Understanding Impact: Indirect and Direct systems...

 Hi Paul, I recently enjoyed one of your webinars. Thanks for the information! I am hoping you can clarify something: Do you consider an environmental monitoring system a direct or indirect system when monitoring chambers?

Paul writes:

Thanks for attending and forwarding your question. It's a good one. Many organizations and publications have been careful to define the terms. In short: I consider an environmental monitoring system to be a direct system. But, my long answer is, well, a bit longer!

First, let's start with some definitions: According to the ISPE, an Indirect Impact System is: "A system that is not expected to have a direct impact on product quality, but typically will support a Direct Impact System. These systems are designed and commissioned following Good Engineering Practice only." From the ISPE Baseline® Guide, Vol. 1: Active Pharmaceutical Ingredients, Second Edition in 2007. It follows therefore that a Direct Impact system is a system that has a direct impact on product quality. In what I call a "standard pharmaceutical scenario," we are dealing with a product that is sensitive to temperature, has published storage specifications from stability studies, and the product will be considered adulterated if the manufacturer is unable to prove, through gap-free records, that the product was stored within the published storage specs.

Generally, the GMP System of record that is used to show that the product was stored appropriately is the monitoring system. In this sense, a monitoring system has a direct impact on product quality. One could argue that a company's decision to release or not release a product are dependent directly on records and data collected by this system.

As a form of evidence for considering an environmental monitoring system a direct system, we have yet to encounter a GxP company who has implemented our CMS but did not validate the system. This ubiquitous validation makes me think that most companies consider a monitoring system to be a direct system. Keep in mind that many auditors consider Good Manufacturing Practices to be defined collectively by the solutions/practices used for the same problem by our peers in similar businesses. A good example is the SOP. Nowhere in the EMA or FDA regulations are SOPs mentioned. Rather, "written procedures" are specified and the collective industry solution is the SOP.

Similarly, maintaining records of environmental conditions where GxP-regulated products are stored is specified by the regulations. The collective industry solution seems to be a monitoring system that is treated as a direct impact system.Personally, I would rather just validate a system involved in ensuring and proving product quality than try to get an auditor to understand why I didn't. Pardon my enthusiasm! I hope that somewhere in that rant I managed to answer your question. If not, contact me... This question is exactly in line with the spirit of risk assessment.

A risk-based approach guides us to ask if the system plays a role that is critical enough to require the investment of time and energy necessary to even do a risk assessment! If you haven't seen it already, please check out this webinar on doing just that...