ML20056H091

Forwards Proprietary Findings & Supporting Documents by Smithkline Beechman Clinical Labs & Elsohly Labs Re Rept of Unsatisfactory Performance Testing.Encl Withheld

ML20056H091
Person / Time
Site:	Farley
Issue date:	08/30/1993
From:	Dennis Morey SOUTHERN NUCLEAR OPERATING CO.
To:	NRC OFFICE OF INFORMATION RESOURCES MANAGEMENT (IRM)
Shared Package
ML19310D678	List: ML20056H091
References
NUDOCS 9309080215
Download: ML20056H091 (17)

Text

l Southsrn Nuctrar Opetating Company l

Post O*fice !}cx 1295 l

Bamingham, Alabamf35201 Telephone (205) 866-5131 a

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Southem Nuclear Operating Company i

om umy Nehr$?eY the soa:hern electnc system l

I AUGUST 30, 1993 Docket Nos.

50-348 i

50-364 U.S. Nuclear Regulatory Commission Attn: Document Control Desk i

Washington, DC 20555 Joseph M. Farley Nuclear Plant Reoort of Unsatisfactory Performance Testino Gentlemen-In accordance with 10 CFR 26 Appendix A, paragraph 2.8, Southern Nuclear j

Operating Company (Southern Nuclear) requires that blind performance test specimens be submitted to an HHS-certified laboratory used to confirm the presumptive positive on-site screens. On July 7, 1993 a presumptive positive sample was forwarded from the Southern Nuclear screening facility 3

at the Joseph M. Farley Nuclear Power Plant to SmithKline Beecham Clinical Laboratories (SKBL) located in Atlanta, Georgia for confirmation testing.

On July 13, 1993 the sample was reported as negative by the Medical Review Officer. An investigation was begun immediately upon receipt of the Medical Review Officer report.

l The subsequent investigation determined that various changes in the Olympus analyzer used by SKBL had been made to try to ascertain the underlying cause of the error. SKBL's investigation involved, but was not limited to, changing a Teflon ferrule inside a reagent valve, a source lamp change and-a readjustment of the reagent probe and sensor probe.

Corrective actions by SKBL include requesting a biomechanical engineer i

representative from the Olympus company to perform a sample probe alignment on the Olympus machine.

In addition, SKBL has added a special precision check after every. calibration to verify probe alignment and precision in i

order to prevent reoccurrence of this error. The enclosures contain the corrective action documentation.

Within the past two months, Southern Nuclear has experienced five.

unsatisfactory performance testing events. All events were blind i

performance samples, provided by ElSohly Laboratories, involving false negative reports either on amphetamine.or cannabinoids.

Three of these event investigations were conducted by Southern Nuclear on behalf of 1

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U. S. Nuclear Regulatory Commission Page 2 i

b Georgia Power Company, the licensee for Vogtle Electric Generating Plant.

i Reports on all events either have been or will be transmitted to the NRC in accordance with the regulations. Southern Nuclear's Corporate Quality Services in cooperation with a consulting toxicologist, Dr. Chris Frings, conducted a follow-up audit on August 2, 1993 of SKBL's investigation of i

the events and subsequent resolutions. The report of the audit was I

satisfactory.

Enclosed are the findings and supporting documents by SKBL and E1Sohly-Laboratories. This letter is considered to satisfy the reporting -

l requirements of 10 CFR Part 26 appendix A, paragraph 2.8.

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Should yot.. ave any questions, please advise.

Respectfully submitted,.

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i SOUTHERN NUCLEAR OPERATING COMPANY t

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l Dave Morey DNM/JMG i

Enclosures cc: Southern Nuclear Operatina Company

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Mr. R. D. Hill, General Manager - Plant Farley l

U. S. Nuclear Reaulatory Commission. Washinoton. DC l

Mr. T. A. Reed, Licensing Project Manager - Farley j

U. S. Nuclear Reaulatory Commission. Reaion II I

Mr. S. D. Ebneter, Regional Administrator l

Mr. G. F. Maxwell, Senior Resident Inspector - Farley il I

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SmithKimo Bxcham

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ClinicalLaboratories l

August 9,1993 i

i Ms. Sheree Carter Health Services Coordinator Southern Nuclear Operating Company P.O. Box 1295 Birmingham, Alabama 35201 j

Dear Sheree:

Now that our investigations are complete, I am writing to respond to the concerns brought up in your letter of June 16,1993.

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As requested, we did perform audits and fax reports weekly to Paul Bizjak for a period of one j

i month.

The second false negative amphetamine (V931494) was included in the overall investigation l

since both were due to the same interference as explained in the enclosed summary report. I previously forwarded the report from Doctors and Physicians Laboratory.

i The problem with channel one on the Olympus was originally attributed to a reagent valve seal l

(which was replaced as explained in my letter of June 10,1993 to Paul). Further investigations were devised employing a protocol to recreate the symptom / problem by using large batches of repeat analyses. This is explained in detail in the enclosed summary report. We were successful in capturing real-time evidence of the sympton. This allowed us to investigate stepwise every aspect of the testing procedure, both instrument and reagent-dependent, that could generate a change in performance. The problem was finally isolated and identified as _ sample _ probe j

alignment.

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To solve the problem, the sample probe was aligned to extend 1-2 mm beyond the liquid level sensor. The manufacturer only requires that the probe be level with the sensor. In channel one, j

the probe was actually found to be 1-2 mm shorter than the sensor, which is consistent with the j

more frequent occurrence of these random outliers on this channel. Since adjusting the probe in all analytical units. random suppression in all channels has been eliminated. Data are still being collected to monitor this.

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P.O. Box 50122 + Atlanta, GA 30302 * (404) 934-9205

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l 12tter - Carter Page 2

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To prevent reoccurrence of this incident, weekly maintenance of tl.e Olympus now includes a I

• special" precision check after recalibration to verify probe alignment and precision.

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t This problem was isolated to the probe alignment and was al related in any way to the use of l

extender with the Syva EMIT kits. We have verified that this would have occurred even if we f

l used the manufacturer's recommended reconstitution protocol.

The enclosed summary reports are included for your review. If you need any additional detail, j

please let me know. I hope that this report to you exemplifies our commitment to excellence j

l and service.

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Sincerely, r

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Michael S. Feldman, Ph.D.

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Technical Manager - Substance Abuse Testing l

SmithKline Beecham Clinical Laboratories - Atlanta i

MsF:jmr l

ENCLOSURE l

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FALSE NEGATIVE AMPIIETAMINES

SUMMARY

REPORT August 9,1993 Specimens:

781969G 811391G Results Reported:

Negative Expected Results:

Methamphetamine Amphetamine Reason:

All QC criteria for the confirmation load was acceptable. Methamphetamine was detected by GC/MS at a concentration of 2046. A compound which appeared to be amphetamine was detected at a concentration 2358. However, there was an interference with the 91 m/z fragment of amphetamine. Consequently, not all l

identification criteria for amphetamine were satisfied and, due to the

" amphetamine rule" (positive methamphetamine requires amphetamine), both methamphetamine and amphetamine were reported as negative.

S-phenethylamine is a natural putrification product of phenylalanine normally found in fresh urine at levels of about 30 ng/ml, which is much lower than our detection limit. The compound is structurally similar to amphetamine and they share extraction and chromatographic properties. Our method, at the time, could not adequately separate these compounds, and, since they both generate a 91 m/z ion fragment, interference would exist if the phenethylamine concentration increased to a high enough level. In theory, this could happen if pooled human urine is used over a period of time to make up QC materials.

i Resolution: Since this is likely to be a recurring issue, we took the position that our method needs to achieve separation between amphetamine and S-phenethylamine, without introducing other chromatographic problems. We were able to achieve this by changing our chromatographic method to utilize a DB-1 (dimethylpolysiloxane) column rather than a DB-5 (5% phenyl-methylpolysiloxane) column. The daily retention time standard will include phenethylamine to document resolution daily.

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i Appendixes A.

Original chromatograms of 781969G and 811391G showing interference on DB-5.

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B.

Chromatograms of 781969G and 811391G showing acceptable chromatography.

C.

Section of the SOP that documents the change to DB-1.

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APPENTIX A Original chromatograms of 781969( and 811391G showing interference on DB-5.

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Amphetamine Confirmation

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C:\\HPCHEM\\1\\ DATA \\AM0510\\AM051012.D erator

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10 May 93 7: 2 pm using AcqMethod NEWAMP.M on MSD-13 Acquire'd Sample Name: 781969G ll Misc Info Via1 Number: 12 l

l CuzIentMeth: C:\\HPCHEM\\1\\ METHODS \\NEWAMP.M 1

Amphetamine-D5 :ESTD1

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Merged 144.00 123.10 l

.LLTphetamine f

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t 12.89 3.16 2.89 3.16 2.89 3.16 2.89 3.16 Merged 140.10 91.10 118.10 Compound Signal RT Resp Ra*.io Limits Conc.

Amphetamine-D5 ISTI 144.001 2.90l 36925l 100.0%

l 333.0 l 123.101 2.90l 16212l 43.9 36.2-54.2 l Amphetamine l 140.10l 2.931 242805) 100.0%

l 2358.7 l

91.10l 2.93]

1078081 44.4 36.7-55.1 lN l 118.10l 2.931 201712 l 83.1 69.1-103.7 Amphetamine Response Ratio i

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Amount Ratio l

Resp Ratio = 9.28e-001 Amt l

RF Rel Std Dev = 1.1% [ Curve Fit: Avg RF 1

AM051012.D Mon May 10 19:33:06 1993 Page 2 l

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Amphotomino Confirmation C:\\HPCHEM\\1\\ DATA \\AM604\\AM060018.D Filo Op3rator

DBS Acquired 4 Jun 93 10:53 pm using AcqMethod NEWAMP.M on MSD-13 Scmple Name:.811391G [5]

Micc Info Vini Number: 18 CurrentMeth: C:\\HPCHEM\\1\\ METHODS \\NEWAMP.M Amphetamine-D5.:STD1 l

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_ 1i 2.71 3.07 2.71 3.07 2.71 3.07 Merged 144.00 123.10 Amphetamine l

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3.08 2.71 3.08 Merged 140.10

- 91.10 118.10 Compound Signal RT Resp Ratio Limits Conc.

Amphetamine-D5 ISTl 144.00l 2.84l 45063l 100.0%

l 333.0 l 123.10l 2.84l 19281l 42.8 33.5-50.3 l l

Amphetamine l 140.10l 2.861 576101 100.0%

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l 91.10l 2.86l 232591 40.4 33.0-49.

l-l 118.10l 2.86l 46557l 80.8 64.0-96.0 Response Ratio Amphetamine 5-e t

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6 Amount Ratio Resp Ratio = 8.46e-001

• Amt RF Rel Std Dev = 2.4%

Curve Fit: Avg RF AMD60018.D Fri Jun 04 23:04:00 1993 Page 2 j

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Chromatograms of 781%9G and 811391G showing acceptable chromatography..

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Amphetamine Confirmation i

C:\\HPCHEM\\1\\ DATA \\AM0731\\AM731009.D File Operator

JMK Acquired 2 Aug 93 3:24 pm using AcqMethod NEWAMP.M on MSD-13 Sample Name: 781969G Misc Info Via1 Number: 9 CurrentMeth: C:\\HPCHEM\\1\\ METHODS \\NEWAMP.M

).mphetamine-D5

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2.97 3.25 2.97 3.25 2.97 3.25 Merged 144.00 123.10 Amphetamine f

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2.99 3.27 2.99 3.27 2.99 3.27 2.99

'3.27 Merged 140.10 91.10 118.10 Compound Signal RT Resp Ratio Limits Conc.

t Amphetamine-D5 ISTl 144.00l 3.11]

43841l 100.0%

l 333.0 l 123.10l 3.111 17948]

40.9 33.7-50.5 l Amphetamine l 140.10l 3.131 262857l 100.0%

l 2161.1 l

91.10]

3.13l 122967]

46.8 39.0-58.6 l l 118.10l 3.13l 206848]

78.7 64.6-97.0 l Amphetamine Response Ratio 5-l l

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Amount Ratio Resp Ratio = 9.24e-001

• Amt RF Rel Std Dev = 2.4%

Curve Fit: Avg RF AM731009.D Mon Aug 02 15:34:33 1993 Page 2

Amphatamino confirmation C:\\HPC EM\\1\\ DATA \\AML731\\AM731010.D

• File-Operator

JMK Acquir.ed 2 Aug 93 3:41 pm using AcqMethod NEWAMP.M on MSD-13 Sample Name: 811391G Misc Info Vial Number: 10 CurIentMeth: C:\\HPCHEM\\1\\ METHODS \\NEWAMP.M Amphetamine-D5

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2.97 3.25 2.97 3.25 2.97 3.25 Merged 144.00 123.10 Amphetamine f

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3 2.99 3.27 2.99 3.27 2.99 3.27 2.99 3.27 r

Merged 140.10 91.10 118.10 Compound Signal RT Resp Ratio Limits Conc.

Amphetamine-D5 ISTl 144.00l 3.11l 41369l 100.0%

l 333.0 l 123.101 3.11l 16725l 40.4 33.7-50.5 l Amphetamine l 140.10; 3.13l 268576l 100.0%

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91.10l 3.13l 124749l 46.4 39.0-58.6 l l 118.10l 3.13l 2107171 78.5 64.6-97.0 l l

Amphetamine Response Ratio a

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Resp Ratio = 9.24e-001

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RF Rel Std Dev = 2.4%

Curve Fit: Avg RF AM731010.D Mon Aug 02 15:51:54 1993 Page 2

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f APPENDIX C Section of the SOP that documents the change to DB-1.

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' ImphetamineIMethainphetamine Analysis by GC/MS v2.2 Page 4 of 15 l

15.

Transfer the derivatized extracts to GC/MS autosampler vials and cap immediately.

INSTRUMENT PARAMETERS Hardware Gas Chromatogr:ph

- 5890 HP Mass Selective Detector

- 5970 HP Autoinjector

- 7673 HP 2

Data System

- DOS Analytical Column DB-1 (J&W or equivalent) 15 meter 0.25 mm ID 0.25 m film thickness l

Carrier Gas

- Helium (ultra pure) 60 psi Regulated pressure Gas Chromatograph Linear Velocity 55 cm/sec. @ 200*C Split Vent

- 12 mL/ min

+2 Septum Purge

- 2 mL/ min 0.2 Injection Liner

- 4 mm ID split /splitiess, with silanized glass wool l

i Septum

- Low bleed septum - any brand Autoinjector Injection volume

-2 Injection mode

- Fast Sample viscosity

-0 Sample wash

-0 Sample pump

-2 Solvent wash A

- 5 Methanol Solvent wash B

- 5 Isooctane NOTE: Wash / Waste vials should be replaced every 40 injections.

JUL 2 71993 u

Date:

Approved by:

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FALSE NEGATIVE THC

SUMMARY

REPORT August 9,1993 l

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Specimens:

817844G 867883G 877678G 1

t Results Reported:

Negative Expected Results:

THC Reason:

These specimens all screened borderline negative initially. All QC was acceptable. Other blind THC specimens submitted by the client were j

correctly reported as positive. Repeat analysis of problem specimens by -

l immunoassay and GC/MS gave positive results. This data suggested random outliers were being generated since QCs were acceptable. A i

l special protocol to recreate these." fliers" was initiated to determine the l

cause. By looking at precision oflarge numbers of repeat analyses (n =

80 or 50) we were able to reproduce and verify that randomLfliers were indeed being generated, although statistical precision was acceptable.-

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Using this special precision protocol we were able to investigate, in a' stepwise fashion, potential causes of random outliers.

The ' items i

investigated, but determined n01 to be the cause of these outliers, were.

UV Lamp Valve seals Analytical unit comparison i

Instrument comparison Channel comparison l

Optics

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Specimen aging / handling THC absorption to sample cups -

Water Parity (pH and bacterial contamination) j Mixing bar function -

Reagent equilibration -

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l False Negative THC Summary Report l

Page 2 8/4/93 i

J Reagent dispensing.

Reagent recipes (SBCL vs reagent manufacturer's recommended reconstitution) l The problems was not determined to be specific to an analytical unit or channel, i

although one channel exhibited more fliers than others, which was consistent with j

close examination of the probe alignment on that channel. Our investigation into l

sample dispensing uncovered the need to adjust the sample probe so.that it extends 1-2 mm beyond the liquid level sensor (this goes beyond the instrument manufacturer's specification.) It was found that short sampling was occurring without instrument detection. This could occur if the sensor made contact with ~

j the sample and the probe did not (the instrument did not know it was not picking j

up enough sample). The instrument is designed to signal a problem if the sensor i

failed to make contact with the liquid in the sample cup. Since the meniscus of the liquid in the sample cup is not flat but concave, it was determined that it is possible for a " properly aligned" sample probe to short sample occasionally,

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with the meniscus.

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Resolution: To solve the problem, the probe was adjusted to extend 1-2 mm beyond'the -

sensor to insure its immersion into the sample. Since this adjustment, we have generated more than 10 consecutive days of special precision data (n = 50 each day) which indicates that the random outliers have been eliminated. These sets -

l also included precision on a portion of the specimen, forwarded by Sheree Carter 1

on July 22,1993, which was a part of the same lot of material that generated the l

false negative results.' We will continue to collect precision data for an additional l

2 weeks. We will modify our weekly instrument maintenance to include a special precision check to monitor prebe alignment.

j In addition, the investigation showed that specifications for the optical system that are more stringent than the manufacturer's recommendation also help eliminate random " fliers". All of these new specifications have been incorporated into the laboratories SOP.

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SUMMARY

OF FALSE NEGATIVE INVESTIGATION SPECIMEN #

ORIGINAL RESULT DATE REPEAT RESULTS DATE CC/MS RESULT 817S44G 0.980 6/3 1.034 6/5 000 ng/ml 1.091 7/16 867883G 0.879 7/9 1.058 7/14 142 ng/ml (1.11)*

1.079 7/76 877675G 0.999 7/15 1.163 7/17 139 ng/mi 831665G 1.269 6/12 1.042 7/14 (1.14)*

1.011 7/16 207 ng/ml 844673G 1.106 6/22 1.051 7/14 155 ng/ml (1,12)*

1.062 7/16 (Result reported by SNOC)

Recalculated using SBCL ratio