(349 days)
Sterilization: Aldahol III High-Level Disinfectant is a sterilant intended for the sterilization of reusable, clean, heat-sensitive medical devices when used as directed at or above its minimum recommended concentrations (MRC) of 2.1% alkaline glutaraldehyde and 15.0% isopropanol with an exposure of 10.0 hrs at 20 C.
High-Level Disinfection: Aldahol III High-Level Disinfectant is a high-level disinfectant intended for the disinfection of reusable, clean, heat-sensitive medical devices when used as directed at or above its MRC of 2.1% alkaline glutaraldehyde and 15.0% isopropanol with an exposure of 10.0 min at 20 C.
Aldahol III High-Level Disinfectant is a liquid chemical sterilant and high-level disinfectant. It is a glutaraldehyde-based disinfectant with a glutaraldehyde concentration in the range of 2.4 to 3.4%. When activated with buffer salts to an alkaline pH value of about 7.6, the glutaraldehyde concentration can remain constant over a 14-day use and reuse life. It also contains about 25% isopropanol to enhance mycobactericidal (TB) activity.
The provided text describes a liquid chemical sterilant and high-level disinfectant called "Aldahol III High-Level Disinfectant" and its substantial equivalence to the predicate device "Cidex Activated Dialdehyde Solution." The document focuses on the efficacy testing of Aldahol III.
Here's an analysis of the acceptance criteria and the studies that prove the device meets these criteria, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The text doesn't explicitly state "acceptance criteria" as a set of quantified thresholds in a table format. Instead, it describes various tests performed and the positive results achieved. The implicit acceptance criterion for each test is the complete elimination or reduction of the target microorganisms to undetectable levels within specified exposure times and conditions.
| Acceptance Criteria (Implicit from Test Results) | Reported Device Performance (Aldahol III HLD) |
|---|---|
| High-level Disinfection: | |
| Kill 100% of Salmonella choleraesuis | 100% killed (3.0, 5.0, 10.0 min @ 20°C) |
| Kill 100% of Staphylococcus aureus | 100% killed (3.0, 5.0, 10.0 min @ 20°C) |
| Kill 100% of Pseudomonas aeruginosa | 100% killed (3.0, 5.0, 10.0 min @ 20°C) |
| Kill Trichophyton mentagrophytes | Killed (3.0, 5.0, 10.0 min @ 20°C) |
| Kill Aspergillus niger | Killed (3.0, 5.0, 10.0 min @ 20°C) |
| Kill Candida albicans | Killed (3.0, 5.0, 10.0 min @ 20°C) |
| Kill Poliovirus type 1 | Killed within limits of detection (5.0 min @ 20°C) |
| Kill Influenza A Virus | Killed within limits of detection (5.0 min @ 20°C) |
| Kill Herpes Simplex Virus type 1 | Killed within limits of detection (5.0 min @ 20°C) |
| Kill Adenovirus type 2 | Killed within limits of detection (5.0 min @ 20°C) |
| Kill 6 log10 of M. terrae (mycobactericidal) | Killed 6 log10 of M. terrae (10.0 min @ 20°C) |
| Kill 6 log10 of M. terrae in flexible endoscope biopsy channels | Killed at least 6 log10 of M. terrae (5.0 min @ 20°C) |
| No bacteria recovered from clinically-used endoscopes after disinfection | No bacteria recovered (5.0 min @ 20°C) |
| Sterilization: | |
| Pass AOAC Sporicidal Test for C. sporogenes and B. subtilis | Passed (10.0 hrs @ 20°C) for C. sporogenes and B. subtilis |
| Confirmatory Sporicidal Test | Passed (10.0 hrs @ 20°C) |
Notes on reported performance:
- All tests for Aldahol III HLD were conducted at a "worst case" glutaraldehyde concentration of 2.0% (from a 14-day EPA Re-Use Test), which is below its initial concentration of 3.4%.
- The high-level disinfection goal exposure time is 10.0 minutes at 20°C.
- The sterilization goal exposure time is 10.0 hours at 20°C.
2. Sample Size Used for the Test Set and Data Provenance
The text describes experimental setups rather than typical clinical trial sample sizes.
- Bacterial Use Dilution Tests (i-1): Stainless steel "penicylinders" were labeled with cultures. The number of cylinders per test is not explicitly stated, but standard AOAC methods typically involve multiple replicates (e.g., 10-60 carriers per organism per disinfectant dilution). The data provenance is laboratory-based efficacy testing.
- Fungicidal Tests (i-2): Cultures of Trichophyton mentagrophytes, Aspergillus niger, or Candida albicans were tested. Methodology similar to bacterial tests. Data provenance is laboratory-based efficacy testing.
- Virucidal Tests (i-3): Poliovirus type 1, Influenza A Virus, Herpes Simplex Virus type 1, and Adenovirus type 2 were tested. Data provenance is laboratory-based efficacy testing.
- Mycobactericidal Tests (i-4): M. terrae (6 log10 challenge). Data provenance is laboratory-based efficacy testing.
- Sterilization Exposure Studies (i-5, i-6, i-7):
- Initial study (i-5) tested 40 spore-labeled carriers for C. sporogenes (4 positive at 4.0 hrs, all others disinfected). This indicates a sample size of 40 carriers per exposure time for initial optimization.
- Full three Lot test (i-6) passed the AOAC Sporicidal Test with an exposure of 10.0 hours. Standard AOAC Sporicidal Test (966.04) involves multiple spore carriers (often around 60 per condition/lot).
- Confirmatory Sporicidal Test (i-7) also passed. Implies similar sample sizes to the full Lot test.
- Data provenance is laboratory-based efficacy testing.
- Simulated Use Tests with Flexible Endoscopes (i-8): Flexible endoscopes' biopsy channels were labeled with M. terrae. The number of endoscopes is not specified but usually involves a representative number for such tests (e.g., 3-10). Data provenance is simulated-use laboratory testing.
- Clinical In-use Tests (i): "Various colonoscopes and gastroscopes" as received directly from patients at an endoscopy clinic. The exact number is not stated but implies real-world clinical samples. Data provenance is prospective clinical in-use testing, likely U.S. based given the FDA submission.
3. Number of Experts and Qualifications for Ground Truth
This type of submission is for a disinfectant, not for an image-based diagnostic or AI algorithm. Therefore, the concept of "experts establishing ground truth" in the medical imaging sense (e.g., radiologists, pathologists) is not directly applicable.
Instead, the "ground truth" is established by:
- Standardized microbiological methods: Adherence to AOAC (Association of Official Analytical Chemists) protocols (e.g., 955.14, 955.15, 964.02 for bacteria; 955.17 for fungi; 966.04 for sporicidal) for determining the presence or absence of viable microorganisms.
- Laboratory Technicians/Scientists: These individuals, qualified in microbiology and sterilization/disinfection testing, perform the tests and interpret the results according to the established protocols. Their qualification is implied by their ability to successfully execute these validated methods.
- Clinical Personnel: For the clinical in-use tests, clinic personnel followed standard cleaning procedures and microbiologists determined the presence/absence of bacteria.
4. Adjudication Method for the Test Set
Adjudication methods like 2+1 or 3+1 consensus are typically used for subjective assessments in clinical trials or image interpretation. For microbiological efficacy testing, the outcome is generally objective: growth or no growth, colony count reduction, or presence/absence of detectable virus. The "adjudication" is inherent in the rigorous, standardized nature of the AOAC methods and the clear criteria for positive/negative results. Any discrepancies would likely trigger re-testing or investigation, but not a consensus process among human readers.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This is not applicable to a liquid chemical sterilant/disinfectant. MRMC studies are used for evaluating the reader performance of diagnostic tools, particularly in medical imaging, and assessing the impact of AI assistance on human readers.
6. Standalone Performance
Yes, the studies described are all "standalone" in the sense that they evaluate the efficacy of the Aldahol III High-Level Disinfectant itself, without human intervention in the disinfection process beyond proper application. The results (e.g., 100% kill, 6 log10 reduction) directly reflect the algorithm's (the chemical formulation's) performance.
7. Type of Ground Truth Used
The ground truth used is primarily microbiological culture results and virological assays (for virucidal tests). This involves:
- Direct observation of microbial growth/no growth: After exposure to the disinfectant, samples are cultured to see if any viable organisms remain.
- Quantitative reduction: For some tests (e.g., mycobactericidal), the ground truth involves measuring the reduction in the number of colony-forming units (CFUs) or viral particles.
- Absence of detectable organisms: The ultimate ground truth for disinfection and sterilization is the absence of the target microorganisms.
8. Sample Size for the Training Set
The concept of a "training set" is not applicable here as this is a chemical disinfectant, not a machine learning model. The formulation of Aldahol III HLD (3.4% glutaraldehyde, 25% isopropanol) and its activation (alkaline pH) are based on chemical and microbiological principles developed over time through research and previous product development, not through training a model on a dataset.
9. How the Ground Truth for the Training Set was Established
Again, the concept of a "training set" in the context of AI development does not apply. The "ground truth" for the development of glutaraldehyde-based disinfectants and the concept of enhanced mycobactericidal activity with alcohol are established through decades of traditional chemical and microbiological research, understanding of antiseptic mechanisms, and empirical testing. This would involve laboratory experiments, dose-response curves, kinetics studies, and comparisons with known effective agents, not a "training set" with established ground truth.
§ 880.6885 Liquid chemical sterilants/high level disinfectants.
(a)
Identification. A liquid chemical sterilant/high level disinfectant is a germicide that is intended for use as the terminal step in processing critical and semicritical medical devices prior to patient use. Critical devices make contact with normally sterile tissue or body spaces during use. Semicritical devices make contact during use with mucous membranes or nonintact skin.(b)
Classification. Class II (special controls). Guidance on the Content and Format of Premarket Notification (510(k)) Submissions for Liquid Chemical Sterilants/High Level Disinfectants, and user information and training.