(324 days)
The Rapid-i™ Kit is a cryopreservation device designed to contain 4-8 cell and blastocyst stage human embryos.
Rapid-iTM Kit, a cryopreservation device designed to contain, vitrify and maintain 4-8 cell and blastocyst stage human embryos, consists of the following three items:
• 80 mm PMMA stick (Rapid-iTM)
• 135 mm Mediprene straw equipped with a stainless steel weight, (RapidStraw)
• 115 mm stainless steel rod inserted in the RapidStraw
Here's an analysis of the acceptance criteria and supporting studies for the Rapid-i™ Kit, based on the provided FDA 510(k) summary:
1. Table of Acceptance Criteria and Reported Device Performance
| Test Type | Acceptance Criteria | Reported Device Performance (Rapid-i™ Kit) | Study Proving Performance (Relevant part of the document) |
|---|---|---|---|
| Nonclinical Testing | |||
| Mouse Embryo Assay (MEA) | % expanded blastocyst within 96 hours ≥ 80% | All devices met acceptance specifications (implicitly ≥ 80%). | "Mouse Embryo Assay (re-expanded blastocyst within 96 hours ≥80%) has been performed on three individually tested samples from each of three lots of the proposed device. All devices met acceptance specifications..." (Page 9) |
| Endotoxin Testing (LAL assay) | ≤ 1.0 EU/device | < 1.0 EU/device | "Specification: Bacterial Endotoxins (LAL assay) ≤ 1.0 EU/device." (Page 5) and "Endotoxin (<1.0 EU/device): endotoxins do not change during the shelf life..." (Page 9) |
| Sterilization Validation | Sterilized using ethylene oxide SAL 10^-6^ | Sterilized using ethylene oxide SAL 10^-6^ | "Specification: Sterilized using ethylene oxide SAL 10^-6^." (Page 5) |
| Clinical Testing | |||
| Clinical Pregnancy Rate | Comparable to 2011 ART success rates (mean 36.6%) | Range between 32% and 47%, average 42% | "The clinical pregnancy rates range between 32% and 47%, and to date, birth of 124 children. ... The average blastocyst survival rate was 91% and the average clinical pregnancy rate was 42%." (Page 10) |
| Blastocyst Survival Rate | Not explicitly stated as acceptance criteria, but reported. | Average 91% | "The average blastocyst survival rate was 91% and the average clinical pregnancy rate was 42%." (Page 10) |
| Shelf-Life Evaluation | |||
| Sterility Testing | Negative, no growth | Negative, no growth | "Sterility Testing (Negative, no growth): sterile integrity is dependent on the primary packaging and the sealing procedure. This has not changed from the predicate." (Page 9) |
| Endotoxin (Shelf-Life) | < 1.0 EU/device | < 1.0 EU/device | "Endotoxin (<1.0 EU/device): endotoxins do not change during the shelf life if packaging maintains a sterile barrier." (Page 9) |
| Mouse Embryo Assay (Shelf-Life) | Re-expanded blastocyst within 96 hours ≥ 80% | All devices met acceptance specifications (implicitly ≥ 80%). | "Mouse Embryo Assay (re-expanded blastocyst within 96 hours ≥80%) has been performed on three individually tested samples from each of three lots of the proposed device. All devices met acceptance specifications, and support the 22 month shelf-life of the device." (Page 9) |
2. Sample Sizes and Data Provenance
-
Nonclinical Testing (MEA, Endotoxin, Sterilization):
- MEA: "three individually tested samples from each of three lots of the proposed device." (Page 9)
- Endotoxin: No specific sample size given for this device, but testing is performed according to USP<85>. The statement implies this testing is done routinely. (Page 5)
- Sterilization: No specific sample size given, but validation was performed according to ISO 11737-2:2009. (Page 5)
- Data Provenance: Likely internal lab studies by Vitrolife Sweden AB, prospective.
-
Design Validation (Comparative Studies, predicate device K090832):
- "Effects of sealing before and after vitrification": Compared post-seal Rapid-i™ (predicate), pre-seal Rapid-i™ and HSV straw. No specific sample counts for embryos, but compared "different non-liquid nitrogen (LN2) contact vitrification methods of previously frozen day 1 embryos." (Page 8)
- "A comparative mouse study": Compared post-seal Rapid-i™ (predicate), pre-seal Rapid-i™ and HSV straw, using "fresh F1 mouse embryos." (Page 8)
- "A comparative Swiss outbred study": Compared post-seal Rapid-i™ (predicate) and pre-seal Rapid-i™ using "Swiss outbred mice." (Page 8)
- "A vitrification study": No embryos used; visually verified vitrification of media. (Page 8)
- Data Provenance: These were studies related to the predicate device (K090832) for design validation and likely conducted by or for Vitrolife. The nature of the studies suggests prospective experimental designs.
-
Clinical Testing (Blastocyst Vitrification):
- Patients: 426 patients with embryo transfer. (Page 10)
- Data Provenance: Conducted at four sites. It appears to be retrospective collection of results from historical clinical use, stating "The clinical pregnancy rates range between 32% and 47%, and to date, birth of 124 children." and "Clinical blastocyst vitrification was conducted at four sites..." (Page 10)
3. Number of Experts and Qualifications for Ground Truth
- Nonclinical & Shelf-Life Testing (MEA, Endotoxin, Sterilization): No independent experts are explicitly mentioned for establishing ground truth for these tests. These are standard laboratory assays with predefined control samples and acceptance criteria.
- Design Validation (Comparative Studies on Mice/Embryos): No external experts are mentioned. Ground truth was based on defined measurable outcomes like blastocyst development, cell count, and visual assessment of vitrification.
- Clinical Testing: This section references "standard procedures" for embryo assessment and "clinical pregnancy rates" and "birth of 124 children." While embryologists and clinicians are inherently experts, the document does not specify how many or their specific qualifications for establishing ground truth in terms of a consensus panel for this specific submission. The "ground truth" here is objective clinical outcomes (pregnancy, live birth, survival rates) as reported by the clinics.
4. Adjudication Method
- There is no mention of an adjudication method (e.g., 2+1, 3+1) in the document. This type of adjudication is typically for subjective assessments (e.g., image interpretation). Given the nature of these tests (laboratory assays, survival rates, clinical outcomes), such a method would not commonly be applied.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
- No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done for this device. This type of study is more common for diagnostic imaging devices where human readers interpret data, and the comparison is how AI assistance changes their diagnostic accuracy. The Rapid-i™ Kit is a cryopreservation device, not a diagnostic tool requiring human interpretation for its primary function.
6. Standalone (Algorithm Only) Performance Study
- No, a standalone (algorithm only) performance study was not done. The Rapid-i™ Kit is a hardware device for cryopreservation, not an algorithm. Therefore, "algorithm only" performance is not applicable.
7. Type of Ground Truth Used
- Nonclinical & Shelf-Life Testing: Objective laboratory measurements (e.g., growth in MEA, endotoxin levels, sterility confirmation).
- Design Validation: Objective experimental outcomes (e.g., blastocyst development rate, cell count, visual assessment of vitrification).
- Clinical Testing: Objective clinical outcomes (embryo survival rate, clinical pregnancy rate, live birth). This is a form of outcomes data.
8. Sample Size for the Training Set
- The concept of a "training set" is not applicable here as the Rapid-i™ Kit is a medical device (hardware) rather than an AI/ML algorithm that requires training data. The studies performed are for validating the product's functional performance and safety.
9. How Ground Truth for the Training Set Was Established
- As the device is not an AI/ML algorithm, there is no "training set" or ground truth for it in that context. The "ground truth" for evaluating the device's performance as a cryopreservation tool is established through the objective measurements and clinical outcomes described above.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
December 18, 2014
Vitrolife Sweden AB % Anthony T. Pavel Regulatory Counsel Morgan, Lewis & Bockius LLP 1111 Pennsylvania Avenue NW Washington, DC 20004
Re: K140207
Trade/Device Name: Rapid-i™ Kit Regulation Number: 21 CFR 884.6160 Regulation Name: Assisted reproduction labware Regulatory Class: II Product Code: MOK Dated: November 24, 2014 Received: November 25, 2014
Dear Anthony T. Pavel,
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. 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device
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related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Herbert P. Lerner -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) K140207
Device Name Rapid-i™ Kit
Indications for Use (Describe)
The Rapid-i™ Kit is a cryopreservation device designed to contain 4-8 cell and blastocyst stage human embryos.
Type of Use (Select one or both, as applicable)
2 Prescription Use (Part 21 CFR 801 Subpart D)
_ Over-The-Counter Use (21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FDA USE ONLY
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
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510(k) Summary
| Submitted by: | Vitrolife Sweden ABBox 9080SE-400 92 GöteborgSWEDEN | |
|---|---|---|
| Date: | December 16, 2014 | |
| ManufacturingSites: | Vitrolife Sweden ABBox 9080SE-400 92 GöteborgSWEDEN | Vitrolife Inc.3601 Inca StreetEnglewood, CO 80110USA |
| ContactPerson: | Nina ArvidssonRegulatory Affairs ManagerVitrolife Sweden ABBox 9080SE-400 92 GöteborgSWEDENTel: +46 31 721 80 77Fax: +46 31 721 80 90E-mail: narvidsson@vitrolife.com | |
| EstablishmentRegistrationNumbers: | 3003995932Vitrolife Sweden AB | 9037178Vitrolife Inc., Englewood, CO |
| Device TradeName: | Rapid-iTM Kit | |
| 510(k)Number: | K140207 | |
| DeviceCommonName: | Cryopreservation container and microtool | |
| DeviceClassification: | Regulation: 21 C.F.R. § 884.6160Classification Name: Assisted Reproduction LabwareProduct Code: MQKClassification: Class II (special controls) | |
| DeviceClassification: | Class II |
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| PredicateDevice: | Vitrolife Rapid-iTM (K090832) | ||
|---|---|---|---|
| Indications forUse: | The Rapid-iTM Kit is a cryopreservation device designed to contain, vitrify andmaintain 4-8 cell and blastocyst stage human embryos. | ||
| DeviceDescriptionand Principlesof Operation: | Rapid-iTM Kit, a cryopreservation device designed to contain, vitrify andmaintain 4-8 cell and blastocyst stage human embryos, consists of the followingthree items: | ||
| • 80 mm PMMA stick (Rapid-iTM) | |||
| • 135 mm Mediprene straw equipped with a stainless steel weight,(RapidStraw) | |||
| • 115 mm stainless steel rod inserted in the RapidStraw | |||
| SubstantialEquivalence toPredicateDevices: | 4-8 cell and blastocyst stage embryos are vitrified using the Rapid-iTM Kit bypre-cooling the RapidStraw (steel rod inserted) with the open end extendingfrom the liquid nitrogen. A 30 nanoliter drop of vitrification solution holdingembryos is placed in a capillary sized hole in the Rapid-iTM. The stainless steelrod is removed 20-30 seconds before the Rapid-iTM is inserted in the pre-cooledRapidStraw in liquid nitrogen to effect vitrification of the embryos. The openend of the straw is then sealed.The Rapid-iTM Kit is substantially equivalent to the Rapid-iTM, as previouslycleared by FDA (K090832).The following table compares the Rapid-iTM Kit to the predicate device (Rapid-iTM) with respect to intended use, technological characteristics, and principles ofoperation. | ||
| Manufacturer | Vitrolife Sweden AB | Vitrolife Sweden AB | |
| Trade Name | Rapid-iTM Kit | Rapid-iTM | |
| 510(k) Number | K140207 | K090832 | |
| Product Code | MQK | MQK | |
| Regulation Number | 884.6160 | 884.6160 | |
| Regulation Name | Assisted ReproductionLabware | Assisted ReproductionLabware | |
| Indications for Use | The Rapid-iTM Kit is a | Rapid-iTM is a |
| Manufacturer | Vitrolife Sweden AB | Vitrolife Sweden AB |
|---|---|---|
| Trade Name | Rapid-iTM Kit | Rapid-iTM |
| 510(k) Number | K140207 | K090832 |
| Product Code | MQK | MQK |
| Regulation Number | 884.6160 | 884.6160 |
| Regulation Name | Assisted ReproductionLabware | Assisted ReproductionLabware |
| Indications for Use | The Rapid-iTM Kit is acryopreservation devicedesigned to contain,vitrify and maintain 4-8cell and blastocyst stagehuman embryos. | Rapid-iTM is acryopreservation devicethat is intended to beused to contain, vitrifyand maintain 4-8 cellstage embryos. |
| Manufacturer | Vitrolife Sweden AB | Vitrolife Sweden AB |
| Method of Action(vitrification) | Precool a straw with theopen end extendingfrom the liquidnitrogen. A 30 nanoliterdrop of vitrificationsolution holdingembryos is placed in acapillary sized hole inthe stick. The stick inturn is inserted in thepre cooled straw inliquid nitrogen to effectvitrification of theembryos. Subsequently,the open end of thestraw is sealed. | Precool a straw with theopen end extendingfrom the liquidnitrogen. A 30 nanoliterdrop of vitrificationsolution holdingembryos is placed in acapillary sized hole inthe stick. The stick inturn is inserted in thepre cooled straw inliquid nitrogen to effectvitrification of theembryos. Subsequently,the open end of thestraw is sealed. |
| Cooling Rate | 1400°C/min at -50°C | 1400°C/min at -50°C |
| Method of Action(rewarming) | While the distal end ofthe straw remains inliquid nitrogen, cut thesealed proximal end ofthe straw. Withdrawthe stick and directlyimmerse thestick/vitrified drop inwarming media. | While the distal end ofthe straw remains inliquid nitrogen, cut thesealed proximal end ofthe straw. Withdrawthe stick and directlyimmerse thestick/vitrified drop inwarming media. |
| Rewarming Rate | 10,000°C/min at -50°C | 10,000°C/min at -50°C |
| Warming: ContactWith the WarmingMedium | Direct immersion ofsample in the warmingsolution forsimultaneous thawingand dilution. | Direct immersion ofsample in the warmingsolution forsimultaneous thawingand dilution. |
| Materials in ContactWith Tissue (embryos) | Polymethylmethacrylate (PMMA)stick with hole, 2x80mm | Polymethylmethacrylate (PMMA)stick with hole, 2x80mm |
| Straw | Mediprene straw withfunnel and weight, OD3.45 mm, ID 2.5 mm,wall thickness 0.47 mm,length 135 mm | Poly vinyl chloride(PVC) straw withfunnel and weight, OD3.3 mm, ID 2.6 mm,wall thickness 0.35 mm,and length 165 mm |
| Stainless Steel Rod | Stainless steel, 2.2 x115 mm | ---- |
| Manufacturer | Vitrolife Sweden AB | Vitrolife Sweden AB |
| Sterility AssuranceLevel | Sterilized by ethyleneoxide. SAL is 10-6 | Sterilized by ethyleneoxide. SAL is 10-6 |
| MEA Specification | Mouse Embryo Assay(1 -cell)% expanded blastocyst,within 96h ≥80 | Mouse Embryo Assay(1 -cell)% expanded blastocyston day 5 ≥80 |
| EndotoxinSpecification | Bacterial endotoxins(LAL assay) <1EU/device | Bacterial endotoxins(LAL assay) <1EU/device |
| liquid nitrogen storage tanks. The straw diameter was increased to aid ininsertion of the Rapid-i™ stick into the RapidStraw. Also, the wall thickness ofthe straw was increased. None of these changes raises new questions of safetyor effectiveness. | ||
| Accordingly, Vitrolife has concluded that the technology of the proposeddevice is substantially equivalent to the predicate device and that differences donot raise new questions of safety or effectiveness. | ||
| NonclinicalTesting | The Rapid-i™ Kit is substantially equivalent to the previously-cleared Rapid-i™ (K090832), and is subject to the following tests: | |
| A. Mouse Embryo Assay | ||
| Rapid-i™ Kit is subject to the 1-cell Mouse Embryo Assay (MEA). | ||
| Specification: Mouse Embryo Assay (1-cell) [% expanded blastocyst within 96hours] ≥ 80 %. | ||
| B. Endotoxin Testing | ||
| Rapid-i™ Kit is subject to bacterial endotoxin testing by use of the LAL assay. | ||
| Specification: Bacterial Endotoxins (LAL assay) ≤ 1.0 EU/device. | ||
| Testing is performed according to USP<85> Bacterial Endotoxins Test. | ||
| C. Sterilization Validation | ||
| Sterility of the device is assured through the use of ethylene oxide sterilization. | ||
| Specification: Sterilized using ethylene oxide SAL 10-6. | ||
| Sterilization validation was performed according to ISO 11737-2:2009Sterilization of Medical devices – Microbiological Methods, Part 2: Tests ofSterility Performed in the Validation of the Sterilization Process. | ||
| D. Design Validation | ||
| As part of the design validation process, the following tests were conducted onthe Rapid-i™ (K090832) (which is substantially similar to the Rapid-i™ Kit): | ||
| The design validation testing on the post-seal Rapid-i™ described below isvalid for Rapid-i™ Kit as well. The minimal physical differences between thepost-seal Rapid-i™ and the Rapid-i™ Kit are only in the straw material and the |
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Discussion of Similarities and Differences
The indication for the cleared Rapid-i™ is "a cryopreservation device that is intended to be used to contain, vitrify and maintain 4-8 cell stage embryos." The addition of blastocyst stage embryos to the proposed device's indication does not represent a new intended use. Both the proposed and predicate devices are intended to cryopreserve embryos from patients undergoing assisted reproductive procedures for later use. Blastocyst stage embryos and 4-8 cell stage embryos are similar in size and morphology and therefore the same carrier devices may be used for the vitrification of embryos in both of these stages. Therefore, addition of blastocyst vitrification does not represent a new intended use as it does not raise different questions of safety or effectiveness.
The operation of both devices is substantially similar, as both involve the precooling of a straw with the open end extending from the liquid nitrogen. The proposed device utilizes a stainless steel rod, which acts to keep the straw straight and also helps limit condensation in the straw during the cooling procedure, and is removed prior to insertion of the Rapid-i™ stick. The inclusion of the stainless steel rod does not raise any new questions of safety or effectiveness. A 30 nanoliter drop of vitrification solution holding embryos is placed in a capillary sized hole in the stick. The stick in turn is inserted in the pre-cooled straw in liquid nitrogen to effect vitrification of the embryos. Subsequently, the open end of the straw is sealed. The warming procedures are the same for both devices, and the cooling and warming rates of the devices are the same, as are the materials in contact with the embryos.
The straw in the proposed device is comprised of mediprene (straw with funnel and weight, 3.45 x 135 mm), whereas in the predicate, the straw is comprised of polyvinyl chloride (PVC) (straw with funnel and weight, 3.3 x 165 mm).
The change in material from PVC to mediprene has no impact on function and was made because of improved color properties of the material. The difference in material does not raise any new questions of safety or effectiveness.
The RapidStraw was shortened to fit better in devices used to hold samples in
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straw thickness. Neither of these parameters affects the embryo, as the straw is
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not in direct or indirect contact with the embryo. The changes do not affect cooling or warming rates. Hence, the differences do not affect vitrification. warming, or embryo development after vitrification.
- Effects of sealing before and after vitrification- the purpose of the study ● was to evaluate different non-liquid nitrogen (LN2) contact vitrification methods of previously frozen day 1 embryos. The methods were: (a) post-seal Rapid-iTM (i.e., the predicate device); (b) pre-seal Rapid-i™; and (c) the HSV straw. A non-vitrified group was used as control. The methods were evaluated with respect to expanded blastocyst development, cell count of expanded blastocysts on day 5, and ease of use and time in the final solution prior to vitrification. The study showed that the three methods did not differ from each other significantly in terms of expanded blastocyst development.
- A comparative mouse study- similar to the study above, the purpose was . to evaluate different non-LN2 contact vitrification methods of fresh F1 mouse embryos. The methods were: (a) post-seal Rapid-i™ (i.e., the predicate device); (b) pre-seal Rapid-i™; and (c) the HSV straw. A non-vitrified group was used as control. The methods were evaluated with respect to blastocyst development on day 4 and 5 and cell count of expanded blastocysts on day 5. The study showed that the three methods did not differ from each other significantly in terms of blastocyst development on day 4 and 5.
- A comparative Swiss outbred study- similar to the studies above, the ● purpose was to evaluate different non-LN2 contact vitrification methods of Swiss outbred mice. The methods were: (a) post-seal Rapid-i™ (i.e., the predicate device); and (b) pre-seal Rapid-i™. A non-vitrified group was used as control. The methods were evaluated with respect to blastocyst development on day 4 and 5 and cell count of expanded blastocysts on day 5. The study showed that method (a) showed a significantly higher blastocyst development rate on day 5 and cell count of expanded blastocysts compared to method (b).
- A vitrification study- the purpose of the study was to visually verify that ● the post-seal Rapid-i™ and pre-seal Rapid-i™ vitrification methods result in total vitrification of the media. The methods were: (a) post-seal Rapid-i™ (i.e., the predicate device) loaded with the final vitrification media: (b) pre-seal Rapid-i™ loaded with the final vitrification media: and (c) pre-seal Rapid-i™ loaded with the an intermediate vitrification media with lower osmolality. No embryo was used. The methods were evaluated by capturing images of the media in the device under LN2. The study showed that methods (a) and (b) resulted in transparent media indicating that vitrification had taken place and method (c) resulted in opaque media indicating that freezing had occurred.
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E. Shelf-life Evaluation
The initial shelf-life report provided in the prior submission (K090832) for the Rapid-i™ device was based on sterile integrity of the packaging. A verifying stability study was also performed on the Rapid-i™ device. The testing included sterility testing according to USP<71> Sterility Tests, bacterial endotoxins according to USP<85> Bacterial Endotoxins Test, and Mouse Embryo Assay.
The data provided supports the proposed shelf-life for the updated version of the device because:
- Sterility Testing (Negative, no growth): sterile integrity is dependent on . the primary packaging and the sealing procedure. This has not changed from the predicate.
- . Endotoxin (<1.0 EU/device): endotoxins do not change during the shelf life if packaging maintains a sterile barrier. This has not changed from the predicate.
Mouse Embryo Assay (re-expanded blastocyst within 96 hours ≥80%) has been performed on three individually tested samples from each of three lots of the proposed device. All devices met acceptance specifications, and support the 22 month shelf-life of the device.
F. Cooling/Warming Rate Testing
Cooling and warming rate testing was conducted on the predicate device (K090832). New testing is not required for the current submission for the following reasons:
- The design of the Rapid-i™ stick has not changed. Therefore, this . component does not raise any new design features that may impact cooling/warming rates.
- . The RapidStraw material and dimensions have been modified in comparison to the predicate device (see Substantial Equivalence to Predicate Devices section above). These changes to the straw do not impact the cooling rate of the device for the following reasons (Note: the Rapid-i™ stick is removed from the RapidStraw prior to warming, and does not impact device warming rates):
- The RapidStraw is placed in an infinite heat sink (liquid nitrogen o bath) which assures that the temperature of the inside of the RapidStraw is very close in thermal balance with the surrounding liquid nitrogen prior to loading the Rapid-i™ stick. Changes in wall thickness and use of a comparable material support comparable cooling rates when using this pre-cooling procedure.
- Dimensional changes resulted in a decrease of 0.1 mm in the o internal diameter of the RapidStraw. Therefore, the amount of space containing air between inner RapidStraw wall and the
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| vitrification solution has decreased by 0.05 mm, which would have an insignificant impact on cooling rates when using the pre-cooling method described above. | |
|---|---|
| G. Dimension Testing | |
| The dimensions of the finished product were measured to confirm conformance to the specifications. | |
| Clinical Testing | The indication was modified to expand use with blastocyst stage embryos, and additional testing was performed to assess the ability to vitrify blastocyst stage embryos using the device, as discussed below. |
| All laboratory procedures including embryo assessment were performed according to standard procedures. For vitrification and warming, respectively, Vitrolife's RapidVit Blast and RapidWarm Blast solutions were used while the Rapid-i™ Kit was used as a carrier device. During the vitrification and warming procedures, the instructions for use for the respective procedures were followed. After vitrification, blastocysts were stored in liquid nitrogen until the time of warming. After warming, cultured and surviving embryos were transferred into the uterus using standard procedures. | |
| The use of the Rapid-i™ Kit as carrier device for clinical blastocyst vitrification provides good results. The clinical pregnancy rates range between 32% and 47%, and to date, birth of 124 children. Clinical blastocyst vitrification was conducted at four sites, including 426 patients with embryo transfer. The average blastocyst survival rate was 91% and the average clinical pregnancy rate was 42%. | |
| When compared with the most recent Assisted Reproductive Technology ("ART") National Summary Report, published by the Centers for Disease Control and Prevention (“CDC"), the success rates with the Rapid-i™ Kit are comparable to the 2011 ART success rates. For example, in 2011, CDC reported a mean of 36.6% of frozen embryos from nondonor eggs transferred (all ages combined) resulted in pregnancy. By comparison, the clinical pregnancy rates for the Rapid-i™ Kit ranged between 32% and 47%. | |
| Conclusion | The nonclinical and clinical testing described above demonstrate that the Rapid-i™ Kit is substantially equivalent to the predicate device. |
§ 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.