Guidance for Industry and FDA Staff
Premarket Notification [510(k)] 
Submissions for Chemical 
Indicators
Document issued on: December 19, 2003 
The draft of this document was issued January 27, 2003 
For questions regarding this document contact Chiu Lin, Ph.D., 240-276-3700. 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health 
Infection Control Devices Branch 
Division of Anesthesiology, General Hospital, Infection Control, and Dental Devices 
Office of Device Evaluation  Contains Nonbinding Recommendations 
 
Preface 
 
Public Comment 
 
Written comments and suggestions may be submitted at any time for Agency consideration to 
Dockets Management Branch, Division of Management Systems and Policy, Office of Human 
Resources and Management Services, Food and Drug Administration, 5630 Fishers Lane, 
Room 1061, (HFA-305), Rockville, MD, 20852.  Alternatively, electronic comments may be 
submitted to http://www.fda.gov/dockets/ecomments.  When submitting comments, please 
refer to Docket No.02D-0525.  Comments may not be acted upon by the Agency until the 
document is next revised or updated. 
 
Additional Copies 
 
Additional copies are available from the Internet at:  
http://www.fda.gov/cdrh/ode/guidance/1420.pdf or to receive this document by fax, call the 
CDRH Facts-On-Demand system at 800-899-0381 or 301-827-0111 from a touch-tone 
telephone.  Press 1 to enter the system.  At the second voice prompt, press 1 to order a 
document.  Enter the document number (1420) followed by the pound sign (#).  Follow the 
remaining voice prompts to complete your request.   
 
    Contains Nonbinding Recommendations 
Table of Contents 
I. INTRODUCTION........................................................................................................................................1 
II. BACKGROUND.......................................................................................................................................2 
A. SCOPE......................................................................................................................................................2 
B. EXCLUSIONS............................................................................................................................................3 
C. DEFINITIONS............................................................................................................................................3 
III. DEVICE COMPARISON........................................................................................................................5 
IV. DEVICE DESCRIPTION........................................................................................................................6 
V. INTENDED USE......................................................................................................................................7 
A. PROCESS INDICATOR................................................................................................................................7 
B. CHEMICAL INTEGRATORS........................................................................................................................7 
C. AIR REMOVAL INDICATORS.....................................................................................................................7 
VI. FDA-RECOGNIZED STANDARDS......................................................................................................7 
VII. PERFORMANCE CHARACTERISTICS.............................................................................................8 
A. PROCESS INDICATORS.............................................................................................................................9 
B. CHEMICAL INTEGRATORS......................................................................................................................10 
C. CHEMICAL INTEGRATOR TEST PACKS...................................................................................................11 
D. PROCESS INDICATORS FOR NEW TECHNOLOGY STERILIZERS................................................................11 
E. CHEMICAL INTEGRATORS FOR NEW TECHNOLOGY STERILIZERS...........................................................12 
F. NEW TECHNOLOGY CHEMICAL INTEGRATOR TEST PACKS....................................................................12 
G. AIR REMOVAL INDICATORS...................................................................................................................12 
VIII. BIOCOMPATIBILITY.....................................................................................................................13 
IX. ENDPOINT STABILITY FOR CHEMICAL INDICATORS...........................................................13 
X. SHELF LIFE...........................................................................................................................................13 
XI. LABELING.............................................................................................................................................14 
XII. REFERENCES.......................................................................................................................................16 
XIII. CHEMICAL INDICATOR 510(K) CHECKLIST..........................................................................17  Contains Nonbinding Recommendations 
Guidance for Industry and FDA Staff 
Premarket Notification [510(k)] 
Submissions for Chemical Indicators  
This guidance represents the Food and Drug Administration's (FDA's) current thinking 
on this topic.  It does not create or confer any rights for or on any person and does not 
operate to bind FDA or the public.  You can use an alternative approach if the approach 
satisfies the requirements of the applicable statutes and regulations.  If you want to discuss 
an alternative approach, contact the FDA staff responsible for implementing this 
guidance.  If you cannot identify the appropriate FDA staff, call the appropriate number 
listed on the title page of this guidance.  
I. Introduction
A chemical indicator intended for use in health care facilities to monitor sterilization 
processes is a class II device as identified in 21 Code of Federal Regulation (CFR) 
section 880.2800.  Chemical indicators are also known as physical/chemical sterilization 
process indicators.  The term chemical indicators used in this document includes 
process indicators, chemical integrators, and air removal indicators used in test packs 
such as the Bowie Dick Test Pack.   
A person intending to market a chemical indicator to be used in health care facilities must 
submit to FDA, and have cleared, a premarket notification submission prior to 
introduction of the device into interstate commerce, in accordance with section 510(k) of 
the Federal Food, Drug, and Cosmetic Act (the act). 
Regulations governing the general content and format of 510(k) submissions for chemical 
indicators are codified under 21 CFR Part 807.  These and other regulatory requirements 
pertaining to the marketing of a new medical device are discussed in guidance documents 
available from CDRH, Division of Small Manufacturers, International, and Consumer 
Assistance (DSMICA).  These requirements are also explained on the Internet in CDRH 
Device Advice, http://www.fda.gov/cdrh/devadvice/ . 
Management of current sterilization technologies requires the use of more than one type of 
monitoring procedure.  Chemical indicators are an integral part of this monitoring process.  
Along with biological indicators and mechanical monitors, they can provide an effective 
program to detect sterilization process failures.  As part of a complete quality control 
program, they can help guard against problems associated with user error, sterilizer 
1 Contains Nonbinding Recommendations 
malfunction or inadequate sterilant penetration.  The adequate performance of sterilizers in 
health care facilities is important to prevent nosocomial infections.  Chemical indicators can 
provide health care facilities with information on the effectiveness of a sterilization process.  
FDA recognizes the importance of providing submitters and other interested parties with 
the Agencys recommendations for chemical indicators in order to facilitate the assembly 
of data to maintain consistency of review, and to provide for a more efficient regulatory 
process.  This guidance is intended to provide specific recommendations to 510(k) 
submitters about information that they should include in 510(k)s for chemical indicators 
used in health care facilities. 
This guidance replaces the draft document entitled, Chemical Indicators Premarket 
Notification [510(k)] Submissions; Draft Guidance for Industry and FDA, which was made 
available on January 27, 2003.  There have been no major changes from the previous draft 
version.  
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agencys current thinking on a topic and 
should be viewed only as recommendations, unless specific regulatory or statutory 
requirements are cited.   The use of the word should in Agency guidances means that 
something is suggested or recommended, but not required.   
Least Burdensome Approach 
The issues identified in this guidance document represent those that we believe need to be 
addressed before your device can be marketed. In developing the guidance, we carefully 
considered the relevant statutory criteria for Agency decision-making.  We also considered 
the burden that may be incurred in your attempt to follow the guidance and address the issues 
we have identified.  We believe that we have considered the least burdensome approach to 
resolving the issues presented in the guidance document. If, however, you believe that there 
is a less burdensome way to address the issues, you should follow the procedures outlined in 
the A Suggested Approach to Resolving Least Burdensome Issues document.  It is 
available on our Center web page at: https://www.fda.gov/downloads/MedicalDevices/ .    
DeviceRegulationandGuidance/GuidanceDocuments/UCM588914.pdf
II. Background
A. Scope
This document provides guidance concerning the content and format of 510(k) 
submissions for chemical indicators intended to monitor sterilization processes in health 
care facilities.  Chemical indicators for use in health care facilities are class II devices.  
The product code is JOJ.  Section 21 CFR 880.2800 (b), Physical/chemical sterilization 
process indicator identifies these devices as: 
2 Contains Nonbinding Recommendations 
 
A physical/chemical sterilization process indicator is a device 
intended for use by a health care provider to accompany 
products being sterilized through a sterilization procedure and 
to monitor one or more parameters of the sterilization process.  
The adequacy of the sterilization conditions as measured by 
these parameters is indicated by a visible change in the device. 
 
FDA has cleared, through the 510(k) process, the following three types of chemical 
indicators for use in health care facilities:1  
  process indicators 
  chemical integrators  
  air removal indicators for test packs.   
 
Therefore, this guidance addresses only these three types of chemical indicators.   
 
The FDA encourages you, the 510(k) submitter, to contact DSMICA or the Infection Control 
Devices Branch, Division of Anesthesiology, General Hospital, Infection Control, and Dental 
Devices, Office of Device Evaluation, if you have any questions before submitting a 510(k) 
for chemical indicators.  
B.  Exclusions 
This document does not cover the following chemical indicators and indicator related 
products: 
  chemical indicators intended to be used with liquid chemical sterilants2   
  chemical indicators intended for use in a manufacturing setting 
  chemical indicators used for radiation sterilization. 
C.  Definitions 
The following are definitions of terms used throughout the document.   Many of the 
definitions have been standardized by organizations such as the International 
                                                           
1 These devices react physically or chemically during sterilization.  For purposes of being 
consistent with terminology used in consensus standards, we refer to them as chemical indicators 
throughout this document.  
 
2  For these devices, please refer to Guidance for Industry and FDA Reviewers  Content and 
Format of Premarket Notification [510(k)] Submissions for Liquid Chemical Sterilants/High 
Level Disinfectants, Section III.K. at http://www.fda.gov/cdrh/ode/397.html. 
 
 
  3 Contains Nonbinding Recommendations 
Organization for Standardization (ISO), the American National Standards Institute 
(ANSI), and the Association for the Advancement of Medical Instrumentation (AAMI).  
The standards cited for each definition are cited in full in XII. References.   
 
Air Removal Indicator:  A chemical indicator to be used in the standard test pack to 
determine the efficacy of the air removal phase in the steam sterilization process.  
(ANSI/AAMI, 1999) 
 
Biological Indicator:  Microbiological test system providing a defined resistance to a 
specified sterilization process. (ANSI/AAMI/ISO, 2002) 
 
Bowie Dick Test: A diagnostic test of a dynamic-air-removal steam sterilizers 
ability to remove air from the chamber and prevent air re-entrainment. (ANSI/AAMI, 
2  002)    
Chemical Indicator:  System that reveals change in one or more predefined process 
variables based on a chemical or physical change resulting from exposure to a 
process.  (ANSI/AAMI/ISO, 2002) 
 
Chemical Integrator:  A chemical indicator designed to react to all critical 
parameters over a specified range of sterilization cycles. (ANSI/AAMI, 1996)   
 
Critical Parameters: Parameters identified as being essential to the sterilization 
process. (ANSI/AAMI, 1996) 
 
D-Value:  The time or radiation dose required to achieve inactivation of 90% of a 
population of the test microorganism under stated exposure conditions.3 
(ANSI/AAMI/ISO, 2002) 
 
Endpoint:  The observable change specified by the manufacturer that occurs after the 
chemical indicator has been exposed to certain predefined physical conditions. 
(ANSI/AAMI, 1996) 
 
Indicator Agent: An active ingredient or combination of ingredients that is 
contained in a chemical indicator. (ANSI/AAMI, 1996) 
 
Medical Device:  As defined in the Act (21 USC 321(h)): 
 
[a]n instrument, apparatus, implement, machine, 
contrivance, implant, in vitro reagent, or other similar or 
                                                           
3 This is the definition for D-value in the standard cited.  However, radiation sterilization is 
not discussed in this guidance document because it is not a sterilization method generally 
used in health care facilities. 
  4 Contains Nonbinding Recommendations 
related article, including any component, part, or accessory, 
which is 
 
1. recognized in the official National Formulary, or the 
United States Pharmacopoeia, or any supplement to 
them,  
 
2. intended for use in the diagnosis of disease or other 
conditions, or in the cure, mitigation, treatment, or 
prevention of disease, in man or other animals, or  
 
3. intended to affect the structure or any function of the 
body of man or other animals, and  
 
which does not achieve its primary intended purposes 
through chemical action within or on the body of man or 
other animals and which is not dependent upon being 
metabolized for the achievement of its primary intended 
purposes.   
 
Process Challenge Device (PCD):  Item designed to simulate product to be sterilized 
and to constitute a defined challenge to the sterilization process, and used to assess 
the effective performance of the process. (ANSI/AAMI/ISO, 2002) 
 
Process Indicator: A chemical indicator that is intended for use with individual 
units, (e.g., packs, containers) to demonstrate that the unit has been exposed to the 
sterilization process and to distinguish between processed and unprocessed units.  
(ANSI/AAMI, 1996) 
 
Resistometer: A test instrument designed to rapidly produce and precisely control 
critical parameters associated with a given sterilization process.  Notes: 1) In addition 
to routine quality system testing of indicator performance consistency, it is used to 
characterize cause and effect relationships associated with the given sterilization 
process and devices used to evaluate the efficacy of the sterilization process, and 2) 
Resistometers were formerly referred to as a Biological Indicator Evaluator 
Resistometers (BIER) or Chemical Indicator Evaluator Resistometer (CIER) test 
systems.  (ANSI/AAMI, 2002) 
 
III.  Device Comparison 
FDA recommends that you include a section or table comparing the new device to the legally 
marketed predicate device.  The following table is an example of the type of information that 
you should provide.  
  5 Contains Nonbinding Recommendations 
 
Table 1- Comparison of the New Device to the Predicate 
ELEMENT  NEW DEVICE  PREDICATE 
     
Intended use, e.g., process indicator, 
chemical integrator, Bowie Dick Test 
 
     
Device design  
 
     
Indicator agent  
 
     
Sterilization method and cycles 
 
     
Endpoint specifications 
 
     
Shelf-life  
 
 
IV.  Device Description 
You should provide a detailed description of your chemical indicator.  The description for 
your chemical indicator should include the general characteristics regarding the device 
design and manufacturing specifications.  The bulleted list below is an example of the type of 
information that you should provide in the description for your device.  We may request 
additional information, if the differences in design, formulation, or performance warrant. 
  chemical name of indicator agent, e.g., ink, dye, chemical reagent 
  chemical composition or formulation of the indicator 
  reaction that takes place to achieve its intended endpoint  
  sterilization cycles for which the chemical indicator is intended  
  critical parameters that the indicator is intended to monitor 
  minimum exposure parameters to achieve the endpoint 
  recommended storage conditions 
  any interfering substances or conditions 
  stability of the endpoint reaction, e.g., the stability of the endpoint color 
  shelf life  
  6 Contains Nonbinding Recommendations 
V.  Intended Use 
You should clearly state the intended use of the chemical indicator.  The following are 
examples of intended use for each type of indicator.  
A.  Process indicator 
The process indicator is intended to be used by a health care provider with sterilization 
wraps, containers, cassettes, or pouches to distinguish between processed and 
unprocessed units. 
B.  Chemical Integrators 
The chemical integrator is intended to be used by a health care provider to demonstrate 
that the parameters over a specified range of sterilization cycles have been met in a 
specified sterilization wrap, container, cassette, or pouch. 
C.  Air Removal Indicators 
The air removal indicator is intended to be used by a health care provider in a 
standardized test pack, e.g., Bowie Dick Test Pack, to assess the ability of a prevacuum 
sterilizer to remove air and allow steam to penetrate into wrapped goods and porous 
loads.  The test pack is usually positioned over the chamber drain in an otherwise empty 
chamber.  An inefficient air removal stage, an air leak, or non-condensable gases in the 
steam supply are some of the conditions that could cause an incomplete change in the air 
removal indicator, e.g., uneven color change.  The Bowie Dick Test is not an indication 
that the sterilizer has reached the parameters for sterilization.   
 
VI.  FDA-Recognized Standards 
If any part of the device design or testing relies on an FDA-recognized standard, you may 
submit (1) a statement that testing will be conducted and meet specified acceptance criteria 
before the product is marketed, or (2) a declaration of conformity to the standard in lieu of 
data.4  Please note that testing must be completed before submitting a declaration of 
conformity to a recognized standard. (Section 514(c)(1)(B) of the act).  For more 
information, refer to the FDA guidance, Use of Standards in Substantial Equivalence 
Determinations; Final Guidance for Industry and FDA, 
http ://www.fda.gov/cdrh/ode/guidance/1131.html.  
Recognized standards that apply to chemical indicators are discussed in the following 
sections. 
 
                                                           
4 See Required Elements for a Declaration of Conformity to a Recognized Standard 
(Screening Checklist for All Premarket Notification [510(K)] Submissions), 
http://www.fda.gov/cdrh/ode/reqrecstand.html. 
 
  7 Contains Nonbinding Recommendations 
VII. Performance Characteristics 
You should provide sufficient information to allow FDA to evaluate the endpoint 
specifications and performance of the chemical indicator.  In order to provide the user with 
adequate instructions for use, there should be a high visual contrast between the initial and 
endpoint appearance or physical/chemical change that takes place after processing the 
chemical indicator, e.g., colors change.   
 
You should provide the critical parameters to which the chemical indicator is intended to 
respond.  For the traditional sterilization processes that are generally used in the health care 
facility, ANSI/AAMI ST 60 (see XII. References) specifies the parameters shown in Table 2 
as critical.  
 
Table 2  Critical Parameters of Traditional Sterilization Processes 
STERILIZATION PROCESS  CRITICAL PARAMETERSa 
Steam   Time, temperature, saturated steam 
Dry Heat  Time, temperature 
Ethylene Oxide (EO)   Time, temperature, humidity, and EO concentration 
aThe critical parameters not normally tested for chemical indicators are steam quality or 
degree of saturated steam in a steam sterilization process and relative humidity in an 
EO sterilization process.  The performance of the chemical indicator is evaluated while 
controlling these critical parameters under specified conditions.  These specified 
conditions are called limiting values.  The limiting values for saturated steam, referred 
to as dryness values, are 0.85 1.0.  The limiting value for EO relative humidity is 
greater than 30%. 
 
FDA recommends that you provide the following information in your 510(k): 
 
  clear statement of the study objective(s) 
 
  description of the sterilization process used in health care facility for which the 
indicator is intended, e.g., steam, EO 
 
  description of the health care facility sterilization cycle for which the indicator is 
intended, e.g., gravity cycle for 15 minutes at 121C 
 
  critical parameters to which the indicator responds 
 
  specifications for the pass/fail criteria 
 
  pass/fail results obtained from a resistometer   
 
  pass/fail results from an actual sterilization cycle used in a health care facility 
 
  information on the resistance of the biological indicator used in the parallel study, if 
applicable 
  8 Contains Nonbinding Recommendations 
 
  information showing that you used a statistically valid sample size, e.g., 3 lots from 3 
different manufacturing runs (i.e., one lot from each manufacturing run) 
 
  description of the positive and negative controls 
 
  conclusion drawn from study. 
 
 
If feasible, you should also provide actual samples of unprocessed and processed indicators. 
A.  Process Indicators  
You should provide the following information for process indicators. 
 
To characterize the process indicator and demonstrate substantial equivalence, you 
should provide pass/fail results demonstrating how the indicator reacts to the critical 
parameters in a resistometer.  FDA recommends that the resistometer used for chemical 
indicator performance testing meet ANSI/AAMI ST 44 (see XII. References).    
 
FDA also recommends that the submission include pass/fail results showing how the 
process indicator would react in an actual sterilizer used in a health care facility.  These 
results should be compared to the resistometer vessel results.  If there is a discrepancy 
between the resistometer and health care facility sterilizer results, you should provide this 
information in the labeling.  
 
Steam Process Indicators  
You should demonstrate, as specified in ANSI/AAMI ST 60, that the chemical 
indicator does not reach its endpoint when exposed to dry heat at 140C for 30 
minutes. 
 
EO process indicators  
You should evaluate EO process indicators as specified in ANSI/AAMI ST 60 to 
show that after being exposed to 60C2C at greater than 85% relative humidity for 
not less than 90 minutes, the indicator does not reach its endpoint.  This test is done 
without EO present.   
 
The following table provides the criteria that a process indicator should meet according 
to the consensus standard ANSI/AAMI ST 60 for the indicated sterilization methods.   
  9 Contains Nonbinding Recommendations 
 
 
Table 3 - Process Indicators Criteria  
METHOD  TEMPERATURE  GAS  ENDPOINT 
CONCENTRATION REACTION 
Steam  121C              N/A  2 min - 10 min 
Steam  132C  135C3C              N/A  20 sec - 2 min 
EO  30C 1C  60030 mg/l  5 min - 10 min 
Dry Heat  160C 5C               N/A  20 min - 40 min 
 
B.  Chemical Integrators 
The testing described in Section VII. Performance Characteristics and VII. A. Process 
Indicators also applies to chemical integrators, with the exception of the performance 
criteria shown in Table 3.  There are no specific performance criteria established for 
chemical integrators in any published consensus standard.  You should provide the 
specifications for the endpoint reaction for each critical parameter identified and provide 
the following pass/fail results to support the specifications.   
 
Critical Parameters  
You should describe the pass/fail criteria for each critical cycle parameter and 
provide the pass/fail results to show how the chemical integrator reacts to all the 
critical parameters in the sterilization cycle for which it is intended.  We recommend 
that you evaluate one parameter at a time in a resistometer while holding the other 
parameter or parameters constant.  The reproducibility of the endpoint reaction 
should be within the 15% tolerance level of the stated value, as specified in 
  ANSI/AAMI ST 60. 
Side-by-Side Testing with the Biological Indicator  
You should conduct side-by-side testing of the biological indicator and the subject 
chemical integrator in an appropriate resistometer.  You should use a biological 
indicator in the study that is legally marketed for the intended sterilization process 
and cycles.  You should also state the D-value for the biological indicator used in the 
study.  The chemical integrator should parallel the performance of an appropriate 
biological indicator.  The results of this study should demonstrate that the integrator 
does not reach its endpoint before the biological indicator is inactivated, as specified 
in ANSI/AAMI ST 60.  
 
  10 Contains Nonbinding Recommendations 
C.  Chemical Integrator Test Packs 
Chemical integrators may be used in test packs to simulate products being sterilized.5  
These test packs are intended to create a challenge to the sterilization process that is 
equal to or greater than the most difficult item routinely processed.   
 
For chemical integrator test packs, you should provide the following information: 
 
  pass/fail results comparing the performance of the chemical integrator in the test 
pack to the AAMI reference biological indicator test packs in their respective 
processes  (The AAMI standardized test packs are considered the gold 
standards.)   
 
  information to show that the integrator test pack provides an equivalent or greater 
challenge than the AAMI standardized test pack 
 
  additional information to show that the integrator test pack provides a greater 
challenge to the process than the integrator by itself. 
 
D.  Process Indicators for New Technology Sterilizers 
There are no specific performance criteria for chemical indicators for use with new 
technology sterilizers; however, we believe that the criteria outlined above can be used to 
evaluate the performance of these chemical indicators.  Chemical indicators intended to 
monitor new technology sterilizers, e.g., vaporized hydrogen peroxide, microwave, gas 
plasma, ozone, may be determined substantially equivalent to any legally marketed 
chemical indicator, including a pre-amendments chemical indicator or a chemical 
indicator found substantially equivalent through the 510(k) process.  You should provide 
pass/fail results characterizing your chemical indicator according to its indications.  In 
general, you should: 
 
  identify the critical parameters of the sterilization cycle, e.g., temperature, time, 
sterilant concentration 
 
  identify the minimum exposure parameters needed to affect the change of the 
indicator 
 
  establish the pass/fail criteria 
 
  describe in detail the endpoint reaction or change that is intended to occur 
 
  provide pass/fail results demonstrating how the chemical indicator reacts to the 
critical parameters specified in an appropriate resistometer vessel, if available,  
for characterization and compare it to the results obtained above  
 
  demonstrate reproducibility using a statistically valid number of samples. 
 
                                                           
5 These test packs are also called process challenge devices (PCDs). 
  11 Contains Nonbinding Recommendations 
E.  Chemical Integrators for New Technology Sterilizers 
The testing described in sections VII. B. Chemical Integrators and VII. D. Process 
Indicators for New Technology Sterilizers also applies to new technology sterilizer 
integrators.   
 
In addition, FDA recommends that the biological indicator used to validate the new 
technology sterilizer cycle also be used to validate the performance of the chemical 
integrator.  The integrator should not reach its endpoint before the biological indicator is 
inactivated. 
F.  New Technology Chemical Integrator Test Packs 
For new technology integrator test packs, there are no gold standards.  We recommend 
that you use the performance criteria for traditional sterilization methods to demonstrate 
the resistance of the new technology chemical integrator.  These performance criteria are 
identified in ANSI/AAMI ST 46 and ST 41 (see XII. References).  You should provide 
pass/fail results demonstrating that the test pack provides a greater challenge to the 
process than the biological indicator that was used to validate the new technology 
sterilization process and the integrator itself.  For example, the challenge should be 
equivalent to the increase in the D-value that is provided by the ANSI/AAMI ST 46 and 
ST 41 standard biological indicator test packs in their respective processes.   
 
G.  Air Removal Indicators  
For air removal indicators, FDA recommends that you determine the following 
performance criteria and endpoint specifications inside a test pack (Bowie Dick Test). 
 
You should provide pass/fail results demonstrating that the indicator does not reach its 
endpoint when exposed to dry heat at 1402C for 30 minutes. 
 
You should also provide pass/fail results demonstrating the tolerances for the detection of 
air in a prevacuum sterilizer.  You can simulate this fault condition by injecting air or by 
not pulling a complete vacuum to produce a non-uniform change in the indicator agent.  
You should include a thermocouple graph showing the decrease in temperature during 
the fault condition at the different locations in the cycle. 
 
The thermocouple graph demonstrating a failed result should be compared to the graph 
showing that the indicator passed.  As specified in ANSI/AAMI ST 66, the test 
temperature within the test pack should be less than 0.5C for a pass. 
 
For greater sensitivity in detecting air over a larger area, FDA recommends that the air 
removal indicator sheet in the test pack measure approximately 8 inches by 10 inches 
(ANSI/AAMI ST 60).  The indicator agent should cover a large percentage of the test 
sheet and it should be uniform. 
   
  12 Contains Nonbinding Recommendations 
You should provide specification for the porosity of the material used to construct the air 
removal indicator.  The standard, ANSI/AAMI ST 66 (see XII. References) recommends 
using a standard densitometer to measure the time required for a given volume of air 
(25ml to 300ml) to flow through a standard area of the indicator being tested to measure 
the porosity of the test material. 
 
VIII.  Biocompatibility 
There is the possibility that an active ingredient in some chemical indicators may leach onto 
the surgical instruments when it comes in contact.  You should address this concern by 
demonstrating that your chemical indicator does not release any substance known to be toxic 
in sufficient quantities to cause a health hazard or deleterious effect to the user or the devices 
that are sterilized. 
 
IX.  Endpoint Stability for Chemical Indicators 
You should demonstrate the stability of the specified endpoint reaction (e.g., color stability) 
for the chemical indicator at the end of its shelf life.   
 
X.  Shelf Life 
You should demonstrate that the specification for the endpoint reaction of the chemical 
indicator is maintained throughout its labeled shelf life.  For all studies, you should test at 
least 3 lots of the production chemical indicators using a sample size that is statistically 
significant.  You should use storage conditions described in the device labeling.   
 
You should provide the following information about shelf life: 
 
  labeled shelf life of the chemical indicator 
 
  dates and length of time for each testing interval, e.g., 0, 6 months, 1 year, 2 years 
 
  resistometer vessel data for each testing interval that demonstrates that the established 
endpoints are maintained. 
 
Chemical indicators may be unstable at elevated temperatures; therefore, accelerated aging 
studies may be inappropriate and are not recommended.   
 
In lieu of complete real time shelf life data, the FDA will consider preliminary real time shelf 
life data (e.g., 6 months) along with a detailed protocol and sampling plan for an ongoing 
real time (e.g., 2 years) study that you will continue after your device is cleared.  These study 
protocols should include the shelf life information listed above.  We also recommend that 
  13 Contains Nonbinding Recommendations 
you document the results in your design history file as a part of the Quality Systems 
Requirements (21 CFR 820.30).   
XI.  Labeling 
The premarket notification should include labeling in sufficient detail to satisfy the 
requirements of 21 CFR 807.87(e).  The following suggestions are aimed at assisting you in 
preparing labeling that satisfies the requirements of 21 CFR 807.87(e).6 
 
FDA suggests that you provide in the labeling: 
 
  performance characteristics, so that users can determine whether your indicator will 
meet their needs 
 
  any interfering substances or conditions known to affect the performance of the 
indicator 
 
  clear description of the physical change that is designed to occur, with descriptions of 
the indicator both before and after the change, if applicable 
 
  any intermediate changes between the initial and endpoint appearance  
 
  adequate directions for interpretation of the endpoint results or provide a mechanism 
by which a clearly defined endpoint can be determined by the user, if the endpoint is 
not clearly obvious 
 
  storage conditions 
 
  expiration date of the unused indicator under specific storage conditions 
 
  any safety precautions required during use 
 
  stability of the endpoint color reaction 
 
  the minimum exposure parameters necessary to affect the change (for chemical 
integrators only) 
 
In addition to the above, labeling for a Bowie Dick Test Pack should contain the following: 
 
  statement indicating that the device is for use in determining air removal 
 
                                                           
6 Although final labeling is not required for 510(k) clearance, final labeling must comply 
with the requirements of 21 CFR 801 before a medical device is introduced into interstate 
commerce.  Labeling recommendations in this guidance are consistent with the requirements 
of part 801. 
 
  14 Contains Nonbinding Recommendations 
  warning indicating that extending the manufacturers recommended time for the 
Bowie Dick Test may result in false endpoints developing because entrapped air 
diffuses over time 
 
  warning indicating that Bowie Dick Test should be performed in an empty chamber. 
 
  15 Contains Nonbinding Recommendations 
 
XII. References 
 
 
ANSI/AAMI ST 41:1992, Good Hospital Practice: Ethylene Oxide Sterilization and Sterility 
Assurance 
 
ANSI/AAMI ST 44:2002, Resistometers for Characterizing the Performance of Biological 
and Chemical Indicators 
 
ANSI/AAMI ST 46:1993, Good Hospital Practice: Ethylene Oxide Sterilization and Sterility 
Assurance 
 
ANSI/AAMI ST 60:1996, Sterilization of Health Care Products - Chemical Indicators, Part 
1: General Requirements  
 
ANSI/AAMI ST 66:1999, Sterilization of Health Care Products  Chemical Indicators  Part 
2: Class 2 Indicators for Air Removal Test 
 
ANSI/AAMI/ISO TIR 11139:2002, Sterilization of Health Care Products - Vocabulary 
 
FDA:  Labeling: Regulatory Requirements for Medical Devices  (HHS Publication FDA  
89-4203) Food and Drug Administration, 9200 Corporate Blvd., Rockville, MD 20850, 1989 
(http://www.fda.gov/cdrh/dsma/470.pdf). 
 
 
  16 Contains Nonbinding Recommendations 
XIII. Chemical Indicator 510(k) Checklist 
Yes   No   N/A  Item 
      510(k) Summary or Statement 
      Indication for Use Statement 
      Truthful and Accurate Statement 
      Comparison of new chemical indicator to the predicate 
      Description  
      Formulation of indicator ink 
      Chemical reaction with sterilant 
      Design description and type of indicator, e.g., process, integrator, Bowie Dick  
      Critical parameters to which the indicator responds 
      Pass/Fail criteria or minimum exposure parameters that effect the change 
      Performance 
      Data supporting endpoints with pass/fail criteria 
      Data supporting integrator parameters  
      Additional data for the Bowie Dick Test 
          Data demonstrating tolerance for detection of air 
          Porosity of paper carrier 
      Biocompatibility information     
      Data supporting shelf-life  
      Data supporting endpoint color stability 
      Labeling  
      Name and address of manufacturer 
      Intended use including the sterilization process and cycles 
      Adequate directions for use 
      A clear description of the change that is designed to occur (for color changes 
examples of the color both before and after the change) 
      The storage conditions both before and after use 
      Expiration date of the unused indicator under specific storage conditions 
      Lot number or other identifiers 
      Any safe precautions required during use 
      Stability of the endpoint color change 
      For integrators, the minimum exposure parameters necessary to effect the change 
      Labeling for a Bowie Dick Test should also include:  
      Statement indicating that the device is for use in determining air removal 
      Warning indicating that extending the manufacturers recommended time for the 
Bowie Dick Test may result in false endpoints because entrapped air diffuses 
over time 
      Warning indicating that the Bowie Dick Test should be performed in an empty 
chamber 
 
  17