoring and validation systems, we enjoy delving a little deeper into some of the issues that come up in the validation applications of our customers and contacts. We often receive questions from customers in logistics regarding simulating a worst case scenario as a method for qualifying containers used to transport pharmaceuticals. In this article we discuss considerations for qualifying a transport container that will be used for regulated products like pharmaceuticals, medical devices, or biologicals/HCT/ps.
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Route & Time Span: Consider a situation where you are attempting to simulate the circumstances of a transport application by
performing a mapping study of a transportation vehicle. The vehicle –
let's say a one-ton truck – must be qualified with an IQ/OQ/PQ in both
empty and loaded conditions. So, the first question we ask is: Is it necessary to perform the study along
the actual distribution route?
Many customers trying to lean out their validation processes have asked us: Is it effective to
simulate the distribution route, I.E., parking with engine on,
cooling/heating unit power on?
Well, let's imagine a case where the route is domestic and approximately four hours in transit. To simulate the route, you want to design a test method based on the
worst-case that could be encountered on that route. For instance, one worst-case scenario is that due to traffic problems (or some similar delay) the truck ends up sitting in full sunlight during the hottest part of
So, to profile the scenario for a longer-than-expected transit time, it's justifiable to create a simulation where you map for six hours, while
the truck is sitting out under the sun for the hottest part of the day. You will get key information from such a test.
Actual Product or Analog in Loaded Conditions: Another question on simulation is whether to use actual product in your studies? Obviously you can't put actual product at risk if you are stress testing to a point of failure. You can't afford to lose the produce. We suggest using a simulation product, because we are only trying to mimic the thermal response of a given
product, not its chemical properties. For the chemical properties we look to the stability testing data of that product, and that
data informs your product’s specifications: I.E., Between 2°C and 8°C.
Simply challenging a material with similar thermal behavior would
be sufficient to qualify the trailer under the worst conditions it will
encounter; the maximum length of shipping time and the hottest or
coldest temperatures along the route.
Options upon Establishing a Point of Failure: If you challenge the route, the shipping equipment, and timing only to find that the temperature cannot be maintained within
specifications over the route, you have several options. But the first and most critical point of validating the scenario is to KNOW what you are testing for... so that when a failure (Out-of-Spec conditions) occurs, you will know what element of your shipping application to fix.
For example, you may need to adjust
the truck’s cooling system settings and retest. Or, the cooling system
of the trailer may need maintenance. It may even be that you need a different truck, a different
route, or a different packing system. Just be certain you don't end up fixing an element of the shipment that didn't actually cause the out-of-spec conditions.
Remember: THIS is the purpose of a mapping
study! Identifying the weakest points in your shipping application was why you decided to create worst-case scenarios. You are looking for where the failure happens so you can offset or eliminate it as a risk.
The goal of validation is defined as:
"The action of proving, in
accordance with the principles of GDP, that any procedure, process,
equipment, material, activity or system actually leads to the expected
results. It is a process using documented evidence that provides a high
degree of assurance that a specific process will consistently produce
the predetermined outcome." - WHO guide Quality Assurance for Pharmaceuticals
Further Reading: Here are some great resources on validation to review and reference in your mapping documents: