Rapid-i™ Kit is a modified version of the predicate device (K140207). This device is a cryopreservation storage device intended for embryo/oocyte vitrification. Rapid-i™ Kit is provided sterile and is for single-use only. This device consists of the following items:

Rapid-i Stick – A 80 mm long Polymethyl methacrylate (PMMA) stick with a 0.4 mm diameter hole located near the distal tip of the device. The hole on the stick is used to hold one to five embryos or oocytes for vitrification in a 30 nL drop of vitrification medium. Users suspend samples across the hole via surface tension. Therefore, the medium containing the samples only touches the periphery of the hole. The stick has one flat side that aids in correct orientation of the device during oocyte/embryo loading procedures.
RapidStraw A 130 mm long Mediprene straw equipped with a stainless steel weight to maintain device orientation in liquid nitrogen (LN). The straw has a flared open end to allow for insertion of the Rapid-i Stick. This component functions as a protective sleeve around the Rapid-i Stick to prevent direct contact with LN during loading and after sealing the open end with an ultrasonic sealing device.
Stainless steel rod - This 115 mm long stainless steel rod resides within RapidStraw during pre-cooling procedures in LN. It aids in keeping RapidStraw straight in LN during pre-cooling. Rod removal occurs 20-30 seconds prior to Rapid-i Stick loading into the RapidStraw.

AI/ML Overview

Here is a breakdown of the acceptance criteria and the study that proves the device meets the acceptance criteria, based on the provided FDA 510(k) summary for the Rapid-i™ Kit (K181461).

Acceptance Criteria and Reported Device Performance

The device is a cryopreservation system for human embryos and oocytes. The acceptance criteria are implicitly tied to maintaining the viability and developmental potential of these biological materials after cryopreservation, demonstrated through various post-thaw outcomes.

Acceptance Criteria Category	Specific Criteria (Implicitly Derived)	Reported Device Performance
Non-Clinical Performance
Dimensional Testing	Conformance to predefined design specifications.	Device passed.
Bacterial Endotoxin Testing	< 1.0 EU/device per USP <85> and ANSI/AAMI ST72:2002/(R)2010.	Device passed.
Mouse Embryo Assay (MEA)	≥80% of 1-cell embryos developed to blastocysts at 96 hours.	Device passed.
Shelf-life Testing (Package)	Proper package integrity (dye penetration, seal strength, visual inspection).	Device passed.
Shelf-life Testing (Device)	Maintenance of acceptable dimensional, endotoxin, and MEA results over shelf-life.	Device passed.
Clinical Performance (2PN Embryos)
Embryo Survival Rate (2PN)	High survival rate after warming (no explicit threshold stated, but strong performance expected).	90.1% (1458/1618)
Clinical Pregnancy Rate (2PN)	Acceptable clinical pregnancy rates after embryo transfer (no explicit threshold stated).	25.1% for embryos cultured 1-3 days (418 transfers).
		36.3% for embryos cultured 4-5 days (92 transfers).
Clinical Performance (Oocytes)
Oocyte Survival Rate	High survival rate after warming (no explicit threshold stated, but strong performance expected).	Study 1: 94% (555/593). Study 2: 93.7% Published Article: 90.5% (374/413)
Fertilization Rate (Oocytes)	Acceptable fertilization rates (no explicit threshold stated).	Study 1: 78% (434/555 of survived oocytes). Study 2: 58.5%. Published Article: 64.2% (240/374 of survived oocytes).
Cleavage Rate (Oocytes)	Acceptable day 2 cleavage rates (no explicit threshold stated).	Study 1: 95% (414/434 of fertilized oocytes). Published Article: 90.4% (217/240 of fertilized oocytes).
Blastulation Rate (Oocytes)	Acceptable day 5 blastulation rates (no explicit threshold stated).	Study 1: 24% (102/434 of fertilized oocytes).
Clinical Pregnancy Rate (Oocytes)	Acceptable clinical pregnancy rates after embryo transfer (no explicit threshold stated).	Study 1: 50% (27/54 blastocyst transfers). Study 2: 40% (16/40 embryo transfers). Published Article: 40.9% (18/44 embryo transfers).

Study Details:

Sample sizes used for the test set and the data provenance:
- 2PN Embryos:
  - N = 1618 vitrified 2PN embryos.
  - N = 510 embryo transfers (418 transfers for embryos cultured 1-3 days, 92 transfers for embryos cultured 4-5 days).
  - Data provenance: Not explicitly stated beyond "Data from clinical studies using the Rapid-i™ Kit were used..." This suggests it could be retrospective collection from fertility clinics where the device was in use, but without further detail, it's difficult to confirm. The document does not specify country of origin for this particular dataset.
  - Study type: Prospective or retrospective collection based on the wording "Data from clinical studies." It is not described as a controlled clinical trial.
- Oocytes:
  - Study 1: N = 593 vitrified oocytes; N = 54 blastocyst stage embryo transfers.
  - Study 2: Data on survival, fertilization rates, and N = 40 embryo transfers. (Exact N of vitrified oocytes not stated for this study, only percentages).
  - Published Article (Gook et al. 2016): N = 413 vitrified oocytes; N = 44 embryo transfers.
  - Data provenance: Similar to 2PN embryos, "Data from clinical studies." The published article indicates a clinical setting. The Gook et al. 2016 paper is from Australia. Thus, at least some of the oocyte data likely originates from Australia.
  - Study type: Prospective or retrospective collection from clinical practice.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is a medical device for assisted reproduction purposes. The "ground truth" (i.e., successful cryopreservation, pregnancy outcomes) is established through standard clinical and laboratory procedures performed by trained embryologists, reproductive endocrinologists, and other healthcare professionals in fertility clinics. This is not a diagnostic device where image interpretation by experts creates a "ground truth." The outcomes (survival, fertilization, pregnancy) are objective biological results.
- Therefore, the concept of "experts used to establish ground truth" in the way it applies to AI diagnostic tools (e.g., radiologists annotating images) is not directly applicable here. The data points themselves (e.g., number of embryos surviving, number of pregnancies) are the ground truth, generated by the normal operations of an IVF clinic.
Adjudication method for the test set:
- Not applicable in the context of this type of device and study design. Adjudication methods like "2+1" are typically used for establishing ground truth in diagnostic studies where there might be inter-reader variability in interpreting data (e.g., medical images). Here, the outcomes measured are direct biological results.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No. This is not an AI-assisted diagnostic device that involves human readers interpreting output. It is a cryopreservation device. The study is evaluating the device's performance in preserving reproductive cells, not assisting human interpretation.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Not applicable. This is a physical medical device (cryopreservation kit), not an algorithm or software. Its performance is inherent to its design and material properties in facilitating the cryopreservation process. Human interaction is required for its use (loading, vitrifying, warming).
The type of ground truth used:
- Clinical Outcomes and Biological Performance Markers: The ground truth is established by the observed biological outcomes of human embryos and oocytes after being processed with the device. This includes:
  - Survival rates post-warming.
  - Fertilization rates for oocytes.
  - Developmental rates (cleavage, blastulation) for embryos.
  - Clinical pregnancy rates following embryo transfer (which are typically confirmed by ultrasound).
- For non-clinical tests, ground truth was established by laboratory standards and assays (e.g., bacterial endotoxin testing, mouse embryo assay).
The sample size for the training set:
- Not applicable. This is a physical medical device, not an AI/machine learning model that requires a training set. The "training" for such a device would be its iterative design and manufacturing process, combined with quality control and verification, rather than a data-driven training set in the AI sense.
How the ground truth for the training set was established:
- Not applicable, as no training set was used for an AI/machine learning model.

Summary

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January 4, 2019

Vitrolife Sweden AB Nina Arvidsson Regulatory Affairs Manager Gustaf Werners gata 2 SE-421 32 Västra Frölunda Sweden

Re: K181461 Trade/Device Name: Rapid-i™ Kit Regulation Number: 21 CFR& 884.6160 Regulation Name: Assisted Reproduction Labware Regulatory Class: II Product Code: MQK Dated: December 4, 2018 Received: December 7, 2018

Dear Nina Arvidsson:

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.

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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); 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 medical devices and radiation-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.

Michael T. Bailey -S

for

Benjamin R. Fisher, Ph.D. Director Division of Reproductive, Gastro-Renal, and Urological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K181461

Device Name Rapid-i™ Kit

Indications for Use (Describe)

Cryopreservation device intended to be used to contain, vitrify and maintain human embryos and/or oocytes (MI).

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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510(k) Summary - K181461

1. Submitter Information

Submitter:	Vitrolife Sweden ABGustaf Werners gata 2SE-421 32 Västra FrölundaSweden
Contact Person:	Nina Arvidsson
Phone:	+46 31 721 80 00
Fax:	+46 31 721 80 90
Email:	narvidsson@vitrolife.com

1. Date Prepared:
  January 3, 2019

3. Device Identification

Trade Name:	Rapid-i™ Kit
Common Name:	Cryopreservation Storage Device
Classification Name:	Assisted Reproduction Labware
Regulation Number:	21 CFR 884.6160
Product Code:	MQK (Labware, Assisted Reproduction)
Regulatory Class:	II

4. Predicate Device:

Rapid-i™ Kit (K140207) manufactured by Vitrolife Sweden AB. This predicate device has not been subject to any design related recalls.

5. Device description:

. Rapid-i Stick – A 80 mm long Polymethyl methacrylate (PMMA) stick with a 0.4 mm diameter hole located near the distal tip of the device. The hole on the stick is used to hold one to five embryos or oocytes for vitrification in a 30 nL drop of vitrification medium. Users suspend samples across the hole via surface tension. Therefore, the medium containing the samples only touches the periphery of the hole. The stick has one flat side that aids in correct orientation of the device during oocyte/embryo loading procedures.

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RapidStraw A 130 mm long Mediprene straw equipped with a stainless steel weight to . maintain device orientation in liquid nitrogen (LN). The straw has a flared open end to allow for insertion of the Rapid-i Stick. This component functions as a protective sleeve around the Rapid-i Stick to prevent direct contact with LN during loading and after sealing the open end with an ultrasonic sealing device.
. Stainless steel rod - This 115 mm long stainless steel rod resides within RapidStraw during pre-cooling procedures in LN. It aids in keeping RapidStraw straight in LN during pre-cooling. Rod removal occurs 20-30 seconds prior to Rapid-i Stick loading into the RapidStraw.

6. Indications for use:

Cryopreservation device intended to be used to contain, vitrify and maintain human embryos and/or oocytes (MII).

Devices	Subject device (K181461)	Predicate device (K140207)
Indicationsfor Use	A cryopreservation device intended tobe used to contain, vitrify and maintainhuman embryos and/or oocytes (MII).	A cryopreservation device designed to contain,vitrify and maintain 4-8 cell and blastocyst stagehuman embryos.
Design	Same as the predicate device	The stick has a tip where the samples are loadedin a 0.4 mm diameter hole. The stick is sealedwithin in a straw that contains a stainless steelweight to maintain device orientation in LN.
Dimension	- Rapid-i stick: 2mm×80mm- RapidStraw: 3.40mm (OD)/2.40mm(ID)×130mmStainless Steel Rod: 2.2mm × 115mm	- Rapid-i stick: 2mm×80mm- RapidStraw: 3.45mm (OD)/2.45mm (ID)×135mm- Stainless Steel Rod: 2.2mm × 115mm
Cooling rate	Same as the predicate device	1400°C/min (at -50°C)
Warming rate	Same as the predicate device	10000°C/min (at -50°C)
Devicematerials	Same as the predicate device	Polymethyl methacrylate (PMMA)MedipreneStainless steel
Vitrificationand warmingmethods	Same as the predicate device	Precool a straw (with steel rod inserted) with theopen end extending above the LN level. A 30 nLdrop of vitrification medium holding samples isloaded in a sample hole in the stick. The stick isthen inserted into the pre-cooled straw (aftersteel rod removal) to vitrify samples. The end ofthe straw is sealed and the device is stored inLN.

7. Substantial Equivalence Discussion

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The subiect device is indicated to contain. vitrify and maintain human embryos and oocytes (MII). whereas the predicate device is indicated to vitrify and maintain 4-8 cell and blastocyst stage embryos. Inclusion of the oocyte indication and expansion of the embryo indication to also include 2 PN embryos does not represent a new intended use because processing of the embryos or oocytes is applicable to same patient population with same clinical needs – infertility treatment or fertility preservation. Therefore, the subject and predicate devices have the same intended use.

The subject and predicate devices have similar technological characteristics. The only difference between the subject and predicate device is that the subject RapidStraw has a length of 130 mm and 3.40 mm OD/2.40 mm ID whereas the predicate RapidStraw has a length of 135 mm and 3.45 mm OD/2.45 mm ID. This difference is minor and does not raise different questions of safety and effectiveness as compared to the predicate device.

8. Summary of Non-Clinical Performance Data

Non-clinical performance testing was conducted to support substantial equivalence to the predicate device. Rapid-i™ Kit passed all the tests shown below in accordance with internal requirements and/or applicable standards.

Dimensional Testing per predefined design specifications. .
. Bacterial Endotoxin Testing - < 1.0 EU/device per USP <85> and ANSI/AAMI ST72:2002/(R)2010
Mouse Embryo Assay (MEA) - ≥80% of 1-cell embryos developed to blastocysts at 96 hours
Shelf-life Testing: ●
- Package integrity testing:
  - Dye penetration test of sterile packages per ASTM F1929-15 o
  - Seal strength of sterile packages per ASTM F88/F88M-15 o
  - Visual inspection per ASTM F1886/F1886M-16 o
- Dimensional testing, endotoxin testing and MEA in accordance with the methods and acceptance criteria mentioned above

In addition, information regarding cooling/warming rate testing and sterilization validation per ISO 11135:2014 and ISO 10993-7:2008 provided in K140207 was leveraged to support substantial equivalence.

9. Summary of Clinical Performance Data

Data from clinical studies using the Rapid-i™ Kit were used to demonstrate the ability of the subject device to be used as a cryopreservation device for oocytes and 2 PN embryos.

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Vitrification of 2PN embryos: .
Of 1618 2 PN embryos vitrified with Rapid-i™ Kit, 1458 (90.1%) survived after warming. Five hundred ten (510) embryo transfers were conducted using the embryos cultured for 1-3 days (418 transfers) or for 4-5 days (92 transfers). The clinical pregnancy rate resulting from the embryos cultured for 1-3 days was 25.1%. The clinical pregnancy rate resulting from the embryos cultured for 4-5 days was 36.3%.
Vitrification of oocytes: .
- In one study, 94% (555/593) oocytes vitrified with Rapid-i™ Kit survived after warming. The fertilization rate, day 2 cleavage rate, day 5 blastulation rate were 78% (434/555), 95% (414/434) and 24% (102/434), respectively. Of the 54 blastocyst stage embryo transfers, 27 (50%) resulted in a clinical pregnancy.
- In another study, the survival rate and fertilization rate of oocytes vitrified with the Rapidi™ Kit were 93.7% and 58.5%, respectively. Of the 40 embryo transfers performed, 16 (40%) resulted in clinical pregnancy.
- In a published journal article, 90.5% (374/413) occytes vitrified with Rapid-i™ Kit survived after warming. The fertilization rate of survived oocytes was 64.2% (240/374). The cleavage rate on day 2 was 90.4% (217/240). Of the 44 embryo transfers performed, 18 (40.9%) resulted in clinical pregnancy. [Ref: Gook et al. (2016) Closed vitrification of human oocytes and blastocysts: outcomes from a series of clinical cases. J Assist Reprod Genet 33:1247-1252]

10. Conclusions:

The subject and predicate devices have the same intended use and comparable technological characteristics. The differences in technological characteristics between the subject and predicate devices do not raise different questions of safety and effectiveness. The performance data demonstrate that the subject devices are substantially equivalent to the predicate device.

Regulation Number and Section

§ 884.6160 Assisted reproduction labware.

(a)
Identification. Assisted reproduction labware consists of laboratory equipment or supplies intended to prepare, store, manipulate, or transfer human gametes or embryos for in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), or other assisted reproduction procedures. These include syringes, IVF tissue culture dishes, IVF tissue culture plates, pipette tips, dishes, plates, and other vessels that come into physical contact with gametes, embryos or tissue culture media.(b)
Classification. Class II (special controls) (mouse embryo assay information, endotoxin testing, sterilization validation, design specifications, labeling requirements, and clinical testing). The device, when it is a dish or plate intended for general assisted reproduction technology procedures, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 884.9.