During a recent webinar I gave, hosted by Tungsten Shield Group, on the topic of Cold Chain storage and shipping, I was asked a question by an attendee. It went this way:
Should I validate the shipping or can I just put a temperature monitor in? What do the regulations require?
This question was interesting on two fronts:
- Do we do things to please regulators? and
- what is the purpose of validation versus verification?
I personally treat regulations as wisdom handed to us by regulators to help guide our thinking. So I tend to turn the question of “what do regulations require?” into
What are the regulators trying to tell us?
I believe the decision to validate or put a temperature monitor in should be driven by what makes sense from a scientific / logical perspective and a business perspective as well. The regulations are simply telling us that shipping can be risky and can put the drug into jeopardy. Do what you can to prevent problems from occurring and if not fully possible, at least understand if there is a problem.
So in the case of road shipment (or air for that matter), there are measures you can take to protect the product. I recommend the following logic
- Validate what makes sense – the shipping container can be validated to hold product for x hours and an outside temperature of y degrees. But what happens if the shipment takes longer or is exposed to temperature above the range in the validation?
- For things that can not be validated, put controls or measures to minimize the risk or at least measures to tell you if there might be a problem. In this example, you can not really validate the operation of a refrigerated truck. So the measures you put in place are to assure the operation runs smoothly or at least you know what went wrong. That might include training of the driver on the critical elements, having a contingency plan in place if the truck breaks down or loses refrigeration etc.
- For those areas where you want more assurance, you can add a temperature monitor as well to tell you if things were outside the validated ranges. The data then becomes critical in assessing whether you should use the materials or not.
So what might trigger the use of a temperature monitor in addition? If the product is valuable or in short supply, you want to know if it’s still OK. That makes good business sense. Similarly, if it is a clinical product, the risk to the trial results of using a suspect material is just too high. I would include a temperature monitor so if an excursion of time or temperature occurred, I would have data on the condition of the product to justify using it or not.
From my perspective, I would prefer to delay a patient getting a clinical drug, especially in a Phase 3, until I was sure the material was acceptable than blindly dosing with a suspect drug where the conditions were unknown.