Worst Case Scenario Simulation: the deeper, darker side of Environmental Validation/Equipment Qualification

This week, in the wake of our Validation Webinar  our Senior Regulatory Expert Paul Daniel answers a more detailed question...

We often stay at the level of principles and best practices when discussing validation because each 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 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. In this week's blog, Paul answers a question on simulating a worst-case scenario as a method for qualifying a truck used to transport pharmaceuticals. Please comment in the field provided below if you have a similar question, an experience of your own, or more information.

Paul writes:
I received a question on simulating the circumstances of a transport application from a validation professional in the pharmaceutical manufacturing industry who was performing a temperature mapping test of a transportation vehicle. The vehicle – a one-ton truck – was to be qualified with an IQ/OQ/PQ in both empty and loaded conditions. He asked if it were necessary to perform the study along the actual distribution route. This would entail performing the study from the point of origin to the final destination. Is it allowable and feasible, he wanted to know, to simulate the distribution route, I.E., parking with the engine on, cooling/heating unit power on? His route was a domestic route, approximately four hours in transit.

My solution would be to simulate the route, designing a test method based on the worst case scenario that could be encountered on the actual route. For instance, one worst case is that the truck is in full sunlight during the hottest part of the day. Another possible worst case is that the truck is in traffic, idling and not moving. (I should note here that this does not apply if your product is sensitive to vibration, that’s a separate issue. I’m going to stick with thermal parameters.) Additionally, another worst case is a longer than expected transit time. Thus, I would propose a justifiable and challenging simulation would map for six hours, while the truck idles in full sun in the middle of the day.

The engineer also asked if he had to use actual product in his studies. In the case of the loaded condition, I would use a simulation product. Recall that we are only trying to mimic the thermal response of a given product, not its chemical properties. The chemical properties were already evaluated during the stability testing of that product, and that data informs your product’s specifications: I.E., Between 2°C and 8°C. Simply challenging a placebo product 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.

If the engineer performs this mapping study challenging the equipment in a worst case scenario and finds that the temperature cannot be maintained within specifications, he has several options. It may be necessary to adjust the truck’s cooling system settings and retest. Or, the cooling system of the trailer may need maintenance. It may be that a different truck, route, or packing system is required. This is the purpose of a mapping study using a worst case scenario; along with proving your system works, you are also stress testing it in order to identify a point of failure. The goal of validation is defined as:

The action of proving, in accordance with the principles of GMP, 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.

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.