(202 days)
OpTmizer™ CTS™ T-Cell Expansion SFM is a liquid tissue culture media product intended for human ex vivo tissue and cell culture processing applications.
OpTmizer™ CTS™ T-Cell Expansion SFM has been developed for the growth and expansion of human T lymphocytes. OpTmizer™ CTS™ T-Cell Expansion SFM is a complete serum-free and xeno-free 1X medium consisting of the OpTmizer™ T-Cell Expansion Basal Medium with the addition of the OpTmizer™ T-Cell Expansion Supplement. OpTmizer™ CTS™ T-Cell Expansion Medium is designed for the expansion of CD3+ densities of > 3 x 10° cells/mL in static conditions and > 2 x 10′ cells/ML in Wave bags.
Acceptance Criteria and Device Performance Study for OpTmizer™ CTS™ T-Cell Expansion SFM
Based on the provided 510(k) summary (K113566), the OpTmizer™ CTS™ T-Cell Expansion SFM is a tissue culture medium intended for human ex vivo tissue and cell culture processing applications. The device's performance is demonstrated through pre-clinical testing aligning with the "Class II Special Controls Guidance Document: Tissue Culture Media for Human Ex Vivo Tissue and Cell Culture Processing Applications".
1. Table of Acceptance Criteria and Reported Device Performance
| Special Control Objective (Acceptance Criteria) | Life Technologies Corporation OpTmizer™ CTS™ T-Cell Expansion SFM (Reported Device Performance) |
|---|---|
| Demonstrate lack of potential toxicity of materials in the media to cells or tissue | OpTmizer QC Performance Assay (demonstrates support of tissue and cell growth and non-toxicity during storage) |
| Demonstrate support of tissue and cell growth | OpTmizer QC Performance Assay (demonstrates support of tissue and cell growth and non-toxicity during storage) |
| Demonstrate lack of endotoxin or pyrogen contamination | Limulus Ameobocyte (LAL) test (25 USP Monograph <85>) |
| Validation of Aseptic Processing and Sterility Assurance Level (SAL) | Determination of SAL to be ≥ 10⁻³; compliance with GMP requirements regarding aseptic processing |
| Demonstrate Chemical purity | Incoming Raw Material testing using USP, ACS, FCC, GIBCO, or Cell Culture requirements |
| Stability/Shelf-Life: pH continues to meet specifications | pH is tested to demonstrate that the media is not chemically altered during storage. |
| Stability/Shelf-Life: Media is not cytotoxic and supports the growth of mammalian cells during storage | Assessed through functional aspects of media, demonstrating the media functions in supporting the growth of mammalian cells and does not become toxic during storage. |
| Container/closure system provides protection from microbial contamination (Stability/Shelf-Life) | Results from studies indicate the container/closure system provides protection from microbial contamination. |
| Expansion of CD3+ T lymphocytes | > 3 x 10⁶ cells/mL in static conditions and > 2 x 10⁷ cells/ML in Wave bags. |
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state a specific "test set" sample size in terms of number of human subjects or distinct samples for the OpTmizer™ CTS™ T-Cell Expansion SFM. The pre-clinical testing outlined refers to:
- OpTmizer QC Performance Assay: This assay would involve specific sample sizes of cells or tissues tested under defined conditions. The exact number is not provided.
- LAL test: This is a standard test for endotoxins and would be performed on samples of the manufactured medium. The specific number of lots or samples tested is not detailed.
- Sterility Assurance Level (SAL): This is a validation process typically involving multiple sterilization cycles and microbiological challenging, not a "sample size" in the conventional sense of a clinical study.
- Incoming Raw Material testing: This is a quality control process for the components of the medium.
- Stability/Shelf-Life testing: This involves testing "a minimum of one new production lot of OpTmizer™ CTS™ T-Cell Expansion SFM" each year. Retained product stored at 2-8°C is also tested (no specific number of retained lots specified).
The data provenance is not explicitly stated as retrospective or prospective in the context of a "study" involving human data. Instead, it refers to ongoing quality control and product development testing within Life Technologies Corporation. The data originates from internal company testing and adherence to established regulatory and scientific methodologies for tissue culture media. There is no mention of country of origin for the data as it pertains to clinical data, but the manufacturing facility is in Grand Island, New York, implying internal testing would be conducted within the US or its affiliated labs.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This information is not applicable and not provided. The "ground truth" for this device is based on established scientific and regulatory standards for biocompatibility, sterility, chemical purity, and functional performance of tissue culture media. There is no mention of external "experts" establishing a "ground truth" for a test set in the way one would for diagnostic imaging. Rather, the device's performance is validated against predefined technical specifications and regulatory guidelines.
4. Adjudication Method for the Test Set
This information is not applicable. Adjudication methods (e.g., 2+1, 3+1) are typically used in studies where human interpreters are assessing and classifying data, and disagreements need to be resolved. This is not a human-in-the-loop diagnostic device requiring such an adjudication process.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for diagnostic devices that involve human interpretation of results, often with AI assistance, and aims to measure the improvement in human performance. The OpTmizer™ CTS™ T-Cell Expansion SFM is a consumable tissue culture medium, not a diagnostic or AI-assisted interpretation tool.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, the testing described is effectively "standalone" performance, as it evaluates the properties and functionality of the medium itself without human intervention in operating the device for its core function. The "device" (the medium) performs its function (supporting cell growth, sterility, etc.) inherently. The performance is assessed by laboratory assays and quality control measures.
7. The Type of Ground Truth Used
The "ground truth" for this device is based on objective laboratory measurements and established scientific and regulatory standards. This includes:
- Cell growth and viability metrics: Quantifiable measures of cell expansion (e.g., cell counts, viability percentages), functionality, and lack of cytotoxicity as measured by the OpTmizer QC Performance Assay.
- Microbiological testing: Absence of endotoxins (LAL test) and demonstration of sterility (SAL determination).
- Chemical purity specifications: Conformance to USP, ACS, FCC, GIBCO, or Cell Culture requirements for raw materials.
- pH specifications: Maintaining pH within a defined range over time.
- Container/closure integrity: Absence of microbial contamination.
There is no "expert consensus," "pathology," or "outcomes data" in the clinical sense directly establishing a ground truth for the medium itself, as it is a foundational research/manufacturing material rather than a diagnostic or therapeutic medical device applied directly to patients where clinical outcomes are the primary ground truth.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of machine learning or AI. The development of OpTmizer™ CTS™ T-Cell Expansion SFM involved research and development, where various formulations and conditions would have been tested to optimize its performance ("OpTmizer™ CTS™ T-Cell Expansion SFM has been developed for the growth and expansion of human T lymphocytes"). This iterative development process would have involved numerous experiments and data points, but these are not quantified as a "training set" in the presented information.
9. How the Ground Truth for the Training Set Was Established
Given that a "training set" in the AI/machine learning sense is not explicitly discussed, the "ground truth" for product development and optimization would have been established through:
- Experimental results: Direct measurements of cell growth (e.g., T-cell expansion, viability) under various medium formulations.
- Literature and scientific understanding: Utilizing existing knowledge about nutrient requirements for T-cell growth and factors affecting cell culture media performance.
- Internal research and development objectives: Setting specific performance targets (e.g., target CD3+ cell densities) and developing formulations to achieve these targets.
- Adherence to regulatory guidelines: Ensuring that the medium's components and intended use comply with relevant standards.
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K113566 page 1 of 3
JUN 2 1 2012
510(k) Summary
Life Technologies Corporation - OpTmizer™ CTS™ T-Cell Expansion SFM
| Device Name: | OpTmizer™ CTS™ T-Cell Expansion SFM |
|---|---|
| Common/Usual Name: | OpTmizer |
| Classification Name: | Tissue culture media for human ex vivo tissue and cell culture processing applications (per 21 CFR § 876.5885) |
| Product Code: | NDS |
| Submitter: | Life Technologies Corporation3175 Staley RoadGrand Island, New York 14072 |
| Telephone: | (716) 774-3122 |
| Facsimile: | (716) 774-0230 |
| Email: | kelli.tanzella@lifetech.com |
| Contact: | Kelli Tanzella, Ph.D. |
| Date Prepared: | November 30, 2011 |
| Predicate Device: | |
| Trade Name | Manufacturer 510(k) |
AIM-V® Medium
Life Technologies Corporation
Intended Use
OpTmizer™ CTS™ T-Cell Expansion SFM is a 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 liquid form for use in supporting the growth or maintenance of human tissue and cells.
A. Intended Uses
OpTmizer™ CTS™ T-Cell Expansion SFM tissue culture product is 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
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Page 2
510(k) Summary – Life Technologies OpTmizer™ CTS™ T-Cell Expansion SFM
OpTmizer™ CTS™ T-Cell Expansion SFM has been developed for the growth and expansion of human T lymphocytes. OpTmizer™ CTS™ T-Cell Expansion SFM is a complete serum-free and xeno-free 1X medium consisting of the OpTmizer™ T-Cell Expansion Basal Medium with the addition of the OpTmizer™ T-Cell Expansion Supplement. OpTmizer™ CTS™ T-Cell Expansion Medium is designed for the expansion of CD3+ densities of > 3 x 10° cells/mL in static conditions and > 2 x 10′ cells/ML in Wave bags.
C. Pre- Clinical Testing
Performance standards under Section 514 of the Federal Food, Drug, and Cosmetic Act have been established in "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 are noted in the following table.
| Special Control Objective | Life Technologies CorporationOpTmizerTM CTSTM T-CellExpansion SFM |
|---|---|
| Demonstrate lack of potential toxicityof materials in the media to cells ortissue and demonstrate support oftissue and cell growth | OpTmizer QC Performance Assay |
| Demonstrate lack of endotoxin orpyrogen contamination | Limulus Ameobocyte (LAL) test (25USP Monograph <85>) |
| Validation of Aseptic Processing andSterility Assurance Level (SAL) | Determination of SAL to be ≥ 10-3compliance with GMP requirementsregarding aseptic processing |
| Demonstrate Chemical purity | Incoming Raw Material testing usingUSP, ACS, FCC, GIBCO, or CellCulture requirements |
D. Stability/Shelf-Life
Life Technologies Corporation performs shelf life testing for StemPro® MSC SFM Medium using retained product stored at 20 - 8° C. In addition, a minimum of one new production lot of OpTmizer™ CTS™ T-Cell Expansion SFM is tested each year to verify that the product continues to meet the established shelf life. Based on analysis of product performance over time, Life Technologies Corporation has established a shelf life of twelve months for the OpTmizer™ CTS™ T-Cell Expansion SFM formulation. Stability testing involves the assessment of these functional aspects of media, including demonstrating: (1) that the pH continues to meet specifications; and (2) the media is not cytotoxic and supports the growth of mammalian cells. The pH is tested to demonstrate that the media is not chemically altered during its storage. In assessing cytoxicity, Life Technologies Corporation demonstrates
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510(k) Summary - Life Technologies OpTmizer™ CTS™ T-Cell Expansion SFM
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 the studies indicate the container/closure system provides protection from microbial contamination.
E. Conclusion
OpTmizer™ CTS™ T-Cell Expansion SFM 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. Both products (OpTmizer™ CTS™ T-Cell Expansion SFM and AIM-V® Medium) are manufacturer in accordance with QSR requirements and are labeled as aseptically processed. Thus, OpTmizer™ CTS™ T-Cell Expansion SFM is substantially equivalent to the legally marketed device intended for the human ex vivo tissue and cell culture processing applications.
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Image /page/3/Picture/0 description: The image shows the logo for the Department of Health & Human Services USA. The logo features a stylized eagle with its wings spread, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" are arranged in a circular pattern around the eagle. The logo is black and white.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Food and Drug Administration 10903 New Hampshire Avenue Document Control Room -W066-G609 Silver Spring, MD 20993-0002
Kelli L. Tanzella, Ph.D. Director, Americas Regulatory Affairs Life Technologies Corporation 3175 Staley Road GRAND ISLAND NY 14072
JUN 2 1 2012
Re: K113566
Trade/Device Name: OpTmizer™ CTS™ T-Cell Expansion Serum Free Medium Regulation Number: 21 CFR§ 876.5885 Regulation Name: Tissue culture media for human ex vivo tissue and cell culture Regulatory Class: II Product Code: NDS Dated: June 11, 2012 Received: June 12, 2012
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 r toase be devices and its in that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must or urf I vatural babatos t'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 1
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device-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 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 (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.
Sincerely yours,
Benjamin K. Evanko
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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510(k) Number (if known): K | | 3566
Device Name: OpTmizer™ CTS™ T-Cell Expansion Serum Free Medium
Indications for Use:
OpTmizer™ CTS™ T-Cell Expansion Serum Free Medium is a 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)
X
Prescription Use
(Per 21 CFR 801.109) 1999, 2000, 2001, 2002, 2003, 2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012, 2013, 2014, 2015, 2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023
OR
(Division Sign-off)
(Division Sign-Off)
Division of Reproductive, Gastro-Renal, and
Urological Devices
510(k) Number: K113566
Over-The -Counter Use_ (Optional Format 1-2-96)
§ 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing applications.
(a)
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.(b)
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.”