(110 days)
CORNISOL is a corneal storage solution for storage of human cornea suitable for keratoplasty for up to 14 days under refrigeration (2-8°C).
Cornisol is a sterile hypothermic corneal storage medium intended for human corneal storage between 2 and 8℃ for up to 14 days. Cornisol is for single use and to be used only by physicians or highly skilled personnel such as eye bank operators. Corneas are directly placed in Cornisol medium after surgery with a storage time based on the time needed to obtain serology results of the donor but for a period of time of no more than 14 days.
Here's an analysis of the provided text, focusing on the acceptance criteria and the study proving the device meets them:
The provided document is a 510(k) summary for a medical device called "Cornisol," a corneal storage solution. It discusses the device's characteristics, intended use, and comparison to a predicate device (Optisol-GS) to demonstrate substantial equivalence.
However, the document does not provide specific acceptance criteria or detailed results of a comparative effectiveness study with human readers. It focuses on the chemical, physical, and in-vitro performance of the solution itself, rather than an AI-assisted diagnostic device.
Therefore, many of your requested items, such as multi-reader multi-case studies, AI assistance, ground truth establishment for training/test sets, and sample sizes for AI model training/testing, are not applicable to this type of device (a corneal storage solution). The performance evaluation here is about the preservation efficacy of the solution, not the diagnostic accuracy of an AI algorithm.
Here's what can be extracted and inferred based on the provided text, and where information is missing:
Device Under Review: Cornisol (Corneal Storage Solution)
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the comparison to the predicate device and the in-vitro study results. The key performance characteristic is the ability to preserve human corneas for up to 14 days under refrigeration (2-8°C) for keratoplasty.
| Acceptance Criteria (Implied) | Reported Device Performance (Cornisol) |
|---|---|
| Similar Intended Use: Hypothermic corneal storage. | Met: Cornisol is a hypothermic corneal storage solution. |
| Similar Indications for Use: Storage for up to 14 days at 2-8°C for keratoplasty. | Met: CORNISOL is a corneal storage solution for storage of human cornea suitable for keratoplasty for up to 14 days under refrigeration (2-8°C). |
| Sterility: Must be sterile. | Met: Cornisol is a sterile solution. Sterilization by sterile filtration (0.2 micron polyether sulfone membrane filters) validated for aqueous extracts (< 0.25 EU/ml endotoxin) and finished product endotoxin specification (5 EU/device) confirmed. Vial caps sterilized by EO (limits for EO/ECH exposure met). |
| Physical/Chemical Stability: Maintain pH, contain proper nutrients, etc. | Met: Buffered corneal preservation medium with ingredients (Chondroitin Sulphate, Dextran 40, HEPES Buffer, Sodium Pyruvate, Gentamycin, Streptomycin, Sodium Bicarbonate, Medium 199, Minimum Essential Medium, Glutamax i200, Vitamin B12, Phenol Red Indicator, Recombinant Human Insulin, Purified Water IP). Designed to maintain pH for endothelial cell viability, nutrient delivery, and prevent degradation. |
| Biocompatibility: Non-toxic, non-sensitizing, non-irritating. | Met: Chemical characterization performed. No novel ingredients. Biocompatibility testing conducted: Cytotoxicity (ISO 10993-5), Sensitization (ISO 10993-10), Acute ocular irritation testing (ISO 10993-10). These tests would confirm non-toxicity and safety for use with human tissue. |
| Preservation Efficacy (Implied Equivalence to Predicate): Maintain endothelial cell viability and structural/functional integrity for 14 days. | Met: Two in-vitro studies conducted: 1. Prospective, in vitro, randomized study using paired donor corneas. Assessments: endothelial cell loss, endothelial cell density (ECD), coefficient of variance, and percentage hexagonality on days 3, 7, 10, and 14. Result: Indicated Cornisol adequately preserved the cornea for up to 14 days in storage. 2. Comparison study with Optisol-GS (predicate) on donor corneas. Immunostaining for structural integrity (ZO-1, Phalloidin) and functionality (Na+/K+ ATPase). Result: Cornisol had similar performance in preserving cell structural integrity and functionality. |
| Shelf-Life: 12 months. | Met: Shelf life of 12 months when stored at 2℃ to 8℃. |
| Packaging Integrity: Maintain sterile barrier. | Met: Tested on every batch of components (vial and caps) by dye ingress/egress vacuum testing. Finished product also tested using inverted vacuum challenge testing. Confirmed ability to maintain sterile barrier. |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set Sample Size:
- Study 1 (Prospective, in vitro, randomized): "paired donor corneas" - The exact number is not specified in the provided text.
- Study 2 (Comparison with Optisol-GS): "donor corneas" - The exact number is not specified.
- Data Provenance: The studies were "in vitro," implying lab studies using donated human corneas. The country of origin for the donor corneas is not specified. It is retrospective in the sense that they are studying the effect on previously donated corneas, but the study design (e.g., "prospective, in vitro, randomized") refers to the execution of the experimental work.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This is not applicable as this is a biochemical/biophysical product evaluation, not an AI diagnostic device. Ground truth is established by objective measurements (e.g., endothelial cell counts, protein expression via immunostaining) on the preserved corneas, not by expert interpretation of images.
4. Adjudication Method for the Test Set
Not applicable for this type of product testing. The "ground truth" is measured objectively.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, this type of study is for diagnostic AI devices involving human interpretation of medical images. Cornisol is a storage solution.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Not applicable. There is no AI algorithm.
7. The Type of Ground Truth Used
The ground truth for the performance evaluation was based on objective biological and physical measurements from ex-vivo human corneas after storage. These included:
- Endothelial cell loss
- Endothelial cell density (ECD)
- Coefficient of variance of endothelial cells
- Percentage hexagonality of endothelial cells
- Immunostaining for markers of structural integrity (ZO-1, Phalloidin)
- Immunostaining for markers of functionality (Na+/K+ ATPase)
8. The Sample Size for the Training Set
Not applicable. There is no AI model being trained. The "training" for this product type involves R&D and formulation optimization, not data-driven machine learning.
9. How the Ground Truth for the Training Set was Established
Not applicable.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
October 5, 2022
Aurolab % Sean Griffin President Allied Regulatory Consulting 1540 Keller Parkway, Suite 108 #170 Keller, Texas 76248
Re: K221759
Trade/Device Name: Cornisol Regulatory Class: Unclassified Product Code: LYX Dated: July 6, 2022 Received: July 11, 2022
Dear Sean Griffin:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's 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
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devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
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/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Anjana Jain, PhD Assistant Director DHT1A: Division of Ophthalmic Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K221759
Device Name Cornisol
Indications for Use (Describe)
Cornisol is a corneal storage solution for storage of human cornea suitable for keratoplasty for up to 14 days under refrigeration (2-8°C)
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
This 510(k) summary has been prepared in accordance with 21 CFR 807.92.
Submitter
- Aurolab No.1, Sivagangai Main Road Veerapanjan Madurai, 625020 Tamil Nadu India Registration Number: 9710098 FEI Number: 3002957101
Application Correspondent:
Sean Griffin President Allied Regulatory Consulting 1540 Keller Parkway, Suite 108 #170 Keller, TX 76248 Phone: (817) 805-8392
Date Prepared: September 30, 2022
Device
Device Subject to this 510(k):
| Trade Name: | Cornisol |
|---|---|
| Common Name: | Hypothermic corneal storage media |
| Product Code: | LYX (Media, Corneal Storage) |
| Classification: | Unclassified |
Predicate Device
- Optisol-GS Corneal Storage Media (Product Code: LYX Media, Corneal K924165 Storage; Regulation: Unclassified)
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K221759 / PAGE 2 OF 6
Device Description
Cornisol is a sterile hypothermic corneal storage medium intended for human corneal storage between 2 and 8℃ for up to 14 days. Cornisol is for single use and to be used only by physicians or highly skilled personnel such as eye bank operators. Corneas are directly placed in Cornisol medium after surgery with a storage time based on the time needed to obtain serology results of the donor but for a period of time of no more than 14 days.
Cold storage of cornea is traditionally performed by keeping corneas in a cold storage medium containing deswelling agent(s) between 2°C and 8°C.
Indications for Use
CORNISOL is a corneal storage solution for storage of human cornea suitable for keratoplasty for up to 14 days under refrigeration (2-8°C).
Physical and Performance Characteristics
CORNISOL is a sterile, buffered corneal preservation medium comprised of the ingredients shown in Table 1. It is supplied ready to use with a volume of 20 mL in a 20 mL type 1 glass vial with a polyethylene cap and PVC shrink wrap.
| Ingredient | Function |
|---|---|
| Chondroitin Sulphate | Osmotic agent/membrane stabilizer |
| Dextran 40 | Osmotic agent |
| HEPES Buffer | To maintain pH |
| Sodium Pyruvate | Energy source for endothelial cellviability |
| Gentamycin | Antibiotic |
| Streptomycin | Antibiotic |
| Sodium Bicarbonate | pH adjustment |
| Medium 199 | Nutrient and electrolyte |
| Minimum Essential Medium | Nutrient and electrolyte |
| Glutamax i200 | Energy production and helps preventdegradation |
| Vitamin B12 | Cofactor for enzymatic reactions andmembrane stabilizing agent |
| Phenol Red Indicator | pH indicator |
| Recombinant Human Insulin | Cell metabolism enhancer |
| Purified Water IP | Vehicle |
Table 1: Cornisol ingredients and their function
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Comparison of Technological Characteristics with the Predicate Device
Cornisol has similar technological characteristics as the predicate device (Table 2). Cornisol and the predicate device use Dextran as a deswelling agent. Cornisol and its predicate are provided sterile, are intended for single use and are provided in glass vials.
| Features andCharacteristics | Proposed DeviceCornisol | PredicateOptisol-GS(K924165) | Comparison ofProposed Deviceand PredicateFeatures |
|---|---|---|---|
| Intended Use | Hypothermic cornealstorage | Hypothermic cornealstorage | Same |
| Indications foruse | CORNISOL is a cornealstorage solution forstorage of human corneasuitable for keratoplastyfor up to 14 days underrefrigeration (2-8°C). | OPTISOL is abiocompatible, enhancedtissue culture media forstorage of human corneassuitable for keratoplastyfor up to 14 days underrefrigeration (2 - 8°C). | Same |
| Description | Sterile solution | Sterile solution | Both are sterilesolutions |
| TargetPopulation | Cornea for keratoplasty | Cornea forkeratoplasty | Same |
| Where used | Eye bank, hospital | Eye bank, hospital | Same |
| Energy used | Refrigeration at 2 to 8°C | Refrigeration at 2 to 8°C | Same |
| Design | Single use glass vials | Single use glass vials | Similar design(single use vials) |
| Packaging/How Supplied | Glass vial with screwcap top | Glass vial with screw captop | Similar packaging(glass vial withscrew top cap) |
| Key Ingredients | Dextran and chondroitinsulfate as osmotic agentsand gentamycin andstreptomycin asantibiotics | Dextran and chondroitinsulfate as osmotic agentsand gentamycin andstreptomycin asantibiotics | Both contain dextranand chondroitinsulfate as osmoticagents andgentamycin andstreptomycin asantibiotics |
| Sterility | Sterile | Sterile | Both are providedsterile |
| Performance | Demonstrated to beequivalent to predicatedevice at storing corneasfor up to 14 days whenstored at 2 to 8°C | 510(k) cleared for thestorage of corneas for upto 14 days when stored at2 to 8°C | Substantiallyequivalent topredicate device |
Table 2: Comparison between Cornisol and Predicate Device
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K221759 / PAGE 4 OF 6
Performance Data
Cornisol has undergone various testing including physicochemical testing, microbiological testing, sterilization validation, stability (shelf-life), packaging integrity testing as well as biocompatibility and in vitro testing.
Chemical characterization to assess the biocompatibility profile of the corneal storage media and primary packaging was conducted. The selected ingredients are commonly used in corneal storage media and no novel ingredients were selected. Cornisol is a buffered corneal preservation medium that includes additives like buffering agents, osmotic agents and pH adjusters/indicators, and there are no residues and process contaminants present in the solution. In addition, Cornisol does not contain polymers, ceramics and metals in the formulation that would produce degradation products of this nature.
Cornisol is a solution that is manufactured and sterilized by sterile filtration using 0.2 micron polyether sulphone membrane filters. The filters have been validated for aqueous extracts to exhibit < 0.25 EU/ml as established by Limulus Amebocyte Lysate (LAL) testing per USP<85>. A finished product endotoxin specification for Cornisol of 5 EU/device has been established and batch results confirm that Cornisol conforms with this specification.
Although Cornisol solution is sterilized by sterile filtration, the vial caps are sterilized by ethylene oxide (EO). The average daily exposure of EO to a patient shall not exceed 1.25 ug/device for EO and 5 µg/device for ECH (4 times EO limit), in compliance with the limits for IOLs in the ANSI/AAMI/ISO 10993-7:2008(R)2012 (Table C.1 in Annex C) standard. The shelf life for Cornisol is 12 months when stored at 2℃ to 8℃.
Package integrity testing is performed on every batch of packaging components (vial and caps) for Cornisol by dye ingress/egress vacuum testing to ensure that the components can maintain the sterile barrier. In addition, each batch of Cornisol finished product is also tested using inverted vacuum challenge testing. Representative samples of packaging components have been tested and these results confirm ability to maintain the sterile barrier.
In addition, biocompatibility testing of Cornisol has been conducted.
- Cytotoxicity in accordance with ISO 10993-5 .
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- Sensitization in accordance with ISO 10993-10 .
- . Acute ocular irritation testing in accordance with ISO 10993-10
The Cornisol formulation was tested in two in vitro studies. The first was a prospective, in vitro, randomized study using paired donor corneas was performed. The assessments to determine equivalent performance were endothelial cell loss, endothelial cell density (ECD), coefficient of variance, and percentage hexagonality on days 3, 7, 10, and 14. The results indicated that Cornisol adequately preserved the cornea for up to 14 days in storage. The second study was on donor corneas to compare the structural and functional integrity of the donor corneas following storage in Cornisol or Optisol-GS. Corneas were immunostained for markers of structural integrity (ZO-1, Phalloidin) and functionality (Na+/K+ ATPase). The results indicated that Cornisol had similar performance in preserving cell structural integrity and functionality.
Conclusion
Cornisol is substantially equivalent to the predicate device, Optisol-GS. There are not different questions of safety and effectiveness with respect to the intended use and technologically characteristics between Cornisol and the predicate device.
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