ASTM E2614-15(2020)e1
(Guide)Standard Guide for Evaluation of Cleanroom Disinfectants
Standard Guide for Evaluation of Cleanroom Disinfectants
SIGNIFICANCE AND USE
5.1 Requirements for aseptic processing areas include readily cleanable floors, walls, and ceilings that have smooth, non-porous surfaces; particle, temperature, and humidity controls; and cleaning and disinfecting procedures to produce and maintain aseptic conditions. These controls, 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. Qualification of disinfectants in pharmaceutical, biotechnology, medical device facilities, and associated controlled environments, along with validation of the cleaning and disinfection process, is subject to scrutiny by regulatory agencies.
5.2 An effective cleaning and disinfection program in aseptic processing areas of a Good Manufacturing Practice (GMP) - regulated facility is critical to assure product quality. Manufacturers are held to a high standard when it comes to product sterility, and regulatory agencies increasingly request validation data to support sanitization and disinfection procedures. Regulatory authorities expect evidence of the effectiveness of disinfection agents against environmental microorganisms isolated from the facility. 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.”7
5.3 Basic knowledge regarding the effectiveness of different chemical agents against vegetative bacteria, fungi, and spores will aid in selecting chemical agents.
5.4 An understanding of test methods used to assess disinfectant effectiveness is important. Most methods are adaptable, allowing the user to customize the methods to their specific requirements.
SCOPE
1.1 This 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 agent combined with qualification testing is a key element of a successful disinfection program. Regulatory guidance such as United States Pharmacopoeia Chapter , “Disinfectants and Antiseptics” and the FDA Guidance for Industry, “Sterile Drug Products Produced by Aseptic Processing–Current Good Manufacturing Practice” address the necessity of disinfectant effectiveness testing but do not clearly define acceptable test methods.
1.2 An understanding of microbiology and microbiological techniques is essential. Knowledge in the following areas is recommended: microorganisms, antimicrobial products (disinfectants, sporicides, and decontamination agents), the chemistry of disinfection, mechanism of activity of disinfectants on cells, application procedures, cleanroom surfaces, and environmental conditions within a cleanroom. This information is available in several published texts listed in the bibliography.
1.3 The theoretical basis for disinfectant activity is not addressed in this guide. An understanding of the effect of disinfectant concentration on microbial reduction (concentration exponent) and kinetics is desirable in determining the use-dilution of different disinfectants and in using dilution to neutralize a disinfectant for efficacy testing. USP chapter provides further information on this topic.
1.4 This guide is written for the cleanroom environment, although many of the principles outlined in this standard are applicable to manufacturing and processing environments outside of the cleanroom.
1.5 Evaluation of disinfectants for biofilm control is outside the scope of this document.
1.6 This international standard was developed in accordance with internationally recognized principles on standar...
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Standards Content (Sample)
This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the
Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
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Designation: E2614 − 15 (Reapproved 2020)
Standard Guide for
Evaluation of Cleanroom Disinfectants
This standard is issued under the fixed designation E2614; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
ε NOTE—Section 2.3 was editorially corrected in April 2020.
1. Scope 1.6 This international standard was developed in accor-
dance with internationally recognized principles on standard-
1.1 This guide identifies important factors to consider when
ization established in the Decision on Principles for the
selecting a disinfectant for use in a cleanroom or similar
Development of International Standards, Guides and Recom-
controlled environment and recommends test methods suitable
mendations issued by the World Trade Organization Technical
for evaluating disinfectants. The proper selection of disinfect-
Barriers to Trade (TBT) Committee.
ing agent combined with qualification testing is a key element
ofasuccessfuldisinfectionprogram.Regulatoryguidancesuch
2. Referenced Documents
as United States Pharmacopoeia Chapter <1072>, “Disinfec-
2.1 ASTM Standards:
tants and Antiseptics” and the FDA Guidance for Industry,
“Sterile Drug Products Produced by Aseptic Processing–Cur- E2111 Quantitative Carrier Test Method to Evaluate the
Bactericidal,Fungicidal,Mycobactericidal,andSporicidal
rent Good Manufacturing Practice” address the necessity of
disinfectant effectiveness testing but do not clearly define Potencies of Liquid Chemicals
E2197 Quantitative Disk Carrier Test Method for Determin-
acceptable test methods.
ing Bactericidal, Virucidal, Fungicidal, Mycobactericidal,
1.2 An understanding of microbiology and microbiological
and Sporicidal Activities of Chemicals
techniques is essential. Knowledge in the following areas is
E2315 Guide for Assessment of Antimicrobial Activity Us-
recommended: microorganisms, antimicrobial products
ing a Time-Kill Procedure
(disinfectants, sporicides, and decontamination agents), the
2.2 BSI Standards:
chemistry of disinfection, mechanism of activity of disinfec-
BS EN 1040 Chemical disinfectants and antiseptics. Quan-
tants on cells, application procedures, cleanroom surfaces, and
titative suspension test for the evaluation of basic bacte-
environmental conditions within a cleanroom. This informa-
ricidal activity of chemical disinfectants and antiseptics.
tion is available in several published texts listed in the
Test method and requirements (phase 1)
bibliography.
BS EN 1276 Chemical disinfectants and antiseptics. Quan-
1.3 The theoretical basis for disinfectant activity is not
titative suspension test for the evaluation of bactericidal
addressed in this guide. An understanding of the effect of
activity of chemical disinfectants and antiseptics used in
disinfectant concentration on microbial reduction (concentra-
food, industrial, domestic and institutional areas. Test
tion exponent) and kinetics is desirable in determining the
method and requirements (phase 2, step 1)
use-dilution of different disinfectants and in using dilution to
BS EN 1650 Chemical disinfectants and antiseptics. Quan-
neutralize a disinfectant for efficacy testing. USP chapter
titative suspension test for the evaluation of fungicidal or
<1072> provides further information on this topic.
yeasticidal activity of chemical disinfectants and antisep-
1.4 This guide is written for the cleanroom environment,
tics used in food, industrial, domestic and institutional
although many of the principles outlined in this standard are
areas. Test method and requirements (phase 2, step 1)
applicable to manufacturing and processing environments
BS EN 13704 Chemical disinfectants. Quantitative suspen-
outside of the cleanroom.
sion test for the evaluation of sporicidal activity of
chemical disinfectants used in food, industrial, domestic
1.5 Evaluation of disinfectants for biofilm control is outside
the scope of this document.
1 2
This specification is under the jurisdiction of ASTM Committee E35 on For referenced ASTM standards, visit the ASTM website, www.astm.org, or
Pesticides, Antimicrobials, and Alternative Control Agents and is under the direct contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
responsibility of Subcommittee E35.15 on Antimicrobial Agents. Standards volume information, refer to the standard’s Document Summary page on
Current edition approved April 1, 2020. Published April 2020. Originally the ASTM website.
approved in 2008. Last previous edition approved in 2015 as E2614–15. DOI: Available from British Standards Institute (BSI), 389 Chiswick High Rd.,
10.1520/E2614-15R20E01. London W4 4AL, U.K., http://www.bsi-global.com.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
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E2614 − 15 (2020)
and institutional areas. Test method and requirements 3.1.12 qualification, n—to determine effectiveness in the
(phase 2, step 1) context of a given process.
BS EN 13697 Chemical disinfectants and antiseptics. Quan-
3.1.13 sanitizer, n—chemical or physical agent(s) used to
titative non-porous surface test for the evaluation of
reduce the number of microorganisms to a level judged to be
bactericidal and/or fungicidal activity of chemical disin-
appropriate for a defined purpose and/or claim.
fectantsusedinfood,industrial,domesticandinstitutional
3.1.14 soil load, n—a chemical or physical material(s)
areas. Test method and requirements without mechanical
included in a test procedure to simulate conditions or use.
action (phase 2, step 2)
3.1.15 sporicide, n—achemicalorphysicalagent(s)thatkill
2.3 Other Standards:
spores.
AOAC International, Official Methods of Analysis, Chapter
3.1.16 substrate, n—surface on which an organism can
6—Disinfectants, 21st Edition, 2019
grow.
ISO 14644-1 Cleanrooms and associated controlled environ-
ments -- Part 1: Classification of air cleanliness
3.1.17 surfactant, n—an agent that reduces the surface
United States Pharmacopeia 43, Chapter <1072> Disinfec-
tension of water or the tension at a water-liquid interface
tants and Antiseptics, 2020
3.2 Acronyms:
3. Terminology
SDS = Safety Data Sheet
3.1 Definitions: GMP = Good Manufacturing Practice
IPA = Isopropyl Alcohol
3.1.1 antimicrobial, n—describes an agent that kills bacteria
USP = United States Pharmacopeia
or suppresses their growth or reproduction.
3.1.2 bioburden, n—the number and type of viable micro-
4. Summary of Guide
organisms that can be estimated using prescribed recovery
4.1 Selecting and qualifying the appropriate disinfection
procedures.
agents is an integral factor in developing a compliant cleaning
3.1.3 biocide, n—a physical or chemical agent that kills
and disinfection program for a cleanroom. Significant factors
organisms.
to consider when selecting disinfectant for use in cleanrooms
3.1.4 carrier, n—a surrogate surface or matrix that facili-
and controlled environments are discussed in this guide. A
tates the interaction of test microorganisms and treatment.
summary of the most common test methods used to determine
disinfectant effectiveness is also presented.
3.1.5 cleanroom, n—an area that establishes and maintains
the level of microbial control necessary for the intended
5. Significance and Use
manipulations.
5.1 Requirements for aseptic processing areas include read-
3.1.6 contact time, n—predetermined time that a test micro-
ily cleanable floors, walls, and ceilings that have smooth,
organism is exposed to the activity of a test material.
non-porous surfaces; particle, temperature, and humidity con-
3.1.7 disinfectant, n—a physical or chemical agent or pro-
trols; and cleaning and disinfecting procedures to produce and
cess that destroys pathogenic or potentially pathogenic micro-
maintain aseptic conditions. These controls, combined with
organisms on inanimate surfaces or objects.
carefulandthoroughevaluationofthechemicalagentsusedfor
3.1.8 effıcacy, n—the proven performance of a product
thecleaninganddisinfectionprogram,shouldleadtoachieving
established under defined conditions.
the specified cleanliness standards and control of microbial
contamination of products. Qualification of disinfectants in
3.1.9 effectiveness, n—a measure of the performance of a
pharmaceutical, biotechnology, medical device facilities, and
product.
associated controlled environments, along with validation of
3.1.10 inoculum, n—the viable microorganisms used to
the cleaning and disinfection process, is subject to scrutiny by
contaminate a sample, device, or surface, often expressed as to
regulatory agencies.
number and type.
5.2 An effective cleaning and disinfection program in asep-
3.1.11 neutralization, n—the process for inactivating or
tic processing areas of a Good Manufacturing Practice (GMP)
quenching the activity of a microbiocide, often achieved
- regulated facility is critical to assure product quality. Manu-
through physical (for example, filtration or dilution) or chemi-
facturers are held to a high standard when it comes to product
cal means.
sterility, and regulatory agencies increasingly request valida-
tion data to support sanitization and disinfection procedures.
Regulatory authorities expect evidence of the effectiveness of
Available from AOAC International, 481 North Frederick Ave., Suite 500,
Gaithersburg, Maryland 20877-2417, http://www.aoac.org.
disinfection agents against environmental microorganisms iso-
Available from International Organization for Standardization (ISO), Chemin
lated from the facility. The FDA Guideline for Aseptic Pro-
de Blandonnet 8, CP 401, 1214 Vernier, Geneva, Switzerland, http://www.iso.org.
6 cessing states, “The suitability, efficacy, and limitations of
Available from U.S. Pharmacopeia (USP), 12601Twinbrook Pkwy., Rockville,
MD 20852-1790, http://www.usp.org. disinfecting agents and procedures should be assessed. The
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E2614 − 15 (2020)
effectiveness of these disinfectants and procedures should be 6.1.5 Critical Factors in Selection of Chemical Agents:
measured by their ability to ensure that potential contaminants 6.1.5.1 Product Information—One of the first steps in selec-
are adequately removed from surfaces.”
tion of a chemical agent is to collect all pertinent and available
information from the potential supplier. This would include
5.3 Basic knowledge regarding the effectiveness of different
EPA registration information, technical data sheets, SDS,
chemical agents against vegetative bacteria, fungi, and spores
recommended directions for use as well as data on substrate
will aid in selecting chemical agents.
compatibility, stability, and microbiocidal efficacy performed
5.4 An understanding of test methods used to assess disin-
according to acceptable standards.
fectant effectiveness is important. Most methods are adaptable,
6.1.5.2 Cleanroom Bioburden—A review of environmental
allowing the user to customize the methods to their specific
monitoring data is necessary to determine the number and
requirements.
types of microorganisms to be controlled. Not all chemical
agents are effective against all microorganisms and not all are
6. Procedure
sporicidal. Knowing the types of microbial flora in the area to
6.1 Selection Procedure:
be disinfected aids in selecting an appropriate disinfectant with
6.1.1 In the pharmaceutical, biotechnology, and associated
the desired spectrum of activity. From this information, a
industries, the selection of one sanitizer, one or two
facility can determine what efficacy is needed and identify
disinfectants, and one sporicide is typical. More than one type
potential product candidates.
of chemical agent may be needed to obtain the proper balance
6.1.5.3 Contact Time—For a biocide to be effective, a
of effective microbial control and minimal surface damage
surface must remain in contact with the agent for a defined
because products vary in spectrum of activity and formulation.
period of time. The contact time may vary depending on the
Most facilities select one or two disinfecting agents to use on
target microbial contamination, air temperature, as well as the
a routine basis and supplement them with a sporicide which is
type of surface being treated.
used on a less frequent routine basis to address spores that may
6.1.5.4 Preparation—Products can be purchased in concen-
notbekilledbytheroutinedisinfectant.Allthreeproducttypes
trate form or a ready-to-use form. If a concentrated product is
should be evaluated for effectiveness with appropriate test
selected, dilution will be necessary. Accurate preparation of a
methods. Typical agents used in cleanrooms are:
use-dilution is critical for optimal performance. Regulatory
Sanitizers: 70 % v/v Isopropyl Alcohol (IPA)
standards require that disinfectants used in ISO Class 5
70 % v/v Ethanol
environments are sterile; therefore, it may be necessary to
purchase the agent sterile or to sterilize it in-house.The quality
Disinfectants: Phenolic Detergent Compounds
Quaternary Ammonium Compounds
of water used for dilution is also important. Water hardness or
Hydrogen Peroxide 3%
softness can interfere with the action of some disinfectants. It
Sodium Hypochlorite <0.10%
is recommended that purified water or better be used to dilute
Sporicides: Sodium Hypochlorite > 0.3 %
the concentrate.
Hydrogen Peroxide > 6 %
6.1.5.5 Safety and Toxicity—The product SDS should be
Peracetic Acid
reviewed to determine special storage and handling require-
Chlorine Dioxide
Vaporized Hydrogen Peroxide
ments and to identify any potential hazards to personnel
working with the agent. Appropriate regulations should be
6.1.2 Sanitizers such as 70% solutions of IPAor ethanol are
not intended for use as primary microbial control agent in reviewed regarding disposal.
cleanrooms. Their use should be limited to specific purposes 6.1.5.6 Compatibility—Some disinfectants are incompatible
suchasglovedecontamination,cleaningprocesses,andresidue with others and can cause problematic residues. Performance
removal. of disinfectants can be decreased if they are incompatible with
6.1.3 It is important to choose a disinfectant that incorpo- cleaning agents used in the area. Additionally, compatibility
rates a surfactant in its formulation to help clean surfaces.
with surface types in the cleanroom should be evaluated.
Occasionally, the choice will be made to rotate different
disinfectants
...
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