Cleanroom Operators - Recommended Research Papers: Oct 2016 - Apr 2017

In an article on Why Training Matters in pharmaceutical manufacturing, Gordon Haines and Marcus Spreen insist on the importance of continuous learning. When considering the number of research studies undertaken to create new and improved cleanroom technologies, I wholeheartedly agree. Staying abreast of the latest research gives a company a chance to be more competitive while ensuring that team leaders and managers have a firm grasp of the scientific reasoning that underlies cleanroom protocol. 

Most cleanroom operators will agree with me on the value of keeping up with industry-relevant research, and yet many of us find it easier said than done. Smaller companies might only be able to subscribe to a minimal number of journals. Operators working in bigger companies that manufacture a broad range of products might not have enough hours in the day to keep up with the spectrum of studies that could impact them.

Cherwell’s recommended research papers for cleanroom operators

In light of time pressures, I’ve put together a summary of the most important and useful research studies in the field of pharmaceutical manufacturing I’ve come across recently. This is the first in a series of periodical updates I’ll be publishing, to help other time-strapped professionals stay on top of the latest research. 

Risk of Microbial Spores to Cleanrooms – Part 1: Introduction to microbial spores and survival mechanisms

Clean Air and Containment Review is one of the trustiest journals in my research library. It is peer reviewed and does not promote any particular products or businesses, which makes it a highly recommended source.

In this first of a series of two articles, Tim Sandle details the science behind spore survival and the potential sources for them in the cleanroom.

Abstract:

Spores, both bacterial and fungal, pose a risk to cleanroom environments. This article presents an overview of spores and considers the microbiological aspects of their ability to spread and survive in the inhospitable environment of the cleanroom.

A second article will consider sporicidal disinfectants for cleanrooms. Bacterial spores and fungal spores both pose risks to pharmaceutical manufacturing environments. They are, however, biologically different. This article examines both spore types. 

Source references and availability:

Author: Tim Sandle

Published: October 2016

Available from: ResearchGate.net

Risk of Microbial Spores to Cleanrooms – Part 2: Selection of Sporicidal Disinfectants

In part two of Tim Sandle’s articles on the risk of microbial spores to cleanrooms, Sandle concentrates on the various types of sporicidal disinfectant, their mode of action in killing or inactivating spores and factors to consider when choosing one. 

Abstract:

The article considers the use of sporicidal disinfectants, examining different types and considering the range of factors that affect sporicide efficacy. Importantly, the selection of sporicidal agents is not straightforward. Several types of sporicidal agent are extremely corrosive to stainless steel, plastic and soft metals as well as being a potential health hazard to operators. For this reason, such agents tend to be used sparingly alongside other disinfectants.

Source references and availability:

Author: Tim Sandle

Published: March 2017

Available from: ResearchGate.net

Sanitisation with vapour phase hydrogen peroxide – practical cycle development and future improvements

I enjoyed this article, particularly the section on cycle development because it reminded me of how I would develop the fumigation cycles in new or refurbished labs when I worked in the public sector. It also mentions the use of enzyme indicators as an alternative to biological and/or chemical indicators.

Abstract:

Vapour phase hydrogen peroxide (VPHP) has been in use as a sanitising agent, particularly for isolators, for over 20 years. During this time the process has gained a reputation for lengthy and complex cycle development, and for some unreliability. These problems stem from two points:

a. Lack of understanding how the vapour phase hydrogen peroxide process actually works.

b. Lack of consistency in the biological indicators used to challenge the process.

This paper starts by explaining how the vapour phase hydrogen peroxide rapid sporicidal process works and continues with a description of the present methods of cycle development. The paper continues with some suggestions as to how cycle development can be sped up considerably and introduces enzyme indicators (EIs) as a recent development to add to chemical indicators (CIs) and possibly to replace biological indicators (BIs). The paper offers practical solutions to both the problems mentioned above, based on long experience with the design, construction and validation of vapour phase hydrogen peroxide generators.

Source references and availability:

Author: Tim Coles

Published: January 2017

Available to subscribers of Ingenta Connect

Assessing contamination control of pre-sterilised container tub transfers into an aseptic manufacturing filling isolator via a de-bagging/no-touch –transfer step

For anyone looking for a good assessment of the virtues of using multiple layers of sterile packing versus the spray and wipe process, this makes an interesting read.

Abstract:

Experimental contamination transfer challenge studies were designed to assess whether contamination control and sterility are maintained when using a no-touch-transfer (NTT) de-bagging tub transfer method to introduce pre-sterilised containers into a FlexPro50 aseptic manufacturing isolator/restricted-access barrier system filling line system. Importantly, the sterile tubs of product containers are enclosed in double steri-bags, and remain sterile through the supply chain to point of filling. Use of NTT means that any of the current automated bio-decontamination steps usually employed prior to material transfer into Grade A areas are rendered unnecessary; since the bag contents remain sterile and protected and can be transferred without exposing the Grade A aseptic processing zone to the outer bag. To support this rationale, two key contamination control studies were undertaken during processing of tub transfers with the NTT/de-bagging technology; 1) surface-to-surface transfer of human commensal microorganisms representing the challenge of "worst case" operator handling, and 2) a structured approach evaluating the risk of airborne contamination as tubs move through the NTT process steps into the Grade A isolator environment by a particle challenge method (limitation of risks method). In these studies, the barrier-isolator environment remained robust to adverse particle movement, without microbial contamination transfer. In addition, the sterile tub outer surfaces were confirmed as maintaining sterility during the NTT process step. These results provide proof of concept of NTT technology.

Source references and availability:

Authors: Ljungqvist, B., Reinmüller, B., Maier, C. and Roth, A.

Published: November 2016

Available from Chalmers Public Library

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