National Institutes Of Health

Summary Statement of Deficiencies D0000 A recertification onsite survey was conducted 08/29/2024 and standard level deficiencies were cited. D5203 SPECIMEN IDENTIFICATION AND INTEGRITY CFR(s): 493.1232 The laboratory must establish and follow written policies and procedures that ensure positive identification and optimum integrity of a patient's specimen from the time of collection or receipt of the specimen through completion of testing and reporting of results. This STANDARD is not met as evidenced by: Based on review of the laboratory's procedure, client specimen handling instructions, patient log sheet, final test reports, patient information sheets, and interview with testing person 1, the laboratory failed to ensure documentation of the integrity (frozen) of 5 of 5 specimens when collected and received for catecholamines testing (04/27/2023 through 07/23/2024). Findings included: 1. Review of the laboratory's procedure "PART I: Sampling and Shipping of Samples ...3. Sample Processing: ... The plasma should be separated into plastic tubes clearly marked with the date and patient ID and frozen immediately (e.g., dry ice). The sample should be stored at -70C or colder. Catechols in plasma stored at -20C are not stable." Further review stated, "4. Specimen Shipping: ...Samples of plasma should be shipped frozen (e.g., on dry ice in a Styrofoam container) to the NIH." The above instructions were provided to the laboratory's clients via electronic mail (email) along with a "Patient Information Sheet." The information sheet included at the bottom right, "Stored at -70C? __." 2. Review of the laboratory's patient log sheet included 5 patients that had been received and tested for plasma catecholamines on high performance liquid chromatography (HPLC) method. The log sheet did not include whether the specimens were received on dry ice and patient information sheets did not include how clients/collectors stored Statement of Deficiencies (X1) Provider/Supplier/CLIA Identification Number (X3) Date Survey Completed Name of Provider or Supplier Street Address, City, State -- 1 of 3 -- the specimens, as follows: Patient Log #1736 (one tube of plasma) collected 04/25 /2023 and analyzed 04/27/2023 Patient Log #1737 (four tubes of plasma) collected 05 /18/2023 and analyzed 05/23/2023 The above two patients did not include patient information sheets because it had not been created yet. There was no documentation of how the specimens were stored by the collectors. Patient Log #1741 (two tubes of plasma) collected 08/02/2023 and analyzed 08/09/2023 and 08/10/2023 Patient Log #1743 (one tube of plasma) collected 12/18/2023 and analyzed 12/19/2023 Patient Log #1745 (one tube plasma) collected 07/22/2024 and analyzed 07/29/2024 The above three patients included patient information sheets and the question, "Stored at -70C? __" was not checked off. 3. During an interview on 08/29/2024 at 2:30 pm, testing person 1 reviewed and confirmed the above information. She stated all specimens come with dry ice but did not have documentation of ensuring those conditions. D5413 TEST SYSTEMS, EQUIPMENT, INSTRUMENTS, REAGENT CFR(s): 493.1252(b) The laboratory must define criteria for those conditions that are essential for proper storage of reagents and specimens, accurate and reliable test system operation, and test result reporting. The criteria must be consistent with the manufacturer's instructions, if provided. These conditions must be monitored and documented and, if applicable, include the following: (1) Water quality. (2) Temperature. (3) Humidity. (4) Protection of equipment and instruments from fluctuations and interruptions in electrical current that adversely affect patient test results and test reports. This STANDARD is not met as evidenced by: Based on review of manufacturer's instructions, direct observation, and interview with testing person 1, the laboratory failed to monitor and document room temperature and humidity for 3 of 3 stored reagents and 4 of 4 analyzers according to manufacturer's requirements. Findings included: 1. Review of Waters 2707 Autosampler manufacturer's instructions stated on page 73, "General specifications ...Working temperature 10 to 40C ...Humidity 20 to 80%" Review of Water 515 HPLC Pump manufacturer's instructions stated on page B-1, "Environmental specifications ... Operating temperature 4 to 40C; Humidity 20 to 80%, noncondensing." Review of Coulochem III manufacturer's instructions stated on page A-4, "Environmental: Operating Temperature: 10-35C; Humidity: Maximum 80% RH (35C), non- condensing." (RH - Relative Humidity) 2. During a tour of the laboratory on 08/29 /2024 at 11:30 am, two Waters 2707 Autosamplers, one Waters 515 HPLC Pump, and one Coulochem III electrochemical detector were observed on the countertop. The Waters with the Coulochem were used for plasma catecholamine testing. In addition, the following sampling of reagents were observed stored on shelves: Supelco Buffer, reference standard B5020-500 mL, expiration date 02/01/2026, manufacturer's storage requirements: 15C to 25C. Supelco Buffer, reference standard B4770-500 mL, expiration date 11/24/2024, manufacturer's storage requirements: 25C. Sigma-Aldrich LiChropur Octane-1-sulfonic acid sodium salt, manufacturer's storage requirements: 15C to 25C. 3. During an interview on 08/29/2024 at 11:30 am, testing person 1 was asked whether room temperature and humidity was monitored and documented, she stated no. D5801 TEST REPORT CFR(s): 493.1291(a) -- 2 of 3 -- The laboratory must have an adequate manual or electronic system(s) in place to ensure test results and other patient-specific data are accurately and reliably sent from the point of data entry (whether interfaced or entered manually) to final report destination, in a timely manner. This includes the following: (a)(1) Results reported from calculated data. (a)(2) Results and patient-specific data electronically reported to network or interfaced systems. (a)(3) Manually transcribed or electronically transmitted results and patient-specific information reported directly or upon receipt from outside referral laboratories, satellite or point-of-care testing locations. This STANDARD is not met as evidenced by: Based on review of HPLC analyzer patient results, final test reports, and interview with testing person 1, the laboratory failed to ensure catecholamine test results were entered accurately for 1 of 5 patient final reports (from 04/27/2023 through 07/23 /2024). Findings included: 1. Review of Patient Log #1742 "upright" position results from the HPLC analyzer were analyzed 08/09/2023 and included catecholamines dihydroxypheylglycol (DHPG) value of 1683 pg/ml and norepinephrine (NE) value of 2744 pg/ml. Review of the final test report for Patient Log #1742 "upright" position results included a DHPG value of 2428 pg/ml and NE value of 3379 pg/ml. 2. During an interview on 08/29/2024 at 2:11 pm, testing person 1 was asked how results were transmitted from the HPLC analyzer to the final test report. She explained results are entered manually into a final test report template by the laboratory director. Testing person 1 was unable to locate HPLC analyzer results that were consistent with the final test report results (DHPG value of 2428 pg/ml and NE value of 3379 pg/ml). The laboratory failed to ensure catecholamine test results were entered accurately for 1 of 5 patient final reports. -- 3 of 3 --

Summary Statement of Deficiencies D5805 TEST REPORT CFR(s): 493.1291(c) The test report must indicate the following: (c)(1) For positive patient identification, either the patient's name and identification number, or a unique patient identifier and identification number. (c)(2) The name and address of the laboratory location where the test was performed. (c)(3) The test report date. (c)(4) The test performed. (c)(5) Specimen source, when appropriate. (c)(6) The test result and, if applicable, the units of measurement or interpretation, or both. (c)(7) Any information regarding the condition and disposition of specimens that do not meet the laboratory's criteria for acceptability. This STANDARD is not met as evidenced by: Based on record review and interview, 2 of 4 patient reports were missing a patient identification number. Findings: 1) During record review on March 28, 2023 around 2 P.M., 4 patient reports were reviewed, and two were missing patient identification numbers on the test report. The laboratory has an annual test volume of about 10 tests per year. 2) In an interview on March 29, 2023 around 9:30 A.M., the laboratory director confirmed the findings. Statement of Deficiencies (X1) Provider/Supplier/CLIA Identification Number (X3) Date Survey Completed Name of Provider or Supplier Street Address, City, State -- 1 of 1 --

Summary Statement of Deficiencies D5423 ESTABLISHMENT AND VERIFICATION OF PERFORMANCE CFR(s): 493.1253(b)(2) Each laboratory that modifies an FDA-cleared or approved test system, or introduces a test system not subject to FDA clearance or approval (including methods developed in-house and standardized methods such as text book procedures), or uses a test system in which performance specifications are not provided by the manufacturer must, before reporting patient test results, establish for each test system the performance specifications for the following performance characteristics, as applicable: (2)(i) Accuracy. (2)(ii) Precision. (2)(iii) Analytical sensitivity. (2)(iv) Analytical specificity to include interfering substances. (2)(v) Reportable range of test results for the test system. (2)(vi) Reference intervals (normal values). (2)(vii) Any other performance characteristic required for test performance. This STANDARD is not met as evidenced by: Based on review of laboratory relocation verification of assay performance and interview with the technical supervisor, the laboratory failed to ensure all re- establishment characteristics for performance of plasma Catecholamines testing were performed and documented on two esa Coulachem III analyzers prior to patient testing after the laboratory moved into a new location in January 2018. Findings include: 1. The laboratory uses two instruments for analysis of Catecholamines in patient plasma: instrument named 'RED" having Serial No CC6987 and instrument 'YELLOW; having Serial No CC6818. 2. For instrument 'RED' there was no documented evidence the laboratory performed: precision study testing that included assessment of day-to-day, run-to-run and within run variation. 3. For instrument 'YELLOW' there was incomplete documentation of precision study testing as only one run was performed and there was no assessment of day-to-day, run-to-run and within Statement of Deficiencies (X1) Provider/Supplier/CLIA Identification Number (X3) Date Survey Completed Name of Provider or Supplier Street Address, City, State -- 1 of 3 -- run variation. 4. During interview with the technical supervisor at approximately 12: 20pm, there was an admission the laboratory was unaware of these requirements and that is why they were not documented as required under the standard. D5805 TEST REPORT CFR(s): 493.1291(c) The test report must indicate the following: (c)(1) For positive patient identification, either the patient's name and identification number, or a unique patient identifier and identification number. (c)(2) The name and address of the laboratory location where the test was performed. (c)(3) The test report date. (c)(4) The test performed. (c)(5) Specimen source, when appropriate. (c)(6) The test result and, if applicable, the units of measurement or interpretation, or both. (c)(7) Any information regarding the condition and disposition of specimens that do not meet the laboratory's criteria for acceptability. This STANDARD is not met as evidenced by: Based on review of laboratory procedure manual, patient reports and interview with the technical supervisor, the laboratory failed to ensure patient plasma catechols reports included appropriate interpretative information related to the how the final interpretation is derived by the laboratory on one of one Menkes patient report reviewed of ten. Findings include: 1. The surveyor reviewed the procedure manual, Section 2 titled 'Reference Ranges for Plasma Catechols', Menkes Reference Range Ratios are listed for 3,4-dihydroxyphenylalamine (DOPA):3,4- dihydroxyphenypenylglycol (DHPG) and 3,4-dihydroxyphenylacetic acid (DOPAC): DHPG ratios for patients with Menkes disease as well as pediatric control sample ranges. 2. In patients with Menkes disease, the DOPA:DHPG ratio range is listed as 6.2-34.2 and for DOPAC:DHPG ratio the range is listed as 4.4-19.7. 3. Pediatric control subject samples without evidence of Menkes disease, the DOPA:DHPG ratio is listed as 1.7-3.3 and the DOPAC:DHPG ratio is listed as 1.5-3.2. 4. For the pediatric patient having DOB 9-27-2017 with an assay date of 5-31-2018; the DOPA: DHPG ratio was listed as 5.3 and the DOPAC:DHPG ratio listed as 1.6, DA:NE ratio listed as 0.01, Interpretation as 'Unaffected' without any interpretative information provided by the laboratory on the report. 5. This information was confimed during interview with the technical supervisor at approximately 1:30pm. D6094 LABORATORY DIRECTOR RESPONSIBILITIES CFR(s): 493.1445(e)(5) The laboratory director must ensure that the quality assessment programs are established and maintained to assure the quality of laboratory services provided and to identify failures in quality as they occur. This STANDARD is not met as evidenced by: Based on review of the laboratory quality assurance (QA) manual and interview with the technical supervisor and laboratory director, the laboratory director failed to ensure the facility's quality assessment program monitors were established and maintained to assure the quality of laboratory services in performance of plasma catecholamine testing and identied failures in quality as they occurred. Findings include: 1. The current laboratory QA plan is dated October 2018; 2. Monitors in the General lab systems areas of plasma catecholamine testing were not included in the -- 2 of 3 -- laboratory QA manual; 3. Monitors in the Pre-analytic systems areas of plasma catecholamine testing were not included in the laboratory QA manual; 4. Monitors in the Analytic systems areas of plasma catecholamine testing were not included in the laboratory QA manual; 5. Monitors in the Post-analytic systems areas of plasma catecholamine testing were not included in the laboratory QA manual; 6. These findings were confirmed by interview with the laboratory director at approximately 2: 00pm. D6095 LABORATORY DIRECTOR RESPONSIBILITIES CFR(s): 493.1445(e)(6) The laboratory director must ensure the establishment and maintenance of acceptable levels of analytical performance for each test system. This STANDARD is not met as evidenced by: Based on review of the laboraotry relocation re-establishment studies and interview with the laboratory director, the lab director failed to ensure verification of accuracy and/or precision of plasma catecholamines on two of two esa Coulachem III analyzers. Findings include: Cross-reference D5423. D6098 LABORATORY DIRECTOR RESPONSIBILITIES CFR(s): 493.1445(e)(8) The laboratory director must ensure that reports of test results include pertinent information required for interpretation. This STANDARD is not met as evidenced by: Based on review of the laboraotry procedure manual, patient reports and interview with the laboratory director, the lab director failed to ensure patient Menkes disease reports included appropriate interpretative information. Findings include: Cross- reference D5805. -- 3 of 3 --