(77 days)
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.
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).
Knockout™ 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.
The provided document describes the acceptance criteria and the study that demonstrates the performance of Knockout™ SR Medium and Knockout™ SR Xenofree Medium, which are tissue culture media. This is not a medical device in the typical sense of a diagnostic or therapeutic AI-powered tool. Therefore, many of the requested categories for AI-based device performance studies (like MRMC studies, number of experts for ground truth, sample size of test/training sets, adjudication methods, and standalone performance metrics of an algorithm) are not applicable to this type of product.
However, I can extract the relevant performance criteria and how the manufacturer demonstrates compliance.
1. Table of Acceptance Criteria and Reported Device Performance
| Special Control Objective (Acceptance Criteria) | Life Technologies Corporation Knockout™ SR Medium Performance |
|---|---|
| Demonstrate lack of potential toxicity of materials in the media to cells or tissue and demonstrate support of tissue and cell growth | ES Cell Morphology: Demonstrated through specific morphology observed. |
| Relative Plate Efficiency: Demonstrated as comparable to predicate. | |
| Relative Type 1 Colonies: Demonstrated as comparable to predicate. | |
| Also, noted that ES and iPSC grown in Knockout™ SR supplemented media are "substantially less differentiated than those grown in fetal bovine serum (FBS) supplemented media." For stability testing, it was demonstrated that the media was not cytotoxic and supported the growth of mammalian cells throughout its shelf life. | |
| Demonstrate lack of endotoxin or pyrogen contamination | Limulus Ameobocyte (LAL) test (25 USP Monograph ) was performed and met acceptance criteria. |
| Validation of Aseptic Processing and Sterility Assurance Level (SAL) | Determination of SAL to be ≥ 10⁻³ compliance with GMP requirements regarding aseptic processing. |
| Demonstrates Chemical purity | Incoming Raw Material testing using USP, ACS, FCC, GIBCO, or Cell Culture requirements. |
| Stability/Shelf Life | Established a shelf life of 14-months when stored between 2°C-8°C. This was demonstrated by assessing: |
- pH continued to meet specifications.
- Media was not cytotoxic and supported the growth of mammalian cells.
- Container/closure integrity testing confirmed protection from microbial contamination. |
2. Sample Size Used for the Test Set and Data Provenance
This is not applicable as the studies described are laboratory-based assays and stability tests for a cell culture medium, not clinical studies with patient data. The "test set" would refer to internal lab samples and batches of the media.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Not applicable. The "ground truth" for chemical purity, sterility, and cell growth support is established through standardized laboratory assays and protocols, not by expert human review in the context of radiology or pathology, for example.
4. Adjudication Method for the Test Set
Not applicable. Laboratory test results are typically objective measurements against predefined specifications, not subjective assessments requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance
Not applicable. This device is not an AI-powered diagnostic or therapeutic tool for human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Not applicable. This device is a cell culture medium, not an algorithm.
7. The Type of Ground Truth Used
The ground truth is based on:
- Established laboratory assay specifications: For LAL test ( USP Monograph), SAL determination (≥ 10⁻³), and incoming raw material testing (USP, ACS, FCC, GIBCO, or Cell Culture requirements).
- Scientific and biological principles: For ES cell morphology, relative plate efficiency, and relative type 1 colonies, indicating proper cell growth and differentiation status.
- Physical and chemical specifications: For pH and container integrity over time.
8. The Sample Size for the Training Set
Not applicable. This is not a machine learning or AI model that requires a training set. The development of the media involved formulation and optimization, but not in the sense of an algorithm training on data.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no training set in the context of an AI device. The "ground truth" for the medium's development would have been empirically determined optimal conditions for cell culture based on literature, prior research, and internal experiments to achieve desired cell growth and maintenance characteristics. The company mentions a long history and substantial literature (300+ references) for Knockout™ SR, suggesting a robust scientific foundation for its formulation.
§ 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.”