(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.
{0}------------------------------------------------
2/17/99
Premarket Notification 510 Factor VIII Immunodepieted Plasma
| 7.0 | PREMARKET NOTIFICATION 510(K) SUMMARY |
|---|---|
| Applicant: | Laura A. Worfolk, Ph.D.Pacific Hemostasis11515 Vanstory DriveHuntersville, NC 28078704-875-0494Fax # 704-875-2092 |
| Contact: | Mark Ellis, Regulatory Affairs Manager704-948-3279Fax # 704-875-2092 |
| Date: | January 6, 1999 |
| Trade Name: | Pacific Hemostasis Immunodepleted Factor VIII Deficient Plasma |
| Common Name: | Factor VIII Deficient Plasma |
| Classification Name: | Plasma, Coagulation Factor Deficient(per 21 CFR section 864.7290) |
| Comparison Device: | Biopool Factor VIII Deficient Plasma, K893525 |
Description of Immunodepleted Factor VIII Deficient 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.
Intended Use of Immunodepleted Factor VIII Deficient Plasma
This product is intended for use in a clinical laboratory for the quantitative measurement of Factor VIII activity. Factor VIII activity in patient or control plasma is assayed by the amount of Activated Partial Thromboplastin Time (APTT) correction produced by the test plasma when mixed with Factor VIII deficient plasma. Results are compared to the degree of APTT correction of a reference plasma with known Factor VIII activity.
{1}------------------------------------------------
Summary of Performance Data for Substantial Equivalence Comparisons
Pacific Hemostasis (PH) Immunodepleted Factor VIII Deficient Plasma was compared to Biopool (BP) Factor VIII Deficient Plasma. Both products are lyophilized preparations of normal human plasma, the PH product contains added stabilizer. The Factor VIII level in both is less than 1%; all other coagulation factors are within the normal range. The intended use for both products is identical; for the quantitative measurement of Factor VIII activity in patient plasma. Biopool FVIII deficient plasma may also be used as a negative control in von Willebrand Factor assays, however this claim is not made for the PH product.
Comparison studies performed for this application support the claim of substantial equivalence. Dav-to-day precision studies were performed by preparing standard curves using both plasmas, and measuring FVIII activity contained in control plasmas over a 10 day period. The control plasmas tested contained FVIII activity levels ranging from normal to markedly abnormal low. The standard curves obtained using each plasma were indistinguishable over the 10 day testing period (R2 = 0.98-0.99). Further, recovery of Factor VIII activity contained in six control plasmas was equivalent for both (Table 1). The correlation coefficient for recovered FVIII activity contained in the control plasmas was 0.98, with a regression line equation of y = 0.9911x + 0.8692.
Table 1. Recovery of FVIII Activity (%) Contained in Control Samples. Testing with PH or BP FVIII Deficient Substrate Plasmas**
| PNP* | Control 1 | Control 2 | Control 3 | Control 4 | Control 5 | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PH | BP | PH | BP | PH | BP | PH | BP | PH | BP | PH | BP | |
| mean | 114.7 | 117.0 | 130.9 | 127.1 | 95.5 | 96.6 | 65.6 | 65.7 | 33.6 | 34.1 | 18.0 | 18.1 |
| 1 SD | 16.1 | 21.29 | 6.46 | 8.73 | 4.63 | 5.35 | 1.82 | 4.82 | 2.13 | 1.57 | 1.32 | 0.98 |
| % CV | 14.0% | 18.2% | 4.9% | 6.9% | 4.8% | 5.5% | 2.8% | 7.3% | 6.3% | 4.6% | 7.3% | 5.4% |
| n (days oftesting) | 10 | 10 | 8 | 8 | 8 | 8 | 10 | 10 | 8 | 8 | 8 | 8 |
*PNP = pooled normal plasma, ** Testing on the MLA - 1000C™.
Several different instruments were used to assess the performance of the deficient plasmas, these included the Amelung KC 4 A™, MLA®-700, MLA®-1000C™ and the ACL-3000PUS. Standard curves were prepared, and the recovery of FVIII activity contained in control plasmas was determined using both products. The combined instrument data vielded a correlation coefficient of 0.99, with a regression line equation of y = 1.037x + 0.5603. Last, reconstituted stability studies were performed. Standard curves prepared with fresh or 8-hour aged deficient plasma were indistinguishable for both products. Further, there were no clinically significant differences observed in FVIII activity recovered in control plasmas between fresh and aged deficient plasmas, for PH and Biopool substrate plasmas,
{2}------------------------------------------------
In summary, the similar intended use, technological characteristics and combined performance data support the substantial equivalence claim for Pacific Hemostasis Immunodepleted Factor VIII Deficient Plasma to Biopool Factor VIII Deficient Plasma. Therefore based on the data provided, it is our conclusion that Pacific Hemostasis Immunodepleted Factor VIII Deficient Plasma is substantially equivalent to Biopool Factor VIII Deficient Plasma.
/
{3}------------------------------------------------
PREMARKET NOTIFICATION
TRUTHFUL AND ACCURATE STATEMENT [As required by 21 CFR 807.87(j)]
I certify that, in my capacity as a Research Scientist at Pacific Hemostasis, a Fisher Scientific Company, I believe to the best of my knowledge, that all data and information submitted in the premarket notification are truthful and accurate and that no material fact has been omitted.
Laura A. Worfolk 1/6/99
Laura A. Worfolk, Ph.D.
K990046
*(Premarket Notification [510(k)] Number)
{4}------------------------------------------------
FEB 1 7 1999
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. Mark Ellis Regulatory Affairs Manager Pacific Hemostasis 11515 Vanstory Drive, Suite 125 Huntersville, North Carolina 28078-8144
K990046 Trade Name: Pacific Hemostasis Immunodepleted Factor VIII Deficient Plasma Regulatory Class: II Product Code: GJT Dated: January 6, 1999 Received: January 7, 1999
Dear Mr. Ellis:
Re:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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.
If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (OS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
{5}------------------------------------------------
Page 2
Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.
This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".
Sincerely yours,
Steven Butman
Steven I. Gutman, M.D, M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
{6}------------------------------------------------
Page_ of I
510(k) Number (if known): _ (99004/2
Device Name:_
Indications For Use:
Statement of Indications for Use
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.
יי הייני היינו
Peter E. Madlem
(Division Sign-Off)
Division of Clinical Laboratory Devices K190046
510(k) Number
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use_
(Optional Format 1-2-96)
§ 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).