KNOCKOUT SR MEDIUM, KNOCKOUT SR XENOFREE MEDIUM MODEL 10828, 12618

K100616 · Life Technologies Corporation · NDS · May 20, 2010 · Gastroenterology, Urology

Device Facts

• Record ID: K100616
• Device Name: KNOCKOUT SR MEDIUM, KNOCKOUT SR XENOFREE MEDIUM MODEL 10828, 12618
• Applicant: Life Technologies Corporation
• Product Code: NDS · Gastroenterology, Urology
• Decision Date: May 20, 2010
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 876.5885
• Device Class: Class 2

Intended Use

Knockout™ SR Medium and Knockout™ SR Xenofree Medium are liquid tissue culture media product intended for human ex vivo tissue and cell culture processing applications.

Device Story

Knockout™ SR and Knockout™ SR Xenofree are liquid, serum-free tissue culture media; used for ex vivo processing, growth, and maintenance of human embryonic stem cells (ESC) and patient-specific induced pluripotent stem cells (iPSCs). Knockout™ SR contains defined nutrient materials; Knockout™ SR Xenofree replaces animal-derived components with human-derived or synthetic alternatives. Media are used in laboratory settings by trained personnel to provide consistent growth conditions. Products are stored at 2°C-8°C; shelf life is 14 months. Efficacy is demonstrated by cell morphology, plate efficiency, and colony formation. Benefits include reduced differentiation compared to fetal bovine serum and consistent, defined formulation for cell culture applications.

Clinical Evidence

Bench testing only. Performance validated against Class II Special Controls Guidance Document. Testing included: ES cell morphology, relative plate efficiency, and relative type 1 colonies to demonstrate growth support and lack of toxicity; LAL testing (USP <85>) for endotoxin/pyrogen levels; sterility assurance level (SAL) ≥ 10^-3; and raw material purity testing per USP, ACS, FCC, and GIBCO standards. Stability testing confirmed pH maintenance, lack of cytotoxicity, and container/closure integrity over 14-month shelf life.

Technological Characteristics

Liquid, serum-free, chemically defined tissue culture media. Knockout™ SR Xenofree is animal-origin-free. Sterilized via aseptic processing. Storage: 2°C-8°C. Raw materials tested per USP, ACS, FCC, and GIBCO standards. No electronic components or software.

Indications for Use

Indicated for human ex vivo tissue and cell culture processing applications to support the growth or maintenance of human tissue or cells in culture.

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 (K022080)

Submission Summary (Full Text)

{0}------------------------------------------------

K100616
163

# 510 (k) Summary

MAY 2 0 2010

Life Technologies Corporation - Knockout™ SR Medium and Knockout™ SR Xenofree Medium

| Device Name: | KnockoutTM SR Medium<br>KnockoutTM SR Xenofree Medium |
|----------------------|-------------------------------------------------------------------------------------------------------------------------|
| Common/Usual Name: | KSR<br>KSR Xenofree |
| Classification Name: | Tissue culture media for human <i>ex vivo</i> tissue and cell<br>culture processing applications (per 21 CFR § 876.5885 |
| Product Code: | NDS |
| Submitter: | Life Technologies Corporation<br>3175 Staley Road<br>Grand Island, New York 14072 |
| Telephone: | [phone] |
| Facsimile: | [phone] |
| Email: | [e-mail] |
| Contact: | Kelli Tanzella, Ph.D. |
| Date Prepared: | March 01, 2010 |

| Trade Name | Manufacturer | 510(k) |
|---------------|--------------------------------------------------------------------|---------|
| AIM-V® Medium | Life Technologies Corporation<br>(formerly Invitrogen Corporation) | K022080 |

### Intended Use

Knockout™ SR Medium and Knockout™ SR Xenofree Medium are liquid tissue culture media product intended for human ex vivo tissue and cell culture processing applications.

## Substantial Equivalence

AIM-V® Medium is the predicate device for tissue culture media intended for human ex vivo tissue and cell culture processing applications. It is composed of chemically defined nutrient materials in solution (with or without supplements) that are essential for the survival and development of tissue or cells of human or other animal origin. These nutrients are provided in liguid form for use in supporting the growth or maintenance of human tissue and cells.

{1}------------------------------------------------

Page 2 510(k) Summary - Life Technologies Knockout™ SR Medium and Knockout™ SR Xenofree Medium

#### A. Intended Uses

Knockout™ SR Medium and Knockout™ SR Xenofree Medium and AIM-V® Medium tissue culture products are intended for human ex vivo tissue and cell culture processing applications. These devices are chemically defined tissue culture media used to support the growth or maintenance of human tissue or cells in culture.

# B. Principles of Operation and Technological Characteristics

# Knockout™ SR

Knockout™ SR is a serum-free medium with a defined formulation that provides consistent growth conditions for human and mouse embryonic stem cell (ESC) and patient-specific induced pluripotent cell lines (iPSCs). Both ESC and iPSC grown in Knockout™ SR supplemented media are substantially less differentiated than those grown in fetal bovine serum (FBS) supplemented media. This media was introduced in 1998 and there are over 300 literature references to Knockout™ SR.

# Knockout™ SR Xenofree

Knockout "M SR Xenofree is a serum-free and animal origin-free defined formulation that provides consistent growth conditions for human and mouse embryonic stem cell (ESC) and patient-specific induced pluripotent cell lines (iPSCs). All animal derived components have been replaced with human derived or synthetic components to yield a xenogeneic-free formulation. This media was developed and marketed in 2008.

# C. Pre-clinical Testing

#### Performance Standards

Performance standards under Section 514 of the Federal Food, Drug, and Cosmetic Act have been established in Guidance Document "Class II Special Controls Guidance Document: Tissue Culture Media for Human Ex Vivo Tissue and Cell Culture Processing Applications: Final Guidance for Industry and FDA Reviewers," issued May 16, 2001. The specific assay tests and Life Technologies Corporation's equivalent tests that were conducted are identified in the table below.

{2}------------------------------------------------

K100616
313

### Page 3 1 age 3
5 10(k) Summary - Life Technologies Knockout™ SR Medium and Knockout™ SR Xenofree Medium

| Special Control Objective | Life Technologies Corporation<br>KnockoutTMSR Medium |
|------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------|
| Demonstrate lack of potential<br>toxicity of materials in the media to<br>cells or tissue and demonstrate<br>support of tissue and cell growth | ES Cell Morphology, relative plate<br>efficiency, and relative type 1<br>colonies |
| Demonstrate lack of endotoxin or<br>pyrogen contamination | Limulus Ameobocyte (LAL) test (25<br>USP Monograph <85>) |
| Validation of Aseptic Processing and<br>Sterility Assurance Level (SAL) | Determination of SAL to be ≥ $10^{-3}$ compliance with<br>GMP requirements regarding aseptic processing |
| Demonstrates Chemical purity | Incoming Raw Material testing using USP, ACS,<br>FCC, GIBCO, or Cell Culture requirements. |

# Stability/Shelf Life

Based on analysis of product performance over time, Life Technologies Corporation has established a shelf life of 14-months for Knockout™ SR Medium and Knockout™ SR Xenofree Medium formulations, when stored between 2°C-8°C. Stability testing involved the assessment of these functional aspects of media, including demonstrating: ( ) that the pH continued to meet specifications; and (2) the media was not cytotoxic and supported the growth of mammalian cells. The pH was tested to demonstrate that the media was not chemically altered during its storage. In assessing cytoxicity/biocompatibility, Life Technologies Corporation demonstrated that the media functions in supporting the growth of mammalian cells and that the media does not become toxic to mammalian cells during storage. In addition, results from container/closure integrity testing have demonstrated that the container/closure system provides protection from microbial contamination.

# D. Conclusion

Knockout™ SR Medium and Knockout™ SR Xenofree Medium and AIM-V® Medium are used for human ex vivo tissue and cell culture processing applications and have the same principles of operation, technological characteristics, efficacy (generic cellular growth and maintenance) and safety (consistency in chemical content and formulation, biocompatibility with cells, and purity). Their efficacy in supporting the survival, growth, development, and maintenance of human cells or tissue culture systems has been well established in scientific publications included in this submission. These products (Knockout 10) SR Medium and Knockout™ SR Xenofree Medium and AIM-V® Medium) are manufacturer in accordance with QSR requirements and are labeled as aseptically processed. Thus, Knockout™ SR Medium and Knockout™ SR Xenofree Medium are substantially equivalent to the legally marketed device intended for the human ex vivo tissue and cell culture processing applications.

{3}------------------------------------------------

Image /page/3/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of two main elements: the department's seal and the agency's symbol. The seal is a circular emblem with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. The symbol is a stylized depiction of an eagle, with three lines representing the bird's body and wings.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-G60 Silver Spring, MD 20993-0002

Kelli L. Tanzella, Ph.D. Senior Manager, Americas Regulatory Affairs Life Technologies . 3175 Staley Road GRAND ISLAND NY 14072

MAY 2 0 2010

Re: K100616

Trade/Device Name: Knockout™ SR Medium

Knockout™ SR Xenofree Medium

Regulation Number: 21 CFR \$876.5885

Regulation Name: Tissue culture media for human ex vivo tissue and cell culture processing applications

Regulatory Class: II Product Code: NDS Dated: March 4, 2010 Received: March 4, 2010

Dear Dr. Tanzella: .

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 of medical device-related

{4}------------------------------------------------

Page 2 -

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 go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Janine M. Morris

Acting Director, Division of Reproductive. Abdominal, and Radiological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

{5}------------------------------------------------

510(k) Number (if known):

K100616

Device Name: Knockout™ SR Medium Knockout™ SR Xenofree Medium

# Indications for Use:

Knockout™ SR Medium and Knockout™ SR Xenofree Medium are liquid tissue culture medium products intended for human ex vivo tissue and cell culture processing applications.

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHRE PAGE IF NEEDED)

Concurrence of CDRH, Office of Evaluation (ODE)

Prescription Use ***_***_
(Per 21 CFR 801.109)

OR

Over-The --Cour
(Optional Forma

(Division Sign-Off)
Division of Reproductive, Abdominal and
Radiological Devices

510(k) Number

Over-The --Counter Use (Optional Format 1-2-96)