Cleanroom and Aseptic Manufacturing Disinfectant Validations: What Are They All About?

Posted on: February 12, 2012

Cleanroom and Aseptic Manufacturing Disinfectant Validations: What Are They All About?

The terms “cleanroom disinfectant validation”, “disinfectant validation”, and “cleaning validation” are bounced around by quality managers in the pharmaceutical, biologic and aseptic manufacturing industries all the time, but how many of us really understand what they mean and why they are important?

These validations are critical to assuring that your company complies with current good manufacturing practices (cGMP). They are also crucial to assuring that you are in control of the production environment and are effectively limiting the potential for contamination. Most importantly, these validations are regularly being reviewed by auditors during inspections.  Having a validation in place assures you are in compliance with regulatory requirements and ensures that you know how the products you’ve chosen to disinfect your manufacturing environment perform when used according to your SOPs.

What is a cleanroom disinfectant validation?

A cleanroom disinfectant validation is a formal evaluation and validation of the products and procedures you use to disinfect your cleanroom.  It should minimally include the key surfaces in your cleanroom (epoxy or tile flooring, stainless steel, glass, plastics) and key organisms (vegetative, fungal and spore formers, as well as specific environmental organisms from your site). A good guideline to consider is USP <1072>. This document provides information on how to select disinfectants for use in your cleanrooms as well as suggested testing methodology and acceptance criteria.

How is the testing done?

Standard and environment-specific test organisms are grown by the testing laboratory in a fashion that assures they are healthy, pure cultures. On the day of test, the organism suspension is applied to carriers representative of the surfaces in your facility.

The inoculated organisms are dried onto the surface then treated with the disinfectants in a manner consistent with the application procedures outlined in your internal SOPs. If you have not yet developed a procedure, ATS Labs suggests following the instructions for use on the disinfectant label. Following treatment, the surviving organisms on the carriers are enumerated and compared to a population control to determine the percent and log reduction achieved by the disinfectant. USP <1072> indicates that for bacterial spore formers (eg.,Bacillus subtilis), a minimum of a 2 log10 reduction should be demonstrated. Likewise, for vegetative bacteria (eg.,Pseudomonas aeruginosa or Staphylococcus aureus) and fungal organisms (eg., Aspergillus brasiliensis or Penicillium chrysogenum) a minimum of a 3 log10 reduction should be demonstrated.

When should a cleanroom disinfectant validation be performed?

The short answer is that a disinfectant validation can be performed at any time. However, ideally a disinfectant validation should be performed at the time that your procedures for disinfecting your cleanroom are developed, and before you begin manufacturing product. At a minimum, this validation must be done before a FDA cGMP audit occurs. Additionally, if there have been changes to your disinfection procedures or if new materials have been introduced, you should consider verifying that the changes made do not impact your ability to disinfect the area. Finally, you should consider revalidating your procedures or verifying efficacy if you begin to consistently recover specific isolates during routine environmental monitoring.