Exp. No. 14 Disinfectant Qualification test

 

Disinfectant Qualification test

Introduction

The use of disinfectants as agents to control microbiological contamination of an environment is well established and is governed by regulatory bodies in both Europe and the United States. Under FIFRA, chemical disinfectants are considered “antimicrobial pesticides”. For disinfectant end-users within the pharmaceutical sector, regulations also state the need for them to demonstrate disinfectant efficacy. The US Food and Drug Administration (FDA) guidance for pharmaceutical industry states “The suitability, efficacy, and limitations of disinfecting agents and procedures should be assessed. The effectiveness of these disinfectants and procedures should be measured by their ability to ensure that potential contaminants are adequately removed from surfaces”. The disinfection process should be validated. Validation studies should demonstrate the suitability and effectiveness of disinfectants in the specific manner in which they are used and should support the in-use expiry periods of prepared solutions.”

Aim

            To demonstrate the efficacy of the commonly used disinfectants by various methods.

Materials and Methods

·         Typical surface materials (eg: stainless steel, glass, PVC, etc.)

·         Chemical disinfectant (bactericide, sporicide, sanitizer, etc)

·         Correct contact time to be established.

·         Application method (spraying, wiping, mopping)

·         Test Organisms (eg: reference cultures, environmental isolates)

Procedure

Methods to Demonstrate Efficacy:

            Association of Official Analytical Chemists (AOAC) methods) to be used by disinfectant manufacturers to support claims of microbiocidal activity. The test types can be split into two categories:

Suspension Testing

            Chemical disinfectants and antiseptics. Quantitative suspension test for the evaluation of bactericidal activity of chemical disinfectants and antiseptics used in food, industrial, domestic and institutional areas.

Testing Disinfectants against Staphylococcus aureus by Dilution Method.

Surface Testing

            Chemical disinfectants and antiseptics – Quantitative non-porous surface test for the evaluation of bactericidal and/or fungicidal activity of chemical disinfectants used in food, industrial, domestic and institutional areas – Test method and requirements without mechanical action.

Germicidal Spray Products as Disinfectants

            The standard test methods are usually used as they are robust, reproducible and well recognized. It can also be useful for end users to be able to refer to results from standard method testing to enable them to compare products from different manufacturers.

            For an end user of a disinfectant, the standard test methods may not accurately reflect the conditions in their own pharmaceutical clean room. End users will typically have different surface materials in their clean rooms, different microorganisms present and different environmental conditions (such as low humidity, rapid drying due to HVAC systems).

            To demonstrate the efficacy of a disinfectant within a pharmaceutical manufacturing environment, it may be deemed necessary to conduct the following tests: (1) use dilution tests (screening disinfectants for their efficacy at various concentrations and contact times against a wide range of standard test organisms and environmental isolates); (2) Disinfectant surface challenge tests (using standard test microorganisms and microorganisms that are typical environmental isolates, applying disinfectants to surfaces at the selected use concentration with a specified contact time, and determining the log reduction of the challenge microorganisms); and (3) a statistical comparison of the frequency of isolation of microorganisms isolated prior to and after the implementation of a new disinfectant.

            This is considered necessary because critical process steps like disinfection of aseptic processing areas, as required by GMP regulations, need to be validated, and the EPA registration requirements do not address how disinfectants are actually used in the pharmaceutical, biotechnological, and medical device industries.

            In line with the USP guidance it is relatively easy to use different microorganisms and test surfaces with standard test methods. However, achieving the specified contact times of the standard test methods can be challenging within the environmental conditions of a pharmaceutical clean room. The evaporation rate of a disinfectant wiped onto a surface in a clean room with a high air change rate could be significantly different to evaporation rate under laboratory conditions. This raises questions as to whether the surface must be visibly wetted with disinfectant for the specified length of time to achieve efficacy, and therefore what exactly the expectation of a contact time is.

            The EN and AOAC methods do not specify a ‘wet contact time’. In suspension tests, a ‘wet contact time’ is always used as the test involves addition of the disinfectant product to an organism suspension held in solution for the required contact time, with product neutralizer added at the end of this contact time. It is not as clear for surface tests, however, as an amount of disinfectant, as defined by the standard, is pipetted onto surface without spreading it out. Because of the small volumes that are pipetted, and the relatively high surface tension of most disinfectants tested, it is likely that a wet contact time will be achieved under laboratory conditions.

            The contact times for surface disinfectants are chosen on the basis of the practical conditions of the product. The recommended contact time for the use of the product is within the responsibility of the manufacturer.” It could be inferred from the wording “practical conditions of the product” that they are referring to volumes applied by mopping or wiping and evaporation rates, for example an alcohol compared to a quaternary ammonium compound, but again this is not a clear definition.

            The coupons are exposed to disinfectant for the defined wet / residence contact time. Time a disinfectant is in direct contact with the surface or item to be disinfected. For surface disinfection, this period is framed by the application to the surface until complete drying has occurred.

            The contact time used in efficacy testing should be the same or shorter than the contact time identified on the product label. If a contact time is different from the range identified in the test method or guideline is preferred, consultation with the agency prior to testing is recommended and a modification to the standard approach may be needed. In most cases, a modification to provide a longer exposure period is limited by the practical considerations of the use patterns (e.g., an exposure period of >10 min for a product that will likely evaporate from the treated surface within 10 min). Clearly identify and justify all method modifications in the test protocol. For liquid or spray products containing volatile active ingredients where the product is applied to a hard non-porous surface, the maximum contact time may be determined by visually inspecting evaporation over the proposed contact period.” Once again, this statement clearly indicates an expectation for a wet contact time. It is not inconceivable that there is a continuation of disinfectant efficacy after the surface is visibly dry as the action is taking place at a cellular level. The first stage of microbial kill is the uptake of the active ingredient in the disinfectant by the cell. It can therefore be considered that there are two “times” in play during disinfection

Result

            To demonstrate efficacy a disinfectant supplier is required to execute standard tests under repeatable conditions, from which they will define a contact time. This contact time might prove useful to the end user in selection of the appropriate disinfectant. An end user must also validate disinfectant efficacy, reflecting the conditions of use within their facility including defining a contact time used in practice. Most pharmaceutical guidance organizations define contact time as a wet contact time. To facilitate end user testing that is representative of their facility conditions, they are encouraged to measure the time taken for disinfectants to evaporate when applied using routine techniques (wiping/mopping) and use this contact time for laboratory studies.