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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Worst Case Scenario Simulation:
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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 the day. 

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:

The ICH Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients. ICH Harmonized Tripartite Guideline 2000 (Q7a) requires that facilities, systems, equipment and utilities are properly qualified and maintained to assure data and product integrity.

Additional guidance is provided by the Pharmaceutical Inspection Co-operation Scheme PIC/S Recommendations contained in the document: “Good Practices for Computerised Systems in Regulated GxP Environments” (2007) in the section: “Validation Strategies And Priorities.”

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Please refer to our other validation guidance and recorded webinars.