(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 ) |
| 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.
§ 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.”