PRIME-XV FreezIS DMSO-Free MD

K231804 · Fujifilm Irvine Scientific · NDS · Nov 9, 2023 · Gastroenterology, Urology

Device Facts

• Record ID: K231804
• Device Name: PRIME-XV FreezIS DMSO-Free MD
• Applicant: Fujifilm Irvine Scientific
• Product Code: NDS · Gastroenterology, Urology
• Decision Date: Nov 9, 2023
• Decision: SESE
• Submission Type: Abbreviated
• Regulation: 21 CFR 876.5885
• Device Class: Class 2

Intended Use

PRIME-XV FreezIS DMSO-Free MD is for use in human ex vivo tissue and cell culture processing applications.

Device Story

PRIME-XV FreezIS DMSO-Free MD is a chemically defined, serum-free, animal component-free liquid medium used for cryogenic preservation of human cells. It functions as a cryoprotectant (CPA) to protect cells from osmotic changes and ice crystal formation during freezing at -80°C to -196°C. Used in professional healthcare facilities by laboratory personnel, the medium maintains cell viability and potency post-thaw, serving as an alternative to DMSO-containing solutions to avoid potential DMSO-induced epigenetic changes. Healthcare providers use the medium to preserve cells for ex vivo processing; the output is preserved cell samples suitable for subsequent therapeutic or research applications. The device benefits patients by providing a DMSO-free preservation environment, potentially reducing risks associated with DMSO exposure in cell therapy.

Clinical Evidence

Bench testing only. Performance validated through cell culture assays demonstrating high post-thaw cell viability, robust cell expansion, and maintenance of cell function, phenotype, and differentiation potential. Stability testing confirmed 24-month shelf life at 2–8°C with maintained pH and osmolality. Purity verified via endotoxin (0.0–1.0 EU/mL) and mycoplasma testing per USP standards.

Technological Characteristics

Serum-free, chemically defined liquid medium. Contains amino acids, energy sources, macromolecules, and a proprietary cryoprotectant. Sterile filtered and aseptically filled. pH 6.4–8.0; osmolality 300–380 mOsm/kg. Storage 2–8°C. Animal component-free; does not contain human serum albumin.

Indications for Use

Indicated for use in human ex vivo tissue and cell culture processing applications, specifically for the cryogenic preservation of human cells in a professional healthcare facility.

Regulatory Classification

Identification

Tissue culture media for human ex vivo tissue and cell culture processing applications consist of cell and tissue culture media and components that are composed of chemically defined components (e.g., amino acids, vitamins, inorganic salts) that are essential for the ex vivo development, survival, and maintenance of tissues and cells of human origin. The solutions are indicated for use in human ex vivo tissue and cell culture processing applications.

Special Controls

*Classification.* Class II (special controls): FDA guidance document, “Class II Special Controls Guidance Document: Tissue Culture Media for Human Ex Vivo Processing Applications; Final Guidance for Industry and FDA Reviewers.”

Predicate Devices

• AIM-V® Medium (K022086)
• CT-STOR medium for ex vivo cell preservation (K201789)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, 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.

November 9, 2023

Fujifilm Irvine Scientific Amanda Cinquin Regulatory Affairs Manager, Life Science 1830 E. Warner Ave Santa Ana. California 92705

## Re: K231804

Trade/Device Name: PRIME-XV FreezIS DMSO-Free MD Regulation Number: 21 CFR 876.5885 Regulation Name: Tissue Culture Media For Human Ex Vivo Tissue And Cell Culture Processing Applications Regulatory Class: Class II Product Code: NDS Dated: October 6, 2023 Received: October 6, 2023

Dear Amanda Cinquin:

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 (the 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 available at https://www.accessdata.fda.gov/scripts/cdrb/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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

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## K231804 - Amanda Cinquin

(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.70) and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE(@fda.hhs.gov) or phone [phone] or 301-796-7100).

Sincerely,

Digitally signed by Maura
Maura Rooney Rooney -S
-S
Date: 2023.11.09 08:59:43
-05'00'

Maura Rooney Assistant Director DHT3A: Division of Renal, Gastrointestinal. Obesity and Transplant Devices OHT3: Office of Gastrorenal, ObGyn,

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General Hospital, and Urology Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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# Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: 07/31/2026 See PRA Statement below.

Submission Number (if known)

K231804

Device Name

PRIME-XV FreezIS DMSO-Free MD

Indications for Use (Describe)

PRIME-XV FreezIS DMSO-Free MD is for use in human ex vivo tissue and cell culture processing applications.

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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Image /page/4/Picture/0 description: The image shows the Fujifilm logo. The logo is black with a red accent in the middle of the word. Below the logo is the text "Value from Innovation".

FUJIFILM Irvine Scientific, Inc. 1830 East Warner Avenue Santa Ana, CA 92705-5505 800 437 5706 | 949 261 7800 | Fax: [phone] www.irvinesci.com

#### 510(k) Summary

| Submitter: | FUFJIFILM Irvine Scientific, Inc. |
|------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Address: | 1830 E. Warner Avenue,<br>Santa Ana, CA 92705. USA<br>Phone: [phone] |
| Contact Person: | Amanda Cinquin |
| Date of Preparation: | 05/20/2023 |
| Trade Name: | PRIME-XV FreezIS DMSO-Free MD |
| Common Name: | Culture Media |
| Classification Name: | Media, Culture, ex vivo, Tissue and Cell |
| Regulation Name: | Tissue culture media for human ex vivo tissue and cell culture<br>processing applications |
| Regulatory Class: | II |
| Product Code: | NDS |
| Regulation Number: | 21 CFR 876.5885 |
| Panel: | Gastroenterology/Urology |
| Legally Marketed Devices for<br>Substantial Equivalence<br>Comparison: | AIM-V® Medium, Invitrogen Corporation,<br>510(k) K022086 Invitrogen Corporation.<br>CT-STOR medium for ex vivo cell preservation, Energy Delivery<br>Solutions,<br>510(k) K201789 Energy Delivery Solutions. |

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### Device Description:

PRIME-XV Freez/S DMSO-Free MD is a liquid medium intended for use in human ex vivo tissue and cell culture processing applications.

It is a chemically defined cryogenic preservation solution for human cells for use in a professional Healthcare Facility that performs cell culture and cell handling. It has comparable post-thaw cell viability as solutions containing dimethyl sulfoxide (DMSO), maintains potency of stem cells throughout cryopreservation, eliminates the risk of DMSO in stem cell therapy applications, is animal componentfree, enables cell preservation at -80°C to -196°C environments and is manufactured under cGMP conditions.

#### Intended Use:

PRIME-XV Freez S DMSO-Free MD is for use in human ex vivo tissue and cell culture processing applications.

#### Indications for Use:

Indications for use are the same as the intended use.

#### Technological Characteristics:

PRIME-XV FreezIS DMSO-Free MD was developed in 2014 and is a serum-free medium with a defined formulation. PRIME-XV FreezIS DMSO-Free MD, and predicates AIM-V® and CT-STOR, are for use in human ex vivo tissue and cell culture processing applications. They are chemically defined tissue culture media used to support the growth or maintenance of human tissue or cells in culture.

AIM-V® is a cell culture medium that is used for expansion of cells. PRIME-XV FreezIS DMSO-Free MD and CT-STOR support cells for ex vivo preservation, in the case of PRIME-XV Freez!S DMSO-Free MD, preservation is cryogenic.

PRIME-XV FreezIS DMSO-Free MD, AIM-V® and CT-STOR are formulated based on cell requirements for amnio acids, salts, and other components required for ex vivo maintenance of cells and tissues.

AIM-V® is supplemented with human serum albumin, which is known to be fractionated from plasma still bound to many components that are important for cell growth and maintenance. PRIME-XV Freez!S DMSO-Free MD is chemically defined and human- and animal-derived component free and does not include human serum albumin. Therefore, it also contains in the formulation components that are needed for cell growth and maintenance that would normally be provided by the addition of human serum albumin.

PRIME-XV FreezIS DMSO-Free MD contains a cryoprotectant (CPA) to preserve cells under cryogenic storage. The CPA acts to protect the cells from osmotic changes or ice crystal formation. Common CPA dimethyl sulfoxide (DMSO) is a small molecule penetrating CPA that acts by entering the cell and preserving it by reducing ice crystal formation during freeing and by regulating salt concentration. However, DMSO has been shown to have some negative effects such as inducing epigenetic changes in cells [Murray & Gibson, 2022, Nature Reviews Chemistry 6, 579-593]. Therefore, PRIME-XV Freez!S DMSO-

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Free MD was developed with a proprietary CPA as an alternative to DMSO, but that has comparable performance.

The specifications for PRIME-XV FreezlS DMSO-Free MD are substantially equivalent to AIM-V® including pH, osmolality and storage temperature.

A comparison of device technology between PRIME-XV FreezlS DMSO-Free MD and AIM-V® is listed in the table below.

| Description | PRIME-XV FreezIS DMSO-Free MD | Primary Predicate AIMV® K022086 |
|--------------------------------------|----------------------------------------------------------------------------------------------------------|---------------------------------|
| Intended Use | Liquid tissue culture product<br>intended for ex vivo tissue and cell<br>culture processing applications | Same as subject |
| Prescription/over the<br>counter use | Prescription | Same as subject |
| Constituents | Amino acids, energy source,<br>macromolecules to support cell<br>growth and maintenance | Same as subject |
| Additional components<br>included | Cryoprotectant | Human serum albumin |
| Sterility | Sterile filtered, aseptically filled,<br>sterility release test | Same as subject |
| Presence of serum | Serum-free | Same as subject |
| Storage | 2 – 8 °C | Same as subject |
| Stability | 24 months | 14 months |

A comparison of device specification between PRIME-XV FreezIS DMSO-Free MD and AIM-V® is listed in the table below.

| | Specification | |
|--------------------|-------------------------------|----------------------------------|
| Test | PRIME-XV FreezIS DMSO-Free MD | Primary Predicate AIM-V® K022086 |
| Performance assay | PASS (cell culture assay) | Same as subject |
| Endotoxin testing | 0.0 - 1.0 EU/mL | Same as subject |
| Mycoplasma | PASS | Same as subject |
| pH | 6.4 - 8.0 | 6.8 - 7.3 |
| Osmolality mOsm/kg | 300 - 380 | 310 - 340 |
| Sterility | PASS | Same as subject |

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#### Performance Testing:

#### Performance Standards

Special Controls identified in the FDA document, "Tissue Culture Media for Human ex vivo Tissue and Cell Culture Processing Applications – Final Class II Special Controls Guidance Document for Industry and FDA Reviewers" are addressed in the table below.

| Special Control Objective | PRIME-XV FreezIS DMSO-Free MD |
|---------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------|
| Demonstrate lack of potential toxicity of<br>materials in the media to cells or tissue and<br>demonstrate support of tissue and cell growth | High cell viability, robust cell expansion post-<br>cryopreservation, maintenance of cell function,<br>phenotype and differentiation potential. |
| Demonstrate lack of endotoxin or pyrogen<br>contamination | Endotoxin testing per USP <85>, mycoplasma<br>testing per USP <63> |
| Validation of Aseptic Processing and Sterility<br>Assurance Level (SAL) | Compliance with GMP requirements regarding<br>aseptic processing. |
| Demonstrates chemical purity | Incoming raw materials are of high quality and are<br>lot-tested for identity and purity. |

#### Stability/Shelf Life

Based on analysis of product performance over time, a 24-month shelf life has been established for PRIME-XV Freez!S DMSO-Free MD when stored at 2 – 8 °C. Stability testing involved the assessment of functional aspects of the media to demonstrate that pH and osmolality were maintained, demonstrating that the media was not chemically altered during storage, and that the media was not cytotoxic and continued to maintain cells at high viability and to support cell expansion post-thaw. In addition, pyrogen and sterility testing confirmed that the container/closure provided protection against microbial contamination during storage.

#### Conclusions

PRIME-XV FreezIS DMSO-Free MD, AIM-V® and CT-STOR are used for human ex vivo tissue and cell culture processing applications and have substantially the same technological characteristics, efficacy (generic cell growth and maintenance; post-cryopreservation cell growth is substantially equivalent to AIM-V®) and safety (consistency in chemical content and formulation, biocompatibility with cells, and purity). The efficacy of PRIME-XV FreezIS DMSO-Free MD in supporting the survival, growth, development and/or maintenance of human cells or tissue culture systems has been well established in data and scientific publication included in this submission. PRIME-XV FreezIS DMSO-Free MD, AIM-V® and CT-STOR are manufactured in accordance with QSR requirements and are labeled as aseptically processed. Thus PRIME-XV FreezIS DMSO-Free MD is substantially equivalent to the legally marketed predicate devices

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intended for human ex vivo tissue and cell culture processing applications.