(41 days)
Pacific Hemostasis Immunodepleted Factor VIII (FVIII) Deficient Plasma is intended for use as a substrate in the quantitative determination of Factor VIII activity in citrated plasma.
Pacific Hemostasis (PH) Immunodepleted Factor VIII Deficient Plasma is a lyophilized preparation of fresh human plasma with added stabilizer. The product is prepared from pooled normal citrated plasma, and then depleted of FVIII by immobilized highly specific antibodies. Factor VIII activity is less than 1%, all other coagulation Factors are within the normal range. Each unit of source material used in the preparation of this product has been tested and found negative for HBsAg (Hepatitus B Surface antigen) and negative for antibodies to HIV and HCV. The product is provided in 1.0mL vials, 10 vials per package.
Acceptance Criteria and Study for Factor VIII Immunodepleted Plasma
This document details the acceptance criteria and the study performed to demonstrate substantial equivalence for the Pacific Hemostasis Immunodepleted Factor VIII Deficient Plasma.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for the Pacific Hemostasis (PH) Immunodepleted Factor VIII Deficient Plasma were established through comparison to a legally marketed predicate device, the Biopool (BP) Factor VIII Deficient Plasma. The device performance was assessed across several metrics, as summarized in the table below. While specific numerical "acceptance criteria" were not explicitly stated as pass/fail thresholds, the study aimed to demonstrate "indistinguishable" or "equivalent" performance within acceptable analytical variations for in vitro diagnostic devices.
| Acceptance Criteria Category | Specific Metric | Reported Device Performance (PH vs. BP) |
|---|---|---|
| Day-to-day precision | Standard curves for FVIII activity measurement | - Indistinguishable over a 10-day period. |
- R² = 0.98-0.99 (indicating strong correlation between the two products' standard curves). |
| Recovery of FVIII activity in controls | FVIII activity levels in 6 control plasmas | - Equivalent recovery for both PH and BP. - Correlation coefficient = 0.98 (strong positive linear relationship between results obtained with PH and BP).
- Regression line equation: y = 0.9911x + 0.8692 (indicating close agreement, with a slope near 1 and y-intercept near 0, suggesting minimal systematic bias).
- Individual control mean percentages of FVIII recovery were closely matched (e.g., PH 114.7% vs. BP 117.0%, PH 18.0% vs. BP 18.1%). |
| Instrument compatibility | FVIII activity recovery across multiple instruments | - Tested on Amelung KC 4 A™, MLA®-700, MLA®-1000C™, and ACL-3000PLUS. - Combined instrument data yielded a correlation coefficient of 0.99.
- Regression line equation: y = 1.037x + 0.5603. |
| Reconstituted stability | Performance with fresh vs. 8-hour aged plasma | - Standard curves prepared with fresh or 8-hour aged deficient plasma were indistinguishable for both products. - No clinically significant differences observed in FVIII activity recovered in control plasmas between fresh and aged deficient plasmas for both PH and BP. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size:
- Day-to-day precision: Tested over a 10-day period. The number of control plasmas measured was not explicitly stated in this context but implied to be multiple over this period.
- Recovery of FVIII activity: Six control plasmas were tested. The "n (days of testing)" for each control plasma ranged from 8 to 10 days.
- Instrument compatibility: Not explicitly stated as to the number of samples, but implied to be sufficient for generating standard curves and recovering FVIII activity in control plasmas on each of the four instruments.
- Reconstituted stability: Not explicitly stated, but involved comparison of fresh vs. 8-hour aged deficient plasma performance.
- Data Provenance: The document does not explicitly state the country of origin of the data or whether the study was retrospective or prospective. Given the context of a 510(k) submission for a new device, it is highly likely that the data was generated prospectively as part of the device's validation studies.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This type of in vitro diagnostic device (deficient plasma for Factor VIII activity measurement) does not typically rely on "experts" in the sense of clinical reviewers (e.g., radiologists) establishing a "ground truth" for a diagnostic image or patient case.
Instead, the "ground truth" for the test set is inherent in the known Factor VIII activity levels of the control plasmas used. These control plasmas are analytically characterized materials with established target values. The "experts" involved would be the laboratory personnel performing the testing, who would be qualified clinical laboratory scientists or technicians proficient in coagulation assays. Their qualifications are not specified in the provided text.
4. Adjudication Method for the Test Set
Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical studies involving subjective assessments or where consensus is needed among multiple readers. For this in vitro diagnostic device, where quantitative measurements are performed against known controls, an adjudication method in this sense is not applicable or described. The results are obtained directly from laboratory measurements and statistical comparisons.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
A Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted. This type of study is relevant for evaluating the impact of AI on human reader performance, particularly in medical imaging. The Factor VIII Deficient Plasma is an in vitro diagnostic reagent, not an AI-powered diagnostic system that assists human readers.
6. Standalone Performance (Algorithm Only)
This product is a laboratory reagent, not an algorithm or AI system. Therefore, a standalone (algorithm only) performance study was not performed or is not applicable. The performance evaluation focuses on the reagent's analytical characteristics when used in conjunction with standard laboratory instruments and assays.
7. Type of Ground Truth Used
The ground truth used was analytically established values from characterized control plasmas with known Factor VIII activity levels. This is the standard method for validating in vitro diagnostic assays. The "pooled normal plasma" (PNP) and various "Control 1" through "Control 5" with different FVIII activity percentages serve as the ground truth against which the device's ability to recover FVIII activity is measured.
8. Sample Size for the Training Set
This product is an in vitro diagnostic reagent, not a machine learning model or AI device that requires a "training set." Therefore, a sample size for a training set is not applicable and not provided.
9. How the Ground Truth for the Training Set Was Established
As noted above, a "training set" is not applicable for this type of device. The ground truth for the performance evaluation (test set) was established by using pre-characterized control plasmas with known Factor VIII activity levels, which is a standard analytical validation approach for IVD reagents.
§ 864.7290 Factor deficiency test.
(a)
Identification. A factor deficiency test is a device used to diagnose specific coagulation defects, to monitor certain types of therapy, to detect coagulation inhibitors, and to detect a carrier state (a person carrying both a recessive gene for a coagulation factor deficiency such as hemophilia and the corresponding normal gene).(b)
Classification. Class II (performance standards).