(237 days)
No
The description focuses on qualitative genotyping and analysis using proprietary software, without mentioning AI or ML techniques for interpretation or reporting.
No.
The "Intended Use / Indications for Use" explicitly states that the test "should not be used for diagnosis, to determine any treatments or medical interventions," which are core functions of a therapeutic device. It is for reporting and interpreting genetic health risks, not for therapy itself.
Yes
Explanation: The "Intended Use / Indications for Use" section states that the device is used "for the purpose of reporting and interpreting genetic health risks" and provides information about "increased risk for prostate cancer." While it also explicitly states that it "should not be used for diagnosis," its primary function of identifying specific genetic variants associated with health risks inherently makes it a tool for diagnostic purposes, even if it does not provide a definitive diagnosis on its own.
No
The device description explicitly states that the service involves physical components like a saliva collection kit (Oragene-Dx® Device), laboratory testing using a customized genotyping beadchip, off-the-shelf reagents and instrumentation manufactured by Illumina, and the isolation of DNA from saliva. While software is used for data analysis and report generation, the core function relies on physical sample collection and laboratory processing.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the device is used for "qualitative genotyping to detect select clinically relevant variants in genomic DNA isolated from human saliva... for the purpose of reporting and interpreting genetic health risks". This involves testing a biological sample (saliva) in vitro (outside the body) to gain information about a person's health status or risk.
- Sample Type: The device uses human saliva, which is a biological specimen.
- Testing Method: It performs "qualitative genotyping" using a multiplex assay on isolated DNA. This is a laboratory-based test conducted in vitro.
- Purpose: The purpose is to report and interpret genetic health risks, specifically for Hereditary Prostate Cancer (HOXB13-Related). This information is derived from the in vitro testing of the saliva sample.
- Regulatory Context: The document is a 510(k) submission, which is a premarket submission made to the FDA to demonstrate that the device to be marketed is at least as safe and effective, that is, substantially equivalent, to a legally marketed predicate device. This regulatory pathway is used for medical devices, including IVDs. The predicate devices listed are also IVDs (Genetic Health Risk Reports).
While the service is direct-to-consumer and provides information for exploration, the core function of the device as described in the Intended Use and Device Description is to perform an in vitro test on a biological sample to provide clinically relevant genetic information related to health risks. This aligns with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The 23andMe Personal Genome Service (PGS) uses qualitative genotyping to detect select clinically relevant variants in genomic DNA isolated from human saliva collected from individuals ≥18 years for the purpose of reporting and interpreting genetic health risks, including the 23andMe PGS Genetic Health Risk Report for Hereditary Prostate Cancer (HOXB13-Related). The 23andMe PGS Genetic Health Risk Report for Hereditary Prostate Cancer (HOXB13- Related) is indicated for reporting of the G84E variant in the HOXB13 gene. The report describes if a person has the G84E variant and if a male is at increased risk for prostate cancer. The variant included in this report is most common in people of European descent. The test report does not describe a person's overall risk of developing any type of cancer, and the absence of a variant tested does not rule out the presence of other variants that may be cancer-related. This test is not a substitute for visits to a healthcare provider for recommended screenings or appropriate follow-up and should not be used for diagnosis, to determine any treatments or medical interventions.
Product codes (comma separated list FDA assigned to the subject device)
QAZ
Device Description
The 23andMe Personal Genome Service (PGS) is an over-the-counter (direct-to-consumer), DNA testing service that provides information and tools for consumers to learn about and explore their DNA.
The 23andMe Personal Genome Service (PGS) is a currently marketed, non-invasive genetic information service that combines qualitative genotyping data covering genetic ancestry, traits, and certain heritable health conditions from a single multiplex assay with descriptive information derived from peer reviewed, published genetic research studies. It is a home use, over-the-counter (direct-to-consumer) DNA testing service intended to provide information and tools for consumers to learn about and explore their DNA.
Customer saliva is self-collected using the Oragene-Dx® Device manufactured by DNA Genotek, Inc. (previously cleared for carrier screening indications under K141410, and the same collection kit used to generate performance data for DEN140044, DEN160026, DEN170046, K182784, DEN180028, and K193492, which consists of a sealable collection tube containing a stabilizing buffer solution. Once the sample is collected, it is shipped to one of our Clinical Laboratory Improvement Amendments (CLIA) certified laboratories for testing.
DNA is isolated from the saliva and tested in a multiplex assay using a customized genotyping beadchip, and off the shelf reagents and instrumentation manufactured by Illumina. The multiplex assay simultaneously tests for more than 500,000 variants, including those for the previously authorized indications, as well as for the indications proposed herein.
Raw data is generated using Illumina GenomeStudio software, and then sent to 23andMe. The data is then analyzed using 23andMe's proprietary Coregen software, where a genotype is determined for each tested SNP. The results for certain of these SNPs are used to generate personalized reports for the customer that provide information about the detected genotype.
Personalized reports are generated for each user that provide results of the testing performed. These reports tell the user which genetic health risk variant(s) have been detected in their sample and provide information about the disease associated with the variant(s). If no variant was detected, that information is also provided. The personalized reports are designed to present scientific concepts to users in an easy-to-understand format. The reports provide scientifically valid information about the risks associated with the presence of a particular variant. The reports are designed to help users understand the meaning of their results and any appropriate actions that may be taken based on their results.
The modified components of the Personal Genome Service included in this 510(k) submission are new labeling to include (a) one new variant to be reported, and (b) the qualitative reporting of one's Genetic Health Risk for Hereditary Prostate Cancer (HOXB13-Related).
Engineering drawings, schematics, etc. of Genetic Health Risk Report for Hereditary Prostate Cancer (HOXB13-Related) are not applicable to this device.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
individuals ≥18 years
Intended User / Care Setting
Over-The-Counter Use
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Method Comparison (Accuracy) Study:
- Study Type: Method comparison study to assess accuracy of the 23andMe assay against Sanger bi-directional DNA sequencing.
- Sample Size: Saliva samples selected from the 23andMe customer biobank based on predetermined genotype and minimum volume. Specific number not provided.
- Key Results: Achieved >99% PPA and NPA for all genotypes, meeting the acceptance criteria of a minimum of 99% PPA and NPA for each SNP.
Precision / Reproducibility Study:
- Study Type: Precision study to determine reproducibility, including intra-assay, inter-lot, inter-instrument, inter-operator, inter-day, and inter-lab differences.
- Sample Size: DNA samples from the 23andMe biobank with confirmed genotypes. Specific number not provided.
- Key Results: Yielded 100% correct genotype calls for all samples across multiple days, operator teams, instruments, and reagent lots at two independent laboratory sites. Demonstrated 100% reproducibility and 100% repeatability for a given sample.
DNA Input Study:
- Study Type: Study to determine the lowest concentration of DNA necessary for successful assignment of the correct genotype.
- Sample Size: DNA samples from the 23andMe biobank based on listed genotypes. Specific number not provided.
- Key Results: Yielded 100% correct genotype calls for all samples and all reagent lots tested at sample DNA concentrations of 5, 15, and 50 ng/uL. Performance requirement for the assay is validated for a DNA concentration range of 5 ng/uL to 50 ng/uL.
Interfering Substance (Specificity) Study:
- Study Type: Studies to assess the effects of endogenous substances, exogenous substances, microbial substances, and smoking on the assay, performed in support of submission DEN140044.
- Sample Size: More than 35,000 sample replicates.
- Key Results: No discordant or No Call results across 99 SNPs, for an accuracy of 100% when following the instructions for use (i.e., nothing by mouth for at least 30 minutes prior to collecting saliva). The current device also relies on previously cleared K141410 collection device.
Potentially Interfering Mutations:
- Study Information: One potentially interfering mutation near G84E was identified. Commercially available samples for these mutations were not found, so the impact of interfering mutations has not been evaluated. A statement was added to the limitations section.
Matrix Comparison:
- Study Information: Human saliva is the only suitable sample matrix. Comparison studies are not applicable.
Clinical Performance:
- Study Information: Clinical performance is based on published studies of variant frequencies in various populations, results of analytical studies in this submission, and allele frequencies in the 23andMe customer database for genetic variants and associations. Table 5.3 summarizes HOXB13 G84E Allele Frequencies in 23andMe and gnomAD databases across various ancestry groups.
Labeling Comprehension:
- Study Information: Key report message concepts for the Hereditary Prostate Cancer (HOXB13-Related) test were reviewed and determined to be the same as those previously tested in the Genetic Health Risk device label comprehension study (DEN160026), which was suitable for the predicate devices (DEN170046 and K182784).
- Key Results: Average comprehension rate per comprehension concept ranged from 90.7% to 96.1%, meeting the predefined acceptance criteria of 90% or greater overall comprehension. The content and educational materials were effective in communicating relevant concepts.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Method Comparison (Accuracy): >99% PPA and NPA for all genotypes.
- Precision: 100% correct genotype calls for all samples, 100% reproducibility and 100% repeatability.
- DNA Input: 100% correct genotype calls for all samples and reagent lots at 5, 15, and 50 ng/uL.
- Interfering Substance: 100% accuracy when following instructions for use.
- Labeling Comprehension: 90.7% to 96.1% average comprehension rate per concept.
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
K141410, DEN140044, DEN160026, DEN180028, K193492
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
N/A
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue square. To the right of the square are the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.
January 06, 2022
23andMe, Inc. Marianna Frendo Manager, Regulatory Affairs 349 Oyster Point Blvd. South San Francisco, CA 94080
Re: K211499
Trade/Device Name: 23andMe PGS Genetic Risk Report for Hereditary Prostate Cancer (HOXB13-Related) Regulation Number: 21 CFR 866.6090 Regulation Name: Cancer Predisposition Risk Assessment System Regulatory Class: Class II Product Code: QAZ Dated: May 12, 2021 Received: May 14, 2021
Dear Marianna Frendo:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's
1
requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Soma Ghosh, Ph.D. Chief Molecular Pathology and Cytology Branch Division of Molecular Genetics and Pathology OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K211499
Device Name
23andMe Personal Genome Service (PGS) Genetic Health Risk Report for Hereditary Prostate Cancer (HOXB13-Related)
Indications for Use (Describe)
The 23andMe Personal Genome Service (PGS) uses qualitative genotyping to detect select clinically relevant variants in genomic DNA isolated from human saliva collected from individuals ≥18 years for the purpose of reporting and interpreting genetic health risks, including the 23andMe PGS Genetic Health Risk Report for Hereditary Prostate Cancer (HOXB13-Related). The 23andMe PGS Genetic Health Risk Report for Hereditary Prostate Cancer (HOXB13- Related) is indicated for reporting of the G84E variant in the HOXB13 gene. The report describes if a person has the G84E variant and if a male is at increased risk for prostate cancer. The variant included in this report is most common in people of European descent. The test report does not describe a person's overall risk of developing any type of cancer, and the absence of a variant tested does not rule out the presence of other variants that may be cancer-related. This test is not a substitute for visits to a healthcare provider for recommended screenings or appropriate follow-up and should not be used for diagnosis, to determine any treatments or medical interventions.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
| | Prescription Use (Part 21 CFR 801 Subpart D)
X Over-The-Counter Use (21 CFR 801 Subpart C)
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3
510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of Safe Medical Devices Act of 1990 and 21 CFR §807.92
SUBMITTER / PRIMARY COMPANY
Marianna Frendo, Manager Regulatory Affairs 23andMe Inc. 349 Oyster Point Blvd SSF, CA 94080 mfrendo@23andme.com Establishment Registration Number: 3007699459 Owner Operator Number: 10029404
ALTERNATIVE CONTACT
Nikki Arora, Sr. Manager, Regulatory Affairs 349 Oyster Point Blvd SSF, CA 94080 nikkia@23andme.com
5.1. REGULATORY INFORMATION
| Type of Submission: | Traditional 510k |
|---|---|
| Common/Usual Name: | Hereditary Prostate Cancer (HOXB13-Related) |
| Trade/proprietary Name: | 23andMe Personal Genome Service (PGS) Genetic Health Risk |
| Report for Hereditary Prostate Cancer (HOXB13-Related) | |
| Regulation Description: | A Cancer Predisposition Risk Assessment System is a |
| qualitative in vitro molecular diagnostic system used for | |
| determining predisposition for cancer where the result of the test | |
| may lead to prophylactic screening, confirmatory procedures, or | |
| treatments that may incur morbidity or mortality to the patient. | |
| The test could help to inform conversations with a healthcare | |
| professional. This assessment system is for over-the-counter | |
| use. This device does not determine the person's overall risk of | |
| developing any types of cancer. This test is not a substitute for | |
| visits to a healthcare provider for recommended screenings or |
Table 5.1 Proposed new device
4
| | appropriate follow-up and should not be used to determine any
treatments. |
|--------------------|------------------------------------------------------------------------------|
| Regulation Number: | 21 CFR §866.6090 |
| Product Code: | QAZ |
| Class | Class II |
5.2. LEGALLY MARKETED EXISTING DEVICE
| Trade Name: 23andMe Personal Genome Service (PGS) | ||||
|---|---|---|---|---|
| Report Type | Carrier Status | |||
| Reports | Genetic Health | |||
| Risk Reports | Genetic Health | |||
| Risk Reports | Pharmacogenetic | |||
| Reports | ||||
| Classification | ||||
| Name | Autosomal | |||
| Recessive | ||||
| Carrier | ||||
| Screening Gene | ||||
| Mutation | ||||
| Detection | ||||
| System | Genetic Variant | |||
| Detection and | ||||
| Health Risk | ||||
| Assessment | ||||
| System | Cancer | |||
| Predisposition | ||||
| Risk | ||||
| Assessment | ||||
| System | Direct-to-Consumer | |||
| Access | ||||
| Pharmacogenetic | ||||
| Assessment | ||||
| System | ||||
| Classification | ||||
| Panel | Immunology / | |||
| Clinical | ||||
| Chemistry | Immunology/ | |||
| Hematology | Molecular | |||
| Genetics/ | ||||
| Pathology | Molecular | |||
| Genetics/ | ||||
| Clinical Chemistry | ||||
| Regulation | ||||
| Number | 21 CFR | |||
| §866.5940 | 21 CFR | |||
| §866.5950 | 21 CFR | |||
| §866.6090 | 21 CFR §862.3364 | |||
| Device Class | Class II | Class II | Class II | Class II |
| 510(k) | Exempt | Exempt | Required | Required |
| Product Code | PKB | PTA | QAZ | QDJ |
| DEN/510(k) | ||||
| number | DEN140044 | DEN160026 | DEN170046, | |
| K182784 | DEN180028, | |||
| K193492 | ||||
| Decision | ||||
| Date(s) | 19Feb2015 | 06Apr2017 | 06Mar2018, | |
| 18Jan2019 | 31Oct2018, | |||
| 17Aug2020 |
5
5.3. LEGALLY MARKETED PREDICATE DEVICE(S)
| 23andMe Personal Genome Service (PGS) | ||||
|---|---|---|---|---|
| Predicate | #1 | #2 | ||
| Report Name | Genetic Health Risk Report for | |||
| BRCA1/BRCA2 (Selected | ||||
| Variants) | Genetic Health Risk Report for | |||
| MUTYH-Associated Polyposis (MAP) | ||||
| Classification | ||||
| Name | Cancer Predisposition Risk | |||
| Assessment System | Cancer Predisposition Risk | |||
| Assessment System | ||||
| Classification | ||||
| Panel | Molecular Genetics/ | |||
| Pathology | Molecular Genetics/ | |||
| Pathology | ||||
| Regulation | ||||
| Number | 21 CFR §866.6090 | 21 CFR §866.6090 | ||
| Device Class | Class II | Class II | ||
| Product Code | QAZ | QAZ | ||
| DEN/510(k) | ||||
| number | DEN170046 | K182784 | ||
| Decision | ||||
| Date(s) | 06Mar2018 | 18Jan2019 |
5.5. DEVICE DESCRIPTION
The 23andMe Personal Genome Service (PGS) is an over-the-counter (direct-to-consumer), DNA testing service that provides information and tools for consumers to learn about and explore their DNA.
The 23andMe Personal Genome Service (PGS) is a currently marketed, non-invasive genetic information service that combines qualitative genotyping data covering genetic ancestry, traits, and certain heritable health conditions from a single multiplex assay with descriptive information derived from peer reviewed, published genetic research studies. It is a home use, over-thecounter (direct-to-consumer) DNA testing service intended to provide information and tools for consumers to learn about and explore their DNA.
Customer saliva is self-collected using the Oragene-Dx® Device manufactured by DNA Genotek, Inc. (previously cleared for carrier screening indications under K141410, and the same collection
6
kit used to generate performance data for DEN140044, DEN160026, DEN170046, K182784, DEN180028, and K193492, which consists of a sealable collection tube containing a stabilizing buffer solution. Once the sample is collected, it is shipped to one of our Clinical Laboratory Improvement Amendments (CLIA) certified laboratories for testing.
DNA is isolated from the saliva and tested in a multiplex assay using a customized genotyping beadchip, and off the shelf reagents and instrumentation manufactured by Illumina. The multiplex assay simultaneously tests for more than 500,000 variants, including those for the previously authorized indications, as well as for the indications proposed herein.
Raw data is generated using Illumina GenomeStudio software, and then sent to 23andMe. The data is then analyzed using 23andMe's proprietary Coregen software, where a genotype is determined for each tested SNP. The results for certain of these SNPs are used to generate personalized reports for the customer that provide information about the detected genotype.
Personalized reports are generated for each user that provide results of the testing performed. These reports tell the user which genetic health risk variant(s) have been detected in their sample and provide information about the disease associated with the variant(s). If no variant was detected, that information is also provided. The personalized reports are designed to present scientific concepts to users in an easy-to-understand format. The reports provide scientifically valid information about the risks associated with the presence of a particular variant. The reports are designed to help users understand the meaning of their results and any appropriate actions that may be taken based on their results.
The modified components of the Personal Genome Service included in this 510(k) submission are new labeling to include (a) one new variant to be reported, and (b) the qualitative reporting of one's Genetic Health Risk for Hereditary Prostate Cancer (HOXB13-Related).
Engineering drawings, schematics, etc. of Genetic Health Risk Report for Hereditary Prostate Cancer (HOXB13-Related) are not applicable to this device.
5.6. INDICATIONS FOR USE
The 23andMe Personal Genome Service (PGS) uses qualitative genotyping to detect select clinically relevant variants in genomic DNA isolated from human saliva collected from individuals ≥18 years for the purpose of reporting and interpreting genetic health risks, including the 23andMe PGS Genetic Health Risk Report for Hereditary Prostate Cancer (HOXB13-Related). The 23andMe PGS Genetic Health Risk Report for Hereditary Prostate Cancer (HOXB13- Related) is indicated for reporting of the G84E variant in the HOXB13 gene. The report describes if a person has the G84E variant and if a male is at increased risk for prostate cancer. The variant included in this report is most common in people of European descent. The test report does not describe a person's overall risk of developing any type of cancer, and the absence of a variant tested does not rule out the presence of other variants that may be cancer-related. This test is not a substitute
7
for visits to a healthcare provider for recommended screenings or appropriate follow-up and should not be used for diagnosis, to determine any treatments or medical interventions.
5.7. COMPARISON TO SUBSTANTIALLY EQUIVALENT PREDICATE DEVICES
| BRCA1/BRCA2
(Selected
Variants)
DEN170046 | MUTYH
Associated
Polyposis
K182784 | Hereditary
Prostate Cancer
(HOXB13-Related) | Similarities
and
differences | |
|----------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------|
| Indications
for Use | The 23andMe
Personal Genome
Service (PGS) uses
qualitative
genotyping to
detect select
clinically relevant
variants in genomic
DNA isolated from
human saliva
collected
from individuals ≥18
years with the
Oragene Dx model
OGD500.001 for
the purpose of
reporting and
interpreting genetic
health risks,
including the
23andMe PGS
Genetic Health Risk
Report for
BRCA1/BRCA2
(Selected
Variants) | The 23andMe
Personal Genome
Service (PGS) uses
qualitative
genotyping to
detect select
clinically relevant
variants in genomic
DNA isolated from
human saliva
collected
from individuals ≥18
years with the
Oragene Dx model
OGD500.001 for
the purpose of
reporting and
interpreting genetic
health risks,
including the
23andMe PGS
Genetic
Health Risk Report
for MUTYH
Associated
Polyposis. | The 23andMe
Personal Genome
Service (PGS) uses
qualitative
genotyping to
detect select
clinically relevant
variants in genomic
DNA isolated from
human saliva
collected from
individuals ≥18
years with the
Oragene Dx model
OGD500.001 for
the purpose of
reporting and
interpreting genetic
health risks,
including the
23andMe PGS
Genetic Health
Risk Report for
Hereditary Prostate
Cancer (HOXB13-
Related). | Similar. |
5.7.1 Intended use / Indications for use
8
| BRCA1/BRCA2
(Selected Variants) is
indicated for
reporting of the
185delAG and
5382insC variants
in the BRCA1 gene
and the 6174delT
variant in the
BRCA2 gene. The
report describes if a
woman is at
increased risk of
developing breast
and ovarian cancer,
and if a man is at
increased risk of
developing breast
cancer or may be at
increased risk of
developing prostate
cancer. The three
variants included in
this report are most
common in people
of Ashkenazi
Jewish descent and
do not represent
the majority of
BRCA1/BRCA2
variants in the
general population.
The test report
does not describe a
person's overall risk
of developing any
type of cancer, and
the absence of a
variant tested does
not rule out the
presence of
other variants that | MUTYH Associated
Polyposis is
indicated for
reporting of the
Y179C and the
G396D variants in
the MUTYH gene.
The report
describes if a
person is at
increased risk of
developing
colorectal cancer.
The two variants
included in this
report are most
common and best
studied in people of
Northern European
descent and may
not represent the
majority of the
MUTYH variants in
people of other
ethnicities. The test
report does not
describe a person's
overall risk of
developing any type
of cancer, and the
absence of a
variant tested does
not rule out the
presence of other
variants that may
be cancer-related.
This test is not a
substitute for visits
to a healthcare
provider for
recommended
screenings or | Hereditary Prostate
Cancer (HOXB13-
Related) is
indicated for
reporting of the
G84E variant in the
HOXB13 gene. The
report describes if
a person has the
G84E variant and if
a male is at
increased risk for
prostate cancer.
The variant
included in this
report is most
common in people
of European
descent. The test
report does not
describe a person's
overall risk of
developing any
type of cancer, and
the absence of a
variant tested does
not rule out the
presence of other
variants that may
be cancer-related.
This test is not a
substitute for visits
to a healthcare
provider for
recommended
screenings or
appropriate follow-
up and should not
be used for
diagnosis, to
determine any
treatments or | |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--|
| may be cancer-
related.
This test is not a
substitute for visits
to a healthcare
provider for
recommended
screenings or
appropriate follow-
up and should not
be used to
determine
any treatments. | appropriate follow-
up and should not
be used to
determine
any treatments. | medical
interventions. | |
9
5.7.2 Technological Characteristics
| | BRCA1/BRCA2
(Selected
Variants)
DEN170046 | MUTYH
Associated
Polyposis
K182784 | Hereditary
Prostate Cancer
(HOXB13-
Related) | Similarities
and
differences |
|-----------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------|
| Test Type | Qualitative genetic
test for single
nucleotide
polymorphism
detection | Qualitative genetic
test for single
nucleotide
polymorphism
detection | Qualitative
genetic test for
single nucleotide
polymorphism
detection | Same |
| Sample
Type/Matrix | Genomic DNA
obtained from a
human saliva
sample | Genomic DNA
obtained from a
human saliva
sample | Genomic DNA
obtained from a
human saliva
sample | Same |
| Gene | BRCA1
and BRCA2 | MUTYH | HOXB13 | Different |
| Variant | 185delAG and
5382insC variants
in the BRCA1
gene, and the
6174delT variant | Y179C and G396D | G84E | Different |
| | in the BRCA2
gene | | | |
| SNP | i4000377,
i4000378, and
i4000379 | rs34612342 and
rs36053993 | rs138213197 | Different |
| Genotyping
Principle | DNA is fragmented
and captured on a
beadchip array by
hybridization to
immobilized SNP-
specific primers,
followed by
extension with
hapten-labeled
nucleotides.
Primers hybridize
adjacent to the
SNPs and are
extended with a
single nucleotide
corresponding to
the SNP allele.
The incorporated
hapten-modified
nucleotides are
detected by adding
fluorescently
labeled antibodies
in several steps to
amplify the
signals. Data
analysis is
performed using
scatter plots | DNA is fragmented
and captured on a
beadchip array by
hybridization to
immobilized SNP-
specific primers,
followed by
extension with
hapten-labeled
nucleotides.
Primers hybridize
adjacent to the
SNPs and are
extended with a
single nucleotide
corresponding to
the SNP allele.
The incorporated
hapten-modified
nucleotides are
detected by adding
fluorescently
labeled antibodies
in several steps to
amplify the
signals. Data
analysis is
performed using
scatter plots | DNA is
fragmented and
captured on a
beadchip array by
hybridization to
immobilized SNP-
specific primers,
followed by
extension with
hapten-labeled
nucleotides.
Primers hybridize
adjacent to the
SNPs and are
extended with a
single nucleotide
corresponding to
the SNP allele.
The incorporated
hapten-modified
nucleotides are
detected by
adding
fluorescently
labeled antibodies
in several steps to
amplify the
signals. Data
analysis is
performed using
scatter plots | Same |
| Assay Components and instruments | | | | |
| Collection kit | Oragene.Dx® | Oragene.Dx® | Oragene.Dx® | Same |
| | saliva collection
device (OGD-
500.001)
K141410 | saliva collection
device (OGD-
500.001)
K141410 | saliva collection
device (OGD-
500.001)
K141410 | |
| Reagents | Illumina Infinium
HTS assay
Reagents | Illumina Infinium
HTS assay
Reagents | Illumina Infinium
HTS assay
Reagents | Same |
| Beadchip | Illumina Infinium
Array customized
for the PGS. The
beadchip array is
designed to detect
specific single
nucleotide
polymorphisms
(SNPs) as well as
other genetic
variants; all
markers refer to
specific positions
in the National
Center for
Biotechnology
Information (NCBI)
reference human
genome | Illumina Infinium
Array customized
for the PGS. The
beadchip array is
designed to detect
specific single
nucleotide
polymorphisms
(SNPs) as well as
other genetic
variants; all
markers refer to
specific positions
in the National
Center for
Biotechnology
Information (NCBI)
reference human
genome | Illumina Infinium
Array customized
for the PGS. The
beadchip array is
designed to
detect specific
single nucleotide
polymorphisms
(SNPs) as well as
other genetic
variants; all
markers refer to
specific positions
in the National
Center for
Biotechnology
Information
(NCBI) reference
human genome | Same |
| Instruments | Tecan Evo
Illumina iScan with
GenomeStudio
Software | Tecan Evo
Illumina iScan with
GenomeStudio
Software | Tecan Evo
Illumina iScan
with
GenomeStudio
Software | Same |
| Software | Coregen | Coregen | Coregen | Same |
| Performance | | | | |
| Accuracy /
Method
Comparison | >99% PPA and
NPA for all
genotypes | >99% PPA and
NPA for all
genotypes | >99% PPA and
NPA for all
genotypes | Same |
| Precision | >99%
reproducibility and
99% repeatability | >99%
reproducibility and
99% repeatability | >99%
reproducibility
and >99%
repeatability | Same |
| Minimum DNA
Input | 5ng/uL | 5ng/uL | 5ng/uL | Same |
| Interfering
Substance | 100% accuracy
when following the
instructions for use | 100% accuracy
when following the
instructions for use | 100% accuracy
when following
the instructions
for use | Same |
| Potentially
Interfering
Mutations | Warnings and
Limitations:
The performance
of these tests may
be affected by the
presence of rare
mutations. The
impact of
potentially
interfering
mutations has not
been evaluated | Warnings and
Limitations:
The performance
of these tests may
be affected by the
presence of rare
mutations. The
impact of
potentially
interfering
mutations has not
been evaluated | Warnings and
Limitations:
The performance
of these tests
may be affected
by the presence
of rare mutations.
The impact of
potentially
interfering
mutations has not
been evaluated | Same |
| Matrix
Comparison | Human Saliva
Only | Human Saliva
Only | Human Saliva
Only | Same |
| Stability | Specimen: 8 years
Reagents: 6-12
Months
Collection Kit: 24
months | Specimen: 8 years
Reagents: 6-12
Months
Collection Kit: 24
months | Specimen: 8
years
Reagents: 6-12
Months
Collection Kit: 24
months | Same |
| Labeling
Comprehension | 90% or greater
overall
comprehension
rate | 90% or greater
overall
comprehension
rate | 90% or greater
overall
comprehension
rate | Same |
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5.8. PERFORMANCE TESTING SUMMARY
All performance testing is managed by our ISO 13485:2016 certified Quality Management System, and conforms to design control requirements specified in 21CFR §820.30.
Analytical and Comprehension studies were performed and documented as described in Special Controls published in reclassification order DEN170046.
Software Verification and Validation studies were performed and documented as described in Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices issued on 11Mav2005. 23andMe employs a variety of administrative, technical, and physical safequards in order to efficiently mitigate cybersecurity risks. 23andMe has been certified for compliance with ISO/IEC 27001:2013 Information Security Management System, including control implementation guidance within ISO/IEC 27018:2019 as well as the requirements and control implementation quidance within ISO/IEC 27701:2019 as a data controller. 23andMe is also actively implementing the controls and policies as defined in the "HITRUST CSF" (Common Security Framework), which includes the FDA recommended NIST Cybersecurity Framework (CsF).
5.8.1 Method Comparison (Accuracy)
23andMe performed a Method Comparison study to assess the accuracy of the 23andMe assay. The goal of the study was to show equivalent genotype assignment between the 23andMe assay and Sanger bi-directional DNA sequencing. Saliva samples were selected from the 23andMe customer biobank, based on their predetermined genotype and minimum volume required for testing. All assay genotyping was performed at approved contract laboratory sites. All chosen samples were then sequenced using Sanger bi-directional sequencing by an approved supplier. Genotyping results were compared between genotyping assay and bi-directional sequencing to calculate positive percent agreement (PPA) and negative percent agreement (NPA), with the sequencing results considered to be "truth." The passing criteria were a minimum of 99% PPA and NPA for each SNP. This method comparison study yielded >99% PPA and NPA for all genotypes. Therefore, the study passed the acceptance criteria of at least 99% PPA and NPA.
5.8.2 Precision / Reproducibility
23andMe performed a precision study to determine the reproducibility of the 23andMe assay. The goal of the study was to evaluate the following precision parameters of the assay: intra-assay, inter-lot, inter-instrument, inter-operator, inter-day, and inter-lab differences. DNA samples were selected based on their confirmed genotypes, and were obtained from the 23andMe biobank. To confirm, each sample was sequenced by bi-directional Sanger sequencing. The same samples were genotyped by the assay in a blinded fashion, with 3 lots of reagents, by multiple operator teams per day, using 3 different serial numbers of each of 2 instruments (Tecan and iScan), over 3 days, at each of 2 laboratory sites. Assay genotypes were compared with sequenced genotypes to determine the rates of correct genotype calls.
14
This precision study vielded 100% correct genotype calls for all samples across multiple days, operator teams, instruments, and reagent lots at two independent laboratory sites. Therefore, the study passed the acceptance criteria of at least 99% correct calls at each of the two laboratory sites. There was no variation between any study conditions or any replicates for a given sample. Therefore, the study demonstrated 100% reproducibility and 100% repeatability for a given sample. Therefore, the study had 100% reproducibility and 100% repeatability.
5.8.3 DNA Input
23andMe performed a DNA input study for the genotyping assay. The design of the study was consistent with our previous agreement recorded in Q160823-A001 meeting minutes dated August 9, 2016. The goal of the study was to determine the lowest concentration of DNA that is necessary for successful assignment of the correct genotype. The DNA requirement for the PGS is defined as the lowest DNA concentration at which at least 95% of samples yielded the correct call. DNA samples were obtained from the 23andMe biobank based on their listed genotypes. Each sample was diluted to 3 different DNA concentrations and genotyped in a blinded fashion using 3 lots of reagents. To confirm the genotype call, each sample was also sequenced using bi-directional Sanger sequencing. Genotype results were compared with sequenced genotypes to determine the rates of correct genotype calls at each DNA concentration.
This study vielded 100% correct genotype calls for all samples and all reagent lots tested at sample DNA concentrations of 5, 15, and 50 ng/uL. Therefore, the study passed the acceptance criteria of 95% correct calls at a sample DNA concentration of 5 ng/μL. This study demonstrates that the assay can correctly genotype samples with a DNA concentration range of 5 ng/ul_to 50 ng/µL. The performance requirement specified by contracted laboratory SOPs is conservatively set at a minimum DNA requirement of 15 ng/μL.
5.8.4 Interfering Substance (Specificity)
The PGS assay requires the use of an FDA-cleared collection device (K141410). The device used for the test is the exact same device used for all carrier screening reports (DEN140044) and all genetic health risk reports (DEN160026 & DEN170046). A test for potentially interfering mutations was performed in support of DEN140044, and no new interfering substances have been identified. The cleared device includes labeling in the form of a package insert instructing the user to not eat, drink, smoke or chew gum for 30 minutes prior to collecting their saliva, thus minimizing the availability of potentially interfering substances in the saliva sample. 23andMe performed a series of studies to assess the effects of endogenous substances, exogenous substances, microbial substances, and smoking on the assay in support of submission DEN140044. Over these four studies, more than 35,000 sample replicates were tested, with no discordant or No Call results across 99 SNPs, for an accuracy of 100% when following the instructions for use (i.e., nothing by mouth for at least 30 minutes prior to collecting saliva).
5.8.5 Potentially Interfering Mutations
23andMe has identified one(1) potentially interfering mutation near G84E. The Company was unable to identify commercially available samples for these potentially interfering mutations.
15
Therefore, a statement has been added to the limitations section of the package insert stating that the impact of interfering mutations has not been evaluated.
5.8.6 Matrix Comparison:
Human saliva is the only suitable sample matrix Comparison studies are not applicable.
5.8.7 Shelf life:
The PGS requires the use of the same FDA-cleared collection device and reagents that have been previously reviewed and authorized in K141410 and DEN140044.
5.8.8 Clinical Performance:
Clinical performance is based on published studies of variant frequencies in various populations and the results of analytical studies reported in this submission, as well as allele frequencies in the 23andMe customer database for the genetic variants and associations included in this submission.
The following table summarizes the clinical performance data for the PGS Genetic Health Risk Report for Hereditary Prostate Cancer (HOXB13-Related).
Table 5.3 Clinical Performance
HOXB13 G84E Allele Frequencies (%) in the 23andMe databaseª and the gnomAD database8
| Ancestry group | 23andMe | gnomAD |
|---|---|---|
| European | 0.18% | 0.76%c |
| 0.24%d | ||
| African American | 0.04% | 0.04% |
| Ashkenazi Jewish |