This article is part of a special feature on cleanrooms that was published in the December issue of PTE Digital, available at http://www.pharmtech.com/ptedigital1210.
Before validating a new cleanroom facility, I think it best to first consider the functionality of the facility and then define the desired capabilities that it is intended to satisfy. It is essential to understand:
Environmental monitoring over-emphasised
With respect to environmental monitoring, the expectations of both the FDA and the EMA do not consider the realities of aseptic processing and as a consequence, they overemphasise environmental monitoring to the point where they may actually be causing more problems than they are endeavouring to prevent. There are several aspects that the regulators seem to ignore:
Expectations for perfection in performance may seem reasonable considering the label claim, but is quite unrealistic and unprovable from a scientific perspective. Unfortunately, these scientifically unrealistic expectations result in impractical acceptance criteria and the arbitrary and capricious rejection of product. The cost of monitoring, investigations and identification efforts is borne by the end user, and in many instances fails to bring any real benefit in reduction of product risk.
Can sterility ever be completely assured?
Sterility can never be guaranteed, and this represents a major technical disconnect between current regulatory policy and scientific reality. The sterility test as we know it today dates to the 1930s when processes were markedly less capable. In today's aseptic processing, its utility is highly questionable. The sampling limitations are well documented and, unfortunately, unfixable. Until such time as we have a universally accepted nondestructive sterility test for products, there is simply no means to assure sterility.
The media fill test is also, as many scientists and engineers have noted for years, merely a snapshot in time and not a method by which an aseptic process can be truly validated. It is important to remind ourselves that we can neither test nor monitor sterility (an attribute that can't be analytically measured) into our aseptically produced products.
My recent paper with Jim Akers entitled "The Myth Called Sterility" reviews this in some detail. It outlines what we called 'Sterility by Design', which is a group of interrelated design concepts that can at least assure 'safety' if not 'sterility'.1 If we were honest with ourselves, that is really all we have ever needed to have with respect to parenteral products.