This guidance was written prior to the February 27, 1997 implementation of FDA's 
Good Guidance Practices, GGP's. It does not create or confer rights for or on any person 
and does not operate to bind FDA or the public. An alternative approach may be used if 
such approach satisfies the requirements of the applicable statute, regulations, or both. 
This guidance will be up dated in the nstt  vision to include the standard elemnts of GGP 's.  Guidance on 
Premarket Notification [510(k)] Submissions 
for 
-. 
Sterilizers 
Intended for Use in Health Care Facilities 
Infection Control Devices Branch 
Division of General and Restorative Devices 
March,  1993  Preface 
This guidance was developed by the Infection Control Devices 
Branch, Division of General and ~estorativeD evices (DGRD), 
Office of Device Evaluation (ODE), Center for Devices and 
Radiological Health (CDRH), Food and Drug Administrati~n (FDA). 
FDA regulates the introduction of medical devices into interstate 
commerce.  A  person intending to market a sterilizer intended for 
use in a health care facility must submit a premarket 
notification [510(k)J submission to FDA at least 90 days prior to 
its introduction into interstate commerce.  Regulations governing 
the general content and format of 510(k) submissions are codified 
under 21 Code of Federal Regulations, Part 807.  These general 
510(k)  regulatory requirements are further discussed in guidance 
documents available from the CDRH Division of Small Manufacturers 
Assistance (DSMA).  The intent of this guidance document is to 
provide additional direction regarding information and data which 
should be submitted to FDA in a 510(k) submission for a 
sterilizer intended for use in a health care facility- 
Sterilizer technology is expanding at an accelerating pace. 
Sterilizers can be complex in design and methods of sterilization 
are diverse.  In spite of the complexity and diversity there are 
some common considerations that can be applied to virtually all 
510(k) submissions for sterilizers.  FDA believes it is prudent 
to provide 510(k) applicants, and other interested parties, 
information describing these common elements in order to improve 
the .quality of submissions and subsequently reduce the regulatory 
review processing time. 
The guidance is based upon current publications, the literature, 
the combined experience and expertise of agency personnel 
involved in the evaluation of sterilization processes.  Science 
.and the evaluation of medical devices are not static, rather they 
-  are evolutionary.  As such, FDA may periodically update this 
guidance, as necessary, to keep it current:  Any comments on the 
content of this document are welcome and should be sent to the 
address noted under Section R.  CONTENTS 
I. Introduction  Page 
. . . . . . . . . . . . . . . . . . . . . . . . . .  
scope  3 
Exclusions 
Definitions . . . . . . . . . . . . . . . . . . . -  . .  4 -6 
. . . . . . . . . . . . . . 
Classification of Sterilizers  7 
Related Regulatory Authority.  . . . . . . . . . . . . . .-   7 
11. Documentation 
. -  -  . . . 
Presubmission Considerations for Applicants  8 
.  . . 
Recommendations for Protocols and Data Analysis  ..  8-9 
. - 
. . 
Documentation for Traditional Classified Sterilizers.  9 
EPA Certification . . . . . . . . . . . . . . . . . . . .  9 
Reference to Standards, Practices, Technical 
. . . . -  -  . . . . . 
Reports, Guidelines and Methods  10 
Labeling. . . . . . . . . . . . . . . . . . . . . . .  11-12 
1.  Device Markings 
2.  Information Manual 
3.  Service Manual 
. . . . . . 
Changes to Sterilizers Requiring a New SlO(k)  12 
General Description of the Sterilizer . . . . . . . .  12-14 
1.  Specifications 
2.  Process Parameters and Process Monitors 
3.  Software Documentation 
Cycle Overview  . . .  -  . -  -  -  -  . .  . . -  .  . . .  . 14 
Testpacks  . . . . . . . . -  . . . . . .  . . . . . . .1Q-15 
Equivalent Devices and Previous Submissions . . -  -  .  .  15 
Physical/Chernical Performance Tests . . .  .  . . .  . . .  . 16 
1.  Traditional Steam, Dry Heat, and EtO  Sterilizers 
2.  Other Sterilizers  . . . . . . . . . . . .  
Biolcgical  performance Tests  17-26 
1.  General 
2.  Test Organisms 
3.  Biological Test Battery 
sporicidal Screening Test 
Sterilization Process  Equivalent Time 
0-Value  Determination 
1/2  Cycle  and  Total K i l l  End  Point Analysis 
Simulated and  Actual U s e  Tests 
Derivation  of  the Process  Parameters 
. . . .  
Toxicity of  the Sterilant and  Process  By-products  -27 
. . . . . . . . . .  
Elimination  of Toxic Process Residues  27 
. . . . . . .  
Processed  Device/Material  Qualification  28-29 
1.  Introduction  . -. 
2.  Process  Life ~etermination 
3.  Functional Compatibility of  A r t i c l e s  
4.  Biocompatibility  of  Component  Materials 
. . . . . . . . . . . . . .  
Final  Process Qualification  30 
. . . . . . . . . . . . . . . . .  
Contzcts and  Addresses  30 
. . . . . . . . . . . . . . . . . . . . . . .  
Checklist  31 
. . . . . . . . . . . . . . . . . . . . . . .  
Attachments  32 
Side by  Side Comparison  Chart  I.  Introduction 
A.  scope 
This document  provides guidance concernirq  SlO(k) submissions  for 
s t e r i l i z e r s  intended  for use  i n  health crre facilities,  e.9. , 
hospitals,  clinics,  health  care professional  offices. 
Exclusions 
This document does not address the folloving: 
1.  sterilizers used  i n  the production  or manufacture  of  medical 
devices which  are regulated under  FI?X  good  manufacturinq- 
practices regulations  (GMPs) , 2 1  CF. Part 820; 
2.  technologies used  only i n  the zlanufccturing  setting,  e-g., 
ionizing radiation; 
3.  devices used  solely 'to preclean  or otherwise dwontaminate 
medical devices prior to a.tercina1 sterilization process; 
4.  specific requirements  for sterilizarion wraps,  chenical  and 
biological  indicators; 
5.  s t e r i l i z e r s  intended for use w i t h  ccntact lenses  (separate 
guidance available from the Divisio:;  of  Ophthalmic 
Devices/ODE) ; and 
6.  s t e r i l i z e r s  which  employ  a  liquid c k m i c a l  sterilizing 
environment.  Definitions 
Bioburden:  The naturally occurring microbial contaminatio- 
on a medical device prior to exposure to a microbicidal 
process. 
Bioburden Based Sterilization:  A  sterilization process wi--h 
parameters based upon the predetermined type and 
concentration of bioburden on the medical devices to be 
sterilized.  This method is used in manufacturing processes 
and is not appropriate for health care facilities where the 
bioburden may fluctuate. 
Biological Indicator (BI):  A  measured and calibrated number 
of microorganisms with high resistance to the node of 
sterilization being'monitored, placed in or on a carrier a d  
packaged to maintain the integrity of the carrier and 
microorganisms.  The microorganism count is known and is 
higher than the bioburden on the medical device to be 
sterilized.  The BI is used to test the effectiyeness of the 
sterilization process by assessing the microbial lethality 
of the process. 
Chemical Indicator (CI):  A  carrier impregnated or filled 
with a chemical compound which, when exposed to specific 
chemical and/or physical conditions, will undergo a known 
reaction, such as a color change, or produce a measurable 
quantity of reaction products.  A  CI indicates that the 
medical device has been exposed to one or more process 
conditions, and unless the CI integrates ALL process 
conditions, it is not an adequate test for assessing the 
effectiveness of the process. 
Death Rate Curve (or Survivor Curve):  The graphic 
representation of the microbial sterilization kinetics for a 
specific microbicidal agent on a defined microbial 
population. 
D-value (Dlo):  The time required to kill 90%. (one 
logarithmic cycle) of a homogeneous population of 
microorganisms.  For calculation purposes it is assumed tk?: 
the killing rate follows first-order kinetics. 
Inorganic and Organic Load:  The naturally occurring or 
artificially placed inorganic (e-g., metal salts) or organic 
(e.g., proteins) contaminants on a medical device prior tc 
exposure to a microbicidal process.  The naturally occurrizq 
organic load is also known as bioburden. 
Microbial Sterilization Kinetics:  The quantitative 
mechanisms and effects of physical or chemical sterilizati~a 
agents on the death of microbes.  Overkill Sterilization:  sterilization process that is 
A 
based upon an arbitrarily established higher initial 
concentration and resistance of bioburden than that actually 
expected on the medical devices to be sterilized.  Overkill 
processes typically are based upon a lo6 colony forming unit 
(CFU)/unit  level of bioburden.  This method is to be used 
for establishing process parameters for sterilizers used in 
health care facilities. 
Process and Product Qualification:  Elements of the 
sterilization validation program consisting of selected 
engineering and microbiological demonstrations performed 
according to predefined protocols to show process' 
- 
reproducibility and product acceptability. 
Precleaning:  The removal of foreign material, e.g:,  organic 
or inorganic contaminants, from medical devices prlor to a 
decontamination, disinfection, or sterilization process, 
Process Residue:  The microbicidal agent or by-products of 
sterilization remaining on a medical device after completion 
of the sterilization process. 
Spore:  A dormant state of an organism, typically a 
bacterium or fungus, which exhibits a lack of biosynthetic 
activity and reduced respiratory activity. 
Sterilant:  The active agent(s) which achieves 
sterilization. 
Sterile:  The absolute state where all forms of life have 
been eliminated.  In a practical sense absolute sterility 
cannot be proven, therefore sterility is considered achieved 
when organisms are eliminated, inactivated, or destroyed 
such that they are undetectable in standard media in which 
they have previously been found to proliferate. 
Sterility Assurance Level (SAL):  A value indicating the 
probability of a survivor after a sterilization process. 
For example, an SAL of  is the probability of one in one 
million nonsterile units after exposure to a sterilizat-ion 
process. 
Sterilization:  An act or process which completely 
eliminates or destroys all forms of life, particularly 
microorganisms. 
Unit:  The specified substrate or carrier upon which the 
specified number of test organisms are inoculated.  A unit 
may be a specified volume, weight, or surface area.  For 
example, a unit could be specified as an entire device, a 
component of a device (if the device must be disassembled 
prior to sterilization), or a portion of a device.  19.  Vegetative state:  An active growth phase of an organism. 
20.  Validation:  A documented program which provides a high 
degree of assurance that a specific process will 
consistently produce a medical device that meets its 
predetermined specifications and quality attributes.  C.  Classification of sterilizers 
~ lmled ical  devices in commercial  distribution  prior  t o  the  19-16 
medical  device  amendments  t o  the Federal  Food,  Drug,  and  Cosmetic 
~ c (tth e act), or so-called  pre-amendments  devices,  w e r e  
classified  by  FDA  into one  of  three regulatory  classes, Class I, 
11,  o r  111.  The  class established  the regulatory  control t o  be 
applied  t o  a  device i n  order  t o  provide  reasonable  assurance of 
its safety  and-effectiveness.  Class I  devices are subject t o  
general  controls as defined  i n  the act  (refer to DSMA  guidance on 
general  controls).  Class I1 devices are subject t o  general 
controls and any  performance  standards promulgated  by  FDA. 
Currently,  there are no  FDA  requlatory  standards  for sterilizers. 
- 
Class I11 devices are subject t o  premarket  approval. 
Steam,  dry heat  and ethylene oxide sterilizers are currently  the 
.only sterilizers identified  i n  .the classification regulations. 
They  are all Class I1 devices  (see 21 CFR.880.6860,  880.6870,  and 
880.6880).  A  new traditional or newer  technology  steam,  dry 
heat,  o r  ethylene oxide sterilizer may  .be claimed  equivalent t o  
t h e  specific related classified device.-  Likewise,  a -5-terilizer 
using a  different technology,  e.g.,microwave,  plasma,  etc.,  may 
also be claimed  equivalent t o  one of  the classified devices  or to 
any  other legally marketed  sterilizer (a pre-amendments 
. s t e r i l i z e r  or one  found  equivalent through the  510(k)  process).  . 
Even  though  a  broad range of  sterilizer technologies  may  be 
eligible for equivalency,  FDA  is not precluded  from  finding  a 
s t e r i l i z e r  not  substantially equivalent,  and  thus .a  Class I11 
device. 
D.  Related Regulatory Authority 
The  U.S.  Environmental  Protection Agency  (EPA),  under  the 
authority of  the Federal  Insecticide,  Fungicide  and  Rodenticide 
A c t   (FIFRA) , regulates  liquid chemical germicides  and  other 
'microbicidal  agents.  A  sterilant used  i n  a  sterilizer, 
therefore,  may  be subject to EPA  as w e l l  as FDA  regulations. 
Applicants  of  510 (k)s   for sterilizers that use  self  contained 
sterilants  (e-g.,  a sterilant in a  canister that  is connected  t o  
a  sterilizer) should  contact EPA  for further direction regarding 
any  applicable EPA  regulations. 
EPA  currently  is solely responsible for the regulation  of 
"portabl'e"  ethylene oxide sterilizers.  This type of  sterilizer 
was  intended t o  include  only  a bag  into which  EtO is  injected. 
Sterilizers  (or components  thereof)  regulated  both  by  EPA  and  FDA 
must  comply  with  the  requirements  of  each  agency  before  the 
s t e r i l i z e r  can  be  marketed.  11.  Documentation 
Presubmission Considerations for Applicants 
Establish that the sterilizer is a medical device subject to 
510(k) submission, i-e., it is intended for use in a health 
care facility to sterilize medical products. 
Discuss new technologies with FDA prior to 510(lc) submission 
to identify any unique aspects of testing or documentation. 
Contact the Chief, Infection Control Devices Branch as 
indicated in Part 11, Section Q. 
Determine whether the sterilant must comply with EPA 
regulations.  Prior EPA certification, or concurrent EPA/FDA 
review is desirable to minimize data redundancy. 
Ensure that the 510(k) addresses all sections 21 CFR 807.87, 
Information Required In A Premarket Notification Submission. 
Ensure that the 510(k)  submission addresses all-relevant 
elements of this guidance, or subnit a thorough 
justification for omission of information or data.  Use the 
checklist in Section S. 
Ensure that there are marketed accessories necessary to 
achieve a functional system, or concurrent submission of 
510(k)s  for necessary accessories.  For example, acceptable 
sterilization wraps (except for a flash node), biological  . 
and chemical indicators are necessary to provide a complete 
system for the user.  FDA will not find a sterilizer 
equivalent until a functional system is in place. 
Prereview submissions.  510(k)s  for sterilizers can be 
extensive.  FDA review of a document is facilitated when the 
document is arranged in a well-structured format that has 
undergone a thorough presubmission critique by the applicant 
to eliminate documentation deficiencies. 
Recommendations for Protocols and Data Analysis 
Provide all test protocols which include the objectives, 
experimental methods, controls, observations, statistical 
analyses, if possible, or other quantitative analysis, and 
conclusions and coments. 
Clearly define the aicrobial challenge and justify that it 
is appropriate for the system under examination. 
Specify the recove-  media and ensure that it contains all 
the elements for abundant qro.~th. Validace the recovery 
efficiency of the cedia and submi:  a sumrzry of the  validation. 
Define the  neutralizer  for the sterilant,  i f  needed,  and 
control  for  its affect upon  microbial  growth. 
Ensure that the biological  tests evaluate t h e  safety and 
effectiveness of  the sterilizer  for the entire.specified 
range of  each process parameter. 
Identify and  analyze the  factors that w i l l  lead t o  a  failure 
to achieve the required  level of  effectiveness and  reflect 
these factors i n  the labeling. 
Provide tables and  graphs  t o  i l l u s t r a t e  the results of 
testing. 
Provide literature references used  for protocols and 
analyses. 
Test methods  must  be scientifically sound  and  reproducible, 
and based upon  "state-of-the-art"  procedures,  ideally 
reflecting a  generally recognized  consensus  of  scientific 
opinion. 
Documentation  for Classified Sterilizers 
This guidance identifies the fundamental documentation  needed  to 
evaluate the substantial equivalence  of  a  sterilizer. 
Classified,  traditional  steam,  dry heat,  a s  w e l l  as ethylene 
oxidesterilization processes  are w e l l  established  and much 
information is available regarding these technologies  and  their 
limitations.  As such,  FDA  recognizes t h a t  some  portions of  t h i s  
guidance are either not critical t o  the three originally 
classified traditional sterilizers or the current information 
base on each type of  process  is sufficient to satisfy certain 
'data  provisions. 
-Specific sections of  the guidance w i l l  indicate when  the 
information requested  is not  needed  for a  classified,  traditional 
sterilizer.  For  now,  s m a l l  table top s t e a m  or EtO units are not 
considered traditional  for purposes  of  t h i s  document,  but  FDb may 
. include these devices once industry performance  standards  are 
established. 
D.  EPA  certification 
I f  applicable,  provide  any  registration  number  assigned  by  EPA  co 
an  EPA  regulated  sterilant used  with  the sterilizer,  or  indicate 
whether  a  review  by  EPA  is pending  i n  order  t o  f a c i l i t a t e  EPX/FDA 
interaction on  data.  Provide  a  summary  of  the data  submitted  t o  
EPA  For  registration  purposes.  E.  Reference to Standards, Practicos, ~echnicalR eports, 
Guidelines and Method- 
Identify  a l l  published  standards,  practices,  technical  reports, 
guidelines,  codes,  and  test methods  upon  which  the design, 
labeling,  and  testing of  the sterilizer are based.  Indicate any 
deviations  from  the referenced  docunents.  There  are currently no 
FDA  regulatory  standards,  specifications,  or test methods 
applicable t o  sterilizers. 
The applicant should  carefully consider the content of  referenced 
standards,  technical  reports,  guidelines,  codes,  and  test methods 
in regard  t o  additional design,  testing,  and  documentation 
provisions not  indicated in this guidance.  The referenced  .- 
documents may  indicate specifics that are pertinent and unique t o  
the subject sterilizer,  whereas this guidance  is generalized, 
i-e.,  a  baseline document.  FDA  may  refer the applicant,  i f  
necessary,.to  additional published  documents  germane  t o  the 
subject sterilizer.for further guidance.  A  summary  of  a l l  tests, 
conducted  in accordance with  the ret'crenced  documents  and  i n  
addition t o  t h i s  guidance,  should be submitted.  The submitter 
incurs  an obligation t o  abide by  an).  document which  the 
sterilizer is claimed  t o  m e e t  as supportive evidence of  safety 
and  effectiveness. 
The  following documents  provide a.si?nificant amount of 
information on  validation of  new  sterilizers,  and  have  been  used 
a s  references  i n  developing t h i s  CpziLance: 
AAMI  Sterilization Standards  for steam and  EtO 
Block,  S.E.,  Disinfection.  Sterilization,  and 
Preservation,  Fourth Edittan,  Lea  &  Febiger,  Phila.  Pa. 
1991. 
Sterile Medical  Devices,  A  GMP  workshop  Manual,  FDA 
Publication  884-4174  Labeling 
F. 
The applicant must submit labeling for the sterilizer.  Labeling 
describes the intended use of the device, its operating 
characteristics, and limitations.  These factors are essential in 
establishing whether the device is equivalent to other legally 
marketed sterilizers. 
1.  Device Markings 
Indicate the information affixed to the device.  Markings 
may include identifying information, warnings, directions 
for use, or system requirements.  Provide labeling for any 
accessory sterilants used with the sterilizer, e-g., a 
chemical agent.  Chemical agents regulated by EPA also 
require mandatory labeling in accordance with EPA 
regulations. 
2.  Information Manual 
Submit the instructions for use manuals which shall include: 
the intended use of the sterilizer (listing the medical 
devices, specific types of materials, and other 
compatible medical products that can be sterilized by 
the process) 
; 
limitations of use (medical devices,types of materials, 
and medical products that are incompatible); 
name and address of the manufacturer; 
type and model designation; 
.installation instructions; 
detailed operating instructions for all modes; 
storage and preparation of the sterilant, if 
applicable; 
error or fault indications, their cause; and response; 
interpretation and use of indicator gauges: 
how to prepare articles for processing including 
precleaning recommendations and required packaging; 
post processing information including residue 
information and sterilant exposure guidance; 
environmental or other factors affecting efficacy and 
11  safety of  the device; 
n.  any  applicable warnings,  hazards,  and  precautions; 
o.  instructions for routine monitoring  including use  of 
chemical,  biological  indicators,  and  test  packs;  and 
p.  other relevant information  regarding  the use of  the 
sterilizer and  a  source of  further information should 
the user have a  question. 
3.  Service Manual  [NOT  NEEDED  FOR  TRADITIONAL  STERILIZERS] 
Submit the service manual  for the device which  includes: 
a.  a detailed description of  a l l  the tasks that must be 
accomplished t o  maintain  the s t e r i l i z e r  i n  proper 
operating condition,  e-g.,  routine maintenance  and 
inspection  instructions,  calibration  of  instruments, 
etc. ; 
b.  the schedule for these tasks,  and; 
c.  who  is responsible  for the tasks  (user or authorized 
. 
service personnel) 
G.  Changes  to a Sterilizer Requiring a  New  SlO(k) 
The SlO(k)  regulation states that a  new  510(k)  is needed  whenever 
t h e  device or t h e  manufacturing  process  is changed  i n  a  manner 
t h a t  may  significantly affect its safety and  effectiveness.  The 
following are some types of  conditions which require submission 
of  a  new  510(k)  for a  sterilizer: 
1.  A  new model  number  designation unless  it is solely a 
labeling identification change. 
.2.  Any  change  in sterilization vessel  dimensions. 
3.  A  change  t o  software o r  firmware  from  a  mechanical  control. 
- 
4.  A  change  i n  the specific sterilant used  i n  the device. 
There w i l l  be  a  separate policy available  from  FDA  i n  April 
1993 on  changes  t o  certain EtO  mixtures. 
H.  General  Description of  the Sterilizer 
1.  Specifications:  Design,  Construction,  Components 
a.  Provide  a  complete physical description of  the 
sterilizer.  The  description  can  consist of  detailed 
drawings,  photographs  and  brochures.  The  exterior and  interior dimensions and  component  lOCati0n~s hould  be 
indicated. 
b.  Describe  the materials used  to construct the major 
components  of  the sterilizer,  e.g.,  the sterilization 
vessel,  jacket,  sterilant generator,  etc.,  and  certify 
that the materials m e e t   the sterilizer requirements. 
c.  Identify a l l  manual  or automatic controls, 
instrumentation,  recorders,  vents,  inputs,  outlets, 
filters,  and  safety features. 
d.  Indicate device  installation requirements,  e-g., 
electrical,  venting,  plumbing,  etc.. 
e.  Describe the sterilant formulation  and  its container, 
i f  provided  a s  a  stand alone accessory to t h e  
sterilizer,  i. e. , sterilant provided  i n  cartridge form, 
etc..  Provide shelf-life  data  on  the sterilant i n  its 
container,  including total life i f  i n  a multidose 
container. 
. 
f.  Describe a l l  accessories marketed  with the s t e r i l i z e r  
such as racks,  trays,  carts,  etc.  Certify that the 
accessories  are compatible with the sterilizer process. 
2.  Process Parameters 
a.  Describe a l l  physical and/or  chemical  process 
parameters,  whether primary  to the process  or 
secondary.  For example,  microwave heat generation may 
be the primary  sterilant but  W  irradiation may  be 
generated secondarily.  Parameters may  include,  for 
example,  time,  temperature,  pressure,  humidity,  . 
wavelength,  intensity,  concentration,  preprocessing 
conditions,  and  postprocessing  conditions. 
. 
b.  Provide the specifications for each  parameter. 
3.  Process Monitors 
a.  Describe  the gauges,  chart recorders,  displays,  etc. 
which  monitor the process parameters.  Include 
information  on  specifications  of  the' instruments  and 
sensors  (accuracy,  precision,  range,  specificity', 
sensitivity) and  relation to recognized  standards. 
b.  Describe  the sensor locations  within  the sterilization 
vessel.  Since sterilizing conditions,  e.g., 
temperature,  may  vary  in different locations  i n  a 
vessel,  indicate  how  the sensor locations correspond  t o  
the  relevant  "cold  spot"  i n   the vessel  (least favorable  - 
location  for sterilization)  Describe  hou  the  "cold 
spotw was  deterained,  e.y.,  thermocouples.  State now 
a l l  load  conditions were  considered when  cctermining 
the dynamics  inside  the  chamber. 
c.  Certify that the monitors  correlate t o  a c x a l  chamber 
conditions. 
d.  Describe all fault conditions related  t o  =3ch of  the 
process parameters,  including under what  a n d i t i o n s  a 
fault is detected  and how  the s t e r i l i z e r  r+sponds 
. 
(e-g.,  indicator,  printout,  etc. ) 
3.  Software Documentation 
Provide the data  indicated in t h e  FDA  Software Xeviewers 
Guide  (available from  FDA  Division of  Small  Mazufacturers 
Assistance)  for 510(k).  Unless  otherwise directed  by  FDA, 
s t e r i l i z e r s  are considered  i n  t h e   'moderate* risk category 
described  i n  the software guidance. 
I.  Cycle Overview 
Provide a  detailed overview of  the sterilizaticn process,  i n  
order t o  provide a  foundation  f o r  evaluation 05  t h e  device 
and  test data.  Supplement  the description hy .=?arts,  graphs 
o r  other visuals detailing a l l  parameters  and iades. 
J.  -Test Packs 
Test packs  are used  i n  validating performance  %id  i n  routine 
monitoring  of  the device once  it is commerciall:~ available. 
The  test pack  is constructed  to represent  a  riyarous 
challenge t o  the sterilizer.  A  biological  aoni=or is placed 
i n  the pack  and  the pack  is placed  i n  a worst ase load  i n  
t h e  cold  spot.  There should be a  test pack  for each  type  of 
load  indicated  i n  labeling.  For  example,   tier^  a r e  fasric, 
liquid,  and  wrapped  instrument  test packs  idenzified  for 
steam sterilizers. 
The  applicant should  refer to relevant standar&  f o r  t e s t  
pack  specifications,  when  applicable.  Applicanzs  of  tlrpes 
of  sterilizers with no  validat .:  3  "stand-Y-,U- '"  t e ~ =pa ck  (e-g., 
table top  units and  dry  heat)  :!~ould still devise  and 
validate either test packs  Tot  :Is@ with  their !?vice,  or a t  
least t e s t  load  conditions  for  :mrposes of  roc:ine 
monitoring. 
Submit a  detailed description  .  :' the  test pack  5)  used  i n  
validating  the performance  of  device,  2nd ::?at  w i1  l  be 
' .te 
used  i n  routine  performance  .toring  b;.  -,he _ ~ e r .  
rnt.  Describe the rationale for the composition of the test pack 
including how the test packs represent a rigorous challqnge 
to the sterilization process-  Describe how the test pack 
itself was validated.  Describe the pack and how it is to be 
used in labeling. 
K.  Equivalent Devices and Previous submissions 
, 
Identify and compare the subject sterilizer to another legally 
marketed sterilizer.  A finding of equivalence is facilitaked the 
closer the technology of the legally marketed device matches the 
subject sterilizer.  Reference the 510(k) numbers for the claimed 
predicate devices, if known.  Side bv side comparisons, whenever 
possible are desirable (See Attachment 1). 
1.  Submit labeling for the claimed equivalent sterilizer, if 
possible. 
2.  Compare and contrast the technologies. 
3.  Compare and contrast the specifications.  1.  Traditional Steam, Dry Heat, and EtO Sterilizers 
Certify that the sterilizer will achieve and maintain the 
relevant physical cycle specifications (time, temperature, 
sterilant concentration, humidity, pressure, etc.)'  within 
specifications under appropriate test load conditions.  The 
required lethal conditions are those determined by 
biological performance tests (see following sections). 
2.  Other Sterilizers 
a.  Describe the rationale for the process parameters and 
specifications.  Briefly summarize how the biological 
performance test results described in the following 
sections were used to define the parameters. 
b.  Provide a summary of physical tests which demonstrate 
that the sterilizer achieves and maintains the required 
physical/chemical process lethality conditisms within 
specifications.  These data should be from repeated 
runs with varying load conditions.  14.  Dialogical Performance Tests 
1.  General 
The applicant must unequivocally demonstrate that the device 
can sterilize, to an acceptable SAL, all the medical 
products identified in the labeling, when used.in -accordance 
with the directions for use. 
2.  Test Organisms 
Since a consistent type and concentration of bioburden 
cannot be assured or realistically evaluated in a health 
care facility, an overkill sterilization is necessary.  The 
sterilization cycle is based upon an initial concentration 
of at least lo6 CFU (or Plaque Forming Units - PFU)/unit  of 
a highly resistant organism to the process.  Typically, the 
most resistant organism to a sterilization process is used 
based upon determination of D-values.  Table 1 lists the 
commonly recognized test organisms for the classified 
. - 
sterilizers. 
TABLE 1 
TEST ORGANISMS FOR CLASSIFIED STERILIZERS 
Sterilizer  Organism 
steam  Bacillus stearothermo~hilus (ATCC 7953) 
dry heat  Bacillus subtilis var. niger (ATCC 9372 or 
19659) 
.E tO  Bacillus subtilis var. niger (ATCC 9372 or 
19659) 
The biological lethality profile of a nontraditional 
sterilization technology must be exhaustively evaluated since the 
' 
most resistant organism is initially unknown.  Table 2 identifies 
recommended organisms t= test for determination of the most 
resistant organism.  TABLE  2 
TEST  ORGANISMS  FOR  NONTRADITIONAL  STERILIZERS 
A.  B a c t e r i ~ lS pores 
B a c i l l u s  subtilis var.  niqer  (ATCC  9372  or 196-59) 
B a c i l l u s  s t e a r o ~ h e r m o p h i l u s( ATCC  7953) 
Clostridiuzn  sporoqenes  (ATCC  3584) 
M y c o b a c ~ e r i u mt uberculosis var.  b& 
(or other representative mycobacterium) 
C.  N o n l i p i a  V i r u s e s  
poliovirus  Type  I1 
D.  Fungi 
Tricophvton  rnentacmophvtes  (with  conidia) 
E.  V e q e t a z i v e   B a c t e r i a  
Stz~hvl3coccusa ureus 
Salmonella  choleraesius 
Pseudomnes aer~qinosa 
F.  Lipid V i r u s e s  
herpes s i m p l e x  
G.  T E L  I'i3RATURE  OR  OTHER  INPONCXTION  MAY  SUGGEST ADDITIONAL 
TEST OXGABISMS  DEPENDING  UPON  THE  TECHNOLOGY  OR THE  TYPICAL 
BIOBUR@2N SNCOCNTERED  BY  THE  ARTICLES  INTENDED  FOR 
REI3ROCZSSING  I!;  TEE  STERILIZEP. 
;..  3 .   Biological Test Battery 
The biological test data shall include the following: 
a.  a summary of the sporicidal screenins test (NA* FOR 
TRADITIONAL STERILIZERS]: 
b.  the sterilization process equivalent time (F value) 
[STEAM AND DRY HEAT ONLY]: 
* 
c.  determination of D-values based upon (1) survivor curve 
analysis, and (2) fraction negative analysis [NA POR 
STEAM AND DRY HEAT or as alternative to item b.  above 
for steam and dry heat) ; 
d.  1/2 cycle Analysis, and Total Kill End Point Analysis 
[NA FOR TRADITIONAL STERILIZERS except 1/2  Cycle 
Certification for Traditional Sterilizers]; 
e.  simulated AND in-use tests with representative medical 
products indicated in labeling [NA FOR TRADITIONAL 
STERILIZERS except as noted];  and 
f.  comprehensive analysis of all biological test data and 
determination of the process parametars. 
* 
XA  = Not generally applicable but could be requested if other 
3ata or information are equivocal.  Sporicidal screening Test 
The applicant must provide a summary of the American Association 
of Official Analytical Chemists (AOAC) Sporicidal Test, Section 
966.04, Volume 1, Page 141 [Horowitz, William, ed. Sporicidal 
- 
test  official final action.  Official Methods of Analysis of 
the Association of Official Analytical Chemists.  Current 
Edition.  Association of Official Analytical Chemists, 
Washington, D.C.].  This test is also used for EPA registration 
purposes.  If EPA accepts or requests another test for 
registration purposes for an EPA regulated sterilant used with 
the subject device then a summary of the results from that test 
should be provided.  Indicate the specified time for 
sterilization.  . - 
Sterilization Process Equivalent Time 
Thermal resistance.of microorganisms can be considered in terms 
of equivalent process times (F,) at a given temperature. 
Saturated steam and dry heat sterilizers are special~casesw here 
equivalent times are useful for evaluating the acceptability of 
the process conditions. 
Typically, dry heat and gravity steam sterilizers each employ 
similar operating modes and process conditions as a group (e.g., 
121 C and 15 psi for a regular steam cycle).  Some dry heat and 
steam sterilizers may vary from the norm.  As a general rule, a 
higher temperature results in a higher rate of death of 
microorganisms.  Still, there are constraints to saturated steam 
and dry heat process conditions in order to maintain acceptable 
lethality conditions. 
Physical parameters and microbicidal effectiveness with standard 
test organisms have been extensively characterized for steam and 
'dry heat sterilizers.  Actual operating temperatures can be 
correlated to a sterilization process equivalent time, or Fo 
-value (a special case equivalent time), at standard temperatures. 
Saturated steam operating temperature can be converted to 
equivalent microbial lethality anticipated at 121C while dry 
heat temperatures can be converted to 170C equivalent process 
times.  An Fo of 12 (minutes) for both processes is minimally 
acceptable (12 log reduction).  The method for conversion of 
proc=ss parameters is beyond the scope of this document. 
Mathematical methods are extensively described in the literature. 
Submit the equivalent process time and its method of derivation 
for the saturated steam or dry heat sterilizer for all modes of 
operation.  D-Valuc  Determination 
The  D-value  of  an organism  exposed  to a  specific sterilization 
process  can  be  established by  one  of  two  methods,  survivor curve 
analysis  or fraction negative  analysis.  For  unclassified 
sterilizers the resistance profile of  a  battery  of  test organisms 
should  be  determined  using  survivor curves.  Once  the most 
resistant test organism is identified  (or possible  candidates 
that require more  testing) with  preliminary  D-values  from 
survivor curves,  then  tests should be  conducted  using the 
fraction  negative method.  A  survivor curve  is a  necessary 
precursor  to fraction negative analysis t o  roughly  estimate the 
quanta1 region  (the lo2 - lo-* CFU/unit  vs  t i m e  region) f o r  a 
particular test organism.  I f  different types  of  loads a r e  
provided  in labeling  (e-g. ;l iquid,  fabric,  instruments)  then  the 
applicant must  evaluate the kinetics i n  each  type of  load.  . 
 h he  following  is a brief  overview  of  methods  and  data  t o  be 
reported.  For  moredetail,  refer t o  the literature. 
Survivor  Curve BY D i r e c t  Enumeration  . -. 
A  survivor curve plots the surviving microorganisms  against a 
critical process  parameter,  usually time.  The  curve provides  an 
important graphic representation of  the kinetics of  the 
microbicidal  process.  The curve should be based  upon  a t  least 5 
replicated data  points using  the test organism.  Separate curves 
should be  established  for "clean"  test organisms  and  for test 
organisms prepared  in an  inorganic and  organic load of  hard w a t e r  
and  serum,  respectively.  The  organic load shall be a t  least 59 
bovine  serum.  The organic load shall be hard water as defined 
under AOAC  test method  960.09  E.  (referenced above).  Controls 
must  be  fully described. 
I n  one variation of  a  survivor curve determination,  a  specified 
'concentration  of  the test organism  is prepared  on  a  carrier.  The 
test organism  is placed  in the sterilizer in a  simulated  load 
configuration.  The most  rigorous  load conditions may  vary  with 
the sterilizer technology and mode  of  operation  and  it is up  t o  
the applicant  t o  determine the most  rigorous  load conditions. 
The  process proceeds  for a  fraction of  the total process  t i m e ,  
-the test organisms  are withdrawn  and  neutralized,  if  necessary, 
extracted  from  the carrier,  i f  necessary,  serially diluted,  and 
placed.onto validated  growth  media.  The  surviving  organisms  are 
directly enumerated.  In this method  multiple  fractional  tests 
are needed  to assemble sufficient data  t o  define  the survivor 
curve.  The  tests are repeated  and  curves established with 
different  loads  to evaluate variability  in process  kinetics and 
optimal  load  configurations.  This  information  defines the 
process  conditions  that are  noted  i n  labeling.  O t h e r   test 
variations may  use  B I s  and  B I s  i n  test  packs,  but  the applicant 
must  justify  that whatever  method  was  used  represents worst  case  conditions 
Plot the survivor data  on  semi-logarithmic  paper  and  calculate  a 
line of  best  f i t ,   y  =  mx  +  b  where: 
m  = slope 
x  = t i m e  
y  = log  of  number  of  survivors 
b  = the y  intercept a t  t i m e  0. 
Statistically evaluate the data using  regression analysis  (ANOVA) 
and  submit the analysis.  Any  adjustment  of  the curve o r  
analysis,  e-g.,  dropping  of  points,  must  be  fully justified. 
The  D-value  is the negative reciprocal  of  the slope of  the 
survivor curve  (-l/m).  This analysis is valid i f  the dynamics  of 
microbial  k i l l  follow first order kinetics,  e-g.,  data  are 
linear.  Linear correlation is evaluated as.part  of  the ANOVA 
analysis. 
Care.must be taken not  t o  underestimate a  D-value  which  occurs 
when  (1) there are insufficient replicates  (2)  the intercept 
ratio  (ratio of  the y  intercept t o  the initial inoculum  I R  = 
Yo/logNo)  of  the survivor curve is one o r  greater,  or  (3)  the 
death r a t e  curve is inappropriately extrapolated. 
An  i n i t i a l  test inoculum greater than  lo6 CFU/unit,  i f  possible, 
is recommended  i n  order t o  minimize  the effect of  counting 
inefficiency below  the  lo2 CFU/unit  level and t o  extend the 
assurance of  Linearity  of  lethality beyond  a  6  logarithmic  range. 
Fraction Nesative Method 
The  fraction negative method  is another means  t o  derive D-values. 
In one variation of  a  fraction negative test,  replicate test 
organisms as described  above  are exposed t o  a  fraction of  the 
total process t i m e  that correlates t o  the quanta1 region  (lo2 t o  
CFU/unit  vs t i m e  region),  then  the replicates are 
transferred t o  validated  growth media,  and  incubated.  A s  above, 
repeated  tests w i t h  clean test organisms and  those prepared  i-n  an 
inorganic and  organic  load  should be  accomplished.'  Controls must 
be  fully described.  The  fraction of  samples  in a  test group 
negative  for each  t i m e   interval are used  in deriving t h e  D-value 
using  either  (1) the Stumbo-Murphy-Cochran  Method,  or  (2)  the 
Spearman-Karber  Method.  Again,  riqo~ousl oad conditions  must  be 
considered.  1.  Stumbo-Murphy-Cochran  Method:  The  Most  Probable  Number  of 
organisms  a t  esch  time  point  are determined  using  t h e  
Halvorsen-ziegler  equation 
Nu  =  2-303  log  (r/q) x  (r) where: 
r =  number  of  replicates 
q  = t h e  number  of  negative  replicates 
Nu =  the number  of  survivors i n  r replicates 
- 
The  D-value  is then derived by  D  =  U/Log  a  Log  b  where: 
U = t h e  process  t i m e  
Log  a  = the initial number  of  organisms 
Log  b  = Log  Nu. 
2.  Spearman-Karber  Method:  This method -uses a  mean  t i m e  until 
sterility t o  calculate a  D-value.  This calculaton is 
somewhat  more rigorous  since it permits a  valuable 
statistical evaluation  of  the derived D-value.  The 
following  equa5.on  is used 
D,  = USJ log  No + 0.2507  where: 
Us, = Spezrman-Karber  heatinq  t i m e  estlmate 
No  =  initial  inoculum 
D,  = D-vzlue 
Whenever  possijle,  the Spearman-Karber  method  should be used 
and  statisticzl evaluation submitted.  112  cycle validation,  2nd Total  X i 1 1   End  Point  Validation 
once a  D-value  and  preliminary  ?recess parameters  are established 
(e.g.,  t o  achieve an  SAL of  10.:).  the effectiveness of  the 
process  should be  further confirmed  bf a  1/2  cycle Validation  and 
a  Total  K i l l  End  Point  Bracket 7alidz:ion.  The  t w o  tests can  be 
combined. 
In a  1/2  cycle validation  for zraditional  sterilizers,  replicates 
of  the most  resistant  organism 3n  appropriate carriers  (or BIs  i n  
test packs)  are placed  i n  a  s i x l a t e d  worst  case condition load 
a t  the cold spot and  exposed  tz 1/2  i5e sterilization, process. 
The  test organisms  a r e  then  innbated i n  validated media  under 
appropriate conditions along wi-A  conrrols.  The media  should.-not 
exhibit any growth.  What  consritutes a  1/2  cycle for a 
nontraditional  s t e r i l i z e r   (e. g.,  a  multistep process)  should be 
w e l l  defined.  It may  consist cf a  razio of  steps,  and/or  may 
require several tests of  holdizq one step constant while varying 
other steps. 
For traditional  sterilizers,  FCZ  vill accept a  certification of 
expected  performance  for t h e  1;2  Cycl* Test. 
I n  the Total Xi11 End  Point  Br~cket\' =lidation  a  somewhat more 
rigorous procedure,  replicates units vith a  10'  CFU/unit 
inoculation of  the m o s t  resistcit  tesr organism  (or B I s  i n  test 
packs)  are placed  i n  a  t e s t   loc5 simulating the worst  case 
condition at the cold  spot.  A  zest 13ad  is exposed  t o  1/2  the 
sterilization process  (typical::,  1/2  --he  process t i m e )   and  other 
test loads a t  incremental  times grearsr than and  less than the 
calculated 1/2  cycle.  A t  leas:  f i v e  increments  above and  five 
below t h e  1/2  cycle t i m e  are reconmen5ed  with  a t  least 110 t o t a l  
test units evaluated  (10 per tixe  point  including the 1/2  cycle). 
The  t i m e  increments should  spa::  1/2  c:  t h e  t o t a l  process  t i m e  
(from  1/4  cycle t o  3/4  cycle).  Alterzative methods  should be 
'described  in detail and  jus=if ied. 
The  test organisms a r e  then  grz-3 i n  zedia  that support abundant 
growth  and  a  representative  nui3er  f r ~ mea  ch time point a r e  grown 
a t  differing conditions t o  Groxte gr3wth  of.injured organisms. 
Incubation times  should be  sxt~ndedc 3 a t  least 3-4  weeks  t 7 ~  
optimize the potential  for  recxery 2d:  growth  of-v  iable 
organisms. 
The  data  should  identify no  gr=:-th  a:  conditions  equal  t o  and 
beyond  the 1/2  cycle  ( e , n o  "s:<ips")  and  corresponding  growth 
under  conditions  less than  rhe 1/2 cyzle.  A s   always,  appropriate 
controls  should  be  run  conc-~rreatly. Skips or other  failures 
beyond  the  1/2  cycle must  b= tl-.2rougily  evaluated  and  discussed 
i n  the  submission.  Adjustmsnt  JE  thr  cycle parameters  may  be 
required  to ensure  s t e r i l i t y .   Other  Methods 
A  total  k i l l  validation  is also described  i n  literature where 
replicate  runs  are evaluated  for t o t a l  k i l l .   This process  is 
less  reliable a s  far as basic cycle validation  is concerned,  but 
it conceivably could be appropriate  for a  particular type of 
s t e r i l i z e r  technology  that is not amenable  t o  traditional  forms 
of  analysis.  A  l i m i t e d  total k i l l  method  is used  in the  final 
qualification validation as described  below  i n  Section Q. 
Simulated and In-Use  Tests 
Simulated  or  in-use  tests are not  required  for traditional, 
classified sterilizers  except when  articles are indicated  in t h e  
labeling  for traditional sterilizers that are not identified in' 
predicate devices,  or are not generally  recognized  i n  t h e  
literature and  by  the infection control community  a s  usually 
being  sterilized with the-particular process.  Public health risk. 
concerns may  demand. that FDA  require additional testing from t i m e  
t o  t i m e  to (re)validate traditional sterilizer effectiveness. 
For  example,  additional testing has been  requested  fordental 
handpieces. 
Sterilizers that are tested i n  health care facilities are subject 
t o  the investigational device exemptions  (IDE) regulation,  21 CFR 
Part 812,  i f  t h e  processed medical product  is intended t o  be 
returned  t o  service without  first undergoing  a  follow up 
sterilization procedure with  a  legally marketed  sterilizer. 
S i ~ u l a t e dU se Tests 
.Sterilizer microbicidal performance must  be tested under 
simulated use conditions.  The applicant must  justify how  the 
simulation correlates t o  in-use  worst case conditions. 
'Select  a  representative sample of  medical' products indicated i n  
labeling.  The  tests must consist of  replicates of  devices and 
types of  materials  that are indicated  for sterilization,  e-g., 
metals,  polymers,  elastomers,  adhesive resins,  paper,  and 
fabrics.  The  articles.selected f o r  each material  should  exhibit 
design  configurations  that w i l l  provide  the greatest challenge t o  
'penetration of  the sterilant,  e-g.,  lumens,  mated  surfaces, 
hinges,  gnarled surfaces.  Test loads should be  a s  noted  i n  
labeling,  packaged  properly,  and  oriented  h~cordingt o  labeling. 
The  test  articles must  be  inoculated with  a  10'  CFU/unit  of  the 
most  resistant  test  organism  prepared  with an  inorganic and 
orqanic  load.  Allow  the inoculum  t o  dry  on  the article before 
placement  i n  t h e  sterilizer.  The  inocula  must  be  placed  i n  
various  locations on  the test articles including  those  least 
favorable  to penetration and  contact w i t h   the  sterilant,  e.g., 
l u ~ e n s ,m  ated  surfaces,  hinges.  Include  controls  for each  type  of article. 
In Use Tests 
Sterilizer performance must also be verified under in-use 
conditions.  Articles sampled.after use should be precleaned (or 
decontaminated) according to the normal operationat reprocessing 
protocol of the health care facility where the samples are 
obtained.  Assurance of meeting a stringent precleaning protocol 
is not a precondition since the robustness of the sterilization 
pr.ocess is part of this evaluation.  Multiple tests with 
differing load conditions as indicated in labeling should be 
reported. 
'fter  processing, the test articles are neutralized, if 
.  necessary.  The articles are immersed in the growth media, if 
possible, or subjected to an extraction method with the extract 
placed in growth media.  Publications and the literature contain 
suitable extraction methods. 
Derivation of the Process Parameters 
The process parameters for the sterilizer shall be derived from 
the screening test, process equivalent times, D-value- 
calculations, simulated or actual use testing, 1/2  cycle and End 
Point tests, and any additional safety factors.  For process 
validation an SAL of at least  based upon the most resistant 
test organism, shall be demonstrated.  Provide a thorough 
description of the derivation of the process parameters.  N.  Toxicity of  the sterilant and  Process  By-Products 
The  sterilant and/or  the by-products  of  sterilization may  be 
toxic.  The  applicant  musc  determine  the toxicity  profile of  the 
sterilant,  and  the nature and  level of  the sterilization by- 
products  and  their toxicity profile.  Toxicity data  for the 
sterilant and  its by-products  may  be  part of  a  submission  for EPA 
registration.  If so,  a summary of  the data  should be  submitted 
. 
in the 510 (k) 
Selection of  the appropriate  test protocol and  experimental 
conditions t o  establish the  toxicity of  the sterilant(s) and  by- 
products  is influenced by  several factors,  including the 
potential  routes of  exposure,  the anticipated magnitude  of 
exposure,  and  physical/chemical  properties of  constituents of  the 
agent  o r  its by-products.  The testing may  vary  depending upon 
the antimicrobial agent,  its  intended use,  and  directions for 
use.  It is incumbent  upon  t h e  applicant t o  select reliable 
state-of-the-art  m&thodologies t o  demonstrate the safety of  the 
antimicrobial agent f o r  its intended  use.  Data  submi-t ted t o  EPA 
may  not  address  a l l  of  the above  factors. 
Details of  the types of  tests  necessary t o  derive toxicity data 
are beyond  the scope of  this  document.  The  submitter should 
refer  t o  the Tripartite Biocompatibility  Guidance  for Medical 
Devices,  the literature,  and  other relevant publications  for more 
information. 
0.  Elimination of  Toxic  Process Residues 
The  sponsor must  establish what  sterilant or by-products  residues 
remain  on/in  the medical  product..  The concentration  of  residue 
may  vary  depending on  the product.  The  identity of  the residue, 
its concentration on/in  the various  materials processed  (scope of 
materials defined  in labeling),  and  a  comparative analysis of 
'these values t o  a known  toxic  level  must  be determined  and 
. 
-p resented in the 510 (k) 
The  applicant must describe t h e  means  t o  reduce  a  toxic level  of 
residue t o  an  acceptable level.  Test data must  be  submitted 
which  demonstrate  that  the procedure  to reduce  the residue  is 
-effective under  all potential  conditions.  Labeling must  include 
the procedure.  p.  Processed Device/Naterial Qualification 
Introduction 
Labeling for a sterilizer indicates the types of medical devices 
and other medical products and/or the component materia-1s of a 
medical device or product that are compatible with the 
sterilization process (noted in this section as "articles"). 
Data shall be provided which attest to the compatibility of each 
of the listed articles with the sterilization process.  The data 
shall address the effects of the process on the safety and 
effectiveness, e-g., functionality/specifications, of the claimed 
compatible articles, and the effects on the biocompatibility of 
the articles. 
The applicant must carefully consider labeling and the 
implications of the scope of the compatible articles on the 
potential test regimen.  If the articles in the intended use 
statement in labeling are limited and specifically characterized 
then the scope of testing is a relatively simple matter.  As the 
intended use becomes more generalized the scope of testing 
becomes more complex.  For example, if ASTM  316 stainless steel 
instruments are indicated as compatible devices then the test 
article is basically defined.  On the other hand, reference to 
"metal" instruments connotes a plethora of material 
possibilities.  The same is true regarding a general reference to 
"polymers" rather than a specific class and type of polymer. 
When the labeling indicates a general class of articles that 
could be differentially affected by the sterilization process, 
the applicant must specify and justify a representative sample of 
articles from the class for testing.  Even after 510(k) 
submission the applicant should- continue with a vigorous program 
to analyze new products and those articles that were not tested 
in the defined class.  These data may  serve as a basis for 
'labeling revisions or as a resource for users on the 
compatibility of the sterilizer-  As  noted in the labeling 
' ssction, users should be directed to call the manufacturer to 
obtain any current information on devices and materials not 
listed in the labeling. 
Even though testing may qualify an article for the'subject 
sterilization process the labeling ef  the article may identify a 
specific type of sterilization process to be used.  In this case, 
the labeling for the subject sterilizer cannot supersede the 
device labeling.  The applicant may choose to communicate with 
the manufacturer of the qualified arricle to modify the labeling 
for the article. 
Ic may be possible that certain elt.:...-entso f this battery of 
testing can be combined with the bi>loqical tests noted in 
S2cticn K in order to minimize tes'  'J  .  process  Life Determination 
A  factor  i n  a l l  compatibility  tests  is the duration  of 
compatibility,  i - e . ,   how  many  cycles  an article can  withstand 
before  it fails or  is otherdise unusable.  A r t i c l e s  that are 
compatible with  a  sterilizer are those that retain thei-r safety 
and  effectiveness  for their  intended  use after an acceptable 
number  of  reprocessing  cycles.  The  acceptable number  of  cycles 
t o  failure can  be  correlated  t o  the classified sterilizers  o r  
based  on  user preference.  Unless  there  is adequate 
justification,  i n  no  case should an  a r t i c l e  f a i l  when  exposed  t o  
fewer cycles than possible with a  classified sterilizer. 
Data  shall be  submitted  on  the process l i f e  of  the claimed 
compatible articles.  I n  soae  cases,  the test a r t i c l e  may  not 
exhibit significant,  quantifiable deteriorationafter numerous 
cycles.  If t h i s  is the case,  the applicant may  submit a 
justification  f o r  a  projected  compatibility of  the material  o r  
device based upon  analytical methods  i n  order t o  minimize  the 
extent of  testing. 
Functional compatibilitv of  A r t i c l e s  
Characterize the effect of  repeated  sterilization processes  on 
the functionality of  replicates of  t h e  representative test 
articles.  The  functionality parameters  can be  determined  on  the 
basis of  use  requirements,  specifications of  the device and  t h e  
component  materials.  The nethods  of  evaluation  should be 
objective,  whenever  possible,  e-g.,  tensile properties,  flexural 
properties,  impact r e s i s t a ~ c e ,h ardness,  compressive  strength, 
burst strength,  tear strencth,  color,  dimensions,  permeability, 
optical  transmission,  electrical resistance,  etc..  The  tests 
must  incorporate simulzted use conditions on the test articles 
between  processes.  There .=re extensive published  test methods 
for each  parameter  and  the applicant should refer t o  these 
methods  i n  devising test protocols. 
Biocompatibility  of  Conoon~-ntM  aterials 
The  applicant  shall  identify  the test articles and' the tests 
conducted  on  each article.  The Tripartite Biocompatibility 
Guidance  for Medical  Devices  should  be  used  as a  reference  t o  
identify  the appropriate tests.  The  applicant should  identify 
any  other reference used  for  determination of  tests.  IS0  194  can 
be  used  as 2  reference. 
For  metals,  some  surface tssts may  be  useful,  e.g.,  SEM,  contact 
angle.  Idencify  any  other surface o r  material  degradation 
effects r o  include discoloration,  corrosion,  cracking,  crazing, 
embrittlemen:,  etc.  Q.  Final  Process Qualification 
A  summary  of  data  from  a  final qualification rest bartery  shouid 
be submitted.  The qualification documentation submirted  should 
include three consecutive runs  t i m e s  the varizbles of  operation 
(e-g.,  three runs  for each mode  of  operation) under --'oqst  case 
loading conditions indicated  i n  labeling.  Stzndard.=est packs 
should be  used.  .  The  applicant must  submit dezailed locumentation 
of  failures and  corrective measures  and  retescs. 
A  summary  of  acceptance criteria should be sujmitted regarding 
process parameters,  microbicidal  effectiveness  and processed 
device performance.  Certification t h a t  t h e  system performs  i n  
accordance  with  specifications should  be  provided. 
R.  Contacts and Addresses 
General  questions  regarding t h e  submission  of  premarket 
applications should be  directed t o  t h e  Division  of  -all 
Manufacturers  ~ s s i s t a n c ea t   (800)  638-2041. 
Questions  regarding t h i s  guidance document  shauld be directed t o  
the  following  address: 
FDA 
Division of  General  and  Restorative Devices  (HFZ-410) 
Infection Control  Devices  Branch 
1390 Piccard  Dr. 
Rockville,  MD.  20850 
(301)  427-1307  S.  checklist 
510 (k)# :  Sponsor: 
Date:  Reviewer: 
#  Y/N  Element 
1.  EPA certification and Summary of Data 
References to Standards 
Labeling 
markings 
manual 
service manual 
Description 
design, construction, components 
. process parameters 
process monitors 
software 
Cycle Overview 
Test Packs 
Comparison to Predicate 
Physical/Chemical Performance Tests 
Biological Test Battery 
screen 
F value 
D values 
1/2  cycle and Total Kill Endpoint 
Simulated and In-Use Tests 
Summary 
Toxicity 
Residues 
Processed Device Qualification 
process life 
functionality 
biocompatibility 
Final Qualification  Attachment  1 
Comparison  ~ a b l o  
- 
Feature  New  Device  Predicate 
EPA  Registered  Component  Y/N 
Labeling/Intended  U s e  
Design,  Construction, 
Com~onents 
- 
Process  Parameters: 
t i m e  
temp 
pressures,  etc. 
Process  Monitors : 
recorders 
gauges 
printouts,  etc. 
Software/Firmware  Controlled 
Cycle ( s) Comparison 
Process  Equivalent Time  (for 
steam and dry heat) 
This table illustrates the type of  comparisons  that should be 
made,  not necessarily  the amount of  information.