(183 days)
Not Found
No
The device description and performance studies focus on a qualitative chemical/biological test with visual interpretation, not computational analysis. There is no mention of AI, ML, image processing, or any other technology that would suggest the use of these methods.
No
This device is a diagnostic test kit used to assess a man's fertility status by measuring sperm concentration, not for treating any medical condition.
Yes
The device is described as a "qualitative test that detects sperm concentration" and is "intended for use as an aid in the determination of a man's fertility status," which falls under the definition of a diagnostic device as it helps identify a health condition or state.
No
The device description explicitly lists physical components like a "SwimCount™ Sperm Quality Test Device", "Semen Collection Cup", and "Semen Transfer Pipette", indicating it is a hardware-based in vitro diagnostic device, not software-only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states "For in vitro, over-the-counter use." This is a key characteristic of an IVD. It is designed to be used outside of the body to examine a sample (semen) for diagnostic purposes (aiding in the determination of a man's fertility status).
- Device Description: The device description also reiterates "intended for in vitro, over-the-counter, use."
- Nature of the Test: The test analyzes a biological sample (semen) to provide information about a physiological state (sperm quality related to fertility). This is the core function of an IVD.
- Performance Studies: The document details various performance studies, including a multi-center clinical study comparing the device to standard microscopy, which is a common practice for validating IVDs.
- Predicate Device: The mention of a predicate device (K041039; Fertell Male Fertility Test) further supports its classification as an IVD, as predicate devices are used for comparison in the regulatory submission process for new IVDs.
Therefore, based on the provided information, the SwimCount™ Sperm Quality Test clearly fits the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The SwimCount™ Sperm Quality Test is a qualitative test that detects sperm concentration above or below 5,000,000 Progressive Motile Sperm Cells per mL (PMSCs/mL). The test is intended for use as an aid in the determination of a man's fertility status. For in vitro, over-the-counter use.
The number of progressively motile sperm cells is only one factor that contributes to a male's fertility status. The SwimCount™ Sperm Quality Test does not provide a complete evaluation of a male's fertility status. For a comprehensive assessment of male fertility status then the patient should consult a physician.
Product codes (comma separated list FDA assigned to the subject device)
POV
Device Description
The SwimCount™ Sperm Quality Test is intended for in vitro, over-the-counter, use and is a prescreening sperm quality test that measures the number of Progressive Motile Sperm Cells per mL (PMSCs/mL).
The SwimCount™ Sperm Quality Test is a qualitative test that detects sperm concentration above or below 5,000,000 Progressive Motile Sperm Cells per mL (PMSCs/mL).
The SwimCount™ Sperm Quality Test cut-off value is derived from the WHO laboratory manual for the Examination and processing of human semen, 5th edition guidelines 2010.
The SwimCount™ Sperm Quality Test Kit includes the following components:
- SwimCount™ Sperm Quality Test Box
- SwimCount™ Sperm Quality Test Device
- Semen Collection Cup (used to collect the sperm sample is to remain in the sample cup for 30 minutes)
- Semen Transfer Pipette (syringe) (used to stir the semen sample 10 times before adding the sample to the Device and further used to collect 0.5 mL semen sample from the sperm sample placed in the cup)
- SwimCount™ Sperm Quality Test Instructions for Use
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
0-58 Male
Intended User / Care Setting
For in vitro, 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
A Multi-Center Clinical Study was conducted at 4 different sites in Denmark (2), Spain (1) and Turkey (1) of the SwimCount™ Sperm Quality Test.
The subjects participating in this study were males attending fertility clinics and donors from a sperm bank.
Total No. of Net Samples: 308.
The objective of the Multi-Center Clinical Study was to investigate the performance of the SwimCount™ Sperm Quality Test and compare the test results obtained by standard microscopy.
A Lay-User Usability Study was conducted with 81 Lay-Users participating. They were asked to provide their opinion of the test, labelling and interpreting the result via a Questionnaire including 18 Questions.
The aim was to demonstrate and clarify that the SwimCount™ Sperm Quality Test is simple, accurate and poses no significant risk of erroneous results.
The study was divided into two main parts:
A. Lay-User's ability to perform the test as intended and described in the SwimCount™ Sperm Quality Test Instructions for Use.
B. That Lay-Users can interpret the SwimCount™ Sperm Quality Test result correctly.
In addition to the Consumer Use Study, a Consumer Interpretation Study was carried out.
81 Participants were asked to provide their opinion on 10 SwimCount™ Sperm Quality Test result pictures (N=810). This was accomplished via a Questionnaire including 10 Pictures of a SwimCount™ Sperm Quality Test result, each including both LOW and NORMAL Sperm Quality Test Results.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Non-Clinical Performance Testing:
Repeatability/Reproducibility: A precision study (repeatability/reproducibility) was carried out by three operators using three SwimCount™ Sperm Quality Test batches, two replicates per run and two runs per timepoint (3 x 2 x 2 = 12 samples per time adding up to a total of 36 replicates per sperm concentration (3 time periods)). The three Operators were placed at three different locations. Repeatability was found to vary between 75% to 100%. The reproducibility of the three operators/batches and locations was very good when analyzing semen samples within 60 minutes after collection.
Semen Sample Stability Study: Semen sample stability was investigated at 30 min and 60 min after collection. PMSC concentrations were stable within 60 minutes of producing the sample.
Evaluation of Test Performance. Cut-off level: A pooled semen sample was diluted to progressive motile sperm concentrations of 3.9 M, 4.0 M, 5.0 M, 6.0 M, and 6.2 M PMSCs/mL. Each concentration was tested in 40 replicates. The 4.0 M, 5.0 M and 6.0 M PMSC/mL concentrations were tested on two SwimCount™ Sperm Quality Test lots (i.e. 80 replicates per sample). The results support the 5.0 M PMSCs/mL cut-off level. For 3.9 M PMSCs/mL, 0% positive; for 4.0 M PMSCs/mL, 7.5% positive; for 5.0 M PMSCs/mL, 55.0% positive; for 6.0 M PMSCs/mL, 90.0% positive; for 6.2 M PMSCs/mL, 100% positive.
Analytical Specificity (interference study): Investigated potential cross-reactivity and interference substances (bacteria, saliva, urine, blood contamination, hormones). Urine, Red Blood Cells (RBC) and White Blood Cells (WBC) were identified as interfering substances, and this was included in the Instructions for Use. Hormones, microorganisms, and saliva did not interfere.
Clinical Performance Testing:
Multi-Center Clinical Study:
Sample Size: 308 net semen samples across 4 sites (Denmark (2), Spain (1), Turkey (1)).
Key Results: The SwimCount™ Sperm Quality Test appeared as a useful tool for male fertility assessment. The results obtained were compatible with those obtained with conventional sperm analysis.
Calculated based on Line Data:
Sensitivity: 95.83% (95% Conf. interval: 88.30%-99.13%)
Specificity: 90.68% (95% Conf. interval: 86.23%-94.07%)
Accuracy: 91.88% (95% Conf. interval: 89.90%-95.81%)
Lay-User Usability Study:
Sample Size: 81 Lay-Users.
Key Results:
- 96.30% of participants found "Following and Understanding the Instructions for Use" as "Very Easy" or "Very Difficult".
- 93.83% found "Applying the Semen Sample correctly" as "Very Easy" or "Very Difficult".
- 90.12% found "Finding the result window" as "Very Easy" or "Very Difficult".
- 100% correctly identified what a "Light Blue" color result means (LOW Sperm Quality).
- 100% correctly identified what a "Dark Blue" color result means (NORMAL Sperm Quality).
- 87.66% found "Determine the ease-of-use when reading your SwimCount™ Sperm Quality Test Result" as "Very Easy" or "Very Difficult".
- 79 out of 81 (97.53%) participants correctly read their own result.
Consumer Interpretation Study:
Sample Size: 81 Participants, 810 pictures read (10 pictures per participant).
Key Results:
- 791 out of 810 pictures were read correctly, equating to 97.65% of correct calls by lay-users.
- Correct Calls by Lay-Users: 97.65% (95% Conf. Interval: 96.70%-98.81%)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Multi-Center Clinical Study:
Sensitivity: 95.83%
Specificity: 90.68%
Accuracy: 91.88%
False negative: 4.17%
False positive: 9.32%
Lay-User Usability Study:
% of Correct Calls: 97.53%
Consumer Interpretation Study:
Correct Calls by Lay-Users: 97.65%
False negative: 0.62%
False positive: 3.50%
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.
Not Found
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
§ 864.5220 Automated differential cell counter.
(a)
Identification. An automated differential cell counter is a device used to identify one or more of the formed elements of the blood. The device may also have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood, bone marrow, or other body fluids. These devices may combine an electronic particle counting method, optical method, or a flow cytometric method utilizing monoclonal CD (cluster designation) markers. The device includes accessory CD markers.(b)
Classification. Class II (special controls). The special control for this device is the FDA document entitled “Class II Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells; Final Guidance for Industry and FDA.”
0
Image /page/0/Picture/0 description: The image contains the logos of the Department of Health & Human Services and the Food and Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
June 27, 2019
MotilityCount ApS Jacob Mollenbach Co-Founder G1. Koge Landevej 55 Valby, DK-2500 Dk
Re: K183602
Trade/Device Name: SwimCount Sperm Quality Test Regulation Number: 21 CFR 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: Class II Product Code: POV Dated: January 2, 2019 Received: January 4, 2019
Dear Jacob Mollenbach:
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
1
statutes and regulations administered by other Federal agencies. You must comply with all the Act's 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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (QS) 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Takeesha Taylor-Bell Branch Chief Hematology Devices Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K183602
Device Name SwimCountTM Sperm Quality Test
Indications for Use (Describe)
The SwimCount™ Sperm Quality Test is a qualitative test that detects sperm concentration above or below 5,000,000 Progressive Motile Sperm Cells per mL (PMSCs/mL). The test is intended for use as an aid in the determination of a man's fertility status. For in vitro, over-the-counter use.
The number of progressively motile sperm cells is only one factor that contributes to a male's fertility status. The SwimCount™ Sperm Quality Test does not provide a complete evaluation of a male's fertility status. For a comprehensive assessment of male fertility status then the patient should consult a physician.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) | |
|---|---|
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
Summary - SwimCount™ Sperm Quality Test – Summary
Version: 8
Date: 30th April 2019
510(k) Summary
| Submitter: | MotilityCount ApS |
|---|---|
| Address: | Gl. Køge Landevej 55 |
| DK-2500 Valby, | |
| Denmark | |
| Contact: | Jacob Møllenbach |
| Co-Founder | |
| Telephone Number: | 45-21445919 |
| Email: | jm@motilitycount.com |
| Summary Preparation Date: | 30th April 2019 |
| Device Description: | The SwimCount™ Sperm Quality Test is intended for home use |
| and is a pre-screening sperm quality test that measures the | |
| number of Progressive Motile Sperm Cells per mL (PMSCs/mL) | |
| Trade Name: | SwimCount™ Sperm Quality Test |
| Common Name: | Semen Analysis Device |
| Classification Name: | Automated Differential Cell Counter |
| Regulatory Class: | Class II |
| Product Code: | POV |
| C.F.R. Section: | 21 CFR 864.5220 |
4
Predicate Device
| | Manufacturer | Brand Name | 510(k)
Number |
|---------|--------------|-----------------------------|------------------|
| Primary | Genosis Ltd | Fertell Male Fertility Test | K041039 |
Device Description
The SwimCount™ Sperm Quality Test is intended for in vitro, over-the-counter, use and is a prescreening sperm quality test that measures the number of Progressive Motile Sperm Cells per mL (PMSCs/mL) .
The SwimCount™ Sperm Quality Test is a qualitative test that detects sperm concentration above or below 5,000,000 Progressive Motile Sperm Cells per mL (PMSCs/mL).
The SwimCount™ Sperm Quality Test cut-off value is derived from the WHO laboratory manual for the Examination and processing of human semen, 5th edition guidelines 2010.
The SwimCount™ Sperm Quality Test Kit includes the following components:
- SwimCount™ Sperm Quality Test Box ●
- SwimCount™ Sperm Quality Test Device ●
- Semen Collection Cup (used to collect the sperm sample is to remain in the sample cup for 30 minutes)
- . Semen Transfer Pipette (syringe) (used to stir the semen sample 10 times before adding the sample to the Device and further used to collect 0.5 mL semen sample from the sperm sample placed in the cup)
- SwimCount™ Sperm Quality Test Instructions for Use .
Indications for use
The SwimCount™ Sperm Quality Test is a qualitative test that detects sperm concentration above or below 5,000,000 Progressive Motile Sperm Cells per mL (PMSCs/mL). The test is intended for use as an aid in the determination of a man's fertility status. For in vitro, over-the-counter use.
The number of progressively motile sperm cells is only one factor that contributes to a male's fertility status. The SwimCount™ Sperm Quality Test does not provide a complete evaluation of a male's fertility status. For a comprehensive assessment of male fertility status the patient should consult a physician.
5
Technological Similarities and Differences to the Predicate
| Similarities | ||
|---|---|---|
| Item | Device - | |
| SwimCount™ Sperm | ||
| Quality Test | Predicate - | |
| Fertell Male | ||
| Fertility Test | ||
| Indications for Use | The SwimCount™ | |
| Sperm Quality Test is a | ||
| qualitative test that | ||
| detects sperm | ||
| concentration above or | ||
| below 5,000,000 | ||
| Progressive Motile | ||
| Sperm Cells per mL | ||
| (PMSCs/mL). | The Fertell Male | |
| Fertility Test | ||
| intended use is to | ||
| measure motile | ||
| sperm in semen as | ||
| an adjunctive screen | ||
| of male fertility. | ||
| Intended Use | The SwimCount™ | |
| Sperm Quality Test is | ||
| intended for use as an | ||
| aid in the determination | ||
| of a man's fertility | ||
| status. For in vitro, | ||
| over-the -counter use | Same | |
| Test Type | Qualitative | Same |
| Sample Type | Human Semen | Same |
| Test Setting | For in vitro, over-the- | |
| counter use | Same | |
| Technology | The PMSCs are | |
| separated from the rest | ||
| of the semen sample, | ||
| stained and captured on | ||
| a detection filter. The | ||
| more PMSCs the darker | ||
| the test result | Sperm migration |
6
| Differences | ||
|---|---|---|
| Item | Device – | |
| SwimCount™ Sperm | ||
| Quality Test | Predicate – | |
| Fertell Male | ||
| Fertility Test | ||
| Assay principle | The test result is read | |
| as a color intensity and | ||
| compared to two | ||
| reference colors. The | ||
| darker the color the | ||
| higher the number of | ||
| PMSCs/mL. | Visual line; colored | |
| label bound to sperm. | ||
| Primary cut-off Level | 5 M PMSCs/mL | |
| (derived from WHO | ||
| 5th edition guidelines |
-
| 10 M/mL motile
sperm cells (lower
reference limit, WHO
4th edition guidelines
1999) |
| Test Temperature | Ambient | 98.6° F ~ 37° Celsius |
| Result Reading | The test result is read
as a color intensity and
compared to two
reference colors. The
darker the color the
higher the number of
PMSCs/mL. | Visual line; colored
label bound to sperm |
| Primary cut-off Level | 5 M PMSCs/mL
(derived from WHO
5th edition guidelines
2010) | 10 M/mL motile
sperm cells (lower
reference limit, WHO
4th edition guidelines
1999) |
1. Discussion of Technological Similarities between the SwimCount™ Sperm Quality Test and the Primary Predicate Device: Fertell Male Fertility Test
The SwimCount™ Sperm Quality Test and the Primary Predicate Device have the same indication for use, intended use, sample type and test setting.
2. Discussion of Technological Differences between SwimCount™ Sperm Quality Test and the Primary Predicate Device: Fertell Male Fertility Test
Indications for Use - The SwimCount™ Sperm Quality Test is a qualitative test that detects sperm concentration above or below 5,000,000 Progressive Motile Sperm Cells per mL (PMSCs/mL). The test is intended for use as an aid in the determination of a man's fertility status. For in vitro, overthe-counter use.
The number of progressively motile sperm cells is only one factor that contributes to a male's fertility status. The SwimCount™ Sperm Quality Test does not provide a complete evaluation of a
7
male's fertility status. Sperm concentration and semen volume are only two factors that could impact a man's fertility status and time to pregnancy. For a comprehensive assessment of male fertility status, please consult a physician.
The concentration of progressively motile sperm cells (PMSCs) has consistently been shown to be the most predictive factor with regards to outcome. Around 64% of studies suggest that a reasonable chance of success with artificial insemination requires at least 5x106 motile sperm and this is supported by the WHO's revised reference range for natural conception. (Tomlinson et al. Human Fertility, 2013; 16(3): 175-193).
The SwimCount™ Sperm Quality Test and the Primary Predicate Device both measure the concentration of progressively motile sperms in a fresh semen sample. The difference is that the SwimCount™ Sperm Quality Test has a cut-off level of 5,000,000 PMSCs/mL and the Primary Predicate Device has a cut-off value of 10,000,000 PMSCs/mL. The Primary Predicate Device is derived from the WHO 4th edition guidelines 1999 lower reference level and also mentioned as the reference in their 510(k) decision summary.
The 10,000,000 PMSCs/mL calculation is derived from WHO 4th edition guidelines 1999 as follows:
Total sperm concentration per mL of 20 M x 50% (progressive motile sperm cells) = 10 M PMSCs/mL.
For the SwimCount™ Sperm Quality Test we have used the same method of calculation, however, based on and derived from the WHO 5th edition guidelines 2010 as follows:
The SwimCount™ Sperm Quality Test has a primary cut-off Level of 5 M PMSCs/mL which is derived from WHO's 5th edition guidelines 2010, where in section 2.5.4. it is stated that "The lower reference limit for total motility (PR + NP) is 40% (5th centile, 95% CI 38-42).
"The lower reference limit for progressive motility (PR) is 32% (5th centile, 95% CI 31-34).
The primary cut-off value is calculated using the WHO 5th edition section 2.8.6.: "The lower reference limit for sperm concentration spermatozoa is 15 x 106 spermatozoa per mL (5th centile, 95% CI 12-16 x 106).
The above WHO 5th edition clinical method of calculating the lower reference cut-off value for Progressive Motile Sperm Cells (PMSCs)/mL is then calculated as follows:
Total sperm concentration per mL of 15 M x 32% = 4.8 M PMSCs/mL which is rounded to 5 M PMSCs/mL.
As mentioned, the difference in the %-level to be used is due to SwimCount™ Sperm Quality Test using the latest WHO guidelines and whereas the Primary Predicate Device uses an older WHO version (4th edition guidelines 1999).
8
Please see below a comparison table of the Lower Reference Levels when calculations are based on the WHO 5th edition guidelines 2010 and the WHO 4th edition guidelines 1999:
| Parameter | Lower Reference
Limits (WHO 2010) | Reference Value
(WHO 1999) |
|------------------------------|--------------------------------------|-------------------------------|
| Semen Volume | 1.5 ml | ≥ 2.0 ml |
| Sperm Concentration | 15 million sperm/ ml | ≥ 20 million sperm/ ml |
| Progressive Motility | 32% | ≥ 50%* |
| Total Motility | 40%^ | n/a |
| Vitality | 58% live | ≥ 75% live |
| Morphology (Strict criteria) | 4% normal form | (≥ 15% normal form)* |
Reference: https://specialty.mims.com/topic/semen-analysis---what-a-clinician-should-knowmy?topic-grouper=cme
The difference in indications for use does not raise any new issues of safety and effectiveness.
Assay Principle - The dye used in the SwimCount™ Sperm Quality Test stains the mitochondria of the spermatozoa and works by entering the mitochondria where the dye is cleaved to a colored product (only in living cells) by an enzyme. In practicality the color changes from yellow to purple/blue and the darker the purple/blue color equals a higher sperm detection level. The Primary Predicate device's assay test unit is positioned onto the liquefied sample and the pressing of a button releases a solution of sodium hyaluronate buffer solution over the semen sample and starts heating the fluid to 37℃. Motile sperm swim-up through the sodium hyaluronate for 30 minutes before a valve is opened, by turning a knob, allowing the buffer solution, and motile sperm present, to flow along a capillary channel. Anti-CD59 monoclonal antibody that is conjugated with colloidal gold is released from an absorbent pad in the channel and reacts with the sperm forming an immunocomplex of gold-labeled sperm. The fluid containing this complex, flows onto a nitrocellulose strip where the gold-labeled sperm are trapped, forming a red line. Unreacted conjugate is washed from the strip by the flow of excess buffer. The appearance of a clear red line (test result) indicates motile sperm in the semen sample at a concentration of ≥ 10 M/mL. The differences in assays raise no new issues of safety and effectiveness.
9
Test Temperature - The SwimCount™ Sperm Quality Test's is performed at ambient temperature whereas the Primary Predicate Device is performed at 37° Celsius.
Reading Results - The SwimCount™ Sperm Quality Test provides a color chart with 2 possible outcomes; 1) Light Purple/Blue = LOW Sperm Quality = below 5,000,000 PMSCs/mL and 2) Purple/Blue = NORMAL Sperm Quality = above 5.000.000 PMSCs/mL. The Primary Predicative device provides a clear red line (test result) which indicates motile sperm in the semen sample at a concentration of > 10 M/mL. This level is indicative of normally expected motile sperm concentrations.
The differences in reading results raise no new issues of safety and effectiveness.
Non-Clinical Performance Testing
A series of studies were performed that evaluated the traditional laboratory performance characteristics; a summary of each study follows:
Repeatability/Reproducibility
Our precision study (repeatability/reproducibility) was carried out by three operators using three SwimCount™ Sperm Quality Test batches (Operator 1 using SwimCount™ Sperm Quality Test batch 1; Operator 2 using SwimCount™ Sperm Quality Test Batch 2 and Operator 3 using SwimCount™ Sperm Quality Test Batch 3), two replicates per run and two runs per timepoint i.e. 3 x 2 x 2 = 12 samples per time adding up to a total of 36 replicates per sperm concentration (3 time periods). The three Operators were placed at three different locations.
Repeatability
The repeatability (same PMSCs/mL and device lot/operator/location) is shown in the table below (all data at T=30, i.e. 30 minutes after collection of the semen samples):
| 0 M PMSCs/mL | Correct | Number of tests | % correct |
|---|---|---|---|
| Operator 1 | 4 | 4 | 100% |
| Operator 2 | 4 | 4 | 100% |
| Operator 3 | 4 | 4 | 100% |
| SUM | 12 | 12 | 100% |
| 1.9 M
| PMSCs/mL | Correct | Number of tests | % correct |
|---|---|---|---|
| Operator 1 | 4 | 4 | 100% |
| Operator 2 | 4 | 4 | 100% |
| Operator 3 | 4 | 4 | 100% |
| SUM | 12 | 12 | 100% |
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| 4.1 M
| PMSCs/mL | Correct | Number of tests | % correct |
|---|---|---|---|
| Operator 1 | 3 | 4 | 75% |
| Operator 2 | 4 | 4 | 100% |
| Operator 3 | 4 | 4 | 100% |
| SUM | 11 | 12 | 91,7% |
| 6.2 M | Correct | Number of tests | % correct |
|---|---|---|---|
| PMSCs/mL | |||
| Operator 1 | 4 | 4 | 100% |
| Operator 2 | 4 | 4 | 100% |
| Operator 3 | 4 | 4 | 100% |
| SUM | 12 | 12 | 100% |
| 8.4 M
| PMSCs/mL | Correct | Number of tests | % correct |
|---|---|---|---|
| Operator 1 | 4 | 4 | 100% |
| Operator 2 | 4 | 4 | 100% |
| Operator 3 | 4 | 4 | 100% |
| SUM | 12 | 12 | 100% |
| 10.1 M | Correct | Number of tests | % correct |
|---|---|---|---|
| PMSCs/mL | |||
| Operator 1 | 4 | 4 | 100% |
| Operator 2 | 4 | 4 | 100% |
| Operator 3 | 4 | 4 | 100% |
| SUM | 12 | 12 | 100% |
| 97.2 M | Correct | Number of tests | % correct |
|---|---|---|---|
| PMSCs/mL | |||
| Operator 1 | 4 | 4 | 100% |
| Operator 2 | 4 | 4 | 100% |
| Operator 3 | 4 | 4 | 100% |
| SUM | 12 | 12 | 100% |
| Overall | Correct | Number of tests | % correct |
|---|---|---|---|
| Operator 1 | 27 | 28 | 96.4% |
| Operator 2 | 28 | 28 | 100% |
| Operator 3 | 28 | 28 | 100% |
| SUM | 83 | 84 | 98.8% |
The repeatability was found to vary between 75% to 100%. Operator 1 misjudged one sample at 4.1 M PMSCs/mL and as this sample is very close to the cut-off value of 5.0 M PMSCs/mL it is concluded, that the repeatability of the SwimCount™ Sperm Quality Test is highly satisfactory.
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Reproducibility
The reproducibility of the three operators/batches and locations was very good, but the raw data indicates, that there was a trend towards reduced reproducibility over time.
A new study was performed. This time the actual progressive motile sperm concentration was determined by conventional microscopy at each time points 30 and 60 minutes were investigated.
| Semen Sample PMSC
| Concentration Levels | 30 min. after collection | 60 min. after collection | |
|---|---|---|---|
| 0 M PMSCs/mL | Actual PMSC concentration (counted in a Microscope) | 0 | 0 |
| Reproducibility of SwimCount™ Sperm Quality Test | 100% | 100% | |
| 1.7 M PMSCs/mL | Actual PMSC concentration (counted in a Microscope) | 1.7 M | 1.7 M |
| Reproducibility of SwimCount™ Sperm Quality Test | 100% | 100% | |
| 3.9 M PMSCs/mL | Actual PMSC concentration (counted in a Microscope) | 3.9 M | 3.9 M |
| Reproducibility of SwimCount™ Sperm Quality Test | 100% | 100% | |
| 6.2 M PMSCs/mL | Actual PMSC concentration (counted in a Microscope) | 6.2 M | 6.2 M |
| Reproducibility of SwimCount™ Sperm Quality Test | 100% | 100% | |
| 9.1 M PMSCs/mL | Actual PMSC concentration (counted in a Microscope) | 9.1 M | 9.1 M |
| Reproducibility of SwimCount™ Sperm Quality Test | 100% | 100% | |
| 11.4 M PMSCs/mL | Actual PMSC concentration (counted in a Microscope) | 11.4 M | 11.4 M |
| Reproducibility of SwimCount™ Sperm Quality Test | 100% | 100% | |
| 116.5 M PMSCs/mL | Actual PMSC concentration (counted in a Microscope) | 116.5 M | 116.5 M |
| Reproducibility of SwimCount™ Sperm Quality Test | 100% | 100% |
Conclusion
It is concluded, that the Reproducibility of the SwimCount™ Sperm Quality Test is very good when analyzing the semen samples within 60 minutes after collection.
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Semen Sample Stability Study
| Semen Sample PMSC
Concentration Levels | | 30 min. after
collection | 60 min. after
collection |
|-------------------------------------------|--------------------------------------------------------|-----------------------------|-----------------------------|
| 0 M PMSCs/mL | Actual PMSC concentration (counted
in a Microscope) | 0 | 0 |
| 1.7 M PMSCs/mL | Actual PMSC concentration (counted
in a Microscope) | 1.7 M | 1.7 M |
| 3.9 M PMSCs/mL | Actual PMSC concentration (counted
in a Microscope) | 3.9 M | 3.9 M |
| 6.2 M PMSCs/mL | Actual PMSC concentration (counted
in a Microscope) | 6.2 M | 6.2 M |
| 9.1 M PMSCs/mL | Actual PMSC concentration (counted
in a Microscope) | 9.1 M | 9.1 M |
| 11.4 M PMSCs/mL | Actual PMSC concentration (counted
in a Microscope) | 11.4 M | 11.4 M |
| 116.5 M PMSCs/mL | Actual PMSC concentration (counted
in a Microscope) | 116.5 M | 116.5 M |
As can be seen from the above table, using the produced semen sample within 60 minutes of producing the sample the PMSC concentrations are stable.
Because of the obtained results it is emphasized in the SwimCount™ Sperm Quality Test Instructions for Use that the sperm sample should be analyzed 30-60 minutes after semen collection.
Evaluation of Test Performance. Cut-off level.
A pooled semen sample from sperm donors was diluted with semen plasma to progressive motile sperm concentrations of 3.9 M, 4.0 M, 5.0 M, 6.0 M, and 6.2 M PMSCs/mL. Each concentration was tested in 40 replicates. The 4.0 M PMSCs/mL, 5.0 M PMSCs/mL and 6.0 M PMSC/mL concentrations were tested on two SwimCount™ Sperm Quality Test lots (i.e. 80 replicates per sample). The results support the 5.0 M PMSCs/mL cut-off level.
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| Concentration
(PMSCs/mL) | Percent positive
(Positive/Total) | Percent negative
(Negative/Total) |
|-----------------------------|--------------------------------------|--------------------------------------|
| 3.9 M | 0 (0/40) | 100 (40/40) |
| 4.0 M | 7.5 (6/80) | 92.5 (74/80) |
| 5.0 M | 55.0 (44/80) | 45.0 (36/80) |
| 6.0 M | 90.0 (72/80) | 10.0 (8/80) |
| 6.2 M | 100 (40/40) | 0 (0/40) |
Analytical Specificity (interference study)
The purpose of this study is to identify potential cross-reactivity and interference substances and to investigate if any of these interfere with the test result.
Substances in this context are defined as substances contaminating the sample leading to faulty results.
Such substances include:
-
- Bacteria present on skin surfaces and in the sample cup. As model bacteria a gram-positive and a gram-negative bacteria strain are included and in addition microorganisms responsible for sexually transmitted diseases (Neisseria gonorrhoeae and Chlamydia trachomatis) was tested. The concentration tested is set to 104 bacteria per mL, as bacteriospermia is defined as > 103 bacteria per mL by WHO.
- Saliva and urine which potentially may contaminate the sperm sample. The tested 2. concentration is set to 10%, which is far above the theoretical contamination concentration.
-
- Blood contamination (hematospermia) is very seldom found in semen samples (4) but was investigated at a spike concentration of 1% which corresponds to 107 Red Blood cells (RBC)/ml. The concentration of RBC in blood is approximately 108 RBC/mL.
-
- Possible interfering substances from infections in glands and ureter was investigated using 5 x 106 White Blood Cells /mL. The concentration of WBC in blood is approximately 100 WBC/mL.
-
- Hormones were tested in 10 x the upper reference concentrations found in male serum.
14
Overview of cross-reactivity and interfering testing of the SwimCount™ Sperm Quality Test
| Substance | Source and catalog no. | Test concentration/mL |
|---|---|---|
| Gram positive bacteria: | ||
| Staphylococcus epidermis | ATCC 14990 | $10^4$ |
| Gram negative bacteria: | ||
| Escherichia coli | ATCC 35218 | $10^4$ |
| Neisseria gonorrhoeae | ATCC 19424 | $10^4$ |
| Chlamydia trachomatis | ATCC VR-885 | $10^4$ |
| Urine | - | 10 % |
| Saliva | - | 10 % |
| Red Blood Cells (RBC) | Fractionated from donor | |
| blood at Odense | ||
| University Hospital, | ||
| Denmark | $10^7$ | |
| White Blood Cells (WBC) | Fractionated from donor | |
| blood at Odense | ||
| University Hospital, | ||
| Denmark | $5 x 10^6$ | |
| D-Norgestrel | Cayman Chemical, Cat | |
| no. 10006317 | 10 ng/mL | |
| β-Estradiol | Sigma E8875 | 600 pg/mL |
| Testosterone | Acros Organics | |
| 164410050 | 120 ng/mL |
The test was done in triplicate. Each potential interfering substance was spiked in semen samples from vasectomized men (containing semen plasma, only) to investigate any additive effect of interfering substance and in semen samples containing approximately 20 M progressive spermatozoa/mL to investigate any negative effect.
The following substances were identified as substances that may interfere on the SwimCount™ Sperm Quality Test result:
- Urine ●
- Red Blood Cells (RBC)
- . White Blood Cells (WBC)
Urine, Red Blood Cells (RBC) and White Blood Cells (WBC) were included as possible interfering substances in the SwimCount™ Sperm Quality Test Instructions for Use.
Substances which have been identified NOT to interfere with the test:
- Hormones (D-Norgestrel, B-Estradiol and Testosterone)
- Microorganism (Staphylococcus epidermis, Escherichia coli, Neisseria gonorrhoeae, ●
15
Chlamydia trachomatis)
- Saliva
Summary of results of the Multi-Center Clinical Study of the SwimCount™ Sperm Quality Test
MotilityCount ApS conducted a Multi-Center Clinical Study at 4 different sites in Denmark (2), Spain (1) and Turkey (1) of the SwimCount™ Sperm Ouality Test.
The subjects participating in this study were males attending fertility clinics and donors from a sperm bank with the following Age Brackets:
| Multi-Center Clinical Study of the SwimCount™ Sperm Quality Test - No. of Patients per Age Bracket and Category | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Number of Samples | Number of Samples excluded | Total No. of Net Samples | ||||||||||
| Age | ||||||||||||
| Bracket | Gender | LOW Sperm | ||||||||||
| Quality ~ 5 M PMSCs/mL) as judged by Laboratory Professionals |
- The Lay-Users uploaded a picture of their own SwimCount™ Sperm Quality Test result in . the survey
- . Thus, in the Lay-User study carried out at home with the Lay-User's own semen sample, there was a 97.53% agreement (% of Correct Calls) between the SwimCount™ Sperm Quality Test result read by the Lay-User at home and those obtained by Laboratory Professionals reading and analyzing the same uploaded picture of the SwimCount™ Sperm Quality Test result
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| SwimCount™ Sperm Quality Test - % of Correct Calls - Consumer Use Study | ||||||||
|---|---|---|---|---|---|---|---|---|
| Study | No. | |||||||
| of | ||||||||
| Lay- | ||||||||
| Users | Total | |||||||
| No. of | ||||||||
| Samples | Total No. | |||||||
| of | ||||||||
| Responses | ||||||||
| per Lay- | ||||||||
| User/ID | Corrected | |||||||
| for errors | Total No. | |||||||
| of Net | ||||||||
| Responses | ||||||||
| from Lay- | ||||||||
| Users/ID | Correct | |||||||
| Answers | Not | |||||||
| Correct | ||||||||
| Answers | % of | |||||||
| Correct | ||||||||
| Calls | ||||||||
| by Lay- | ||||||||
| Users | ||||||||
| Consumer | ||||||||
| Use Study |
- Lay User
Study
(Year
-
| 81 | 81 | 1 | 0 | 81 | 79 | 2 | 97.53% |
- Nothing was confusing as the Pre-Performing phase of the SwimCount™ Sperm Quality . Test had 100% of the Participants reading and fully understanding the SwimCount™ Sperm Quality Test Instructions for Use
- Regarding the Post Reading of the SwimCount™ Sperm Quality Test Instructions for Use ● 100% of the Participants could perform the SwimCount™ Sperm Quality Test in a satisfactory way
Consumer Interpretation Study
In addition to the Consumer Use Study a Consumer Interpretation Study was carried out.
81 Participants were asked to provide their opinion on 10 SwimCount™ Sperm Quality Test result pictures (N=810). This was accomplished via a Questionnaire including 10 Pictures of a SwimCount™ Sperm Quality Test result each including both LOW and NORMAL Sperm Quality Test Results.
791 out of the 810 pictures were read correctly and 19 pictures were not read correctly by the participants equal to 97.65% of correct calls by lay-users.
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Consumer Interpretation Study - Lay User Study
| Manual Sperm Count Reference | ||
|---|---|---|
| SwimCount™ Sperm Quality Test | LOW (NORMAL (≥5 M PMSCs/mL) | |
| LOW (NORMAL (≥5 M PMSCs/mL) | 2 | 469 |
| (0.62% false negative) | (3.50% false positive) | |
| 95% Conf. Interval | ||
| Correct Calls by Lay-Users | 97.65% | 96.70%-98.81% |
| Total Number of Participants | 81 | |
| Pictures Read Per Participant | 10 | |
| Total Number of Pictures Read | 810 |
Conclusions from Non-clinical and Clinical testing
The data from the Non-clinical testing indicates that the SwimCount™ Sperm Quality Test is safe and effective for its intended use.