Requirements for participating in pilot program: Accreditation Scheme for Conformity Assessment

Contains Nonbinding Recommendations

Biocompatibility Testing of Medical
Devices – Standards Specific
Information for the Accreditation
Scheme for Conformity Assessment
(ASCA) Pilot Program
Guidance for Industry, Accreditation
Bodies, Testing Laboratories, and
Food and Drug Administration Staff
Document issued on September 25, 2020.
The draft of this document was issued on September 23, 2019.
For questions about this document regarding CDRH-regulated devices, contact the ASCA Pilot
Program at ASCA@fda.hhs.gov. For questions about this document regarding CBER-regulated
devices, contact the Office of Communication, Outreach, and Development (OCOD) at 1-800-8354709 or 240-402-8010, or by email at ocod@fda.hhs.gov.
The OMB control number for this information collection is 0910-0889 (expires 06-30-2023).

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Devices and Radiological Health
Center for Biologics Evaluation and Research

Contains Nonbinding Recommendations

Preface
Public Comment
You may submit electronic comments and suggestions at any time for Agency consideration to
https://www.regulations.gov. Submit written comments to the Dockets Management Staff, Food
and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852.
Identify all comments with the docket number FDA-2019-D-3805. Comments may not be acted
upon by the Agency until the document is next revised or updated.

Additional Copies
CDRH
Additional copies are available from the Internet. You may also send an e-mail request to
CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance. Please include the document
number 20012 and complete title of the guidance in the request.

CBER
Additional copies are available from the Center for Biologics Evaluation and Research (CBER),
Office of Communication, Outreach, and Development (OCOD), 10903 New Hampshire Ave.,
WO71, Room 3128, Silver Spring, MD 20903, or by calling 1-800-835-4709 or 240-402-8010,
by email, ocod@fda.hhs.gov, or from the Internet at
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-informationbiologics/biologics-guidances

Contains Nonbinding Recommendations

Table of Contents
I.

Introduction ............................................................................................................................. 1

II.

Scope ....................................................................................................................................... 2

III. List of FDA-Recognized Consensus Standards and Test Methods in the ASCA Pilot for
Biocompatibility Testing of Medical Devices ................................................................................ 2
IV. Accreditation and Assessment of Testing Laboratories by ASCA-Recognized Accreditation
Bodies ............................................................................................................................................. 4
A.

Scope of Assessments ...................................................................................................... 4

B.

ASCA Program Specifications for Biocompatibility Testing of Medical Devices .......... 4

V. Premarket Submission Contents for FDA-Recognized Consensus Standards and Test
Methods in the ASCA Pilot for Biocompatibility Testing of Medical Devices ........................... 16
A.

Cover Letter.................................................................................................................... 16

B.

Declaration of Conformity ............................................................................................. 16

C.

Supplemental Documentation ........................................................................................ 17

VI. Paperwork Reduction Act of 1995........................................................................................ 20
Appendix A: Example ASCA Declaration of Conformity (DOC) for Biological Evaluation of
Medical Devices Standards in the ASCA Pilot............................................................................. 21
Appendix B: Example ASCA Summary Test Report for Biocompatibility Testing of Medical
Devices: Irritation – Intracutaneous Reactivity (ISO 10993-10) .................................................. 24
Appendix C: Example ASCA Summary Test Report for Biocompatibility Testing of Medical
Devices: Cytotoxicity – MEM Elution (ISO 10993-5) ................................................................. 28
Appendix D: Example ASCA Summary Test Report for Biocompatibility Testing of Medical
Devices: Dermal Irritation (ISO 10993-10) .................................................................................. 31
Appendix E: Example ASCA Summary Test Report for Biocompatibility Testing of Medical
Devices: Guinea Pig Maximization Sensitization (ISO 10993-10) .............................................. 35
Appendix F: Example ASCA Summary Test Report for Biocompatibility Testing of Medical
Devices: Closed Patch Sensitization (ISO 10993-10) .................................................................. 40
Appendix G: Example ASCA Summary Test Report for Biocompatibility Testing of Medical
Devices: Acute Systemic Toxicity (ISO 10993-11) ..................................................................... 44
Appendix H: Example ASCA Summary Test Report for Biocompatibility Testing of Medical
Devices: Material-Mediated Pyrogenicity (ISO 10993-11 and USP 151).................................... 48
Appendix I: Example ASCA Summary Test Report for Biocompatibility Testing of Medical
Devices: Direct and Indirect Hemolysis (ISO 10993-4 and ASTM F756)................................... 52
Appendix J: Example ASCA Summary Test Report for Biocompatibility Testing of Medical
Devices: Complement Activation (ISO 10993-4)......................................................................... 58

Contains Nonbinding Recommendations

Biocompatibility Testing of Medical
Devices – Standards Specific
Information for the Accreditation
Scheme for Conformity Assessment
(ASCA) Pilot Program
Guidance for Industry, Accreditation
Bodies, Testing Laboratories, and
Food and Drug Administration Staff
This guidance represents the current thinking of the Food and Drug Administration (FDA
or Agency) on this topic. It does not establish any rights for any person and is not binding
on FDA or the public. You can use an alternative approach if it satisfies the requirements
of the applicable statutes and regulations. To discuss an alternative approach, contact the
FDA staff or Office responsible for this guidance as listed on the title page.

I.

Introduction

This guidance provides information on how the Biological Evaluation of Medical Devices
standards are incorporated into the Pilot Accreditation Scheme for Conformity Assessment
Program (hereafter referred to as the ASCA Pilot). The ASCA Pilot is described in FDA’s
guidance The Accreditation Scheme for Conformity Assessment (ASCA) Pilot Program. 1
For the edition of the FDA-recognized consensus standard(s) included in the ASCA Pilot, see
the FDA Recognized Consensus Standards Database. 2 For more information regarding use of
consensus standards in regulatory submissions, please refer to the FDA’s guidance
Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for Medical
Devices 3 and Standards Development and the Use of Standards in Regulatory Submissions
Reviewed in the Center for Biologics Evaluation and Research. 4
1

Available at: The Accreditation Scheme for Conformity Assessment (ASCA) Pilot Program
Available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm
3
Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-usevoluntary-consensus-standards-premarket-submissions-medical-devices
4
Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/standardsdevelopment-and-use-standards-regulatory-submissions-reviewed-center-biologics-evaluation
2

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FDA’s guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency’s 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 guidance means that
something is suggested or recommended, but not required.

II. Scope
This guidance includes the following:
•
•
•

A list of the FDA-recognized consensus standards and test methods included in the
ASCA Pilot for biocompatibility testing of medical devices;
The program specifications for the FDA-recognized consensus standards and test
methods in the ASCA Pilot for biocompatibility testing of medical devices; and
The recommended premarket submission contents specific to FDA-recognized
consensus standards and test methods for biocompatibility testing of medical devices
when testing is conducted by an ASCA-accredited testing laboratory.

FDA’s guidance The Accreditation Scheme for Conformity Assessment (ASCA) Pilot
Program describes how accreditation bodies, testing laboratories, device manufacturers, and
FDA staff participate in the ASCA Pilot as well as how FDA-recognized consensus standards
and test methods are selected and how program specifications are developed.
Please see FDA’s guidance Use of International Standard ISO 10993-1, “Biological
evaluation of medical devices - Part 1: Evaluation and testing within a risk management
process” 5 for recommendations on biocompatibility testing to support a premarket
submission. The ASCA Pilot for biocompatibility testing of medical devices does not include
certain types of devices that require customized sample preparation and/or testing
methodologies, or absorbable and in situ polymerizing devices, liquid devices, creams, gels,
hydrogel devices, and devices containing nanomaterials.

III. List of FDA-Recognized Consensus Standards and
Test Methods in the ASCA Pilot for Biocompatibility
Testing of Medical Devices
Biological evaluation assesses the biocompatibility-related risks of medical devices with
direct and/or indirect contact with human tissue. When biocompatibility testing is needed as
part of a premarket submission to FDA to address biocompatibility-related risks, the selected,
cross-cutting biological evaluation standards listed below are relevant to many manufacturers
and the device types are of significant public health importance.

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Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-internationalstandard-iso-10993-1-biological-evaluation-medical-devices-part-1-evaluation-and

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•
•
•
•
•
•
•
•

ASTM F756: Standard Practice for Assessment of Hemolytic Properties of Materials
ASTM F720: Standard Practice for Testing Guinea Pigs for Contact Allergens:
Guinea Pig Maximization Test
ISO 10993-4: Biological evaluation of medical devices – Part 4: Selection of tests for
interactions with blood
ISO 10993-5: Biological evaluation of medical devices – Part 5: Tests for in vitro
cytotoxicity
ISO 10993-10: Biological evaluation of medical devices – Part 10: Tests for irritation
and skin sensitization
ISO 10993-11: Biological evaluation of medical devices – Part 11: Tests for systemic
toxicity
USP <151>: Pyrogen Test
ISO 10993-12: Biological evaluation of medical devices – Part 12: Sample
preparation and reference materials

The eligible test methods included in the ASCA Pilot for biocompatibility testing of medical
devices are:
FDA-Recognized Consensus Standard Test method(s)
ISO 10993-4*
Complement Activation using a U.S. marketed ELISA kit
ISO 10993-4 and ASTM F756
Direct and Indirect Hemolysis
ISO 10993-5
MEM Elution Cytotoxicity
6
ISO 10993-10
Dermal Irritation, Intracutaneous Reactivity Irritation, and
Closed Patch Sensitization
7
ISO 10993-10 and ASTM F720
Guinea Pig Maximization Sensitization
ISO 10993-11
Acute Systemic Toxicity
ISO 10993-11 and USP 151
Material-Mediated Pyrogenicity
ISO 10993-12
Sample preparation for all test types
* See also ISO/TS 10993-20 for information on when complement activation should be considered for
anaphylaxis (Table 2, Hypersensitivity Column).

The extent of FDA recognition (complete or partial) is provided in the Supplemental
Information Sheet (SIS) for each standard listed in the FDA Recognized Consensus
Standards Database. 8 The SIS provides additional information to consider when using FDArecognized consensus standards, such as relevant guidance documents that provide clarity on
FDA recommendations for testing to support premarket submissions.

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We support the principles of the “3Rs,” to reduce, refine, and replace animal use in testing when feasible. We
encourage sponsors to consult with us if they wish to use a non-animal testing method they believe is suitable,
adequate, validated, and feasible. We will consider if such an alternative method could be assessed for
equivalency to an animal test method. See generally: https://www.fda.gov/science-research/advancingregulatory-science/vi-modernizing-safety-testing
7
Ibid
8
Available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm

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IV. Accreditation and Assessment of Testing Laboratories
by ASCA-Recognized Accreditation Bodies
A.

Scope of Assessments

Section 7 of ISO/IEC 17011: Conformity assessment – Requirements for accreditation bodies
accrediting conformity assessment bodies (hereafter referred to as “ISO/IEC 17011”)
describes processes by which accreditation bodies assess testing laboratories. In order to
maintain conformance to ISO/IEC 17011, an accreditation body assesses a sample of the
scope of accreditation of its accredited testing laboratories at least every two years. 9 When
assessing a testing laboratory under the ASCA Pilot, an accreditation body is expected to
assess all (and not a sample of) biological evaluation standards and test methods. That is, in
the ASCA Pilot, ASCA-recognized accreditation bodies are expected to assess all (and not a
sample) of the biological evaluation of medical devices standards and test methods in order
to ensure competence across the testing laboratory’s scope of ASCA Accreditation.

B. ASCA Program Specifications for Biocompatibility
Testing of Medical Devices
The ASCA program specifications in this section provide expectations for the accreditation
of testing laboratories for the biocompatibility testing of medical devices under the ASCA
Pilot. ASCA-recognized accreditation bodies, following the processes of ISO/IEC 17011,
accredit testing laboratories to all relevant elements of ISO/IEC 17025: 2017: General
requirements for the competence of testing and calibration laboratories (hereafter referred to
as “ISO/IEC 17025”) as well as the ASCA program specifications identified in this section.
In addition, all testing should be conducted considering the recommendations in the CDRH
Biocompatibility policy as described in FDA’s guidance Use of International Standard ISO
10993-1, “Biological evaluation of medical devices - Part 1: Evaluation and testing within a
risk management process.” For readability and ease of reference, the numbering and
nomenclature (including the term “requirements”) 10 below correspond to the numbering and
nomenclature of clauses/subclauses in ISO/IEC 17025.
ISO/IEC 17025 Section 4 “General requirements”
4.1 Impartiality
If any services, such as consulting, design, or research, are offered by the testing laboratory,
it agrees to have a policy and procedure for maintaining impartiality through separation of
those services from its testing activities.
A device manufacturer’s internal testing laboratory agrees to have policies and procedures
that specifically ensure and protect the impartiality of the laboratory to test or otherwise
9

See 7.9.3 of ISO/IEC 17011: 2017: Conformity assessment – Requirements for accreditation bodies
accrediting conformity assessment bodies.
10
Some definitions within voluntary consensus standards refer to “requirements.” FDA’s references to them for
the ASCA Pilot do not make them legal or regulatory requirements unless specifically identified as such.

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evaluate devices manufactured by the laboratory’s parent organization and, if applicable,
other manufacturers without regard to the impact of the test results on the parent
organization’s business interests.
4.2 Confidentiality
There are no additional specifications above those set forth in ISO/IEC 17025.
ISO/IEC 17025 Section 5 “Structural requirements”
There are no additional specifications above those set forth in ISO/IEC 17025.
ISO/IEC 17025 Section 6 “Resource requirements”
6.1 General
There are no additional specifications above those set forth in ISO/IEC 17025.
6.2 Personnel
a) The testing laboratory agrees to maintain competent technical personnel that are
knowledgeable in appropriate test method for the requested scope of accreditation:
• For technicians performing in vivo tests, 1 year of relevant test experience
with each standard test included in the ASCA program to which technicians
are assigned OR demonstrated proficiency through completion minimally of
25 tests OR 25 phases as outlined in each study specific training and:
- Bachelor’s or associate degree in relevant science areas to the in vitro/in
vivo biocompatibility testing included in the ASCA Pilot, OR
- a high school degree, and at least one of the following laboratory
technician accreditations: Laboratory Animal Technician (LAT), Assistant
Laboratory Animal Technician (ALAT), and/or Laboratory Animal
Technologist (LATG).
• For technicians performing in vitro tests 1 year of relevant test experience
with each standard test included in the ASCA program to which technicians
are assigned, OR demonstrated proficiency through completion minimally of
25 tests, OR 25 phases as outlined in each study specific training and:
- Bachelor’s or associate degree in relevant science areas to the in vitro/in
vivo biocompatibility testing included in the ASCA Pilot.
• For technicians performing any test specific (e.g., for complement activation)
sample preparation, 1 year of sample preparation experience with the relevant
standard test included in the ASCA program to which technicians are
assigned, OR demonstrated proficiency through completion of sample
preparation for minimally 25 tests as outlined in each study specific training
and:
- Bachelor’s or associate degree in science.
• For technicians performing sample preparation that is applicable for various
tests (e.g., technicians in general sample preparation lab who prepare
samples/extracts for various tests), 1 year sample preparation experience with
any standard test included in the ASCA program OR demonstrated

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•

proficiency through completion of sample preparation for minimally 25 of any
of the standard tests in the ASCA program and:
- Bachelor’s or associate degree in science.
For study directors:
- Bachelor’s or higher degree in scientific discipline; AND
- 2 years of relevant test experience with each standard test; AND
- Direction of at least 25 studies in each relevant test, OR management of
25 studies with someone who has directed at least 25 studies in each
relevant test.

b) The testing laboratory’s management agrees to be knowledgeable in applicable
aspects of the FD&C Act and 21 CFR regulations pertinent to the oversight of
medical devices and the criteria set out in ISO/IEC 17025 and ASCA program
specifications. The testing laboratory further agrees to maintain a list of laboratory
managers and contact information.
c) The testing laboratory agrees to:
• Document and maintain a training program for new and previously trained
technical personnel, which will include the proper procedures for applying
new/updated test procedures and performing required tests.
• Provide new and previously trained technical personnel relevant test-specific
requalification training (e.g., cytotoxicity subjective scoring) every 6-12
months, or when test standards or procedures are updated or developed, as
well as when responsibilities have changed.
• Conduct training on a periodic basis through application of training
approaches, such as on-the-job training and formal classroom training, as
appropriate.
• Document and maintain records of training demonstrating that technical
personnel who participate in the conduct of ASCA testing have been trained
and evaluated to be competent in the performance of each ASCA test. The
training includes the ability to follow test-related standard operating
procedures (SOPs) and documentation, and in person hands-on training.
Training may also include classroom (or online) training. Testing laboratories
further agree to have predefined criteria to qualify that technical personnel
(technicians and study directors) can perform assigned tasks related to the
tests under the scope of ASCA Accreditation, and for when retraining will be
needed.
• Establish procedures for periodic internal test lab proficiency checks of
technicians (e.g., blind scoring of negative and positive controls for MEM
elution assays) for the tests performed under the ASCA Pilot with subjective
analyses, to include when staff would require retraining (e.g., protocol nonconformance, change in assigned activities).
• Maintain records demonstrating trainers have qualifications and at least 2
years’ experience (routinely performing each relevant ASCA test) to train the
technical personnel who will perform the ASCA tests.

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d) The testing laboratory agrees to have procedures to establish how test and control
samples are prepared and training that includes at a minimum the following:
• Procedures for device preparation, including:
- Cutting samples (if appropriate) and documentation (e.g., photographs) of
any particle generation prior to extraction,
- Determination of device surface area for extraction ratio, and the volume
required to complete the study,
- Use of non-standard surface area approaches (e.g., porous devices),
- Exclusion of non-contacting components from extraction,
- Selection of representative portions for direct contact hemocompatibility
studies (i.e., hemolysis, complement activation),
• Selection of extraction conditions (i.e., time, temperature, and extraction
vehicle),
• Assessment and documentation of changes (e.g., photographs) after extraction
to sample (e.g., color changes, integrity, swelling) or extract conditions (e.g.,
pH, particles/precipitates, color changes, or turbidity),
• General and/or test-specific follow-up procedures when changes are noted
(e.g., extract settling techniques to allow particle-free IV injections),
• Use of non-standard extraction approaches (e.g., fluid path approaches,
approaches for extremely large devices, procedures to maintain contact with
extraction vehicle), and
• Handling of extracts prior to testing (e.g., filtration, centrifugation, storage
time and temperature).
e) In addition, for in vitro testing, the testing laboratory agrees that training will include
the following, at a minimum:
• MEM elution cytotoxicity:
- Cell line maintenance
- Cell counting
- Cell seeding
- Addition of test and control samples to the cell cultures
- Scoring of test and control articles
- Mock study to assess technician competence in test performance, data
documentation, and result interpretation (including test-specific
assessment of borderline results)
- Minimally, biannual periodic technician proficiency check of negative and
positive control scoring, and additional technician retraining, if needed
• Hemolysis:
- Timing from blood collection to use in test
- Hemoglobin absorbance standard curve
- Dilution procedures and dilution factor calculations
- Sample and control preparation and documentation
- Representative sample selection(may apply to both direct and indirect
contact tests)

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•

Documentation of supernatant color and presence of dispersed pellet
fragments, if any
- Documentation of presence or absence of pellet, pellet size, and color after
centrifugation if different than negative control
- Supernatant removal to preserve pellet
- Blank sample correction (including if an extract is colored)
- Hemolytic index calculation
- Mock study to assess technician competence in test performance, data
documentation, and result interpretation
- Technician retraining, if needed
Complement activation:
- Serum/blood/plasma handling to minimize complement activation
- Sample and control preparation and documentation
- Representative sample selection
- Small volume pipetting
- Complement absorbance standard curve
- Dilution procedures and dilution factor calculations
- Exposure time
- Complement concentration calculations
- Test validation criteria
- Data analysis and use of historical control data, if necessary
- Mock study to assess technician competence in test performance, and data
documentation, and result interpretation
- Technician retraining, if needed

f) For in vivo studies, as part of the general animal handling training, the testing
laboratory agrees that training will include the following, at a minimum:
• Test-specific animal selection criteria
• Animal identification and traceability within and across studies (e.g., for
pyrogenicity)
• Species- and test-specific animal holding techniques
• Test-specific acclimation techniques
• Body weight measurement
• Species-specific in life observations (e.g., cage accidents, decline in health,
seizures, weight loss, breathing difficulties) and when veterinarian oversight
should be requested
• Test-specific data documentation, calculations, and result interpretation
(including test-specific assessment of borderline results, and re-challenge or
re-test criteria, when applicable)
• Technician retraining, if needed
g) For the following specific in vivo tests, the application organization agrees that
training will include the following, at a minimum:
• Guinea Pig Maximization (GPMT) and Closed Patch Sensitization:
- Shaving techniques (e.g., to avoid razor burn)

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Mixing of extract and adjuvant, if applicable
Intradermal injection (GPMT) including criteria to confirm avoidance of
subcutaneous injections
- Sample application (GPMT and Closed Patch)
- Animal wrapping
- Differentiation for source of redness (e.g., true sensitization versus
mechanical/adhesive irritation)
- Minimally, quarterly periodic technician proficiency check of positive
control scoring (in live animals at least once annually)
- Technician retraining, if needed
• Intracutaneous Reactivity and Dermal Irritation:
- Shaving techniques (e.g., to avoid razor burn)
- Application of test samples
- Injection technique and signs to confirm appropriate injection location
- Differentiation for source of redness (e.g., true irritation versus possible
irritation from shaving)
- Minimally, biannual periodic technician proficiency check of positive
response scoring (in live animals at least once annually)
- Technician retraining, if needed
• Acute Systemic Toxicity:
Balance use and calibration to ensure appropriate sensitivity
Intraperitoneal (IP) and intravenous (IV) injection techniques and signs to
confirm appropriate injection location
Minimally, technician proficiency check on injection techniques prior to
conduct of next test if it has been more than one month between
technician conduct of a study
Technician retraining, if needed
• Material-mediated pyrogenicity:
- Use of pyrogen-free/depyrogenated glassware and pyrogen free saline for
extraction
- Temperature probe use and calibration to ensure appropriate sensitivity
- Intravenous (IV) injection techniques and signs to confirm appropriate
injection location
- Technician retraining if needed.
6.3 Facilities and environmental conditions
Lab personnel should be aware of the FD&C Act and regulations as applicable to medical
device manufacturers. Under 21 CFR 820.50, Purchasing Controls, medical device
manufacturers must communicate as part of contracted work any environmental conditions
necessary for the proper conduct of testing done under the scope of accreditation. In
addition, testing laboratories should have policies and procedures in place to implement 21
CFR part 58, Good Laboratory Practices, for Nonclinical Laboratory Studies.
6.4 Equipment

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a) The testing laboratory agrees to ensure that all equipment used for testing and
evaluating devices is available and in proper working order for the requested scope of
accreditation.
b) The testing laboratory agrees to ensure that its procedures address adding, deleting,
modifying, or maintaining information in equipment records in an accurate and timely
manner, and specify the personnel responsible for these tasks.
c) The testing laboratory agrees to ensure that its procedures specify the steps for
establishing calibration intervals for each type or item of equipment, and specify
criteria, steps, and approvals for extending the calibration interval of an instrument.
d) The testing laboratory agrees to have procedures to examine the effects of equipment
operation outside the equipment tolerances or study specified limits (e.g., temperature
excursions) on test results. The procedures identify the personnel responsible for such
examination of the equipment (e.g., technicians) and determination of acceptability
with respect to test validity (e.g., study directors/toxicologists), specify their
responsibilities, and provide the steps for determining if the equipment variation
would impact the study results, including:
• Determining whether the effects are unacceptable (including the accept/reject
criteria);
• Identifying the conducted tests affected;
• Analyzing the results impacted for these particular tests; and
• Determining whether retesting is required.
6.5 Metrological traceability
a) Testing laboratories agree to use specified methods and/or standards that clearly
describe the following:
• Calibration to three decimal places for spectrophotometer absorbance readings
for hemolysis and complement activation, and
• Particle ranges for calibration of coulter counter use for cell counting.
b) If test-specified positive, negative, and/or reference controls are no longer able to
distinguish between positive and negative responses, the testing laboratory agrees to
have procedures to qualify new controls.
c) The testing laboratory agrees that controls (positive/negative/reagent, if applicable)
will meet assay-specific acceptance criteria.
d) The testing laboratory agrees that, when concurrent positive controls are not
conducted with the test article (i.e., sensitization testing), biannual testing (i.e., within
3 months of the test article) will be conducted to confirm the ability of the test system
to detect a positive sensitization response. If it is determined that the periodic positive
control is no longer valid, all testing conducted after the last validated positive control
run cannot be submitted as part of the ASCA Pilot.

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6.6 Externally provided products and services
a) The testing laboratory agrees to ensure that any subcontractors utilized to conduct
testing under the scope of ASCA Accreditation are ASCA-accredited testing
laboratories for the selected tests.
ISO/IEC 17025 Section 7 (“Process requirements”)
7.1 Review of requests, tenders and contracts
There are no additional specifications to those set forth in ISO/IEC 17025.
7.2 Selection, verification and validation of methods
a) The testing laboratory agrees that its management system will include procedures
governing the development, maintenance, and use of test procedures (including
associated documents such as test data forms and checklists). These management
system procedures include steps for:
• Identifying the personnel responsible for developing, reviewing, and
maintaining these documents
• Specifying the frequency of review by technical personnel and management
• Ensuring consistency with applicable standard(s)
• Ensuring test modifications are reviewed by personnel who are competent to
the applicable standard(s)
• Identifying and documenting the types of modifications to the test procedures that
do not need to be reviewed by FDA for confirmation prior to implementation, if
included in the test lab application. The testing laboratory further agrees that
changes (either at the request of study sponsor or initiated by the test lab) to any
procedures regarding the following as well as any unanticipated changes will be
confirmed with FDA and its Accreditation Body prior to implementation:
- Changes to sample for retesting to achieve a “passing” result
- pH adjustments
- Sample filtration or other extract manipulation
- Removal or modification of documentation associated with color, turbidity
or particles in the test extract, or swelling/degradation of the test article
- Frequency of non-concurrent control testing
- Changes to acceptance criteria outside the validated/qualified laboratoryspecific limits (e.g., for complement activation where the standard
methods do not specify acceptable limits)
- Changes to data calculations and presentation, if applicable (e.g.,
hemolytic index, irritation index, complement activation plots)
- Changes in the criteria for re-challenge or retesting
- Changes in the criteria for reportable adverse clinical observations or
animal deaths
b) The testing laboratory agrees that test procedures will include or specify, as
appropriate, the following:

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•
•
•
•
•
•
•
•

•

Unique identification, including title, document number, revision, and
effective date;
Specific test equipment to use along with their required ratings;
Warnings/caution statements to alert the operators of potential hazards;
Normal and any unusual ambient conditions (including tolerances) for tests;
Test data to be obtained and recorded;
Objective acceptance criteria for results including the essential performance
required to be maintained;
Testing techniques (i.e. test methods) required to ensure consistent results;
Instructions on test conduct, including equipment operation, reagent
preparation, cell line and animal handling, techniques, preparation of test
samples (including instructions for sample traceability during testing, if
applicable), conduct of each step of the test, data recording, and scoring
assessment procedures;
Deviations from the SOP, as well as any equipment deviations and discussion
of why deviations will not impact the validity of the study results.

c) The testing laboratory agrees to ensure that relevant contextual information from the
intended use of the device are reflected in the test procedure to ensure that the types
of biological evaluation assessments recommended by FDA are considered based on
tissue type and duration of contact with the device. In addition, relevant information
from the manufacturers essential performance specifications, including any
metrological stability, are also reflected in each test procedure to ensure that the test
procedures (e.g., extraction temperature and time) are compatible with the device.
d) The testing laboratory agrees to ensure that each test procedure adequately addresses
all the applicable specifications of the standard for the devices being tested.
7.3 Sampling
a) The testing laboratory agrees that the procedure(s) for sample preparation will meet
the specifications of ISO 10993-12 and FDA’s guidance Use of International
Standard ISO 10993-1, "Biological evaluation of medical devices--Part 1: Evaluation
and testing within a risk management process" and include the following:
• Use of surface area/extraction volume ratio (unless mass/extract volume ratio
results in equivalent or higher amount of test sample)
• No dilutions of extract or test solutions, unless required for dose-dependent
cytotoxicity studies
• No filtration/centrifugation
• No pH/osmolality adjustment
• Documentation of any color changes, turbidity or particles in the extract
• How representative portions are selected for testing, if the test system cannot
accommodate all of the direct and indirect tissue contacting device
components, to include documentation of what was excluded
• How extraction vehicle volume will be determined and documented for
absorbent devices (e.g., spongy devices)
12

Contains Nonbinding Recommendations
•
•
•
•
•
•
•

How sample extraction ratios will be selected for devices having multiple
components with different thicknesses
How components with different types and durations of contact will be
separated for sample preparation and testing
Situations when pooled component samples (with same or different types or
duration of tissue contact) will be allowed
Inclusion of only tissue contacting components (unless procedure describes
how inclusion of non-tissue contacting components will be addressed in
determination of extraction ratios)
Submersion of large devices completely in extraction vehicle
How extractions will be conducted for devices containing fluid path
components
That the following types of devices are excluded for the ASCA Pilot:
absorbable and in situ polymerizing devices, liquid devices, creams, gels,
hydrogel devices, and devices containing nanomaterials.

7.4 Handling of test or calibration items
There are no additional specifications to those set forth in ISO/IEC 17025.
7.5 Technical records
There are no additional specifications to those set forth in ISO/IEC 17025.
7.6 Evaluation of measurement uncertainty
There are no additional specifications to those set forth in ISO/IEC 17025.
7.7 Ensuring the validity of results
To confirm the validity of the testing methods, any test-specified positive, negative, and/or
reference controls allow for distinguishing between positive and negative responses. The
testing laboratory agrees that pre-defined criteria for positive/negative/reference control
values will be as follows:
• For cytotoxicity testing (per ISO 10993-5):
- each positive control material replicate is ≥ Grade 3
- each negative control material replicate is Grade 0
- each vehicle control replicate is Grade 0
• For intracutaneous reactivity irritation testing:
- each of five sodium chloride control sites in each animal at all timepoints
is Grade 0
- each of five oil control sites in each animal at all timepoints is ≤ Grade 1
• For primary skin (dermal) irritation testing, each sodium chloride and oil
control site is Grade 0
• For guinea pig maximization sensitization testing (per ASTM F720): 11

11

ASTM F720-17: Standard Practice for Testing Guinea Pigs for Contact Allergens: Guinea Pig Maximization
Test

13

Contains Nonbinding Recommendations
-

•

•
•
•
•

7.8

all sodium chloride and oil vehicle control animals have Grade 0 results at
all sites
- the positive controls are run at least biannually (for each animal source)
and each animal is at least one grade higher than concurrently run sodium
chloride and oil vehicle controls in at least 8 out of 10 positive control
animals (for strong sensitizers such as 0.1-0.5% dinitrochlorobenzene
(DNCB) at induction and 0.05-0.1% DNCB at challenge)
For closed patch sensitization testing:
- all negative control animals (e.g., sodium chloride or oil vehicles or
negative control materials) are Grade 0.
- the positive controls are run at least biannually (for each animal source)
and each animal is at least one Grade higher than concurrently run sodium
chloride and oil vehicle controls in at least 8 out of 10 positive control
animals (for strong sensitizers such as 0.1-0.5% DNCB at induction and
0.05-0.1% DNCB at challenge)
For acute systemic toxicity testing, all sodium chloride and oil control
animals result in no adverse clinical findings, no decrease in body weight >
10% per animal, and no deaths
For material-mediated pyrogenicity testing there are no predefined criteria
For hemolysis testing (per ASTM F756):
- the positive control material mean hemolytic index is ≥ 5%
- the negative control material mean hemolytic index is < 2%
For complement activation testing using SC5b-9 (a product of the terminal
pathway for complement activation),
- the positive control meets one of the following criteria:
o the mean value for the cobra venom factor positive control (if
applicable) is at least 10X greater than both the mean values for the
negative control material and the activated normal human serum,
plasma, or whole blood, or
o the positive material control (if applicable) is statistically significantly
higher than both the negative control material and the activated
normal human serum, plasma, or whole blood,
- any kit-specific high and low controls meet the kit specifications.

Reporting of results
a) The testing laboratory agrees that it will have procedures to record all required
information in ISO/IEC 17025 for each test conducted, including the following:
• Test procedure(s) and test standard(s) used
• Product or component(s) tested
• Test equipment used for testing, measurement, or review (including the
equipment’s ratings and accuracies, unless otherwise readily available)
• Date of the test(s). For example, periodic controls may have different test
dates
• Test report number, including revision number and amendment date, if
applicable, and any related sub-contracted test report number(s)
14

Contains Nonbinding Recommendations
•

•
•

•

•
•
•

Names of the personnel performing the test(s) and the names of all
supervisory personnel involved in the study and for biological studies, the
signature of the study director and quality assurance unit personnel (i.e., per
21 CFR part 58, Good Laboratory Practices for Nonclinical Laboratory
Studies, requirements)
The test conditions as specified by the test standard, if applicable, (e.g.,
required voltage, power, temperature, or humidity for the test)
Sample preparation:
- images of device (or representative portion, if full device is not used) prior
to and post sample preparation
- use of subdivision/cutting
Extraction conditions, if applicable:
- extraction vehicle, time, temperature, and test article/vehicle ratio
- storage time and temperature prior to application to the test system
- images of vehicle post-extraction (color, cloudiness, presence of
particulates)
Sample manipulation:
- filtration, centrifugation, dilution, pH adjustment, osmolality adjustment
or other deviations from the sampling procedures
Any deviations from the laboratory’s ASCA accepted procedures as well as
any amendments to the test report
Test results to include:
- opinions and interpretations included in a test report
- all of the applicable data required by the laboratory's procedures; and
- a statement that testing was conducted according to 21 CFR 58 Good
Laboratory Practices for Nonclinical Laboratory Studies regulations 12

b) The testing laboratory agrees that testing conducted by subcontractors will also
comply with the above test report specifications, as applicable.
c) The testing laboratory agrees that the complete test report and an ASCA Summary
Test Report will be submitted to the client at the end of testing activities
7.9 Complaints
There are no additional specifications than those set forth in ISO/IEC 17025.
7.10 Nonconforming work
There are no additional specifications than those set forth in ISO/IEC 17025.
7.11 Control of data and information management
There are no additional specifications than those set forth in ISO/IEC 17025.
ISO/IEC 17025 Section 8 (“Management system requirements”)
12

As discussed at the public workshop titled “Accreditation Scheme for Conformity Assessment of Medical
Devices to Food and Drug Administration-Recognized Standards,” biocompatibility testing conducted under the
ASCA Pilot will be conducted in accordance with 21 CFR 58 Good Laboratory Practices for Nonclinical
Laboratory Studies regulations.

15

Contains Nonbinding Recommendations
8.1 Options
Regardless of the option selected (i.e., Option A or Option B), the testing laboratory agrees to
maintain an Index of SOPs and any relevant ASCA test-related documents (e.g., SOPs, work
instructions, master protocols, test-specific protocols, data collection worksheets, training
information) applicable to any biological evaluation of medical device standards or test
methods.

V. Premarket Submission Contents for FDA-Recognized
Consensus Standards and Test Methods in the ASCA Pilot
for Biocompatibility Testing of Medical Devices
FDA recommends that the following be included in any regulatory submission that contains
biocompatibility testing conducted by an ASCA-accredited testing laboratory.

A.

Cover Letter

FDA’s recommendations regarding the content to be included in a cover letter for a
premarket submission containing testing results from an ASCA-accredited testing laboratory
are provided in FDA’s guidance The Accreditation Scheme for Conformity Assessment
(ASCA) Pilot Program.

B.

Declaration of Conformity

Section IV.A. of FDA’s guidance Appropriate Use of Voluntary Consensus Standards in
Premarket Submissions for Medical Devices 13 recommends contents for a declaration of
conformity (DOC) to an FDA-recognized consensus standard. For biocompatibility testing
from an ASCA-accredited testing laboratory, FDA recommends the device manufacturer
include the following additional items in the DOC:
• Date(s) the testing was conducted
• Location(s) where the testing was conducted
• Confirmation that the FDA-recognized consensus standards (and specific test
methods) used during testing were within the laboratory’s scope of ASCA
Accreditation and not subject to any temporary labeling constraints as a result of a
suspension of ASCA Accreditation at the time testing was conducted. If the relevant
standard (and specific test method) was impacted by a suspension of ASCA
Accreditation, the DOC should include an explanation of how this suspension may or
may not affect the testing results.
• Limitations on the validity of the DOC:

13

Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-usevoluntary-consensus-standards-premarket-submissions-medical-devices

16

Contains Nonbinding Recommendations
•
•
•
•

How the test article compares with the device provided in this premarket
submission (including selection of “representative” devices/portions) 14
How any concerns communicated by the test lab were resolved
How any observations and/or degradations during testing were resolved
Whether any adverse or unusual findings as described in the list in Section V.C.
occurred and, if so, rationale for acceptability

An example DOC is provided in Appendix A of this guidance. This example provides one
approach to how a single DOC might contain testing to FDA-recognized consensus standards
included and not included in a testing laboratory’s scope of ASCA Accreditation.

C.

Supplemental Documentation

An ASCA summary test report is recommended for all testing conducted under the ASCA
Pilot. Example ASCA summary test reports are provided in Appendices B- J of this
guidance. Note that the ASCA-accredited testing laboratory provides the ASCA summary
test report to the device manufacturer who then includes it with its own DOC in a premarket
submission to FDA. Depending on the information provided in the DOC or the ASCA
summary test report, FDA may or may not need to review the complete test report for
biocompatibility testing, 15 and the testing laboratory and/or device manufacturer may also be
requested to provide a rationale to support a decision on a premarket submission.
During the ASCA Pilot, FDA generally will accept determinations from ASCA-accredited
testing laboratories (i.e., test results) when the standard and test methods are within the
testing laboratory’s scope of ASCA Accreditation at the time of testing. Circumstances where
FDA may request and review additional information related to testing from an ASCAaccredited testing laboratory are described in the bulleted points of Section XIII. A of the
guidance titled The Accreditation Scheme for Conformity Assessment (ASCA) Pilot
Program.
The ASCA Pilot processes and policies enhance confidence in testing results only when
specific test methods and acceptance criteria are used. For example, FDA reviews a copy of
the Index of SOPs and any relevant ASCA test-related documents (e.g., SOPs, work
instructions, master protocols, test-specific protocols, data collection worksheets, training
information) for testing laboratories that apply for a scope of ASCA Accreditation that
includes biocompatibility testing. This review provides FDA an understanding of how testing
is conducted, thereby providing confidence in the competence of ASCA-accredited testing
laboratories. Depending on the specific device or intended use, deviations or amendments
relative to the testing documentation submitted to FDA during the ASCA Accreditation

14

Please see FDA’s guidance Use of International Standard ISO 10993-1, "Biological evaluation of medical
devices - Part 1: Evaluation and testing within a risk management process" for considerations regarding the use
of medical devices in their final finished form or a representative test article for biocompatibility testing.”
15
A complete test report for biocompatibility testing is described in Attachment E of FDA’s guidance Use of
International Standard ISO 10993-1, “Biological evaluation of medical devices - Part 1: Evaluation and testing
within a risk management process”

17

Contains Nonbinding Recommendations
application process 16 may be appropriate. In such cases, FDA recommends a complete test
report be included in the premarket submission. FDA also recommends a complete test
report be included in the premarket submission for specific circumstances when (based on
FDA’s review experience) results may indicate a potential concern; these cases are noted
below and in each example ASCA summary test report (Refer to Appendices B-J).
To allow FDA to determine if any additional information is needed, and whether the ASCA
summary test report was insufficient for evaluation, a complete test report (in addition to the
ASCA summary test report) is recommended for biocompatibility testing of medical devices
in the cases outlined below.
• If test article was prepared per the ASCA Test Article Prep SOP specified on the
ASCA summary test report (Refer to Appendices B-J of this guidance) with
deviations/amendments (e.g., filtering, extract manipulation, pH adjustment)
• If extraction solvent, ratio, or conditions other than those specially called out in the
example ASCA summary test report (Refer to Appendices B-J of this guidance) were
used
• If there were any changes in color/turbidity or particles in the test article and/or
extract OR there was swelling/degradation of the test article
• If testing was conducted per the ASCA Test Method SOP specified on the ASCA
summary test report (Refer to Appendices B-J of this guidance) and per 21 CFR 58
with deviations/amendments.
• For irritation- intracutaneous reactivity (ISO 10993-10) testing:
• If the overall score differences between the test and control are greater than
one (i.e., per ISO 10993-10:2010, Clause 6.4.7), or if there were non-zero
results for any of the sodium chloride control sites in any animal or results
greater than 1 for any of the oil control sites in any animal at any timepoint.
• If adverse clinical findings or animal deaths occurred.
• For cytotoxicity – MEM Elution (ISO 10993-5) testing: if there were non-zero results
for the test article, vehicle control or negative control, or if there were results less
than 3 for the positive control at any timepoint.
• For dermal irritation (ISO 10993-10):
• If direct contact was used and the test article was not the entire final finished
device or a representative sample selection per the ASCA Test Article Prep
SOP
• If the primary irritation score is calculated using different timepoints besides
24hrs, 48hrs and 72hrs, if there were any non-zero test or control (e.g., direct
contact control: gauze; extract test control: sodium chloride or oil) results at
any time point.
• If adverse clinical findings or animal deaths occurred.
• For guinea pig maximization sensitization (ISO 10993-10 and ASTM F720):

16

Testing that includes deviations (and for which a DOC would not be appropriate) does not meet the criteria
for inclusion in the ASCA Pilot as described in Section XII.B. of the guidance titled The Accreditation Scheme
for Conformity Assessment (ASCA) Pilot Program.

18

Contains Nonbinding Recommendations
•

•

•
•

•

•

If the Magnusson and Kligman grades of 1 or greater observed in the test
group, provided grades of less than 1 are seen in corresponding sodium
chloride or oil control animals (i.e., per ISO 10993-10:2010, Clause 7.5.6).
• If differences in source, strain, treatment methods, or timing of the positive
control occurred
• If adverse clinical findings or animal deaths occurred.
For closed patch sensitization (ISO 10993-10):
• If direct contact was used and the test article was not the entire final finished
device or a representative sample selection per the ASCA Test Article Prep
SOP
• If the Magnusson and Kligman grades of 1 or greater observed in the test
group, provided grades of less than 1 are seen in negative control animals (i.e.,
per ISO 10993-10:2010, Clause 7.5.6), or the sodium chloride and oil vehicle
controls are > Grade 0
• If differences in source, strain, treatment methods, or timing of the positive
control occurred
• If adverse clinical findings or animal deaths occurred.
For acute systemic toxicity (ISO 10993-11):
• If any test or control animals died or had any adverse clinical findings
• If any test animals had a body weight loss greater than 10%.
For material-mediated pyrogenicity (ISO 10993-11 and USP 151):
• If any rabbit has a baseline temperature exceeding 39.8°C, or if any rabbit has
a temperature rise ≥0.5°C
• If adverse clinical findings or animal deaths occurred.
For direct and indirect hemolysis (ISO 10993-4 and ASTM F756):
• If direct contact was used and the test article was not the entire final finished
device or a representative sample selection per the ASCA Test Article Prep
SOP
• If direct contact was used and a diluent other than Magnesium and Calcium
Free PBS was used (i.e., per ASTM F756-17, Section 3.1.10)
• If direct contact was used and an exposure ratio other than those specially
called out in the example ASCA summary test report (Refer to Appendix I of
this guidance) was used (i.e., per ASTM F756-17, Section 9.2.1)
• If negative and positive controls did not perform as expected, the negative
control, test article, and blank had absorbance values of 0.000 for all
replicates, or test article scores of ≥2% Hemolytic Index.
For complement activation (ISO 10993-4):
• If the test article was not the entire final finished device or a representative
sample selection per the ASCA Test Article Prep SOP
• If a test medium other than those specifically called out in the example ASCA
summary test report (Refer to Appendix J of this guidance) was used
• If exposure ratio or conditions other than those specially called out in the
example ASCA summary test report (Refer to Appendix J of this guidance)
were used

19

Contains Nonbinding Recommendations
•

If test medium, negative, positive, and comparator controls did not perform as
expected, or there was a statistically significant increase in SC5b-9 for test
article compared to negative or comparator controls.

VI. Paperwork Reduction Act of 1995
This guidance contains information collection provisions that are subject to review by the
Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44
U.S.C. 3501-3521).
The time required to complete this information collection is estimated 17 to average 95 hours
per response for accreditation bodies and 47 hours for testing laboratories. Send comments
regarding this burden estimate or suggestions for reducing this burden to:
FDA PRA Staff,
Office of Operations,
Food and Drug Administration,
PRAStaff@fda.hhs.gov
An agency may not conduct or sponsor, and a person is not required to respond to, a
collection of information unless it displays a currently valid OMB control number. The OMB
control number for this information collection is 0910-0889 (expires 06-30-2023).

17

Rounded to the nearest whole number.

20

Contains Nonbinding Recommendations

Appendix A: Example ASCA Declaration of Conformity
(DOC) for Biological Evaluation of Medical Devices
Standards in the ASCA Pilot
Note: This example is intended to illustrate elements of the Declaration of Conformity per
FDA’s guidance Appropriate Use of Voluntary Consensus Standards in Premarket
Submissions for Medical Devices that the device manufacturer may submit as part of its
premarket submission.
Responsible Party
Name of entity responsible for DOC: ____________________________________________
Address of entity responsible for DOC: ___________________________________________
Product/Device Identification

All identifying information for the product/device including (e.g., product code(s), device
marketing name(s), model number(s), etc.).
Statement of Conformity
The test results demonstrate that the device is in conformity with the standard(s) listed
below: 18
1. Title of Standard: (e.g., ISO 10993-10 Third edition 2010-08-01 Biological
evaluation of medical devices – Part 10: Tests for irritation and skin sensitization)___
• FDA Recognition #: (e.g., 2-174)_______________________________________
• Options Selected
 Standard included no options
 Standard included options

•
•
•

List of options selected in standard (e.g., Clause 7.3 Guinea pig assays for
detection of skin sensitization). No information is needed in this section if
testing is from an ASCA-accredited test laboratory; instead, this section may
reference the ASCA summary test report provided as supplementary
documentation.
Testing Laboratory Name: (e.g., Testing Laboratory ABC)___________________
ASCA Testing Laboratory Identification Number (as applicable): (e.g., ASCA001)
Testing Location(s): (e.g., 1234 Example Road, Silver Spring, MD 20993)______

18

See section 514(c)(3)(A)(i) of the FD&C Act, cited in Section IV.A.(3)(f) of FDA’s guidance Appropriate
Use of Voluntary Consensus Standards in Premarket Submissions for Medical Device.

21

Contains Nonbinding Recommendations
•
•

•

Testing Date(s): (e.g., Sep 1, 2020 – Sep 15, 2020)_________________________
ASCA Accreditation Status on the Date(s) of Testing:
 Standard (and particular test method) was not in testing laboratory’s scope of
ASCA Accreditation
 Standard (and particular test method) was in testing laboratory’s scope of
ASCA Accreditation;_________________________________________________
 ASCA Accreditation was not suspended
 ASCA Accreditation was suspended

Description of reasons for suspension and their impact on testing results,
including date(s) of suspension.
Supplemental Documentation (see Section V.C. of this guidance for specific
recommendations):
 Supplementary documentation is not included
 Supplementary documentation is included at the following location within the
submission, and I have checked that there are no differences regarding
protocol and data between the complete test report and the supplemental
documentation: (e.g., Appendix A of this premarket
submission)________________________________________

Limitations on Validity of DOC

22

Contains Nonbinding Recommendations

Description of any limitation on the validity of the DOC (e.g., how long the declaration is valid,
what was tested, or concessions made about the testing outcomes). For testing from an ASCAaccredited test laboratory, this should include, at a minimum:
•

•

•

•

Information on how the test article compares with the device provided in this
premarket submission 19 (including, selection of “representative” devices/portions)
can be found at the following location in this premarket submission: (e.g., Section V.
pages 45-50)____________
Information on how any concerns communicated by the test lab were resolved can be
found at the following location in this premarket submission: (e.g., Appendix D of
this premarket
submission)_________________________________________________________
Information on how any observations and/or degradations during testing were
resolved can be found at the following location in this premarket submission: (e.g.,
Appendix D of this premarket
submission)___________________________________________________________
A statement that the device/test article does not require customized sample
preparation and/or testing methodologies, or any absorbable or in situ polymerizing
devices, liquid devices, creams, gels, hydrogel devices, and devices containing
nanomaterials, as these types of materials are not eligible for biocompatibility
testing under the ASCA Pilot

Signature
Printed name: ______________________________________________________________
Function within entity responsible for DOC: _______________________________________
___________________________________________________________________________
Signature
Date

19

Please see FDA’s guidance Use of International Standard ISO 10993-1, "Biological evaluation of medical
devices - Part 1: Evaluation and testing within a risk management process" for considerations regarding the use
of medical devices in their final finished form or a representative test article for biocompatibility testing.

23

Contains Nonbinding Recommendations

Appendix B: Example ASCA Summary Test Report for
Biocompatibility Testing of Medical Devices: Irritation –
Intracutaneous Reactivity (ISO 10993-10)
Note: This example is intended to illustrate the supplemental documentation that would
accompany the Declaration of Conformity per FDA’s guidance Appropriate Use of
Voluntary Consensus Standards in Premarket Submissions for Medical Devices. The ASCA
summary test report is provided by the testing laboratory to the device manufacturer.
Administrative Information
1. Testing Laboratory Name:
2. ASCA Testing Laboratory Identification Number:
3. Testing Location(s):
4. Testing Date(s):
5. ASCA Accreditation Status on the Date(s) of Testing:
 Standard (and particular test method) was *NOT* in testing laboratory’s scope of
ASCA Accreditation 20
 Standard (and particular test method) was in testing laboratory’s scope of ASCA
Accreditation
 ASCA Accreditation was not suspended
 ASCA Accreditation was suspended

Description of reasons for suspension and their impact on testing results.
ASCA Test Article Prep SOP#: [ASCATAPrep(date/version)]
 Test Article was prepared per the above protocol (no deviations/amendments); or
 Test Article was prepared per the above protocol, with the following
deviations/amendments 21 (e.g., filtering, extract manipulation, pH adjustment):

Description of deviations/amendments
 For devices that contain fluid paths only, the Test Article was prepared using only the
fluid path for extraction
Extraction Solvent:
 0.9% Sodium Chloride (SC)
20

See FDA’s guidance Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for
Medical Devices for information regarding supplemental documentation necessary to support FDA-recognized
consensus standards that are not in a testing laboratory’s scope of ASCA Accreditation.
21
Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.

24

Contains Nonbinding Recommendations
 Cotton Seed Oil (CSO)/Sesame Oil (SO)
 Other: 22 [DESCRIBE]
Extraction Ratio:
 6cm2/ml (<0.5mm thick)
 3cm2/ml (0.5-1.0mm thick or molded items > 1.0mm)
 1.25cm2/ml (elastomers > 1.0mm thick)
 Other: 23 [DESCRIBE]
Extraction Conditions:
 37°C, 72 h
 50°C, 72 h
 70°C, 24 h
 121°C, 1 h
 Other: 24 [DESCRIBE]
Fluid Path Extractions:
 For fluid path devices or components (where fluids contact the channels in the device or
component, and then the fluid enters the body), the extraction was conducted using protocols
specific to fluid path, with the following approach: 25
 Complete fill with agitation
 Partial fill with agitation (ISO 10993-12 surface/volume ratio)
 Partial fill with agitation (other surface/volume ratio): [DESCRIBE RATIO USED]
 Other: [SUMMARIZE APPROACH]
 The test article and extract DID NOT change color, and the extract DID NOT appear
turbid or have particles.
 There were changes in color/turbidity or particles in the test article and/or extract OR
there was swelling/degradation of the test article. 26
ASCA Test Method SOP #: [ASCAIntracut(date/version)]
 Test was conducted per the above protocol (no deviations/amendments) and 21 CFR 58;
or

22

In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.
23
Ibid
24
Ibid
25
The applicability of various approaches (e.g., partial fill versus complete fill) for a particular device may
impact whether or not a complete test report is requested in addition to the ASCA Summary Test Report.
26
In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.

25

Contains Nonbinding Recommendations
 Test was conducted per the above protocol and 21 CFR 58, with the following
deviations/amendments: 27

Description of deviations/amendments
Results: 28
24 hr Results
48 hr Results
72 hr Results Conclusions
ER^: 0/0/0/0/0
ER: 0/0/0/0/0 ER: 0/0/0/0/0 Performed as
ED: 0/0/0/0/0
ED: 0/0/0/0/0 ED: 0/0/0/0/0 expected
SC Control
ER: 0/0/0/0/0
ER: 0/0/0/0/0 ER: 0/0/0/0/0 Performed as
ED: 0/0/0/0/0
ED: 0/0/0/0/0 ED: 0/0/0/0/0 expected
Animal 2
SC Test
ER: 0/0/0/0/0
ER: 0/0/0/0/0 ER: 0/0/0/0/0 Performed as
ED: 0/0/0/0/0
ED: 0/0/0/0/0 ED: 0/0/0/0/0 expected
SC Control
ER: 0/0/0/0/0
ER: 0/0/0/0/0 ER: 0/0/0/0/0 Performed as
ED: 0/0/0/0/0
ED: 0/0/0/0/0 ED: 0/0/0/0/0 expected
Animal 3
SC Test
ER: 0/0/0/0/0
ER: 0/0/0/0/0 ER: 0/0/0/0/0 Performed as
ED: 0/0/0/0/0
ED: 0/0/0/0/0 ED: 0/0/0/0/0 expected
SC Control
ER: 0/0/0/0/0
ER: 0/0/0/0/0 ER: 0/0/0/0/0 Performed as
ED: 0/0/0/0/0
ED: 0/0/0/0/0 ED: 0/0/0/0/0 expected
Animal 1
SO Test
ER: 1/1/1/1/1
ER: 1/0/1/1/1
ER: 1/0/1/1/1 Performed as
ED: 0/0/0/0/0
ED: 0/0/0/0/0 ED: 0/0/0/0/0 expected
SO Control
ER: 1/1/1/1/1
ER: 1/1/1/1/1 ER: 1/1/0/0/1 Performed as
ED: 0/0/0/0/0
ED: 0/0/0/0/0 ED: 0/0/0/0/0 expected
Animal 2
SO Test
ER: 1/1/1/1/1
ER: 1/1/1/1/0 ER: 1/1/1/1/0 Performed as
ED: 0/0/1/0/0
ED: 0/0/1/0/0 ED: 0/0/0/0/0 expected
SO Control
ER: 1/1/1/1/0
ER: 1/1/1/0/1 ER: 1/1/0/0/0 Performed as
ED: 0/0/1/0/0
ED: 0/0/0/0/0 ED: 0/0/0/0/0 expected
Animal 3
SO Test
ER: 1/1/1/1/1
ER: 1/1/1/1/1 ER: 1/1/1/1/1 Performed as
ED: 0/0/0/0/0
ED: 0/0/0/0/0 ED: 0/0/0/0/0 expected
SO Control
ER: 1/1/1/1/1
ER: 1/1/1/1/1 ER: 1/1/1/1/1 Performed as
ED: 0/0/0/0/0
ED: 0/0/0/0/0 ED: 0/0/0/0/0 expected
[INSERT ROWS FOR ANY ADDITIONAL REPEAT TEST DATA]
^ER = erythema grade; ED = edema grade
Animal 1

Test Article
SC Test

27

Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not need to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.
28
The complete test report should be included with ASCA Summary Test Report during the ASCA Pilot, if the
overall score differences between the test and control are greater than one (i.e., per ISO 10993-10:2010, Clause
6.4.7), or if there were non-zero results for any of the sodium chloride control sites in any animal, or results
greater than 1 for any of the oil control sites in any animal at any timepoint.

26

Contains Nonbinding Recommendations

Extract

Overall Test
Group Mean

SC
SO

0.0
1.0

Overall
Control Group
Mean
0.0
0.9

Overall Mean
Difference
(Test – Control)
0.0
0.1

Conclusion

Non-Irritant
Non-Irritant

 There were no adverse clinical findings or animal deaths; or
 The following adverse clinical findings or animal deaths occurred: 29

Description of adverse clinical findings or animal deaths
I confirm that:
 The above summary information includes all original and any retest data; and
 I have checked that there are no differences between the complete test report and this
ASCA summary test report.

Name: [TYPED NAME POSITION]

Date

29

In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.

27

Contains Nonbinding Recommendations

Appendix C: Example ASCA Summary Test Report for
Biocompatibility Testing of Medical Devices: Cytotoxicity
– MEM Elution (ISO 10993-5)
Note: This example is intended to illustrate the supplemental documentation that would
accompany the Declaration of Conformity per FDA’s guidance Appropriate Use of
Voluntary Consensus Standards in Premarket Submissions for Medical Devices. The ASCA
summary test report is provided by the testing laboratory to the device manufacturer.
Administrative Information
1. Testing Laboratory Name:
2. ASCA Testing Laboratory Identification Number:
3. Testing Location(s):
4. Testing Date(s):
5. ASCA Accreditation Status on the Date(s) of Testing:
 Standard (and particular test method) was *NOT* in testing laboratory’s scope of
ASCA Accreditation 30
 Standard (and particular test method) was in testing laboratory’s scope of ASCA
Accreditation
 ASCA Accreditation was not suspended
 ASCA Accreditation was suspended

Description of reasons for suspension and their impact on testing results.
ASCA Test Article Prep SOP#: [ASCATAPrep(date/version)]
 Test Article was prepared per the above protocol (no deviations/amendments); or
 Test Article was prepared per the above protocol, with the following
deviations/amendments 31 (e.g., filtering, extract manipulation, pH adjustment):

Description of deviations/amendments
Extraction Solvent:
 MEM with 5-10% animal serum
 Other: 32 [DESCRIBE]
30

See FDA’s guidance Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for
Medical Devices for information regarding supplemental documentation necessary to support FDA-recognized
consensus standards that are not in a testing laboratory’s scope of ASCA Accreditation.
31
Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.
32
In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test

28

Contains Nonbinding Recommendations
Extraction Ratio:
 6cm2/ml (<0.5mm thick)
 3cm2/ml (0.5-1.0mm thick or molded items > 1.0mm)
 1.25cm2/ml (elastomers > 1.0mm thick)
 Other: 33 [DESCRIBE]
Extraction Conditions:
 37°C, 24 h
 37°C, 72 h
 50°C, 72 h
 70°C, 24 h
 121°C, 1 h
 Other: 34 [DESCRIBE]
Fluid Path Extractions:
 For fluid path devices or components (where fluids contact the channels in the device or
component, and then the fluid enters the body), the extraction was conducted using protocols
specific to fluid path, with the following approach: 35
 Complete fill with agitation
 Partial fill with agitation (ISO 10993-12 surface/volume ratio)
 Partial fill with agitation (other surface/volume ratio): [DESCRIBE RATIO USED]
 Other: [SUMMARIZE APPROACH]
 The test article and extract DID NOT change color, and the extract DID NOT appear
turbid or have particles.
 There were changes in color/turbidity or particles in the test article and/or extract OR
there was swelling/degradation of the test article. 36
ASCA Test Method SOP #: [######-ASCACytotox(date/version)]
 Test was conducted per the above protocol (no deviations/amendments) and 21 CFR 58;
or
 Test was conducted per the above protocol and 21 CFR 58, with the following
deviations/amendments: 37

report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.
33
Ibid
34
Ibid
35
The applicability of various approaches (e.g., partial fill versus complete fill) for a particular device may
impact whether or not a complete test report should be included with the ASCA Summary Test Report.
36
In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.
37
Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.

29

Contains Nonbinding Recommendations

Description of deviations/amendments
Results: 38

Vehicle Control

24 hr
Results
(optional)
Grade 0/0/0

Negative Control HDPE

Grade 0/0/0

Positive Control Latex

Grade 3/3/3

Test Article Extract (100%
neat)
[INSERT ROWS FOR ANY
ADDITIONAL TEST
ARTICLE
DILUTION/RETEST DATA]

Grade 0/0/0

48 hr
Results
Grade
0/0/0
Grade
0/0/0
Grade
4/4/4*
Grade
0/0/0

72 hr
Results
(implants)
Grade 0/0/0
Grade 0/0/0
Grade 4/4/4
Grade 0/0/0

Conclusion

Performed as
expected
Performed as
expected
Performed as
expected
Non-cytotoxic

*based on prior results (once Grade 4 results are observed, subsequent assessment is not
necessary for cytotoxicity)
I confirm that:
 The above summary information includes all original and any retest data; and
 I have checked that there are no differences between the complete test report and this
ASCA summary test report.

Name: [TYPED NAME POSITION]

Date

Name: [TYPED NAME, POSITION]

Date

38

The complete test report should be included with ASCA Summary Test Report during the ASCA Pilot if there
were non-zero results for the test article, vehicle control or negative control, or if there were results less than 3
for the positive control at any timepoint.

30

Contains Nonbinding Recommendations

Appendix D: Example ASCA Summary Test Report for
Biocompatibility Testing of Medical Devices: Dermal
Irritation (ISO 10993-10)
Note: This example is intended to illustrate the supplemental documentation that would
accompany the Declaration of Conformity per FDA’s guidance Appropriate Use of
Voluntary Consensus Standards in Premarket Submissions for Medical Devices. The ASCA
summary test report is provided by the testing laboratory to the device manufacturer.
Administrative Information
1. Testing Laboratory Name:
2. ASCA Testing Laboratory Identification Number:
3. Testing Location(s):
4. Testing Date(s):
5. ASCA Accreditation Status on the Date(s) of Testing:
 Standard (and particular test method) was *NOT* in testing laboratory’s scope of
ASCA Accreditation 39
 Standard (and particular test method) was in testing laboratory’s scope of ASCA
Accreditation
 ASCA Accreditation was not suspended
 ASCA Accreditation was suspended

Description of reasons for suspension and their impact on testing results.
ASCA Test Article Prep SOP#: [ASCATAPrep(date/version)]
 Test Article was prepared per the above protocol (no deviations/amendments); or
 Test Article was prepared per the above protocol, with the following
deviations/amendments 40 (e.g., filtering, extract manipulation, pH adjustment):

Description of deviations/amendments
Direct contact
Test article:
 Entire final finished device
 Representative sample selection per SOP
39

See FDA’s guidance Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for
Medical Devices for information regarding supplemental documentation necessary to support FDA-recognized
consensus standards that are not in a testing laboratory’s scope of ASCA Accreditation.
40
Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also request to provide a rationale to
support a regulatory decision.

31

Contains Nonbinding Recommendations

 Other: 41 [DESCRIBE]
Extract testing
Extraction Solvent:
 0.9% Sodium Chloride (SC)
 Cotton Seed Oil (CSO)/Sesame Oil (SO)
 Other: 42 [DESCRIBE]
Extraction Ratio:
 6cm2/ml (<0.5mm thick)
 3cm2/ml (0.5-1.0mm thick or molded items > 1.0mm)
 1.25cm2/ml (elastomers > 1.0mm thick)
 Other: 43 [DESCRIBE]
Extraction Conditions:
 37°C, 72 h
 50°C, 72 h
 70°C, 24 h
 121°C, 1 h
 Other: 44 [DESCRIBE]
Fluid Path Extractions:
 For fluid path devices or components (where fluids contact the channels in the device or
component, and then the fluid enters the body), the extraction was conducted using protocols
specific to fluid path, with the following approach: 45
 Complete fill with agitation
 Partial fill with agitation (ISO 10993-12 surface/volume ratio)
 Partial fill with agitation (other surface/volume ratio): [DESCRIBE RATIO USED]
 Other: [SUMMARIZE APPROACH]
 The test article and extract DID NOT change color, and the extract DID NOT appear
turbid or have particles.
 There were changes in color/turbidity or particles in the test article and/or extract OR
there was swelling/degradation of the test article. 46
41

In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.
42
Ibid
43
Ibid
44
Ibid
45
The applicability of various approaches (e.g., partial fill versus complete fill) for a particular device may
impact whether or not a complete test report should be included with the ASCA Summary Test Report.
46
In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.

32

Contains Nonbinding Recommendations
ASCA Test Method SOP #: [ASCADermalIrri(date/version)]
 Test was conducted per the above protocol (no deviations/amendments) and 21 CFR 58;
or
 Test was conducted per the above protocol and 21 CFR 58, with the following
deviations/amendments: 47

Description of deviations/amendments
Results: 48
Table 1 Summary of Scores for Dermal Irritation*
Animal
Number
1

2

3

Test/Control
Article Sites

Score @ 1hr Score @
Score @
24hr
48hr
ER
ED
ER
ED
ER
ED
Test Site-1
0
0
0
0
0
0
Test Site-2
1
0
0
0
0
0
Control Site-1
0
0
0
0
0
0
Control Site-2
0
0
0
0
0
0
Test Site-1
0
0
0
0
0
0
Test Site-2
0
0
0
0
0
0
Control Site-1
0
0
0
0
0
0
Control Site-2
0
0
0
0
0
0
Test Site-1
0
0
0
0
0
0
Test Site-2
0
0
0
0
0
0
Control Site-1
0
0
0
0
0
0
Control Site-2
0
0
0
0
0
0
[INSERT ROWS FOR ANY ADDITIONAL REPEAT TEST DATA]

Score @
72hr
ER
ED
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0

*For extract-based tests: animal data 49 for both polar and nonpolar test extracts and
corresponding vehicle controls should be reported.

47

Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.
48
The complete test report should be included with ASCA Summary Test Report during the ASCA Pilot if the
primary irritation score is calculated using different timepoints besides 24h, 48h and 72h, if there were any nonzero test or control (e.g., direct contact control: gauze; extract test control: sodium chloride or oil) results at any
time point.
49
We support the principles of the “3Rs,” to reduce, refine, and replace animal use in testing when feasible. We
encourage sponsors to consult with us if they wish to use a non-animal testing method they believe is suitable,
adequate, validated, and feasible. We will consider if such an alternative method could be assessed for
equivalency to an animal test method. However, these alternative methods would not be eligible for the ASCA
pilot. See generally: https://www.fda.gov/science-research/advancing-regulatory-science/vi-modernizing-safetytesting

33

Contains Nonbinding Recommendations
^ER = erythema grade; ED = edema grade
Table 2 Summary of Primary Irritation Index*
Animal Test
- Control Individual Combined Primary Response Conclusion
Number Score
Score
Primary
Primary
Irritation Category
Average
Average Irritation Irritation Index
Score
Score
(CPIS÷3)
(CPIS)
1
0.0
0.0
0.0
0.0
0.0
Negligible Non-irritant
2
0.0
0.0
0.0
3
0.0
0.0
0.0
*For extract-based tests: animal data for both polar and nonpolar test extracts and
corresponding vehicle controls should be reported.
 There were no adverse clinical findings or animal deaths; or
 The following adverse clinical findings or animal deaths occurred: 50

Description of adverse clinical findings or animal deaths
I confirm that:
 The above summary information includes all original and any retest data; and
 I have checked that there are no differences between the complete test report and this
ASCA summary test report.

Name: [TYPED NAME POSITION]

Date

50

In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.

34

Contains Nonbinding Recommendations

Appendix E: Example ASCA Summary Test Report for
Biocompatibility Testing of Medical Devices: Guinea Pig
Maximization Sensitization (ISO 10993-10)
Note: This example is intended to illustrate the supplemental documentation that would
accompany the Declaration of Conformity per FDA’s guidance Appropriate Use of
Voluntary Consensus Standards in Premarket Submissions for Medical Devices. The ASCA
summary test report is provided by the testing laboratory to the device manufacturer.
Administrative Information
1. Testing Laboratory Name:
2. ASCA Testing Laboratory Identification Number:
3. Testing Location(s):
4. Testing Date(s):
5. ASCA Accreditation Status on the Date(s) of Testing:
 Standard (and particular test method) was *NOT* in testing laboratory’s scope of
ASCA Accreditation 51
 Standard (and particular test method) was in testing laboratory’s scope of ASCA
Accreditation
 ASCA Accreditation was not suspended
 ASCA Accreditation was suspended

Description of reasons for suspension and their impact on testing results.
ASCA Test Article Prep SOP#: [ASCATAPrep(date/version)]
 Test Article was prepared per the above protocol (no deviations/amendments); or
 Test Article was prepared per the above protocol, with the following
deviations/amendments 52 (e.g., filtering, extract manipulation, pH adjustment):

Description of deviations/amendments
Extraction Solvent:
 0.9% Sodium Chloride (SC)
 Cotton Seed Oil (CSO)/Sesame Oil (SO)

51

See FDA’s guidance Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for
Medical Devices for information regarding supplemental documentation necessary to support FDA-recognized
consensus standards that are not in a testing laboratory’s scope of ASCA Accreditation.
52
Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.

35

Contains Nonbinding Recommendations
 Other: 53 [DESCRIBE]
Extraction Ratio:
 6cm2/ml (<0.5mm thick)
 3cm2/ml (0.5-1.0mm thick or molded items > 1.0mm)
 1.25cm2/ml (elastomers > 1.0mm thick)
 Other: 54 [DESCRIBE]
Extraction Conditions:
 37°C, 72 h
 50°C, 72 h
 70°C, 24 h
 121°C, 1 h
 Other: 55 [DESCRIBE]
Fluid Path Extractions:
 For fluid path devices or components (where fluids contact the channels in the device or
component, and then the fluid enters the body), the extraction was conducted using protocols
specific to fluid path, with the following approach: 56
 Complete fill with agitation
 Partial fill with agitation (ISO 10993-12 surface/volume ratio)
 Partial fill with agitation (other surface/volume ratio): [DESCRIBE RATIO USED]
 Other: [SUMMARIZE APPROACH]
 The test article and extract DID NOT change color, and the extract DID NOT appear
turbid or have particles.
 There were changes in color/turbidity or particles in the test article and/or extract OR
there was swelling/degradation of the test article. 57

53

In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also request to provide a rationale to support a regulatory decision.
54
Ibid
55
Ibid
56
The applicability of various approaches (e.g., partial fill versus complete fill) for a particular device may
impact whether or not a complete test report should be included with the ASCA Summary Test Report.
57
In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.

36

Contains Nonbinding Recommendations

ASCA Test Method SOP #: [ASCAMaximizationSensi(date/version)]
 Test was conducted per the above protocol (no deviations/amendments) and 21 CFR 58;
or
 Test was conducted per the above protocol and 21 CFR 58, with the following
deviations/amendments: 58

Description of deviations/amendments

58

Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.

37

Contains Nonbinding Recommendations
Results: 59

Group

SC Test

SC Control

SO Test

SO Control

Table 1 Summary of Scores for Sensitization
Animal
24hrs
48hrs
Sensitizatio
Numbe
n
r
Frequency
Contr Tes Contr Tes
ol Site t
ol Site t
Site
Site
1
0
0
0
0
0%
2
0
0
0
0
3
0
0
0
0
4
0
0
0
0
5
0
0
0
0
6
0
0
0
0
7
0
0
0
0
8
0
0
0
0
9
0
0
0
0
10
0
0
0
0
1
0
0
0
0
0%
2
0
0
0
0
3
0
0
0
0
4
0
0
0
0
5
0
0
0
0
1
0
0
0
0
0%
2
0
0
0
0
3
0
0
0
0
4
0
0
0
0
5
0
0
0
0
6
0
0
0
0
7
0
0
0
0
8
0
0
0
0
9
0
0
0
0
10
0
0
0
0
1
0
0
0
0
0%
2
0
0
0
0
3
0
0
0
0
4
0
0
0
0
5
0
0
0
0
1
0
2
0
2
100%
2
0
2
0
1

Conclusio
n

Nonsensitizer

Performed
as
expected

Nonsensitizer

Performed
as
expected

59

The complete test report should be included with ASCA Summary Test Report during the ASCA Pilot, if the
Magnusson and Kligman grades of 1 or greater observed in the test group, provided grades of less than 1 are
seen in control animals (i.e., per ISO 10993-10:2010, Clause 7.5.6).

38

Contains Nonbinding Recommendations

Dinitrochlorobenze 3
0
2
0
3
Performed
ne (DNCB) Positive 4
as
0
2
0
2
Control*
expected
5
0
2
0
2
[INSERT ROWS FOR ANY ADDITIONAL REPEAT TEST DATA]
*Periodic/concurrent positive control study
 Positive control induction concentration: [DESCRIBE]
 Positive control challenge concentration: [DESCRIBE]
 The same source, strain, and treatment methods used for positive control testing and done
within 3 months of test article test date
 The following differences in source, strain, treatment methods or timing of the positive
control occurred: 60

Description of differences in source, strain, treatment methods, or timing of the positive
control.
 There were no adverse clinical findings or animal deaths; or
 The following adverse clinical findings or animal deaths occurred: 61

Description of adverse clinical findings or animal deaths.
I confirm that:
 The above summary information includes all original and any retest data; and
 I have checked that there are no differences between the complete test report and this
ASCA summary test report.

Name: [TYPED NAME POSITION]

Date

60

In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.
61
Ibid

39

Contains Nonbinding Recommendations

Appendix F: Example ASCA Summary Test Report for
Biocompatibility Testing of Medical Devices: Closed Patch
Sensitization (ISO 10993-10)
Note: This example is intended to illustrate the supplemental documentation that would
accompany the Declaration of Conformity per FDA’s guidance Appropriate Use of
Voluntary Consensus Standards in Premarket Submissions for Medical Devices. The ASCA
summary test report is provided by the testing laboratory to the device manufacturer.
Administrative Information
1. Testing Laboratory Name:
2. ASCA Testing Laboratory Identification Number:
3. Testing Location(s):
4. Testing Date(s):
5. ASCA Accreditation Status on the Date(s) of Testing:
 Standard (and particular test method) was *NOT* in testing laboratory’s scope of
ASCA Accreditation 62
 Standard (and particular test method) was in testing laboratory’s scope of ASCA
Accreditation
 ASCA Accreditation was not suspended
 ASCA Accreditation was suspended

Description of reasons for suspension and their impact on testing results.
ASCA Test Article Prep SOP#: [ASCATAPrep(date/version)]
 Test Article was prepared per the above protocol (no deviations/amendments); or
 Test Article was prepared per the above protocol, with the following
deviations/amendments 63 (e.g., filtering, extract manipulation, pH adjustment):

Description of deviations/amendments
Direct contact
Test article:
 Entire final finished device
 Representative sample selection per SOP
62

See FDA’s guidance Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for
Medical Devices for information regarding supplemental documentation necessary to support FDA-recognized
consensus standards that are not in a testing laboratory’s scope of ASCA Accreditation.
63
Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.

40

Contains Nonbinding Recommendations
 Other: 64[DESCRIBE]
Extract testing
Extraction Solvent:
 0.9% Sodium Chloride (SC)
 Cotton Seed Oil (CSO)/Sesame Oil (SO)
 Other: 65 [DESCRIBE]
Extraction Ratio:
 6cm2/ml (<0.5mm thick)
 3cm2/ml (0.5-1.0mm thick or molded items > 1.0mm)
 1.25cm2/ml (elastomers > 1.0mm thick)
 Other: 66 [DESCRIBE]
Extraction Conditions:
 37°C, 72 h
 50°C, 72 h
 70°C, 24 h
 121°C, 1 h
 Other: 67 [DESCRIBE]
Fluid Path Extractions:
 For fluid path devices or components (where fluids contact the channels in the device or
component, and then the fluid enters the body), the extraction was conducted using protocols
specific to fluid path, with the following approach: 68
 Complete fill with agitation
 Partial fill with agitation (ISO 10993-12 surface/volume ratio)
 Partial fill with agitation (other surface/volume ratio): [DESCRIBE RATIO USED]
 Other: [SUMMARIZE APPROACH]
 The test article and extract DID NOT change color, and the extract DID NOT appear
turbid or have particles.
 There were changes in color/turbidity or particles in the test article and/or extract OR
there was swelling/degradation of the test article. 69
ASCA Test Method SOP #: [ASCAPatchSens(date/version)]
64

In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.
65
Ibid
66
Ibid
67
Ibid
68
The applicability of various approaches (e.g., partial fill versus complete fill) for a particular device may
impact whether or not a complete test report should be included with the ASCA Summary Test Report.
69
In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.

41

Contains Nonbinding Recommendations
 Test was conducted per the above protocol (no deviations/amendments) and 21 CFR 58;
or
 Test was conducted per the above protocol and 21 CFR 58, with the following
deviations/amendments: 70

Description of deviations/amendments
Results: 71
Table 1 Summary of Scores for Sensitization*
Group

Animal
Numbe
r

24hrs

Contr
ol Site
Test

1
2
3
4
5
6
7
8
9
10
Gauze Negative
1
Control
2
3
4
5
Dinitrochlorobenze 1
ne (DNCB) Positive 2
Control**
3
4
5

0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0

Tes
t
Site
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
2
2
2
2

48hrs

Contr
ol Site
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0

Tes
t
Site
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
1
3
2
2

Sensitizatio Conclusio
n
n
Frequency

0%

Nonsensitizer

0%

Performed
as
expected

100%

Performed
as
expected

70

Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.
71
The complete test report should be included with ASCA Summary Test Report during the ASCA Pilot if the
Magnusson and Kligman grades of 1 or greater observed in the test group, provided grades of less than 1 are
seen in negative control animals (i.e., per ISO 10993-10:2010, Clause 7.5.6), or the sodium chloride and oil
vehicle controls are > Grade 0.

42

Contains Nonbinding Recommendations
[INSERT ROWS FOR ANY ADDITIONAL REPEAT TEST DATA]
*For extract-based tests: animal data for both polar and nonpolar test extracts and
corresponding vehicle controls should be reported.
**Periodic/concurrent positive control study
 Positive control induction concentration: [DESCRIBE]
 Positive control challenge concentration: [DESCRIBE]
 The same source, strain, and treatment methods used for positive control testing and done
within 3 months of test article test date
 The following differences in source, strain, treatment methods or timing of the positive
control occurred: 72

Description of differences in source, strain, treatment methods, or timing of the positive
control
 There were no adverse clinical findings or animal deaths; or
 The following adverse clinical findings or animal deaths occurred: 73

Description of adverse clinical findings or animal deaths
I confirm that:
 The above summary information includes all original and any retest data; and
 I have checked that there are no differences between the complete test report and this
ASCA summary test report.

Name: [TYPED NAME POSITION]

Date

72

In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.
73
Ibid

43

Contains Nonbinding Recommendations

Appendix G: Example ASCA Summary Test Report for
Biocompatibility Testing of Medical Devices: Acute
Systemic Toxicity (ISO 10993-11)
Note: This example is intended to illustrate the supplemental documentation that would
accompany the Declaration of Conformity per FDA’s guidance Appropriate Use of
Voluntary Consensus Standards in Premarket Submissions for Medical Devices. The ASCA
summary test report is provided by the testing laboratory to the device manufacturer.
Administrative Information
1. Testing Laboratory Name:
2. ASCA Testing Laboratory Identification Number:
3. Testing Location(s):
4. Testing Date(s):
5. ASCA Accreditation Status on the Date(s) of Testing:
 Standard (and particular test method) was *NOT* in testing laboratory’s scope of
ASCA Accreditation 74
 Standard (and particular test method) was in testing laboratory’s scope of ASCA
Accreditation
 ASCA Accreditation was not suspended
 ASCA Accreditation was suspended

Description of reasons for suspension and their impact on testing results.
ASCA Test Article Prep SOP#: [ASCATAPrep(date/version)]
 Test Article was prepared per the above protocol (no deviations/amendments); or
 Test Article was prepared per the above protocol, with the following
deviations/amendments 75 (e.g., filtering, extract manipulation, pH adjustment):

Description of deviations/amendments
Extraction Solvent:
 0.9% Sodium Chloride (SC)
 Cotton Seed Oil (CSO)/Sesame Oil (SO)
 Other: 76 [DESCRIBE]
74

See FDA’s guidance Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for
Medical Devices for information regarding supplemental documentation necessary to support FDA-recognized
consensus standards that are not in a testing laboratory’s scope of ASCA Accreditation.
75
Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.

44

Contains Nonbinding Recommendations
Extraction Ratio:
 6cm2/ml (<0.5mm thick)
 3cm2/ml (0.5-1.0mm thick or molded items > 1.0mm)
 1.25cm2/ml (elastomers > 1.0mm thick)
 Other: 77 [DESCRIBE]
Extraction Conditions:
 37°C, 72 h
 50°C, 72 h
 70°C, 24 h
 121°C, 1 h
 Other: 78 [DESCRIBE]
Fluid Path Extractions:
 For fluid path devices or components (where fluids contact the channels in the device or
component, and then the fluid enters the body), the extraction was conducted using protocols
specific to fluid path, with the following approach: 79
 Complete fill with agitation
 Partial fill with agitation (ISO 10993-12 surface/volume ratio)
 Partial fill with agitation (other surface/volume ratio): [DESCRIBE RATIO USED]
 Other: [SUMMARIZE APPROACH]
 The test article and extract DID NOT change color, and the extract DID NOT appear
turbid or have particles.
 There were changes in color/turbidity or particles in the test article and/or extract OR
there was swelling/degradation of the test article. 80
ASCA Test Method SOP #: [ASCAAcuteTox(date/version)]
 Test was conducted per the above protocol (no deviations/amendments) and 21 CFR 58;
or
 Test was conducted per the above protocol and 21 CFR 58, with the following
deviations/amendments: 81

77

In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.
78
Ibid
79
The applicability of various approaches (e.g., partial fill versus complete fill) for a particular device may
impact whether or not a complete test report should be included with the ASCA Summary Test Report.
80
In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.
81
Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.

45

Contains Nonbinding Recommendations

Description of deviations/amendments
Results: 82
Table 1 Summary of Test Results 83
Extract

SC
Test

SC
Control

SO
Test

SO
Control

Animal
Body Weight (g)
Number Day 0 Day 1 Day 2 Day 3
1
2
3
4
5
1
2
3
4
5
1
2
3
4
5
1
2
3
4
5

20.4
19.6
19.6
20.4
17.9
17.9
19.8
19.9
17.9
22.1
22.2
20.2
19.0
18.5
19.4
19.7
19.4
21.2
20.9
20.3

20.8
20.4
19.9
19.8
18.6
19.9
20.0
20.3
17.8
22.9
22.9
21.3
19.2
19.8
202.2
20.2
19.9
21.7
21.7
21.1

21.1
20.3
20.1
20.3
19.0
19.8
20.9
20.8
17.9
23.1
22.8
21.4
19.3
20.5
19.8
20.5
19.7
22.2
22.0
21.6

21.7
21.7
20.7
21.1
19.7
20.4
22.3
21.4
18.6
24.3
23.4
21.8
20.2
21.6
20.0
21.9
20.0
23.6
23.1
23.4

Weight Conclusion (Based on Body
Change Weight and Clinical
Findings)
1.3
No acute systemic toxicity
2.1
No acute systemic toxicity
1.1
No acute systemic toxicity
0.7
No acute systemic toxicity
1.8
No acute systemic toxicity
2.5
Performed as expected
2.5
Performed as expected
1.5
Performed as expected
0.7
Performed as expected
2.2
Performed as expected
1.2
Not systemically toxic
1.6
Not systemically toxic
1.2
Not systemically toxic
3.1
Not systemically toxic
0.6
Not systemically toxic
2.2
Not systemically toxic
0.6
Not systemically toxic
2.4
Not systemically toxic
2.2
Not systemically toxic
3.1
Not systemically toxic

[INSERT ROWS FOR ANY ADDITIONAL REPEAT TEST DATA]
 There were no adverse clinical findings or animal deaths; or
 The following adverse clinical findings or animal deaths occurred: 84

82

The complete test report should be included with ASCA Summary Test Report during the ASCA Pilot if
controls did not perform as expected, any animals were found dead or were euthanized, behavior such as
convulsions or prostration occurred in any animals, or a body weight loss greater than 10 % occurred in any
animals.
83
This is an example of how data from an acute systemic toxicity test could be presented.
84
In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.

46

Contains Nonbinding Recommendations

Description of adverse clinical findings or animal deaths
I confirm that:
 The above summary information includes all original and any retest data; and
 I have checked that there are no differences between the complete test report and this
ASCA summary test report.

Name: [TYPED NAME POSITION]

Date

47

Contains Nonbinding Recommendations

Appendix H: Example ASCA Summary Test Report for
Biocompatibility Testing of Medical Devices: MaterialMediated Pyrogenicity (ISO 10993-11 and USP 151)
Note: This example is intended to illustrate the supplemental documentation that would
accompany the Declaration of Conformity per FDA’s guidance Appropriate Use of
Voluntary Consensus Standards in Premarket Submissions for Medical Devices. The ASCA
summary test report is provided by the testing laboratory to the device manufacturer.
Administrative Information
1. Testing Laboratory Name:
2. ASCA Testing Laboratory Identification Number:
3. Testing Location(s):
4. Testing Date(s):
5. ASCA Accreditation Status on the Date(s) of Testing:
 Standard (and particular test method) was *NOT* in testing laboratory’s scope of
ASCA Accreditation 85
 Standard (and particular test method) was in testing laboratory’s scope of ASCA
Accreditation
 ASCA Accreditation was not suspended
 ASCA Accreditation was suspended

Description of reasons for suspension and their impact on testing results.
ASCA Test Article Prep SOP#: [ASCATAPrep(date/version)]
 Test Article was prepared per the above protocol (no deviations/amendments); or
 Test Article was prepared per the above protocol, with the following
deviations/amendments 86 (e.g., filtering, extract manipulation, pH adjustment):

Description of deviations/amendments
Extraction Solvent:
 0.9% Sodium Chloride (SC)
 Other: 87[DESCRIBE]
85

See FDA’s guidance Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for
Medical Devices for information regarding supplemental documentation necessary to support FDA-recognized
consensus standards that are not in a testing laboratory’s scope of ASCA Accreditation.
86
Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.
87
In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test

48

Contains Nonbinding Recommendations
Extraction Ratio:
 6cm2/ml (<0.5mm thick)
 3cm2/ml (0.5-1.0mm thick or molded items > 1.0mm)
 1.25cm2/ml (elastomers > 1.0mm thick)
 Other: 88 [DESCRIBE]
Extraction Conditions:
 37°C, 72 h
 50°C, 72 h
 70°C, 24 h
 121°C, 1 h
 Other: 89 [DESCRIBE]
Fluid Path Extractions:
 For fluid path devices or components (where fluids contact the channels in the device or
component, and then the fluid enters the body), the extraction was conducted using protocols
specific to fluid path, with the following approach: 90
 Complete fill with agitation
 Partial fill with agitation (ISO 10993-12 surface/volume ratio)
 Partial fill with agitation (other surface/volume ratio): [DESCRIBE RATIO USED]
 Other: [SUMMARIZE APPROACH]
 The test article and extract DID NOT change color, and the extract DID NOT appear
turbid or have particles.
 There were changes in color/ turbidity or particles in the test article and/or extract OR
there was swelling/degradation of the test article. 91

report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.
88
Ibid
89
Ibid
90
The applicability of various approaches (e.g., partial fill versus complete fill) for a particular device may
impact whether or not a complete test report should be included with the ASCA Summary Test Report.
91
In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.

49

Contains Nonbinding Recommendations
ASCA Test Method SOP #: [ASCAPyrogenicity(date/version)]
 Test was conducted per the above protocol (no deviations/amendments) and 21 CFR 58;
or
 Test was conducted per the above protocol and 21 CFR 58, with the following
deviations/amendments: 92

Description of deviations/amendments
Results: 93
Table 1 Pyrogen Test Data 94
Animal Baseline 1.0hr 1.5 hr 2.0 hr
Number Temp
Temp Temp Temp
(°C)
(°C)
(°C)
(°C)
1 (test)
39.0
39.1
39.1
38.9
2 (test)
3 (test)

2.5 hr 3.0 hr Temp
Conclusion
Temp Temp Increase
(°C)
(°C)
(°C)
38.8
39.1
0.1
Nonpyrogenic
39.3
39.3
39.1
38.8
39.1
39.1
0.0
Nonpyrogenic
39.0
38.7
38.8
39.1
39.4
39.4
0.4
Nonpyrogenic
[INSERT ROWS FOR ANY ADDITIONAL REPEAT TEST DATA]

 There were no adverse clinical findings or animal deaths; or
 The following adverse clinical findings or animal deaths occurred: 95

Description of adverse clinical findings or animal deaths
I confirm that:
 The above summary information includes all original and any retest data; and
 I have checked that there are no differences between the complete test report and this
ASCA summary test report.

92

Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.
93
The complete test report should be included with ASCA Summary Test Report during the ASCA Pilot if any
rabbit has a baseline temperature exceeding 39.8oC or if any rabbit has a temperature rise ≥0.5°C.
94
This is an example of how data from a material-mediated pyrogenicity test could be presented.
95
In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.

50

Contains Nonbinding Recommendations

Name: [TYPED NAME POSITION]

Date

51

Contains Nonbinding Recommendations

Appendix I: Example ASCA Summary Test Report for
Biocompatibility Testing of Medical Devices: Direct and
Indirect Hemolysis (ISO 10993-4 and ASTM F756)
Note: This example is intended to illustrate the supplemental documentation that would
accompany the Declaration of Conformity per FDA’s guidance Appropriate Use of
Voluntary Consensus Standards in Premarket Submissions for Medical Devices. The ASCA
summary test report is provided by the testing laboratory to the device manufacturer.
Administrative Information
1. Testing Laboratory Name:
2. ASCA Testing Laboratory Identification Number:
3. Testing Location(s):
4. Testing Date(s):
5. ASCA Accreditation Status on the Date(s) of Testing:
 Standard (and particular test method) was *NOT* in testing laboratory’s scope of
ASCA Accreditation 96
 Standard (and particular test method) was in testing laboratory’s scope of ASCA
Accreditation
 ASCA Accreditation was not suspended
 ASCA Accreditation was suspended

Description of reasons for suspension and their impact on testing results.
ASCA Test Article Prep SOP#: [ASCATAPrep(date/version)]
 Test Article was prepared per the above protocol (no deviations/amendments); or
 Test Article was prepared per the above protocol, with the following
deviations/amendments 97 (e.g., filtering, extract manipulation, pH adjustment):

Description of deviations/amendments
Extract testing
Extraction Solvent:
 Magnesium and Calcium Free PBS

96

See FDA’s guidance Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for
Medical Devices for information regarding supplemental documentation necessary to support FDA-recognized
consensus standards that are not in a testing laboratory’s scope of ASCA Accreditation.
97
Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.

52

Contains Nonbinding Recommendations
 Other: 98 [DESCRIBE]
Extraction Ratio:
 6cm2/ml (<0.5mm thick)
 3cm2/ml (0.5-1.0mm thick or molded items > 1.0mm)
 1.25cm2/ml (elastomers > 1.0mm thick)
 Other: 99 [DESCRIBE]
Extraction Conditions:
 37°C, 72 h
 50°C, 72 h
 70°C, 24 h
 121°C, 1 h
 Other: 100 [DESCRIBE]
Fluid Path Extractions:
 For fluid path devices or components (where fluids contact the channels in the device or
component, and then the fluid enters the body), the extraction was conducted using protocols
specific to fluid path, with the following approach: 101
 Complete fill with agitation
 Partial fill with agitation (ISO 10993-12 surface/volume ratio)
 Partial fill with agitation (other surface/volume ratio): [DESCRIBE RATIO USED]
 Other: [SUMMARIZE APPROACH]
 The test article and extract DID NOT change color, and the extract DID NOT appear
turbid or have particles.
 There were changes in color/turbidity or particles in the test article and/or extract OR
there was swelling/degradation of the test article. 102
Direct Contact
Test article:
 Entire final finished device
 Representative sample selection per SOP
 Other: 103 [DESCRIBE]
Diluent:
 Magnesium and Calcium Free PBS
98

In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.
99
Ibid
100
Ibid
101
The applicability of various approaches (e.g., partial fill versus complete fill) for a particular device may
impact whether or not a complete test report should be included with the ASCA Summary Test Report.
102
In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.
103
Ibid

53

Contains Nonbinding Recommendations
 Other: 104[DESCRIBE]
Exposure Ratio:
 6cm2/ml (<0.5mm thick)
 3cm2/ml (0.5-1.0mm thick or molded items > 1.0mm)
 Other: 105 [DESCRIBE]
 The test article and supernatant DID NOT change color, and the supernatant DID NOT
appear turbid or have particles.
 There were changes in color/turbidity or particles in the supernatant OR there was
swelling/degradation of the test article. 106
ASCA Test Method SOP #: [ASCAHemolysis(date/version)]
 Test was conducted per the above protocol (no deviations/amendments) and 21 CFR 58;
or
 Test was conducted per the above protocol and 21 CFR 58, with the following
deviations/amendments: 107

Description of deviations/amendments

104

In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.
105
Ibid
106
Ibid
107
Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.

54

Contains Nonbinding Recommendations

Results: 108
Table 1 Hemolysis test results 109

Sample

Blank

Absorbance

Mean
Blank
Corrected
Hemolysis
Replicate Replicate Replicate Replicate Replicate Replicate
(%)
#1
#2
#3
#1
#2
#3

Hemolytic Index (%)

0.0022

Negative
0.0020
Control
Positive
0.3233
Control
Test
0.0019
Sample

Extract Hemolysis
Blank corrected % hemolysis

0.0019

0.0026

-0.01

-0.08

0.09

0.00

-

0.0018

0.0019

-0.06

-0.11

-0.08

-0.08

-

0.3258

0.3261

79.68

80.30

80.37

80.11

80.20

0.0015

0.0015

-0.08

-0.18

-0.18

-0.15

-0.07

Mean
Blank
Corrected
Hemolysis
(%)

Hemolytic Index (%)

Absorbance

Direct Hemolysis
Blank corrected % hemolysis

Conclusions

Performed
as expected
Performed
as expected
Performed
as expected
Nonhemolytic
Conclusions

Replicate Replicate Replicate Replicate Replicate Replicate
#1
#2
#3
#1
#2
#3

108

The complete test report should be included with ASCA Summary Test Report during the ASCA Pilot if negative and positive controls did not perform as
expected, the negative control, test article, and blank had absorbance values of 0.000 for all replicates, or test article scores of ≥2% HI.
109
This is an example of how data from a hemolysis test could be presented.

55

Contains Nonbinding Recommendations

Blank

0.0057

Negative
0.0074
Control
Positive
0.3732
Control
Test
0.0096

0.0059

0.0051

0.03

0.08

-0.12

0.00

-

0.0084

0.0103

0.46

0.71

1.18

0.78

-

0.3736

0.3752

91.99

92.09

92.49

92.19

91.41

0.0091

0.0089

1.01

0.88

0.83

0.91

0.13

[INSERT ROWS FOR ANY ADDITIONAL REPEAT TEST DATA]

56

Performed
as expected
Performed
as expected
Performed
as expected
Nonhemolytic

Contains Nonbinding Recommendations

I confirm that:
 The above summary information includes all original and any retest data; and
 I have checked that there are no differences between the complete test report and this
ASCA summary test report.

Name: [TYPED NAME POSITION]

Date

57

Contains Nonbinding Recommendations

Appendix J: Example ASCA Summary Test Report for
Biocompatibility Testing of Medical Devices: Complement
Activation (ISO 10993-4)
Note: This example is intended to illustrate the supplemental documentation that would
accompany the Declaration of Conformity per FDA’s guidance Appropriate Use of
Voluntary Consensus Standards in Premarket Submissions for Medical Devices. The ASCA
summary test report is provided by the testing laboratory to the device manufacturer.
Administrative Information
1. Testing Laboratory Name:
2. ASCA Testing Laboratory Identification Number:
3. Testing Location(s):
4. Testing Date(s):
5. ASCA Accreditation Status on the Date(s) of Testing:
 Standard (and particular test method) was *NOT* in testing laboratory’s scope of
ASCA Accreditation 110
 Standard (and particular test method) was in testing laboratory’s scope of ASCA
Accreditation
 ASCA Accreditation was not suspended
 ASCA Accreditation was suspended

Description of reasons for suspension and their impact on testing results.
ASCA Test Article Prep SOP#: [ASCATAPrep(date/version)]
 Test Article was prepared per the above protocol (no deviations/amendments); or
 Test Article was prepared per the above protocol, with the following
deviations/amendments 111 (e.g., filtering, extract manipulation, pH adjustment):

Description of deviations/amendments
Test article:
 Entire final finished device
 Representative sample selection per SOP

110

See FDA’s guidance Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for
Medical Devices for information regarding supplemental documentation necessary to support FDA-recognized
consensus standards that are not in a testing laboratory’s scope of ASCA Accreditation.
111
Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.

58

Contains Nonbinding Recommendations
 Other: 112[DESCRIBE]
Test Medium:
 Normal Human Serum
 Human Plasma
 Whole Blood
 Other: 113[DESCRIBE]
Exposure Ratio:
 6cm2/ml (<0.5mm thick)
 3cm2/ml (0.5-1.0mm thick or molded items > 1.0mm)
 Other: 114 [DESCRIBE]
Exposure Conditions:
 37°C for 60-90 min
 Other: 115 [DESCRIBE]
 The test article and supernatant DID NOT change color, and the supernatant DID NOT
appear turbid or have particles.
 There were changes in color/turbidity or particles in the supernatant OR there was
swelling/degradation of the test article. 116

112

In this situation, the complete test report should be included with ASCA Summary Test Report during the
ASCA Pilot (depending on the information provided, FDA may or may not request to review the complete test
report). Test Laboratory/Manufacturer may also be requested to provide a rationale to support a regulatory
decision.
113
Ibid
114
Ibid
115
Ibid
116
Ibid

59

Contains Nonbinding Recommendations
ASCA Test Method SOP #: [ASCAComplement(date/version)]
 Test was conducted per the above protocol (no deviations/amendments) and 21 CFR 58;
or
 Test was conducted per the above protocol and 21 CFR 58, with the following
deviations/amendments: 117

Description of deviations/amendments
Results: 118
Table 1 SC5b-9 Protein Concentration (ng/mL) 119
Samples

Dilution

Concentration (ng/mL)
Replicate #1 Replicate #2 Replicate #3 Mean

Std

Conclusion
Not a
complement
activator*
Performed
as expected
Performed
as expected

Test Article

1:160

208

216

212

212

3.8

Test Medium
Control
Negative
Control
Material
Positive
Control
Material 120
Cobra Venom
Factor
Positive
Control 121
US marketed
comparator
(optional)

1:160

205

207

208

207

1.5

1:160

206

205

204

205

1.1

1:160

683

693

688

688

4.8

Performed
as expected

1:8000

10326

10567

10519

10471

127

Performed
as expected

1:160

210

215

223

216

6.6

Performed
as expected

[INSERT ROWS FOR ANY ADDITIONAL REPEAT TEST DATA]
*not statistically different from negative or comparator controls

117

Since deviations/amendments were noted, the complete test report should be included with ASCA Summary
Test Report during the ASCA Pilot (depending on the information provided, FDA may or may not request to
review the complete test report). Test Laboratory/Manufacturer may also be requested to provide a rationale to
support a regulatory decision.
118
The complete test report should be included with ASCA Summary Test Report during the ASCA Pilot if test
medium, negative, positive, and comparator controls did not perform as expected, or there was a statistically
significant increase in SC5b-9 for test article compared to negative or comparator controls.
119
This is an example of how data from a complement activation test could be presented.
120
Depending on the positive control used, this row may be relevant.
121
Ibid

60

Contains Nonbinding Recommendations
I confirm that:
 The above summary information includes all original and any retest data; and
 I have checked that there are no differences between the complete test report and this
ASCA summary test report.

Name: [TYPED NAME POSITION]

Date

61