A review of the associated Environmental Monitoring (EM) trends demonstrated a degree of control that satisfied everyone. One of the words bandied about with abandon was ‘residues’. However, this means many things to different people. For some, it may be evidence of product contamination, or evidence cleaning and disinfection was being performed, and for others, a sign of a lack of control.
Aa member of a not for trade organisation, one of my jobs was to review the draft Annex 1 when it was out for comment in 2017. We looked at the Annex with a microbiological focus, and we found plenty to agree with, and some things to question. Then I joined Ecolab. Suppliers of cleanroom disinfectants are also interested in the contents of Annex 1. There is a lot of literature available, but broadly speaking, most disinfectant suppliers are saying the same thing, which is good news for industry.
The Concern with Residues
As a disinfectant manufacturer, we have seen a prolonged and increased concern from regulators over residues left from disinfectants post-application. The visual aspect of residues has always been of concern and there are records of pharmaceutical companies being cited for the presence of residues in the cleanroom environment. A recent review of FDA 483’s has the following citations.
As another critical topic in review, the draft Annex now calls out the need to control these residues as well as raising concerns over the potential latent effect of residues - as highlighted in Section 6.5 A and B of the draft Annex 1, which reference residues potentially creating a barrier and/or posing a particulate risk to the product being manufactured.
So, here we have the Annex giving an explanation as to why any residues are a risk. They present a physical or chemical contamination risk to the manufacturing process. Love or hate regulations, I always find an explanation for why they exist to be very valuable.
There is a new specific statement about disinfectants, highlighting that cleaning programs should be effective at removing disinfectant residues. This ties in with requirements for low, or minimal, residue products and clearly states that it is no longer an acceptable practice to allow residues to build up uncontrolled on surfaces. Again, the presence of a disinfectant residue represents, at a basic level, a risk to product quality as either a physical or chemical contamination risk. This is not new news to the industry and why products such as alcohols are commonly used in close proximity to open product as they leave little or no residues.
In summary, a residue, be it from product, process, or disinfection, represents a risk to product quality from a physical or chemical contamination risk.
How do you Define Residue?
In my role I still see companies struggle to define residue, what the risk is and how to remove it. I would like to turn to the last point, how do you remove residue? In the first instance we need to understand what a residue is before we can work out how to remove it.
Residues can be broadly classed into two types, those from the manufacturing process and those from the cleaning and disinfection process. Cleanroom disinfectants are usually water-based chemistries and are all readily dissolvable in water. Therefore, the best solvent to remove a disinfectant residue is water. Normally this is WFI or purified grade, depending on the location and risk to the cleanroom. However, as all good microbiologists will tell you, water used in cleanrooms creates another risk – that of microbiological growth. To counter this risk an alternative solvent is commonly used either with, or to replace water – these are the 70% alcohols. While these are disinfectants in their own right, they are also used to reduce the build-up of other disinfectant residues, but without the higher level of microbiological risk when compared to ‘just’ water.
But, what about the other group from the manufacturing process? Again, if these residue forming compounds are water based, or are physical debris, then water or alcohol could be used to remove them. However, some products are rather stubbornly persistent in the cleanroom environment when water is used to try and remove them. This is where detergents come into their own. The surfactant properties of detergents help break down complex molecules and ease the cleaning process. However, these detergents will also leave a residue so therefore will require rinsing.
There is a current focus about how to measure or detect a residue. I would urge baby steps in this process, first, understand what your residues are before reaching for the mop and bucket.
Ecolab continues to publish well founded scientific studies into the science of disinfectant residue removal. At the recent UK Pharmig annual conference Ecolab presented an open session on disinfectant residue removal and how to approach it. It was attended by the pharmaceutical industry and disinfectant suppliers alike. The good news for our industry is that disinfectant suppliers appear to be following Ecolab’s lead. We are seeing complimentary articles being published from different disinfectant suppliers all giving the same message about residue removal. In my experience, when suppliers become aligned, the problem is close to being solved, or the risk reduced, in more modern parlance.