The guide identifies important factors to consider when selecting a disinfectant for
use in a cleanroom or similar controlled environment
and recommends test methods
suitable for evaluating disinfectants. The
proper selection of disinfecting agents combined
with in-house qualification testing is a
key element to a successful disinfection
program.
Recent publications of regulatory guidance/
standards, such as Chapter 1072,
“Disinfectants and Antiseptics” in the
United States Pharmacopoeia, address the
issue of disinfectant testing, but there is
very little published guidance on what criteria
and test methods should be used for
selection and efficacy testing of disinfectants
that will be used in cleanrooms and
controlled environments.
The standard says that an understanding
of microbiology and microbiological
techniques is essential. Knowledge
in the following areas is recommended:
microorganisms, antimicrobial products (disinfectants, sporicides, and decontamination
agents), and the chemistry of
disinfection, mechanism of activity of
disinfectants on cells, application procedures,
cleanroom surfaces, and environmental
conditions within a cleanroom.
Requirements for aseptic processing areas
include readily cleanable floors, walls,
and ceilings that have smooth, non-porous
surfaces; particulate, temperature, and humidity
controls; and cleaning and disinfecting
procedures to produce and maintain
aseptic conditions. These conditions combined
with careful and thorough evaluation
of the chemical agents used for the cleaning
and disinfection program should lead to
achieving the specified cleanliness standards
and control of microbial contamination of
products.
In recent years, the use of disinfectants in
pharmaceutical, biotechnology, medical device
facilities, and associated controlled environments
has been the subject of scrutiny by regulatory agencies.
An effective cleaning and disinfection
program in aseptic processing areas of a
Good Manufacturing Practice (GMP) facility
is critical to assure the quality of
the products. Manufacturers are being
held to a high standard when it comes to
product sterility, and regulatory agencies
are increasingly asking for validation data
to support sanitization and disinfection
procedures.
Regulatory authorities now expect evidence
of the efficacy of disinfection agents
against environmental isolates.
The FDA Guideline for Aseptic Processing
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.”
Selection Procedure:
In pharmaceutical, biotechnology, and associated
industries, the selection of one sanitizer,
one or two disinfectants, and one
sporicide is typical. ASTM E 2614 says,more than one type of chemical agent is
needed to obtain the proper balance of effective
microbial control and minimal surface
damage because products vary in
spectrum of activity and formulation.
Currently, most facilities select one or
two disinfecting agents to use on a routine
basis and supplement with a sporicide,
which is used on a less frequent routine basis
to address spores that may not be destroyed
by the routine disinfectant. All three
product types should be evaluated for effectiveness
with appropriate test methods.
Typical agents used in cleanrooms
are:
• Sanitizers: 70 percent v/v Isopropyl Alcohol
(IPA), 70 percent v/v Ethanol;
• Disinfectants: Phenols, Quaternary Ammonium
Compounds, Hydrogen Peroxide
3 percent Sodium, Hypochlorite < 0.10
percent 70 percent v/v, Isopropyl Alcohol
(IPA) 70 percent v/v, Ethanol;
• Sporicides: Sodium Hypochlorite > 0.3
percent, Hydrogen Peroxide > 6 percent
Peracetic Acid Chlorine, Dioxide Vaporized
Hydrogen Peroxide.
Sanitizers play a role in a cleanroom
disinfection program. Isopropyl alcohol has good broad-spectrum efficacy, but in
the manner which it is used routinely,
minimal product contact time and flammability
are of concern. Classifying 70
percent IPA as a decontamination or
residue control agent is more appropriate
since it is often used during cleaning operations,
as a sanitizer during manufacturing,
and for removal of residues left from
other antimicrobial agents.
It is important to choose a disinfectant
that incorporates a surfactant in its formulation
to help clean surfaces. Occasionally,
the choice will be made to rotate two
different disinfectants. These agents are
designed for frequent use.
Sporicidal formulations typically contain
highly reactive chemicals (for example,
sodium hypochlorite or oxidizers) and
may cause damage to surfaces, even stainless
steel, if used too frequently. However,
they are a necessity in the cleanroom since
routine disinfectants are not effective
against bacterial endospores or resistant
mold spores such as Aspergillus niger.
Typically, they are not used on a daily
basis to avoid damage to substrates and reduce the potential for irritation to cleaning
personnel.
Selection of Chemical Agents:
• One of the first steps in selection of a
chemical agent is to collect all pertinent
and available information from
the potential supplier. This would include
EPA registration, technical data
sheets, MSDS, recommended directions
for use as well as data on substrate compatibility, stability, and microbiocidal
efficacy performed according
to acceptable standards.
• Cleanroom Bioburden: A review of environmental
monitoring data is necessary
to determine the number and types
of microorganisms to be controlled.
Not all chemical agents are effective
against all microorganisms and not all
are sporicidal. Knowing the types of submicrobial
flora in the area to be disinfected
aids in selecting an appropriate
disinfectant with the desired spectrum
of activity. From this information, a facility
can determine what efficacy is
needed and identify potential product
candidates.
• Contact Time: For a disinfectant to be
effective, a surface must remain wet
for a defined period of time. The contact
time may vary depending on the
target microbial contamination, air
temperature, as well as the type of
surface being treated.
• Preparation: Products can be purchased
in concentrate form or a ready-to-use
form. If a concentrated product is selected,
dilution will be necessary. The
accuracy of preparation of a use-dilution
is critical for optimal performance.
• Regulatory standards require that disinfectants
used in cleanrooms are sterile,
therefore it may be necessary to
purchase the agent sterile or sterilize it
in-house. The kind of water available
for dilution is also important. Water
hardness or softness can interfere with
the action of some disinfectants. It is
recommended that purified water or
better be used to dilute the concentrate.
• Safety and Toxicity: The product
MSDS should be reviewed to determine
special storage and handling requirements
and to identify any
potential hazards to personnel working
with the agent. Appropriate regulations
should be reviewed regarding disposal.
• Compatibility: Some disinfectants are
incompatible with others and can cause
problematic residues. Performance of
disinfectants can be decreased if they are
incompatible with cleaning agents used
in the area. Additionally, compatibilitywith
surface types in the cleanroom
should be evaluated.
The choice of disinfectants for contamination
control is an important part of assuring
the effectiveness of a cleaning and
disinfection program for a cleanroom.
Many factors must be considered when
selecting and testing disinfectants for use
in a cleanroom. Companies should consider
all the relevant data and make a reasonable
justification to support their
individual disinfection program and
product choice. FSM
