ASTM F2808-23

Standard Test Method for Performing Behind-the-Knee (BTK) Test for Evaluating Skin Irritation Response to Products and Materials That Come Into Repeated or Extended Contact with Skin

SIGNIFICANCE AND USE
5.1 This test method is intended to assess a combination of inherent chemical irritation and mechanical irritation for products and materials expected to come into contact with the skin. It is a comparative approach whereby the potential irritation of a test material is compared to that of a reference material similar in form and composition. The reference material should have a known safety and irritation profile.
SCOPE
1.1 The behind-the-knee (BTK) method, using the popliteal fossa of human volunteers as a test site, simultaneously evaluates the inherent chemical irritation and the potential for mechanical irritation of substrates and products that are designed to come into repeated or extended close contact with the skin (see validation references (1-7)).2 This is a bilateral test comparing a test material to a reference material with a known safety profile.  
1.2 This test method shall be used by qualified health care professionals experienced in good clinical practice (GCP) procedures.  
1.3 This test method can be performed using human subjects on either intact or compromised skin. Testing should be performed on intact skin for test substrates or products expected to have contact with normal, intact skin, or for direct comparison to products with a known skin irritation profile. Testing can be performed on compromised skin for test substrates or products that may commonly come into contact with damaged skin (for example, skin with diaper rash, or chapped skin) or skin that is expected to be hydrated.  
1.4 Visual scoring of erythema and dryness is performed by a trained skin grader on a predefined scale.  
1.5 Prior to use in this test, materials shall undergo overall favorable biocompatibility testing consistent with the approach outlined in protocol Practice F748 or ISO 10993-1:2009. As a part of this series of testing, irritation per Practice F719 or ISO 10993-10 shall be conducted.  
1.6 The values stated in inch-pound units are to be regarded as standard. No other units of measurement are included in this standard.  
1.7 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.  
1.8 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.

General Information

• Status: Published
• Publication Date: 31-Mar-2023
• ICS: 11.100.99 - Other standards related to laboratory medicine
• Technical Committee: F04 - Medical and Surgical Materials and Devices
• Drafting Committee: F04.16 - Biocompatibility Test Methods

Relations

• Refers: ASTM F748-16 - Standard Practice for Selecting Generic Biological Test Methods for Materials and Devices
• Effective Date: 01-Apr-2016
• Refers: ASTM F719-81(2012) - Standard Practice for Testing Biomaterials in Rabbits for Primary Skin Irritation
• Effective Date: 01-Oct-2012
• Refers: ASTM F748-06(2010) - Standard Practice for Selecting Generic Biological Test Methods for Materials and Devices
• Effective Date: 01-Jun-2010
• Refers: ASTM F719-81(2007)e1 - Standard Practice for Testing Biomaterials in Rabbits for Primary Skin Irritation
• Effective Date: 01-Feb-2007
• Refers: ASTM F719-81(2007) - Standard Practice for Testing Biomaterials in Rabbits for Primary Skin Irritation
• Effective Date: 01-Feb-2007
• Refers: ASTM F748-06 - Standard Practice for Selecting Generic Biological Test Methods for Materials and Devices
• Effective Date: 01-Dec-2006
• Refers: ASTM F748-04 - Standard Practice for Selecting Generic Biological Test Methods for Materials and Devices
• Effective Date: 01-May-2004
• Refers: ASTM F748-98 - Standard Practice for Selecting Generic Biological Test Methods for Materials and Devices
• Effective Date: 10-Aug-1998
• Refers: ASTM F719-81(2002)e1 - Standard Practice for Testing Biomaterials in Rabbits for Primary Skin Irritation
• Effective Date: 24-Apr-1981
• Refers: ASTM F719-81(1996)e1 - Standard Practice for Testing Biomaterials in Rabbits for Primary Skin Irritation
• Effective Date: 24-Apr-1981

Overview

ASTM F2808-23, titled "Standard Test Method for Performing Behind-the-Knee (BTK) Test for Evaluating Skin Irritation Response to Products and Materials That Come Into Repeated or Extended Contact with Skin," provides a comprehensive methodology for assessing the skin irritation potential of materials and products designed for prolonged or repeated contact with human skin. The BTK method specifically uses the popliteal fossa (the area behind the knee) as a test site, which is particularly susceptible to both chemical and mechanical irritation due to movement and friction.

This standard is widely adopted in clinical testing scenarios, especially for medical devices and consumer products that require a robust evaluation of biocompatibility and skin tolerance. The BTK test is significant for its comparative nature, evaluating the irritation potential of the test material against a reference material known for its safety profile.

Key Topics

• Combined Irritation Assessment: The BTK method evaluates both the chemical and mechanical irritation caused by products in close and extended contact with skin.
• Test Methodology:
  • Bilateral, randomized, controlled, and double-blind study design
  • Test and reference materials are worn behind the knees for 6 hours per day over 5 days
  • Visual scoring of erythema (redness) and dryness by trained skin graders
• Inclusion/Exclusion Criteria: Qualified health professionals select healthy adult volunteers. Special considerations are provided for intact or compromised skin, reflecting real-world scenarios such as diaper rash or chapped skin.
• Pre-Testing Requirements: All materials must pass biocompatibility testing per ASTM F748 or ISO 10993-1, including irritation testing as per ASTM F719 or ISO 10993-10.
• Safety and Ethics: Testing must occur under Good Clinical Practice (GCP) and Institutional Review Board (IRB) oversight, with informed consent from all participants.

Applications

The ASTM F2808-23 BTK test method is applicable to a wide range of industries and products, including:

• Medical Devices: Materials for wound dressings, medical adhesives, surgical tapes, orthopedic supports, and wearable monitors.
• Personal Care Products: Cosmetics, skin creams, and body care products that make prolonged contact with the skin.
• Textiles and Wearables: Fabrics and garments (e.g., underwear, compression wear) designed for continuous skin contact.
• Consumer Safety Testing: Ensures new product safety and regulatory compliance by identifying irritation risks early in development.

By simulating real-life wear conditions, this method provides manufacturers, researchers, and regulatory bodies with actionable data on product safety, supporting claims of skin compatibility and helping avoid costly recalls or adverse consumer reactions.

Related Standards

ASTM F2808-23 is closely aligned with other important skin irritation and biocompatibility standards:

• ASTM F719: Practice for Testing Materials in Rabbits for Primary Skin Irritation
• ASTM F748: Practice for Selecting Generic Biological Test Methods for Materials and Devices
• ASTM D6355: Test Method for Human Repeat Insult Patch Testing of Medical Gloves
• ISO 10993-1: Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process
• ISO 10993-10: Biological evaluation of medical devices - Part 10: Tests for irritation and delayed-type hypersensitivity

These standards collectively provide a framework for comprehensive biological and irritation safety evaluations, supporting medical device approval and product development across global markets.

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Keywords: skin irritation, BTK test, ASTM F2808-23, medical device biocompatibility, behind-the-knee test, chemical irritation, mechanical irritation, human clinical testing, skin safety, product assessment, regulatory compliance.

Standards Content (Sample)

This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the
Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
Designation: F2808 − 23
Standard Test Method for
Performing Behind-the-Knee (BTK) Test for Evaluating Skin
Irritation Response to Products and Materials That Come
Into Repeated or Extended Contact with Skin
This standard is issued under the fixed designation F2808; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope 1.7 This standard does not purport to address all of the
safety concerns, if any, associated with its use. It is the
1.1 The behind-the-knee (BTK) method, using the popliteal
responsibility of the user of this standard to establish appro-
fossa of human volunteers as a test site, simultaneously
priate safety, health, and environmental practices and deter-
evaluates the inherent chemical irritation and the potential for
mine the applicability of regulatory limitations prior to use.
mechanical irritation of substrates and products that are de-
1.8 This international standard was developed in accor-
signed to come into repeated or extended close contact with the
2 dance with internationally recognized principles on standard-
skin (see validation references (1-7)). This is a bilateral test
ization established in the Decision on Principles for the
comparing a test material to a reference material with a known
Development of International Standards, Guides and Recom-
safety profile.
mendations issued by the World Trade Organization Technical
1.2 This test method shall be used by qualified health care
Barriers to Trade (TBT) Committee.
professionals experienced in good clinical practice (GCP)
procedures. 2. Referenced Documents
1.3 This test method can be performed using human sub- 2.1 ASTM Standards:
jects on either intact or compromised skin. Testing should be D6355 Test Method for Human Repeat Insult Patch Testing
performed on intact skin for test substrates or products ex- of Medical Gloves
pected to have contact with normal, intact skin, or for direct F719 Practice for Testing Materials in Rabbits for Primary
comparison to products with a known skin irritation profile. Skin Irritation
Testing can be performed on compromised skin for test F748 Practice for Selecting Generic Biological Test Methods
substrates or products that may commonly come into contact
for Materials and Devices
with damaged skin (for example, skin with diaper rash, or
2.2 ISO Standards:
chapped skin) or skin that is expected to be hydrated.
ISO 10993-1:2009 Biological Evaluation of Medical
Devices—Part 1: Evaluation and Testing Within a Risk
1.4 Visual scoring of erythema and dryness is performed by
Management Process
a trained skin grader on a predefined scale.
ISO 10993-10 Biological Evaluation of Medical Devices—
1.5 Prior to use in this test, materials shall undergo overall
Part 10: Tests for Irritation and Delayed-type Hypersensi-
favorable biocompatibility testing consistent with the approach
tivity
outlined in protocol Practice F748 or ISO 10993-1:2009. As a
part of this series of testing, irritation per Practice F719 or ISO
3. Terminology
10993-10 shall be conducted.
3.1 Definitions:
1.6 The values stated in inch-pound units are to be regarded
3.1.1 chemical irritation, n—irritation caused by a physi-
as standard. No other units of measurement are included in this
ological response to the chemical nature of a material. Such
standard.
physiological responses may include: oxidation or reduction
reactions, dehydration, disruption of the keratin ultra-structure,
or direct injury to cellular macromolecules or organelles.
This test method is under the jurisdiction of ASTM Committee F04 on Medical
and Surgical Materials and Devices and is the direct responsibility of Subcommittee
F04.16 on Biocompatibility Test Methods. For referenced ASTM standards, visit the ASTM website, www.astm.org, or
Current edition approved April 1, 2023. Published April 2023. Originally contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM
approved in 2010. Last previous edition approved in 2017 as F2808 – 17. DOI: Standards volume information, refer to the standard’s Document Summary page on
10.1520/F2808-23. the ASTM website.
2 4
The boldface numbers in parentheses refer to the list of references at the end of Available from American National Standards Institute (ANSI), 25 W. 43rd St.,
this standard. 4th Floor, New York, NY 10036, http://www.ansi.org.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F2808 − 23
3.1.2 compromised skin, n—skin that is treated with re- 6. Interferences and Precautions
peated application of surgical tape prior to the first sample
6.1 Possible protocol deviations that could interfere with or
application.
affect the outcome of the study include the fit of the elastic
3.1.3 edema, n—observable swelling from abnormal accu- knee band and the activity level of the subjects. As in any
mulation of fluid in connective tissue. clinical study, adherence to the protocol conditions will offset
any potential confounding issues.
3.1.4 erythema, n—redness of the skin.
6.2 The use of lotions, powders, creams, or skin care
3.1.5 mechanical irritation, n—irritation caused by move-
products in the skin area at the test sites during the course of
ment and friction of products intended to remain in contact
the study may impact the study results. In addition, shaving the
with the skin for extended periods of time.
skin behind the knee, exposing the test sites to tanning or the
3.1.6 popliteal fossa, n—the area at the back of the knee.
sun, or swimming or hot tub use during study participation
should not be permitted, since these practices and activities
3.1.7 reference material, n—a material similar in form and
may produce low levels of skin irritation in some persons.
composition to the test material. The reference material should
have a known safety and irritation profile.
6.3 Anti-inflammatory medications may interfere with the
normal development of the skin irritation reaction and should
3.1.8 skin grades, n—visual assessments of erythema and
not be used during the study.
dryness according to a defined scale (see 10.3).
6.4 Normal showering or bathing cannot be allowed during
3.1.9 test material, n—any material or product expected to
the sample application of 6 h per day, but can be allowed
come into contact with skin.
during the 18 h each day when the test samples are not in place.
3.1.10 trained skin grader, n—personnel who have been
6.5 Some persons will experience some degree of skin
trained to reliably recognize erythema and dryness reactions by
irritation at the test sites. In addition, some persons may
using reference examples, and by performing side-by-side
experience slight discomfort from the manner in which the
scoring with an experienced skin grader.
samples are applied (that is, an elastic knee band). In most
cases, these effects are anticipated to be reversible when
4. Summary of Test Method
sample application concludes.
4.1 Samples are applied to the back of the knee using an
elastic knee band or brace. As the subjects go about their 7. Apparatus
everyday activities, normal movements generate friction be-
7.1 An artificial light source, with a 100 W incandescent
tween the test sample and the skin at the test site, thereby
daylight blue bulb or an alternate light source with a similar
adding the element of mechanical irritation. Thus, the BTK test
coloring rendering index (CRI), is used to illuminate the
protocol evaluates a combination of mechanical irritation and
application areas for erythema grading and an illuminated 10×
the inherent chemical irritation potential of materials and
magnifying lens is used to grade dryness.
products that come into contact with the skin.
8. Reagents and Materials
4.2 This is a randomized, controlled, double blind study in
8.1 Elastic knee bands or braces are used to hold the
which both the subjects and skin grader are unaware of the
samples in place.
treatment assignments. Test and reference materials are applied
for 6 h per day, for five days. Skin reactions are graded for
8.2 Test materials include substrates and products that are
erythema and dryness prior to the first sample application (that
designed to come into repeated or extended close contact with
is, at baseline), each morning prior to subsequent sample
the skin. The appropriate reference sample is a similar material
applications, and upon the removal of the sample at the end of
or product that has been demonstrated through biocompatibil-
each period.
ity testing to be a non-irritant.
4.3 Test materials are applied once each test day to normal,
8.3 If testing is to be conducted on compromised skin, an
intact skin to evaluate potential reactions to products that
appropriate surgical tape is required.
normally come into contact with intact skin. To evaluate
9. Hazards
potential reactions to products that normally come into contact
with damaged skin, the skin can be compromised by using tape
9.1 No specific hazards have been identified for this test
stripping prior to the first sample application.
protocol. However, if any of the test materials tested should fall
under biohazard, then all used test materials should be handled
5. Significance and Use
and discarded by the test site staff following biohazard standard
operating procedures (SOPs).
5.1 This test method is intended to assess a combination of
inherent chemical irritation and mechanical irritation for prod-
10. Calibration and Standardization
ucts and materials expected to come into contact with the skin.
10.1 No calibration of specific equipment is required.
It is a comparative approach whereby the potential irritation of
a test material is compared to that of a reference material 10.2 Skin graders shall be trained to recognize the degrees
similar in form and composition. The reference material should of severity of the irritation reactions described in the grading
have a known safety and irritation profile. scales given in Appendix X7.
F2808 − 23
10.3 The skin irritation grading scales for erythema and (12) Agree to comply with all study protocol requirements.
dryness (Appendix X7) are similar to those scales used by
12.1.1.2 Exclusion Criteria:
contract testing facilities in a variety of skin testing protocols,
(1) Fitzpatrick skin type V to VI (see Appendix X2) due to
including single patch tests placed on the upper arm, multiple
difficulties in scoring visible erythema on highly pigmented
patch tests in cumulative irritation testing, forearm controlled
skin;
application testing, nasal irritation, and human repeat insult
(2) Cuts, scratches, rashes, sunburn, acne, abrasions, scar
patch testing (as outlined in Test Method D6355). Skin graders
tissue, tattoos, or any other skin abnormality at the test sites;
should be trained to recognize erythema and dryness reactions
(3) Psoriasis, eczema, skin cancer, or any active dermatitis
by performing side-by-side scoring of patch tests or BTK tests
that could potentially interfere with interpretation of test results
with an experienced skin grader until the trainee can reliably
at the test sites;
recognize the reactions.
(4) Use of corticosteroids (oral or topical) or other types of
drugs that may interfere with the normal development of
11. Institutional Review and Informed Consent
irritation, inflammation, or immune reactions;
11.1 Institutional Review:
(5) Participation in a behind-the-knee study within the last
11.1.1 The method for this study and qualification of per-
four weeks;
sons conducting the study shall be reviewed by an appropriate
(6) Known irritancy or discomfort in the area behind the
institutional review board (IRB) or equivalent ethics review
knee which would prevent the subject from wearing a knee
board or committee.
brace for 6 h each day during study participation;
11.2 Informed Consent:
(7) Current pregnancy or lactation (self-reported);
11.2.1 An informed consent document should be read,
(8) Diabetes or kidney disease (self-reported) which may
understood, and signed by the subjects prior to initiating the
be associated with potential circulatory problems;
study.
(9) Heart or circulatory disease (including blood clots)
(self-reported) which may be exacerbated by wearing an elastic
12. Procedure
knee band for 6 h each day during study participation;
12.1 Subjects—Each experiment should include a general
(10) Leg varicosities which would interfere with the sub-
sample size calculation done by a statistician to determine the
ject’s wearing a knee brace for 6 h each day during study
number of subjects in the study (see 13.3). A sufficient number
participation;
of subjects should be recruited to give the study sufficient
(11) Arthritis in the lower extremities;
power to achieve a statistically significant difference between
(12) Known allergies to tape(s) and/or adhesives;
the reference and test samples, and to allow for a dropout rate
(13) History of edema in the lower extremities;
consistent with the norms for the test facility. In the course of
(14) Knee circumference greater than 21 in. (since 21 in. is
recruitment, demographic information (age, sex, ethnicity,
the maximum size that can be accommodated by many
height, and weight) should be collected on each subject.
commercial elastic knee bands).
Subjects should be healthy adults between 18 and 65 years of
12.1.2 Once eligibility is confirmed, the areas behind the
age, who meet the inclusion/exclusion criteria and preferably
knees are screened for cuts, scratches, rashes, sunburn, acne,
with Fitzpatrick skin type I to IV mixture.
abrasions, scar tissue, tattoos, or any other condition that could
12.1.1 Specific inclusion/exclusion criteria are as follows
prevent a clear assessment of their skin during the test portion
(see Appendix X1):
of the study.
12.1.1.1 Inclusion Criteria—Subjects who:
12.1.3 At the enrollment visit, subjects are fitted for the
(1) Have read, understood, and signed the informed con-
elastic knee band based on the manufacturer’s recommenda-
sent;
tion. The subject is provided with two identical, unused knee
(2) Are at least 18 years old;
bands to wear throughout the study. However, if a subject is
(3) Are no more than 65 years old;
having a degree of discomfort which he or she finds
(4) Are in general good health (self-declared);
intolerable, adjustments in the size can be made as long as the
(5) Are Fitzpatrick skin type I to IV (see Appendix X2);
identical adjustment is made to both test sites (that is, right and
(6) Agree to refrain from using lotions, creams, powders,
left knee bands). The knee bands are placed in a separate bag
or other skin preparations on the skin in the area behind the
for each subject, and labeled in a manner that will identify the
knee during participation in the study;
subject. One brand of knee bands should be used for all
(7) Agree to refrain from shaving the skin in the area
subjects. A sample worksheet is provided in Appendix X3.
behind the knee during participation in the study;
(8) Agree to refrain from swimming or hot tub use during 12.1.4 Subjects receive an instruction sheet asking them to
participation in the study; refrain from using lotions, powders, creams, or skin care
(9) Agree to refrain from fitness training during sample products in the area behind their knees during their participa-
application; tion in the study (see sample in Appendix X4). Additionally,
(10) Agree to refrain from tanning or sun exposure to the they shall be instructed to refrain from shaving the area behind
test area during participation in the study; their knees, fitness training during sample application, tanning
(11) Agree to refrain from taking anti-inflammatory medi- or sun exposure to the area behind their knees, swimming or
cation such as acetylsalicylic acid (aspirin), acetaminophen, hot tub use, or use of anti-inflammatory medications during
ibuprofen, and naproxen; their participation in the study. Subjects shall be asked to
F2808 − 23
acknowledge compliance with these instructions at each visit, 12.3.2.3 The test materials are applied horizontally to the
and the responses shall be noted on the grading sheet (see assigned test area (based on randomization) and held in place
Appendix X5). with elastic knee bands.
12.3.2.4 Each subject is provided with a subject sample
12.2 Preparation and Test Material Application—The areas
application time sheet (see sample in Appendix X8). The
behind the knees for each subject are randomly assigned to
sample application time shall be recorded on the sheet at the
either the test or reference materials per a randomization
test facility. The subject shall be instructed to record the sample
scheme. The sample assignment for each subject is docu-
removal time on the sheet promptly upon sample removal, and
mented and maintained throughout the test.
to record any problems experienced at or near the test sites.
12.2.1 Test materials include substrates and products that
12.3.2.5 Subjects shall be instructed to remove the knee
are designed to come into repeated or extended close contact
bands and test materials at the completion of the 6 h exposure
with the skin.
time, to note the time on the daily diary sheet, and to return to
12.2.2 The test can accommodate a variety of sample sizes
the test facility 30 to 60 min later for the afternoon skin
up to a maximum of 3 in. by 16 in. The test and reference
evaluation (the post-patch grade), bringing the knee bands, test
materials can be used as is. Should it be necessary, materials
samples, and their daily diary sheet with them. The 30 to
should be manually cut to the same size with clean surgical
60 min rest period between sample removal and grading allows
scissors.
the skin at the test site to recover from any compression effects
12.2.3 Test materials are placed in approximately the same
that may have resulted from the elastic knee bands. Prolonged
location behind each knee and held in place using the provided
compression of the skin may press blood from underlying
elastic knee bands (see Appendix X6).
capillaries, resulting in a whiter appearance. Such compression
12.2.4 All subjects and the skin grader are blinded to the
effects are reversed during the 30 to 60 min rest period. A wear
identity of the test materials.
time equal to or less than 5 h 30 min, or equal to or greater than
12.3 Daily Procedures:
6 h 30 min, is considered a protocol deviation and should be
12.3.1 The enrollment visit of the study occurs four to six
noted as such.
days prior to the start of the study (Day –6 to –4). During the
12.3.2.6 In addition, subjects shall be instructed to remove
enrollment visit, subjects will be asked to sign an informed
the elastic knee band(s) at any time during the study when they
consent and complete an inclusion/exclusion questionnaire
experience any unusual pain, discomfort, or swelling during
(sample included in Appendix X1) by means of an interview
exposure to the test materials. The subjects should contact the
conducted by a representative of the test facility. For those
test facility staff immediately to inform them of their decision
subjects enrolled in the study, an initial examination of the test
and reason for removal.
area shall be made. The test sites shall be measured for the
12.3.2.7 At the test facility, skin evaluations are conducted
elastic knee band, and instructions to the subject reviewed.
and sample application time sheets are collected. If any test
12.3.2 Day 1—Subjects return to the test facility for the test
material is considered biohazard then all used test materials
portion of the study. Compliance to the subject’s study instruc-
shall be discarded by the test site staff as a biohazard, following
tions shall be checked verbally.
biohazard SOPs. The knee bands for each subject shall be
12.3.2.1 The area behind each knee is scored visually for
returned to the labeled bags.
erythema and dryness by a trained skin grader based on
12.3.3 Day 2 through 5—Each subject’s test sites shall be
predefined scales (see Appendix X7). This is considered the
graded for erythema and dryness prior to application of the test
baseline grade. If a subject exhibits an erythema grade of 2.0 or
materials. This is considered the “recovery grade” (that is, the
higher or a dryness grade of 4 or higher on any behind-the-knee
remaining erythema and dryness after overnight recovery).
site at baseline, the test materials shall not be applied on the
12.3.3.1 After the skin grading, the test materials shall be
affected site. If both behind-the-knee sites are affected then the
applied in a manner identical to Day 1, and held securely in
subject is excluded from study participation. Such grades are
place with the elastic knee band. A new subject sample time
recorded and the reason for non-application of the test mate-
sheet (Appendix X8) shall be given to each subject for the day.
rial(s) is (are) noted as either “moderate/severe erythema” or
12.3.3.2 Subjects shall be instructed to remove the knee
“moderate/extreme dryness,” respectively.
bands and test materials at the completion of the 6 h exposure
12.3.2.2 Compromising Skin at the Test Sites—If compro-
time, and to return to the test facility 30 to 60 min later for skin
mised skin is required, the areas behind the knees are treated by
evaluation (that is, the “post-patch grade”) with all test
tape stripping (8). One whole piece of an appropriate surgical
materials and assigned elastic knee bands. A wear time equal to
tape (2 in. wide) should be securely applied to the entire
or less than 5 h 30 min, or equal to or greater than 6 h 30 min,
surface area behind-the-knee which is to be covered by the test
is considered a protocol deviation and should be noted as such.
material, and removed rapidly by pulling it off from the right
12.3.3.3 At the test facility, skin evaluations shall be con-
side of the knee towards the left at around 180°. This procedure
ducted and sample application time sheets collected. All used
should be repeated with fresh strips of tape applied to the same
test materials shall be discarded by the test site staff. The knee
area until an erythema grade of 1.0 to 1.5 is reached. For each
bands for each subject shall be returned to the labeled bags for
subject, the number of tape strippings needed to produce a
use the next day by the same subject.
grade of 1.0 to 1.5 shall be entered on a worksheet. Tape
stripping shall be done only on study day 1, prior to the first 12.3.4 Subsequent Visits, if Needed—Any test site showing
sample application. (See Appendix X3.) a visual erythema response of 2.0 or greater, a dryness grade of
F2808 − 23
4 or greater at the final regularly scheduled grading shall be other circumstances. The test materials shall be removed for 30
asked to report for daily grading until the response has to 60 min prior to grading so that the grader will not see what
regressed to a grade 1.5 or less for erythema, or a dryness grade test materials the subject was wearing.
of 3 or less. In the unlikely event that an erythema reaction of 12.7.1.1 The primary measurements shall be the erythema
greater than 2.0 persists for longer than three days, or at the and dryness at the test site evaluated according to the scales
request of the subject, the subject shall be referred to a provided in Appendix X7. The study light source shall be used
dermatologist for treatment. to illuminate the application areas for erythema grading and the
12.3.5 Daily Activity Chart—See Table 1. illuminated magnifying lens used to grade dryness. The same
trained individual shall score all of the reactions to the test
12.4 Removal of Subjects from the Study—Participation in
materials during the course of the study.
this study shall be completely voluntary. After admission to the
12.7.1.2 As mentioned previously, if a subject exhibits a
study, the subject may withdraw at any time he or she deems it
visual erythema grade of 2.0 or higher or a dryness grade of 4
necessary for any reason and is asked to report such reason
or higher on any behind-the-knee site at any of the morning
fairly and accurately. The principal investigator may elect to
grading sessions, the test materials shall not be reapplied.
discontinue a subject’s participation at any time he or she
However, the site shall be graded to the completion of the test
deems it necessary or if it is in the subject’s best interest. In
to assess the irritation regression response. Any test site
addition, any subject missing an application or scoring day
showing a visual erythema response of 2.0 or greater, a dryness
shall be dropped from the study. The reason for a subject’s
grade of 4 or greater, and/or any elevated response at the final
discontinued participation shall be documented on the subject
regularly scheduled grading shall be followed by a daily
accountability report form, such as the sample shown in
grading until the erythema response has regressed to grade 1.5
Appendix X9.
or less, or the dryness has regressed to 3 or less. In the unlikely
12.5 Adverse Events—An adverse event (or adverse experi-
event that an erythema reaction of greater than 2.0 persists for
ence) is any untoward medical occurrence, such as intercurrent
longer than three days, or at the request of the subject, the
illness or accident, in a study subject administered a test
subject shall be referred to a dermatologist for treatment.
product or material that does not n
...

This document is not an ASTM standard and is intended only to provide the user of an ASTM standard an indication of what changes have been made to the previous version. Because
it may not be technically possible to adequately depict all changes accurately, ASTM recommends that users consult prior editions as appropriate. In all cases only the current version
of the standard as published by ASTM is to be considered the official document.
Designation: F2808 − 17 F2808 − 23
Standard Test Method for
Performing Behind-the-Knee (BTK) Test for Evaluating Skin
Irritation Response to Products and Materials That Come
Into Repeated or Extended Contact with Skin
This standard is issued under the fixed designation F2808; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope
1.1 The Behind-the-Kneebehind-the-knee (BTK) method, using the popliteal fossa of human volunteers as a test site,
simultaneously evaluates the inherent chemical irritation,irritation and the potential for mechanical irritation of substrates and
products that are designed to come into repeated or extended close contact with the skin (see validation references (1-7)). This
is a bilateral test comparing a test material to a reference material with a known safety profile.
1.2 This test method shall be used by qualified health care professionals experienced in good clinical practice (GCP) procedures.
1.3 This test method can be performed using human subjects on either intact or compromised skin. Testing should be performed
on intact skin for test substrates or products expected to have contact with normal, intact skin, or for direct comparison to products
with a known skin irritation profile. Testing can be performed on compromised skin for test substrates or products that may
commonly come into contact with damaged skin (for example, skin with diaper rash, or chapped skin) or skin that is expected to
be hydrated.
1.4 Visual scoring of erythema and dryness is performed by a trained skin grader on a pre-definedpredefined scale.
1.5 Prior to use in this test, materials shall undergo overall favorable biocompatibility testing consistent with the approach outlined
in protocol Practice F748 or ISO 10993-1:2009. As a part of this series of testing, irritation per Practice F719 or ISO 10993-10
shall be conducted.
1.6 The values stated in inch-pound units are to be regarded as standard. No other units of measurement are included in this
standard.
1.7 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility
of the user of this standard to establish appropriate safety and healthsafety, health, and environmental practices and determine
the applicability of regulatory limitations prior to use.
1.8 This international standard was developed in accordance with internationally recognized principles on standardization
established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued
by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
This test method is under the jurisdiction of ASTM Committee F04 on Medical and Surgical Materials and Devices and is the direct responsibility of Subcommittee
F04.16 on Biocompatibility Test Methods.
Current edition approved Nov. 1, 2017April 1, 2023. Published November 2017April 2023. Originally approved in 2010. Last previous edition approved in 20102017 as
F2808F2808 – 17.-10. DOI: 10.1520/F2808-17.10.1520/F2808-23.
The boldface numbers in parentheses refer to the list of references at the end of this standard.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F2808 − 23
2. Referenced Documents
2.1 ASTM Standards:
D6355 Test Method for Human Repeat Insult Patch Testing of Medical Gloves
F719 Practice for Testing Materials in Rabbits for Primary Skin Irritation
F748 Practice for Selecting Generic Biological Test Methods for Materials and Devices
2.2 ISO Standards:
ISO 10993-1:2009 Biological Evaluation of Medical Devices—Part 1: Evaluation and Testing Within a Risk Management
Process
ISO 10993-10 Biological Evaluation of Medical Devices—Part 10: Tests for Irritation and Delayed-type Hypersensitivity
3. Terminology
3.1 Definitions:
3.1.1 chemical irritation, n—irritation caused by a physiological response to the chemical nature of a material. Such physiological
responses may include: oxidation or reduction reactions, dehydration, disruption of the keratin ultra-structureultra-structure, or
direct injury to cellular macromolecules or organelles.
3.1.2 compromised skin, n—skin that is treated with repeated application of surgical tape prior to the first sample application.
3.1.3 edema, n—observable swelling from abnormal accumulation of fluid in connective tissue.
3.1.4 erythema, n—redness of the skin.
3.1.5 mechanical irritation, n—irritation caused by movement and friction of products intended to remain in contact with the skin
for extended periods of time.
3.1.6 popliteal fossa, n—the area at the back of the knee.
3.1.7 reference material, n—a material similar in form and composition to the test material. The reference material should have
a known safety and irritation profile.
3.1.8 skin grades, n—visual assessments of erythema and dryness according to a defined scale (see 10.3).
3.1.9 test material, n—any material or product expected to come into contact with skin.
3.1.10 trained skin grader, n—personnel who have been trained to reliably recognize erythema and dryness reactions by using
reference examples, and by performing side-by-side scoring with an experienced skin grader.
4. Summary of Test Method
4.1 Samples are applied to the back of the knee using an elastic knee band or brace. As the subjects go about their everyday
activities, normal movements generate friction between the test sample and the skin at the test site, thereby adding the element of
mechanical irritation. Thus, the BTK test protocol evaluates a combination of mechanical irritation and the inherent chemical
irritation potential of materials and products that come into contact with the skin.
4.2 This is a randomized, controlled, double blind study in which both the subjects and skin grader are unaware of the treatment
assignments. Test and reference materials are applied for 6 h per day, for 5five days. Skin reactions are graded for erythema and
dryness prior to the first sample application (that is, at baseline), each morning prior to subsequent sample applications, and upon
the removal of the sample at the end of each period.
For referenced ASTM standards, visit the ASTM website, www.astm.org, or contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM Standards
volume information, refer to the standard’s Document Summary page on the ASTM website.
Available from American National Standards Institute (ANSI), 25 W. 43rd St., 4th Floor, New York, NY 10036, http://www.ansi.org.
F2808 − 23
4.3 Test materials are applied,applied once each test day to normal, intact skin to evaluate potential reactions to products that
normally come into contact with intact skin. To evaluate potential reactions to products that normally come into contact with
damaged skin, the skin can be compromised by using tape stripping prior to the first sample application.
5. Significance and Use
5.1 This test method is intended to assess a combination of inherent chemical irritation and mechanical irritation for products and
materials expected to come into contact with the skin. It is a comparative approach whereby the potential irritation of a test material
is compared to that of a reference material similar in form and composition. The reference material should have a known safety
and irritation profile.
6. Interferences and Precautions
6.1 Possible protocol deviations that could interfere with or affect the outcome of the study include the fit of the elastic knee band
and the activity level of the subjects. As in any clinical study, adherence to the protocol conditions will offset any potential
confounding issues.
6.2 The use of lotions, powders, creams, or skin care products in the skin area at the test sites during the course of the study may
impact the study results. In addition, shaving the skin behind the knee, exposing the test sites to tanning or the sun, or swimming
or hot tub use during study participation should not be permitted, since these practices and activities may produce low levels of
skin irritation in some persons.
6.3 Anti-inflammatory medications may interfere with the normal development of the skin irritation reaction and should not be
used during the study.
6.4 Normal showering or bathing cannot be allowed during the sample application of 6 h per day, but can be allowed during the
18 h each day when the test samples are not in place.
6.5 Some persons will experience some degree of skin irritation at the test sites. In addition, some persons may experience slight
discomfort from the manner in which the samples are applied (that is, an elastic knee band). In most cases, these effects are
anticipated to be reversible when sample application concludes.
7. Apparatus
7.1 An artificial light source, with a 100 W incandescent daylight blue bulb or an alternate light source with a similar Coloring
Rendering Indexcoloring rendering index (CRI), is used to illuminate the application areas for erythema grading and an illuminated
10× magnifying lens is used to grade dryness.
8. Reagents and Materials
8.1 Elastic knee bands or braces are used to hold the samples in place.
8.2 Test materials include substrates and products that are designed to come into repeated or extended close contact with the skin.
The appropriate reference sample is a similar material or product that has been demonstrated through biocompatibility testing to
be a non-irritant.
8.3 If testing is to be conducted on compromised skin, an appropriate surgical tape is required.
9. Hazards
9.1 No specific hazards have been identified for this test protocol. However, if any of the test materials tested should fall under
biohazard, then all used test materials should be handled and discarded by the test site staff following Biohazard Standard
Operating Proceduresbiohazard standard operating procedures (SOPs).
F2808 − 23
10. Calibration and Standardization
10.1 No calibration of specific equipment is required.
10.2 Skin graders shall be trained to recognize the degrees of severity of the irritation reactions described in the grading scales
given in Appendix X7.
10.3 The Skin Irritation Grading Scales for Erythema and Drynessskin irritation grading scales for erythema and dryness
(Appendix X7) are similar to those scales used by contract testing facilities in a variety of skin testing protocols, including single
patch tests placed on the upper arm, multiple patch tests in cumulative irritation testing, forearm controlled application testing,
nasal irritation, and Human Repeat Insult Patch Testinghuman repeat insult patch testing (as outlined in Test Method D6355). Skin
graders should be trained to recognize erythema and dryness reactions by performing side-by-side scoring of patch tests or BTK
tests with an experienced skin grader until the trainee can reliably recognize the reactions.
11. Institutional Review and Informed Consent
11.1 Institutional Review:
11.1.1 The method for this study and qualification of persons conducting the study shall be reviewed by an appropriate
Institutional Review Boardinstitutional review board (IRB) or equivalent ethics review board or committee.
11.2 Informed Consent:
11.2.1 An informed consent document should be read, understood, and signed by the subjects prior to initiating the study.
12. Procedure
12.1 Subjects—Each experiment should include a general sample size calculation done by a statistician to determine the number
of subjects in the study (see 13.3). A sufficient number of subjects should be recruited to give the study sufficient power to achieve
a statistically significant difference between the reference and test samples, and to allow for a dropout rate consistent with the
norms for the test facility. In the course of recruitment, demographic information (age, sex, ethnicity, height, and weight) should
be collected on each subject. Subjects should be healthy adults between 18 and 65 years of age, who meet the inclusion/exclusion
criteria and preferably with Fitzpatrick skin type I to IV mixture.
12.1.1 Specific inclusion/exclusion criteria are as follows (see Appendix X1):
12.1.1.1 Inclusion Criteria—Subjects who:
(1) Have read, understood, and signed the informed consent;
(2) Are at least 18 years old;
(3) Are no more than 65 years old;
(4) Are in general good health (self-declared);
(5) Are Fitzpatrick skin type I to IV (see Appendix X2);
(6) Agree to refrain from using lotions, creams, powders, or other skin preparations on the skin in the area behind the knee
during participation in the study;
(7) Agree to refrain from shaving the skin in the area behind the knee during participation in the study;
(8) Agree to refrain from swimming or hot tub use during participation in the study;
(9) Agree to refrain from fitness training during sample application;
(10) Agree to refrain from tanning or sun exposure to the test area during participation in the study;
(11) Agree to refrain from taking anti-inflammatory medication such as acetylsalicylic acid (aspirin), acetaminophen,
ibuprofen, and naproxen;
(12) Agree to comply with all study protocol requirements.
12.1.1.2 Exclusion Criteria:
(1) Fitzpatrick skin type V to VI (see Appendix X2) due to difficulties in scoring visible erythema on highly pigmented skin;
(2) Cuts, scratches, rashes, sunburn, acne, abrasions, scar tissue, tattoos, or any other skin abnormality at the test sites;
(3) Psoriasis, eczema, skin cancer, or any active dermatitis that could potentially interfere with interpretation of test results at
the test sites;
F2808 − 23
(4) Use of corticosteroids (oral or topical) or other types of drugs that may interfere with the normal development of irritation,
inflammation, or immune reactions;
(5) Participation in a behind-the-knee study within the last four weeks;
(6) Known irritancy or discomfort in the area behind the knee which would prevent the subject from wearing a knee brace for
6 h each day during study participation;
(7) Current pregnancy or lactation (self-reported);
(8) Diabetes or kidney disease (self-reported) which may be associated with potential circulatory problems;
(9) Heart or circulatory disease (including blood clots) (self-reported) which may be exacerbated by wearing an elastic knee
band for 6 h each day during study participation;
(10) Leg varicosities which would interfere with the subject’s wearing a knee brace for 6 h each day during study participation;
(11) Arthritis in the lower extremities;
(12) Known allergies to tape(s) and/or adhesives;
(13) History of edema in the lower extremities;
(14) Knee circumference greater than 21 in. (since 21 in. is the maximum size that can be accommodated by many commercial
elastic knee bands).
12.1.2 Once eligibility is confirmed, the areas behind the knees are screened for cuts, scratches, rashes, sunburn, acne, abrasions,
scar tissue, tattoos, or any other condition that could prevent a clear assessment of their skin during the test portion of the study.
12.1.3 At the enrollment visit, subjects are fitted for the elastic knee band based on the manufacturer’s recommendation. The
subject is provided with two identical, unused knee bands to wear throughout the study. However, if a subject is having a degree
of discomfort which he or she finds intolerable, adjustments in the size can be made,made as long as the identical adjustment is
made to both test sites (that is, right and left knee bands). The knee bands are placed in a separate bag for each subject, and labeled
in a manner that will identify the subject. One brand of knee bands should be used for all subjects. A sample worksheet is provided
in Appendix X3.
12.1.4 Subjects receive an instruction sheet asking them to refrain from using lotions, powders, creams, or skin care products in
the area behind their knees during their participation in the study (see sample in Appendix X4). Additionally, they shall be
instructed to refrain from shaving the area behind their knees, fitness training during sample application, tanning or sun exposure
to the area behind their knees, swimming or hot tub use, or use of anti-inflammatory medications during their participation in the
study. Subjects shall be asked to acknowledge compliance with these instructions at each visit, and the responses shall be noted
on the grading sheet (see Appendix X5).
12.2 Preparation and Test Material Application—The areas behind the knees for each subject are randomly assigned to either the
test or reference materials per a randomization scheme. The sample assignment for each subject is documented and maintained
throughout the test.
12.2.1 Test materials include substrates and products that are designed to come into repeated or extended close contact with the
skin.
12.2.2 The test can accommodate a variety of sample sizes up to a maximum of 3 in. by 16 in. The test and reference materials
can be used as is. Should it be necessary, materials should be manually cut to the same size with clean surgical scissors.
12.2.3 Test materials are placed in approximately the same location behind each knee and held in place using the provided elastic
knee bands (see Appendix X6).
12.2.4 All subjects and the skin grader are blinded to the identity of the test materials.
12.3 Daily Procedures:
12.3.1 The enrollment visit of the study occurs 4 to 6four to six days prior to the start of the study (Day –6 to –4). During the
enrollment visit, subjects will be asked to sign an informed consent,consent and complete an inclusion/exclusion questionnaire
(sample included in Appendix X1) by means of an interview conducted by a representative of the test facility. For those subjects
enrolled in the study, an initial examination of the test area shall be made. The test sites shall be measured for the elastic knee band,
and instructions to the subject reviewed.
12.3.2 Day 1—Subjects return to the test facility for the test portion of the study. Compliance to the Subject’s Study
Instructionssubject’s study instructions shall be checked verbally.
F2808 − 23
12.3.2.1 The area behind each knee is scored visually for erythema and dryness by a trained skin grader based on
pre-definedpredefined scales (see Appendix X7). This is considered the baseline grade. If a subject exhibits an erythema grade of
2.0 or higher or a dryness grade of 4 or higher on any behind-the-knee site at baseline, the test materials shall not be applied on
the affected site. If both behind-the-knee sites are affected then the subject is excluded from study participation. Such grades are
recorded and the reason for non-application of the test material(s) is(are) is (are) noted as either “moderate/severe erythema” or
“moderate/extreme dryness,” respectively.
12.3.2.2 Compromising Skin at the Test Sites—If compromised skin is required, the areas behind the knees are treated by tape
stripping (8). One whole piece of an appropriate surgical tape (2 in. wide),wide) should be securely applied to the entire surface
area behind-the-knee which is to be covered by the test material, and removed rapidly by pulling it off from the right side of the
knee towards the left at around 180°. This procedure should be repeated with fresh strips of tape applied to the same area until
an erythema grade of 1.0 to 1.5 is reached. For each subject, the number of tape strippings needed to produce a grade of 1.0 to
1.5 shall be entered on a worksheet. Tape stripping shall be done only on study day 1, prior to the first sample application. (See
Appendix X3.)
12.3.2.3 The test materials are applied horizontally to the assigned test area (based on randomization) and held in place with elastic
knee bands.
12.3.2.4 Each subject is provided with a Subject Sample Application Time Sheetsubject sample application time sheet (see sample
in Appendix X8). The sample application time shall be recorded on the sheet at the test facility. The subject shall be instructed
to record the sample removal time on the sheet promptly upon sample removal, and to record any problems experienced at or near
the test sites.
12.3.2.5 Subjects shall be instructed to remove the knee bands and test materials at the completion of the 6 hour 6 h exposure time,
to note the time on the daily diary sheet, and to return to the test facility 30 to 60 min later for the afternoon skin evaluation (the
post-patch grade), bringing the knee bands, test samples, and their daily diary sheet with them. The 30 to 60 minute 60 min rest
period between sample removal and grading allows the skin at the test site to recover from any compression effects that may have
resulted from the elastic knee bands. Prolonged compression of the skin may press blood from underlying capillaries, resulting in
a whiter appearance. Such compression effects are reversed during the 30 to 60 minutemin rest period. A wear time equal to or
less than 5 h 30 min, or equal to or greater than 6 h 30 min, is considered a protocol deviation and should be noted as such.
12.3.2.6 In addition, subjects shall be instructed to remove the elastic knee band(s) at any time during the study when they
experience any unusual pain, discomfort, or swelling during exposure to the test materials. The subjects should contact the test
facility staff immediately to inform them of their decision and reason for removal.
12.3.2.7 At the test facility, skin evaluations are conducted and sample application time sheets are collected. If any test material
is considered biohazard then all used test materials shall be discarded by the test site staff as a biohazard, following
Biohazardbiohazard SOPs. The knee bands for each subject shall be returned to the labeled bags.
12.3.3 Day 2 through 5—Each subject’s test sites shall be graded for erythema and dryness prior to application of the test
materials. This is considered the “recovery grade” (that is, the remaining erythema and dryness after overnight recovery).
12.3.3.1 After the skin grading, the test materials shall be applied in a manner identical to dayDay 1, and held securely in place
with the elastic knee band. A new Subject Sample Time Sheetsubject sample time sheet (Appendix X8) shall be given to each
subject for the day.
12.3.3.2 Subjects shall be instructed to remove the knee bands and test materials at the completion of the 6 hour 6 h exposure time,
and to return to the test facility 30 to 60 min later for skin evaluation (that is, the “post-patch grade”) with all test materials and
assigned elastic knee bands. A wear time equal to or less than 5 h 30 min, or equal to or greater than 6 h 30 min6 h 30 min, is
considered a protocol deviation and should be noted as such.
12.3.3.3 At the test facility, skin evaluations shall be conducted and sample application time sheets collected. All used test
materials shall be discarded by the test site staff. The knee bands for each subject shall be returned to the labeled bags for use the
next day by the same subject.
12.3.4 Subsequent Visits, if needed—Needed—Any test site showing a visual erythema response of 2.0 or greater, a dryness grade
of 4 or greater at the final regularly scheduled grading shall be asked to report for daily grading until the response has regressed
F2808 − 23
to a grade 1.5 or less for erythema, or a dryness grade of 3 or less. In the unlikely event that an erythema reaction of greater than
2.0 persists for longer than 3three days, or at the request of the subject, the subject shall be referred to a dermatologist for treatment.
12.3.5 Daily Activity Chart—See Table 1.
12.4 Removal of Subjects from the Study—Participation in this study shall be completely voluntary. After admission to the study,
the subject may withdraw at any time he or she deems it necessary for any reason and is asked to report such reason fairly and
accurately. The Principal Investigatorprincipal investigator may elect to discontinue a subject’s participation at any time he or she
deems it necessary or if it is in the subject’s best interest. In addition, any subject missing an application or scoring day shall be
dropped from the study. The reason for a subject’s discontinued participation shall be documented on the Subject Accountability
Report Form,subject accountability report form, such as the sample shown in Appendix X9.
12.5 Adverse Events—An adverse event (or adverse experience) is any untoward medical occurrence, such as intercurrent illness
or accident, in a study subject administered a test product or material that does not necessarily have a causal relationship with the
study interventions. A serious adverse event or serious adverse reaction is any untoward medical occurrence that ((1)1) results in
death, ((2)2) is life-threatening, ((3)3) requires inpatient hospitalization or extended hospitalization, or ((4)4) results in persistent
or significant disability/incapacity. Any adverse events experienced by any subjects during the study shall be documented using
an Adverse Event Report Form,adverse event report form, such as the sample shown in Appendix X10.
12.6 In case of subject discontinuation due to voluntary withdrawal, discontinuation by the Principal Investigator,principal
investigator, or an adverse event, no replacement subjects will be recruited due to the short duration of this study.
12.7 Observations and Measurements:
12.7.1 Skin evaluations shall be conducted by a trained skin grader who is blinded as to the assignment of treatments for each
subject. The same grader shall be used for all examinations unless a substitution is necessary in the event of illness or other
circumstances. The test materials shall be removed for 30 to 60 min prior to grading so that the grader will not see what test
materials the subject was wearing.
12.7.1.1 The primary measurements shall be the erythema and dryness at the test site evaluated according to the scales provided
in Appendix X7. The study light source shall be used to illuminate the
...