The lab I work for purchased a new automated diagnostic machine about a year ago and I had the luxury of validating the device for use. It is called nanoString DX digital analyzer and prep station, the test is called Prosigna and it is a prognostic for the recurrence of breast cancer. The most time consuming part was developing the required Individualized Quality Control Plan (IQCP). Normally you would just follow the regulations for quality control provided by CLIA, CAP, CLIS, FDA, etc. which would consist of the usual controls, lot to lot testing, and accurate record keeping, but in this case the device ran off of kits that had built in controls and the machine itself uses a proprietary algorithm that will either confirm or deny the test, if it is confirmed the results will print out but if the control is denied the results will not print out. The device is 510(k) FDA approved. The problem I ran across was that NJ requires strict quality control documentation and the fact that the algorithm is proprietary the company would not release the results from the controls to the user. All I needed was to show documentation that the controls passed, but the report that prints out only gives a score pertaining to the Prosigna test. I tried talking to the company and they were adamant about not releasing the control data, the only way around it was to create the IQCP which is an extensive document detailing how we would be able to maintain quality control standards for the high complexity test. The IQCP had to be approved before we were able to run tests. In order to save time and money, for non-STAT cases the solution was to receive specimen Saturday-Wednesday at noon, run all samples and controls on Wednesday, and release results on Friday. For STAT cases controls will be run when case is received. The problem with this "solution" was that the kits are expensive and having this new way of running controls wastes an entire kit. Kits include all reagents, plastics, probes, and cartridges. This small detail forces the company to buy extra kits they would not need to buy if they were located in a different state. This continues to be such a hassle and I'm sure that if the company had to do it again they would just go with the competitor Oncotype DX because their system is easier for the lab to get validated and would not have to spend extra money just to run the necessary controls required for NJ state.
3 day turn around time PER KIT:
Day 1 - Tissue Macrodissection and Digestion/Incubation
Day 2 - RNA Isolation and Probe/Incubation
Day 3 - Digital Analyzer and Report release
Controls can be run starting from the end of Day 2 - Probe/Incubation.
The question I propose:
Should a medical device company worry about the regulations required of labs of individual states if they are going to be selling the device in those states? Keep in mind that the above device is 510(k) FDA approved and the only restriction was that the necessary control data is considered proprietary and not released to the user, a crucial quality control problem for the lab.
This is an interesting question and I haven't heard of such a thing before. The short answer is: they have to worry about it. The FDA is a national regulatory agency, but states have the right to pass their own regulations. They usually end up being more strict (I can't say I've heard of the reverse). If states will refuse to let a company create/sell product in their state then they have no alternative. State laws are (theoretically) equal to federal laws. I would think there would be a way around your issues, but since I don't have a clear understanding of the laws/situation I don't know what it could be. Is there any law/regulation that allows the dissemination of that information?
"High Complexity Tests
This category includes those tests that are modified by the laboratory, developed by a laboratory, or a test classified as high complexity under CLIA. Laboratories under CLIA and COLA also must comply with Section §493.1201 (general QC): The laboratory must establish and follow written QC procedures for monitoring and evaluating the quality of the analytical testing process of each method to assure the accuracy and reliability of patient test results and reports. Section §493.1202 states for each test of high complexity performed, the laboratory must meet all applicable standards of this subpart (subpart K). For statistical QC, laboratories must be in compliance with the following sections:
§493.1218: Control procedures are performed on a routine basis to monitor the stability of the method or test system; control and calibration materials provide a means to indirectly assess accuracy and precision of patient test results. Control procedures must be performed as defined in this section unless otherwise specified in sections §493.1223 through §493.1285 (these state specific QC requirements for blood gases, hematology, etc.).
§493.1218(b) for each method that is developed in-house, is a modification of the manufacturer’s test procedure, or is a method that has not been cleared by the FDA as meeting the CLIA requirements for general QC (all highly complex methods), the laboratory must evaluate instrument and reagent stability and operator variance in determining the number, type, frequency of testing calibration or control materials and establish criteria for acceptability used to monitor test performance during a run of patient specimen(s).
§493.1218(d)(1) The stated values of an assayed control material may be used as the target values provided the stated values correspond to the methodology and instrument employed by the laboratory and are verified by the laboratory.
§493.1218(d)(2) Statistical parameters for unassayed materials must be established over time by the laboratory through concurrent testing with calibration materials or control materials having previously determined statistical parameters. (The statistical parameters, e.g. mean and SD, for each lot number must be determined through repetitive testing).
§493.1218(e) Control results must meet the laboratory's criteria for acceptability prior to reporting patient test results. Laboratory criteria for acceptability refers to the particular control limits or control rules chosen by the laboratory."
The issue is being able to document the controls in order to be in compliance with §493.1218(d)(2) and §493.1218(e) at the bare minimum because the control data is considered proprietary and unavailable to the lab.
Reference
U.S. Department of Health and Human Services. Medicare, Medicaid and CLIA programs: Regulations implementing the Clinical Laboratory Improvement Amendments of 1988 (CLIA). Final rule. Fed Regist 1992; 57:7002-186.
U.S. Department of Health and Human Services. Medicare, Medicaid and CLIA programs: Regulations implementing the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and Clinical Laboratory Act program fee collection. Fed Regist 1993:58:5215-37.
