Attachment_8_-_DoD_DRUG_TESTING_LABORATORY_INSPECTION_PROGRAM.pdf

Department of Defense Quality Assurance Laboratory February 2016 DoD Drug Testing bo at y Inspection Program Filename: 015_IN PEC S.doc Page 1 of5

Approved by: Date: _CJ_r_~ __ /;...._b __ _ Thomas , P .D., CDR, USN Chief, Division of Forensic Toxicology

DoD DRUG TESTING LABORATORY INSPECTION PROGRAM

PURPOSE: The purpose of this SOP is to describe the Department of Defense (DoD) Drug Testing Laboratory inspection program managed by the DoD Drug Detection Quality Assurance (QA) Laboratory, Division of Forensic Toxicology (DFT), Armed Forces Medical Examiner System (AFMES), Defense Health Agency (DHA). In accordance with the DoD Instruction (DoDI) 1010.16 and as part of the DoD Drug Testing Program laboratory certification process, each military drug testing laboratory will be inspe~ted three times per fiscal year.

INSPECTION SCHEDULE AND TEAM FORMATION:

1. All inspection team members will arrive at the designated Laboratory by 0800 on

Tuesday

2. All inspection team members must remain at the designated Laboratory through the completion of the Thursday Inspection Outbrief

3. The inspection team must be a minimum of 5 members (less are authorized due to budget constraints) and can be composed of the following:

a. A Service-relevant Drug Testing Program Manager

b. Two contract inspectors (for the two contract inspections per Laboratory per fiscal year and one will be the lead inspector)

c. One or two scientists from the DFT, AFMES (will be lead inspector for DoD inspections)

d. Additional military and civilian scientists from other DoD Drug Testing

Laboratories who are certified in their respective laboratories and sections

e. A Judge Advocate General (JAG) representative (not included for inspection team size requirement)

4. Special testing laboratories may vary from the above requirements

LABORATORY INSPECTION PREP ARA TIO NS:

1. Pre-Inspection Materials: The following items must be uploaded to the DoD

Sharepoint (positive pull list can be forwarded to the DoDQA Laboratory, DFT, AFMES) at the time intervals indicated:

a. Electronic copies of all Laboratory LOPs I SOPs I Ois, Non-conforming event

(NCE) reports, and Memorandum for Record (MFR) summary

1) 30 business days prior to the start of the inspection

b. Positive Data Package Pull-list (covering the four-month inspection period to include single and multi-positive specimens)

1) 15 business days prior to the start of the inspection

2. Required On-Site Inspection Materials: The following items must be present and ready for inspection upon arrival of the inspection team:

a. Hard-copies of all Laboratory LOPs I SOPs I Ois

Department of Defense Quality Assurance Laboratory DoD Drug Testing Laboratory Inspection Program Filename: 015_INSPECTIONS.doc

b. Service-specific SOPs, if applicable

c. DoDI 1010.16 and DoDQA Inspection SOP

February 2016

Page 2 of5

d. AFMES Open and Blind Proficiency Reports for the inspection period

e. All data packages (as well as a printed copy of the specimen event history generated from FTDTL-IMS for each specimen) as requested by the Lead Inspector

f. All documentation packages I bottle request packages for the inspection period

g. All Quality Assurance Reports (NCEs, MFRs) and Quality Assurance Meeting

Minutes and Monthly Reports for the inspection period (see attached Memorandum for QA Program Minimum Requirements)

h. All Quality Control performance reports for the inspection period

i. List of QC material certified during the inspection period J. Immediate Prior Inspection Report & Laboratory Response I Corrective Action

Documentation

k. Laboratory Staff Organizational chart

1. Safety & Industrial Hygiene Inspection reports (for administrative review only, not required to perform separate safety inspection)

m. Physical & Information Security reports

n. Training Documentation for all newly-certified staff (covering the inspection period) to include written exams as well as for any decertified staff members

o. Validation data for all newly-certified analytical methods and annual certification data (see attached Memorandum for Confirmation Validation Requirements)

3. In-Brief Presentations: The following items must be covered during the in-brief presentation given to the inspection team (all information should cover the inspection period):

a. Brief description of Laboratory challenges and accomplishments (method issues, analytical issues, etc.)

b. Laboratory Staff Organizational Chart and staffing changes I vacancies

c. Laboratory Operations schedule (including typical times of various Lab activities)

d. Summary of analytical instrumentation

e. Facilities updates, renovations, Information Technology issues

f. Workload Statistics:

1) Number and types of specimens tested

2) Positive, rejection and discrepancy rates

3) Positive and negative specimen tum-around times (to include the average for the inspection period)

g. Legal Support Statistics:

1) Expert witness support information (requests v. supported)

2) Legal Documentation package numbers and tum-around times

3) Discovery request and bottle send-out request numbers and tum-around times

h. Brief discussion of all Quality Assurance incidents and Laboratory investigations L Brief discussion of major safety and/or security incidents J. Brief discussion of all newly-certified analytical methods

k. Brief discussion of all research and development projects

Filename: 015_INSPECTIONS.doc

CONDUCT OF INSPECTIONS:

February 2016

Page 3 of5

1. Inspections will be conducted for three full business days (typically Tuesday through Thursday). Special testing laboratories may vary.

2. The Lead Inspector will ensure that the inspection assignments cover all significant Laboratory areas. Each inspector will provide the Lead Inspector with notes prior to departure from the inspection (see attached section summary guides). The Lead Inspector will also ensure the distribution of additional review work (e.g., data packages) among the inspection team members so that all required tasks can be completed. Below is an overview of items that should be reviewed, the inspection team is not limited by this list (see attached Memorandum for Consolidated Inspection Minimum Requirements):

a. Specimen receiving

b. Specimen processing and aliquot handling

c. External and internal quality controls

d. Security and safety (general review of proper security and safety measures in place)

e. Information management to include specimen records documentation, maintenance, and storage.

f. Quality Assurance

g. Specimen screening procedures

h. Confirmation testing procedures

1. Personnel training J. Maintenance and calibration records for all laboratory equipment

k. Validation of analytical methodologies utilized to test all specimens

1. Laboratory administration and management

m. Supply procedures and operations

n. Data review and results certification

o. Litigation support

p. Other aspects of laboratory operations that may affect the forensic soundness and scientific supportability of the DoD drug testing program

3. The Lead Inspector is designated to write the Outbrief Executive Summary and the

Final Inspection Report. All inspection team members will be responsible for presenting their findings and recommendations, in writing, to the Lead Inspector each day of the technical inspection for inclusion in the OutbriefExecutive Summary and Final Inspection Report. This documentation must include copies of supporting documentation (e.g., items to be included as tabs to the report).

4. Daily outbriefs of findings will be conducted at the end of each inspection day (at approximately 1600). The inspection team will discuss any and all findings with the senior Laboratory staff, as designated by the Laboratory Commander, so that any misunderstandings or misinterpretations can be reconciled while the inspection team is still on-site.

INSPECTION REPORTS:

1. TheDraft Inspection Report will be forwarded to all inspectors as well as the

Program Manager(s) for review prior to distribution. The scope of the review is to

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February 2016

Page 4 of5 correct grammatical errors and to verify all statements in the Report are accurate.

After comments are returned to DoDQA and the Report is finalized, it is ready for distribution to the program.

2. The Final Inspection Report format will consist of findings and as defined below. All issues found during the inspection will be described by an objective finding. The Laboratory is responsible for addressing all findings. Lead Inspectors I Authors will avoid the use of subjective comments and mandates.

3. Since the Final Inspection Reports are business records that can be subject to discovery by the Courts, the designated Lead Inspector I Author must take care in temperately crafting the language of each Final Inspection Report. All findings and recommendations must be phrased such that the intent is easily understood by all readers, including those outside of the Forensic Toxicology community.

Furthermore, it is important that the lead inspector ensures the tone of each Report is consistent and without bias.

DEFINITIONS OF FINDINGS AT INSPECTIONS:

-Recommendations:

The evaluated area was deemed to be in compliance with forensic laboratory practices and DoD requirements, but there is an alternative procedure/practice that should be considered by the laboratory for possible adoption or inclusion in its standard operating procedure. The laboratory is required to respond to the recommendation but is not required to adopt the proposed change.

-Requirements:

The evaluated area was deemed non-compliant with forensic laboratory practices or DoD requirements and must be reconciled to the satisfaction of AFMES by the time of the next inspection. A problem in the evaluated area did not affect the integrity or credibility of the drug testing laboratory but does require resolution. The finding subjects the laboratory to be questioned or challenged by outside forensic experts or inspectors.

-Deficiencies:

The evaluated area was deemed non-compliant with forensic laboratory practices or DoD requirements to the extent that the integrity and credibility of the testing results might be in jeopardy. The problem is considered serious and failure to address immediately could lead to decertification of the laboratory.

-Unacceptable Performance:

The evaluated area was deemed non-compliant with forensic laboratory practices or DoD requirements. Critical flaws were discovered in analytical practices, reporting, or record keeping procedures. These flaws are ·considered so severe as to warrant immediate suspension of testing and decertification of the laboratory.

LABORATORY RESPONSE TO INSPECTION REPORTS:

1. The laboratory is given approximately thirty days to respond to reports. The laboratory must receive approval from their respective program manager prior to sending the response to AFMES.

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February 2016

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2. The laboratory may non-concur with Recommendations; when they are in compliance with forensic laboratory practices and DoD requirements. When a laboratory non-concurs with anything other than a Recommendation and the Service Program Manager approves, the issue will be forwarded to the BT AB and the Director, DoD Drug Testing Policy and Programs for adjudication.

KEAL.TH ACE CY

OFFICE OF THE ASSISTANT SECRETARY OF DEFENSE

HEALTH AFFAIRS

ARMED FORCES MEDICAL EXAMINER SYSTEM

11 5 PURPLE HEART DRIVE

DOVER AFB, DE 19902-5051

24 Nov 2015

M MORANDUM FOR DIRECTOR, DRUG TESTING AND PROGRAM POLICY-OFFICE

OF THE UNDER ECRET ARY OF DEFENSE FOR PERSONNEL AND READINESS

UBJECT: Updated Minimum Validation Requirements for Confirmation

Validation studies are performed to characterize and certify the laboratory' s confirmation assays and analytical instruments prior to implementation. The Drug Demand Reduction Program DDRP) Confirmation Working Group (CWG) published requirements for Confirmation ·

Validation (No 2012) for use by the DDRP laboratories. The criteria were subsequently approved by the Biochemical Testing Advisory Board. The original requirements have been modified and this document reflects the current minimum requirements for validation at the DDRP laboratories.

Assay Validation. Confirmation assays must be validated on each instrument model. An instrument model is considered to be the instrument components that determine the qualitative and quantitative identification (e.g., Agilent 7890 GCIHP-5MS 15m column/5975 MSD). There are two confirmation assay validation categories: Full and Abbre iated.

a. Full - Prior to programmatic approval and implementation of each new analyte confirmation assay, a laboratory must perform a complete alidation study. The validation data must be reviewed and appro ed by the Armed Forces Medical Examiner ystem (AFMES) Division of Forensic Toxicology prior to use. Validation of a new analyte confirmation assay includes successful analysis of AFMES certification samples. Validation of a new confirmation assay may include validation of a new instrument.

b. Abbreviated - Prior to service program manager approval and implementation of any modified confirmation assay (including modification of instrument parameters), a laboratory must perform a validation study that focuses on those parameters that may impact the quantitative results.

Instrument Validation. All confirmation instruments must be validated. There are two confirmation instrument validation categories: Full and Abbreviated.

a. Full - For each instrument model, a laboratory must perform a complete validation study on at least one of the instruments prior to placing instruments of that model into service.

b. Abbreviated - For each additional instrument of a specific model a laboratory must perform the full validation, excluding precision/accuracy around the cutoff, interference and parallel studies. For LC instrumentation matrix effect is excluded for additional instruments.

Validation Requirements.

a. Linearitv/Limit tudies: Analyze 3 valid replicates at 6 concentrations (3 below and 3 above the cutoff). The mean of each replicate set must be within ±20% of the theoretical concentration. The Coefficient of Variation (CV) must be S I 0%.

I. The Upper Limit of Linearity (ULOL) is the highest concentration at which all acceptance criteria are met.

2. The Limit of Quantitation (LOQ) is the lowest concentration which allows analyte identification and accurate quantitation (i.e. , ion ratios acceptable, quantitation within ±20% of the theoretical concentration).

3. The Limit of Detection (LOO) is the lowest concentration which allows analyte identification, but does not require an accurate quantitation (i.e. , ion ratios acceptable, quantitation outside ±20% of the theoretical concentration). LOO should be ~ LOQ.

4. If a laboratory is evaluating only one end of the linear range (LOQ or ULOL) then they may analyze only 3 concentrations below (LOQ) or above (ULOL) the cutoff with the same acceptability criteria listed above.

b. Precision/ Accuracy Studies: Both intra-run and inter-run precision shall be assessed.

The laboratory must analyze 3 replicates at 3 concentrations in five separate runs and document the mean, standard de iation and CV. The mean of each replicate set must be within ±20% of the theoretical concentration and the CV must be S 10%

c. Specificity/Interference Studies: Laboratories should evaluate assay performance when challenged with compounds (OTC, Rx, illicit) that are commonly ingested by the tested population and could potentially interfere with assay performance.

Compounds with structural similarity to the analytes being validated should be included when possible. The compounds should be spiked at known concentrations in the presence of the analyte at 40-50% and 0% of the cutoff concentration. A proposed interference list is below.

Opiate~!

Alla/gesic

Methadone Buprenorphine

Tramadol

Codeine Fentan I

H drocodone

Hydromorphone

PRESCRIPTION DRUGS

Antidepressa11ts CNS Stimulants A111i11ypertensives Depressants

Amitriptyline Alprazolam Methylphenidate Verapamil Desipramine Clonazepam Caffeine Atenolol fmipramine Diazeparn d-Amphetam ine Propranolol

Doxepin Flunitrazepam Methamphetamine Lorazepam

Nitrazepam Oxazepam

Meperidine

Morphine aloxone altrexone

Oxycodone

Ox morphone

Pentazocine

Antihist{lmines

(HJ}

Dox !amine

Diphenhydram ine

Ph en iram ine

Chlorpheniramine

Temazepam

Methaqualone

Pentobarbital ecobarbital

Glutethimide

Butabarbital

Phenobarbital

OVE.R-THE-COUNTER DRUGS

Antitussive

Dextromethorphan

NSAJDS/Analgesics

Acetaminophen

Ibuprofen

Naproxen

Antil1istamb1es (H2}

Cimetidine

Decongestants

Phenylephrine

Pseudoephedrine

Misc

Cotinine

d. Parallel Studies: A parallel study should be performed on any new or modified method (extraction or instrument) by comparing its performance against the established method. This study should include at least 20 previously-confirmed positive samples, if available. Alternatively, 20 blind samples prepared by another laboratory at concentrations ranging from 50 to 150% of the cutoff concentration may be used.

Additional Validation Requirements for LC-MS/MS.

a. Matrix Effects: The laboratory should evaluate matrix effects for potential signal suppression or enhancement, b e aluating 10 different sources of human urine piked at 40-50% of the cutoff concentration.

b. Parameter Optimization: The laboratory should determine the optimal MS/MS parameters and conditions considering compound characteristics in addition to instrument configuration and manufacturer specificities.

c. Parallel Studies: A parallel study should be performed using LC-MS/MS with the results evaluated against the existing GC-MS method if applicable. This study should include at least 20 previously-confirmed positive samples if available. Alternatively, 20 blind samples prepared by another laboratory at concentrations ranging from 50 to 150% of the cutoff concentration may be used.

<) Comact the undersigned al 302-346-8731 '/!.lra~y i/quiri~: ~eg~rding this request.

I ( / . / I •/ .

i1 .

I ' / ·-:- --- . ) ! .. , C'DR Thonirnfl~B:)sy, r+.D Chief~ Division Fo1'ensic foxicology The Armed Forces Medical Examiner System

COL Thomas M. Martin. Ph.D Director Drug Testing and Program Policy

OEFENSE

lrnA LTlt A<;E'l'C\'

OFFICE OF THE ASSIST ANT SECRET ARY OF DEFENSE

HEALTH AFFAIRS

ARMED FORCES MEDICAL EXAMINER SYSTEM

115 PURPLE HEART DRIVE

DOVER AFB, DE 19902-5051

15 Dec 201.'5

MEMORA~DUM FOR DIRECTOR, DRUG TESTING AND PROGRAM POLICY -OFFICE

OF THE UNDER SECR ETARY OF DEFENSE FOR PERSONNEL

A D READINESS

SUBJE ~T : 1Jpda1ed Do D Mini mum Qualit y Assurance (QAl Requirements

The Biochemical l stin Ad isory Board (BTAB) voled to approve the Quality Assurance minimum requ iremenL<> in December 2012. The STAB has since appro vc<l additional requiremem: to the original guidance; these are listed below. T he updated requi rements are attached .

a. The QA Officer must he aprointcd as a Positive I Final LCO in writing hy the rTDTL Commander with in six months or employment.

b. QA monthly meetings shall occur by the I 51 h of the fol owing month.

c. QA monthl y report !'> shall be completed by Lhc 15 111 of the foll owing month.

Please comact the undersigned at 302-346-873 1 with any inquiries regarding this request.

l~IHll~ li lll\C:tll"

J\t ta<:h ment

CDR Th~Ph.D Chief. Division Forensic Toxicology The Armed Forces Medical Examiner System r~l&dz:- COL Thoma~ M. M artin , Ph.D Director Drug Testing and Program Puli1,:y

DOD QA PROGRAM MINIMUM REQUIR EMENTS

14 Dec 2015

DOD QA PROGRAM MINIMUM REQUIREMENTS

Ref: (a) DoD Instruction 1010.16 of 10 October 2012

(b) DoD DTP QAWG memo of 27 Sep 12 (QA Standardized

Definitions)

(c) QAWG presentation of Jun

10 at the Joint Service Meeting (QAWG Update)

(d) QAWG memo of 6 Jul 11

{Quality Assurance Laboratory Audits Ver 4.0 Reviewed and Approved by BTAB 19 Jul 11)

1. Quality Assurance (QA) Program Role. Makes recommendations to the Command for quality improvement / process improvement based on results from work product audits, work process audits, non-conforming events (NCE) reviews and training records reviews.

2. Local Operating Procedures I Instructions. The Forensic Toxicology Drug Testing Laboratories (FTDTL) must have operating procedures (OP) manuals that describes the QA Program and define the documentation used by the FTDTL to manage the Program.

FTDTL documentation must include the use and tracking of NCEs and Memoranda for Record (MFR) for any occurrence that does not follow the strict guidelines of the FTDTL's OP manual.

3. QA Officer (QAO).

a. A QA Chief or QA Officer (QAO) will be designated in writing by the FTDTL Commander.

b. The QAO is responsible for overall management of the QA Program.

c. The QAO must be independent of the Laboratory Technical Director I Operations Director (i.e., reports directly to Commander I Commanding Officer [CO] or Deputy Commander I Executive Officer [XO])

d. The QAO must be qualified and certified at the positive Laboratory Certifying Official (LCO) level as follows:

(1) Be appointed as a Positive / Final LCO in writing by the FTDTL Commander within six months of employment.

(2) For those appointed subsequent to 10 October 2012, have at a minimum a Bachelor's degree in toxicology, Subj: DOD QA PROGRAM MINIMUM REQUIREMENTS biochemistry, chemistry, or a physical or biological science from an accredited U.S. university.

(3) Complete a comprehensive training program that documents technical understanding of the methodologies and forensic regulations used to process and analyze Service member specimens, review analytical data and report drug-testing results.

(4) Demonstrate proficiency and technical competency to perform testing procedures within the FTDTL and complete certification in all technical areas of the FTDTL.

e. The QAO shall dedicate a minimum of 50% of time to QA duties.

f. The QAO should seek continuing education on NCEs and other quality processes, such as Lean Six Sigma.

g. The QAO should be available during all technical inspections as a partner in the inspection process.

4. Quality Assurance Meetings.

a. Shall be held monthly. Meetings shall occur by the 15th of the following month.

b. Minutes for the meeting must be documented.

c. A member of laboratory's leadership must attend meetings.

d. Shall necessarily include review of work process and work product audits, old and new business, and open and closed items.

5. NCEs and MFRs.

a. The QAO is responsible for ensuring the . investigation of all NCEs for both technical and operational issues and for ensuring the proper use and tracking of MFRs.

(1) NCEs shall be used to document all situations in which requirements are not fulfilled . Requirements include all those items codified in LOPs, SOPs, ors, DODis, and other instructions and pertain to circumstances associated with the forensic integrity of the specimens, which necessarily includes data control (including Information Management I Information Technology) and physical security.

(2 ) NCEs shall be classified as either Category A, B or C, depending on the severity of the event:

(a) NCE Category A - Critical Events: These events cause an immediate and significant risk to maintaining DoD certification. They directly affect the integrity of the laboratory's drug test results. This category will also be used for the repetition of serious (Category B) events, indicating a failure of the laboratory technical or administrative procedures.

{b) NCE Category B - Serious Events: These events negatively impact the integrity of the laboratory's drug test results but do not cause an immediate risk to maintaining DoD certification. These events could have resulted in a Category A

- Critical Event but did not, due to chance or timely intervention. This category will also be used for the repetition of minor {Category C) events indicating discernible trends.

(c) NCE Category C - Minor Events: These events occur outside normal laboratory practice and are documented to maintain forensic data integrity and may be used to monitor trends.

(3) MFRs shall be used to explain situations that are not described in an LOP, SOP, or or DODI. While a MFR may be required to clarify a NCE, there are situations in which a MFR will be required when no NCE category is assigned:

(a) Technical MFRS shall be used to document procedures not explicit in any LOP, SOP, or or DOD instruction.

These are not NCEs as they are not deviations from written instructions, rather they explain extraordinary circumstances not described in any procedures manuals or instructions.

(b) Administrative MFRs shall be used to document administrative matters.

b. NCE Report Contents:

(1) Incident Description

(2) Categorization (A, B or C)

(3) Incident Investigation including event classification as:

{a) System - simple human error

(b) Knowledge - lack of training and/or supervision

(c) Behavior - willful recklessness

(4) Immediate actions taken

(5) Conclusions

(6) Corrective and Preventive Actions Recommendations

(7) Supporting documentation for all corrective action(s):

(a) Training Records

(b) OP manual changes, if applicable

(c) Copies of purchase orders, if applicable

(d) MFRs, if applicable

(8) NCE reports must represent a "closed-loop" product that includes the signature and date of the Commander/CO that documents their review of all NCE supporting material, QAO recommendations, and corrective actions taken.

6. Laboratory Work Process and Work Product Audits.

a. Audits are necessary to ensure accuracy , forensic integrity, and concurrence of practice with policies published in local and higher instructions.

b. There shall be monthly laboratory work product audits performed by the QAO or by a LCO designated by QAO (or the Command) These audits will include the following:

(1) All analytical instrument (immunoassay , chromatographic and mass spectral instrumentation) maintenance records

(2) All temperature records

(3) All physical access records

(4 ) All safety and security records

(5) All pipette calibration verification records

(6) All analytical balance records

(7) Reagents in use: labeling, preparation, storage, expiration, verification of validation I certification records

(8) Quality Control: Labeling of calibrators, controls and internal standards to ensure all materials have a preparation date, an expiration date, and a lot number(s).

(9) Physical inspection of the laboratory (this task may be completed by the laboratory's safety officer I representative)

(a) Clutter

(b) Hazards

{c) Safety violations or potential safety violations (e.g., proper use of PPE)

(10) Technical Personnel training and certification records

[Note: Criteria for technical personnel training and certification are established by each Command. While QA may be a participant in developing the training requirements, QA's pri mary responsibility is auditing the training records to ensure that the training and certification program is followed.]

(11) A review of monthly Armed Forces Medical Examiner System (AFMES) Open and Blind Proficiency Testing Reports and conduct of trend analysis, as needed.

(12) A review of a minimum of 10% of the data for all positive Service member specimens reported each month. These data should be randomly selected and the review should include:

(a) Screening data and all related chain of custody documents

(b) Confirmation batches and all related chain of custody documents

(c) Associated DD Forms 2624 or Form 40-8-3-R-E (external chain of custody documents)

(d) Associated MFRs I NCEs

1. Open Issues

2. Closed Issues

3. Quality of MFRs / NCEs

(e) Legal and external customer support documentation (e.g., affidavits, laboratory documentation packages, technical reviews, etc.).

c. There shall be quarterly laboratory work process audits performed by the QAO or by a LCO designated by QAO (or the Command) . These audits will include physical observations of the following:

(1) At least one process in Specimen Control I Accessioning and Screening / Initial Testing

(2) Staff performing various technical functions in Confirmation (Extractions & instrument laboratory) and LCO review and results certification and reporting.

d. There will be ongoing monitoring performed by the QAO or by a LCO designated by QAO (or the Command) of the following:

(1) Review of MFRs for quality and trend analysis

(2) Review of NCEs for quality and open I closed status

(3) Review of control charts for immunoassay control material and conduct of trend analysis (if applicable)

(4 ) Review control charts for Confirmation control material and conduct of trend analysis (if applicable)

e. At least annually, all sections of the laboratory OP manual and associated practices shall be audited, to ensure agreement between policy and practice. Furthermore, these

· Subj: DOD QA PROGRAM MINIMUM REQUIREMENTS audits should include evaluation of concurrence and compliance with higher policies and instructions.

7. Reporting.

a. On a monthly basis, the QAO shall prepare a concise report detailing findings, trends, recommendations, root causes, summaries, and open and closed items associated with these work product and work process audits. The report shall be completed by the isth of the following month.

b. These monthly reports, along with QA meeting minutes, NCEs (with all associated documentation), and MFRs, shall be presented for periodic external inspections.

DEFENSE

HEALTH AGENCY

OFFICE OF THE ASSISTANT SECRETARY OF DEFENSE

HEAL TH AFFAIRS

ARMED FORCES MEDICAL EXAMINER SYSTEM

115 PURPLE HEART DRIVE

DOVER AFB, DE 19902-5051

12 Jan 16

MEMORANDUM FOR Director, Drug Testing and Program Policy-Office of the Under Secretary of Defense for Personnel and Readiness; Readiness, Programming and Assessment

SUBJECT: DOD QA CONSOLIDATED INSPECTION MINIMUM REQUIREMENTS

Ref: (a) DOD Instruction 1010.16of10 Oct 2012

(b) Minimum Quality Assurance Requirements memo of 15 Dec 15

(c) Updated Minimum DDRP Validation Requirements for Confirmation memo of 24

Nov 15

(d) AFMES DoD Drug Testing Laboratory Inspection Program SOP

Purpose. This memorandum provides minimum requirements for conducting quality assurance (QA) inspections of drug testing' laboratories as required by Department of Defense (DoD) Instruction (DODI) 1010.16 (Technical Procedures for the Military Personnel Drug Abuse Testing Program - MPDATP). Procedures outlined for inspections are also based upon established forensic toxicology principles and appropriate current federal regulations.

Guidance. The extracted elements listed below are the minimum inspection. requirements to be utilized by the laboratory and the inspectors. This information is consolidated from the references listed above.

DODI 1010.16.

A. The following requirements must be met for each forensic toxicology drug testing laboratory (FTDTL) staff member listed below (DODI 1010.16 Enclosure 3):

(1) Commanders: 0-4 or above, PhD and 3 years experience in a DoD FTDTL

(2) Technical Directors:

a. Appointed in writing

b. PhD or Masters degree

(3) Expert Witnesses:

a. Appointed in writing

b. Bachelor's degree

c. Complete a comprehensive training program to include certification as a laboratory certifying official (LCO), expert witness training, and certification requirements of the FTDTL and MPDATP

(4) LCOs:

a. Appointed in writing

b. Bachelor's degree

c. Complete comprehensive training program that documents technical understanding of the methodologies and forensic regulations used to process and analyze specimens, review data, and report results

d. Demonstrate proficiency and technical competency to perform testing procedures within the FTDTL and complete certification in all technical areas of the FTDTL

B. The following are requirements listed by Laboratory sections I processes (DODI

1010.16 Enclosure 4):

Operating Procedures (OP) During Catastrophic Incidents: Each FTDTL shall have documented a continuity of operations plan (COOP) in the event of a catastrophic incident during which operations are temporarily suspended

Laboratory Security:

a. Security of urine specimens and aliquots used in testing shall be maintained at all times

b. Commander will authorize in writing or by electronic means individuals with access to each limited access area

c. FTDTL shall have physical security measures

1. Intrusion alarm system

2. Camera monitors and recording devices

3. Motion detectors

4. Card access

5. Card entry tracking

Internal Laboratory Chain of Custody (CoC):

a. Internal CoC must be used to document all specimen and aliquot transfers

1. During processing

2. To I from storage

3. To specimen disposal (may be captured within laboratory information management system - LIMS)

b. The form will reflect

1. Date of transfer

2. Releaser

3. Receiver

4. Purpose of transfer

c. Specimens will be tracked by unique laboratory accession number that is assigned to DD 2624 upon receipt

d. Specimens are considered to be in custody of technician as long as they remain in same secured area. If technician leaves this area custody must be transferred. Custody of specimens must always be transferred to screening analyzer, mass spectrometer, or other instruments during analysis

Specimen Receipt and Processing:

a. Technician must

1. Examine package

2. Examine specimen

3. Examine CoC

4. Identify and document submission discrepancies

5. Sign and date CoC for receipt.

b. Comply with the list of fatal and nonfatal discrepancy codes established by the respective service

c. Must assign a unique laboratory accession number (LAN) to each specimen and place on CoC, bottle, and bottle lid

Drug Testing:

a. FTDTL must only test the DoD authorized panel of drugs

b. Screen all specimens for

1. THCOOH

2. BZE

3. 6AM

4. Amphetamines (including MDA I MDMA)

5. Morphine I Codeine

6. Oxycodone I Oxymorphone

7. Hydrocodone I Hydromorphone

c. Pulse test (20-100%) of all specimens for other drugs on the authorized panel

1. Benzodiazepines

2. Synthetic Cannabinoids

d. All specimens shall be tested, except for those specimens with discrepancies determined to be fatal according to FTDTL OP manual

Initial Screen Test:

All immunoassay (IA) test kits used for initial screen test must be authorized by the Director, DoD Drug Testing and Program Policy (DDT &PP) and must be approved for commercial sale and distribution by the FDA unless otherwise noted

a. Validation will be described in FTDTL OP manual and must include, at a minimum:

1. IA precision at 0, 50-75, 100, and 125-150% of screening cutoff concentration

2. No data overlap between 0 and I 00% of cutoff concentration

3. IAs ability to discriminate between(+) and(-) specimens near the 100% cutoff concentration

4. IAs ability to differentiate between known(+) and(-) specimens

5. Side by side study of current and new or revised IA

6. Interference from similar or related compounds

b. Technician will complete the intra-laboratory bottle and aliquot CoC documents contemporaneously

c. Technician will work with one specimen bottle at a time

d. A pipette or any other sampling device will not be used to transfer an aliquot from the original specimen bottle

e. Specimen bottles will be transferred to secure storage

f. Aliquots will be transferred to secure storage or to technician conducting initial testing

g. Each batch will contain a minimum of 5% open controls.

h. Instrument will be calibrated daily. Calibration acceptance criteria include:

1. Negative control must test lower than low control

2. Low control (50-75% cutoff) must test negative

3. High controls (125-150% cutoff) must test positive

1. Each batch will contain a minimum of one blind(+) and one blind(-)

j. Controls will be placed randomly in the batch

k. Positives must test positive and negatives must be below the low control I. The FTDTL OP manual will provide guidance for partial batch acceptance

Adjunct Screening Test:

a. Director, DDT &PP shall authorize adjunct screen tests

b. Adjunct test may be conducted on same aliquot as initial test

Confirmatory Test:

a. General guidelines for extraction procedures and confirmatory analysis include:

1. One-to-one extract transfer during extraction procedures and transfer to instrumentation must be performed to maintain forensic integrity

2. Each batch must contain a minimum of:

1. 5% standards and controls

11. Extracted urine calibrator at the cutoff concentration

iii. Drug free(-) control

iv. Open low control (40-50% cutoff)

v. Blind(+) control (120-200% cutoff) v1. If hydrolysis is performed a hydrolysis control is required if available

vn. All standards, controls, and specimens must be processed and analyzed as part of the batch using the same procedures

3. Internal standard will be added to all samples analyzed. It will be a deuterated analog of the analyte, if available.

b. General guidelines for mass spectrometry analysis include:

1. Instrument must have acceptable autotune or system verification sample injected within 24 hours prior to the injection of the calibration standard

2. All calibrators, controls, and specimens will be analyzed simultaneously and under the same conditions

3. Calibrator will be injected as a drift control at the end of each batch run and must be within ± 10% of its theoretical value

4. A minimum of three mass ions for analyte and two for IS must be presented in the data printout for all gas chromatography I mass spectrometry (GC/MS) analyses.

At least two transitions for the analyte and internal standard must be presented in the data printout for all MS/MS analyses

5. Mass ion ratios (MIRs) or multiple reaction monitoring ratios (MRM) must have values within ±20% of the calibrator

6. Retention time must be within ±2% of the calibrator

7. Quantification of controls must be within ±20% of the expected value. The open and blind negative must not quantify above the limit of detection (LOD)

8. A minimum of 8 ms scans are required for each peak

9. Each FTDTL must set minimum criteria for mass ion abundance

10. Batch analyses interrupted by power failure must be restarted with new autotune or system verification sample and reinjection of controls prior to continuing with the batch. Analysis can continue the next day if autotune or system verification sample is validated and reinjection of calibrator meets established criteria

11. All mass ions must include part of the primary structure of the drug

12. Negative specimens in a failed batch may be reported. A diluted specimen may not be reported as positive if the on-column amount is below the low control

13. Instrument conditions can be altered to separate co-eluting peaks as long as all calibrators, controls, and affected specimens are analyzed under same conditions

14. A negative control or solvent blank will be injected prior to each member specimen

15. Disposal of excess urine aliquots will be documented on CoC

16. Peak resolution must be less than 10%

17. Peak asymmetry must be within 0.5-2.0

c. Completion of testing documentation will be forwarded for review

1. Confirmatory test is positive when all criteria of this section are met and specimen quantifies at or above the cutoff

2. The following will be certified as free of interference and verified to contain the analyte(s) of interest at stated values prior to use.

i. Reagent lots

ii. Negative urine

iii. Calibrators, standards, and controls

3. Methods for certification will be described in FTDTL OP manual

4. All confirmatory procedures must be validated prior to implementation and must include at a minimum:

i. LOD I limit of quantitation (LOQ) I limit of linearity (LOL)

ii. Precision at the cutoff

iii. Carryover

iv. Interferences from similar and related compounds

d. New instruments must be validated and will be verified annually or within each run. If there is a major change in a method extraction, method must be validated on each instrument used

Quality Control (QC) and Quality Assurance (QA) Programs:

a. Each FTDTL shall maintain an internal QC program that includes at least 5% (total) open and blind control specimens in a batch

1. Separate sources of QC stock material (or separately prepared solutions from same lot, if necessary) in preparation of controls and standards

2. Calibrators, standards, and QC controls must be certified prior to use

b. Maintain a comprehensive QA program

1. Monitor QC processes to include

1. Method development

ll. Certification (instrument, drug, personnel)

m. Data review 1v. Calibrations

v. External proficiency performance

vi. Internal/external audits

2. OP manual to describe QA program and procedures for documentation and resolution of occurrences outside the LOP (MFR) and deviations from the LOP

(NCE)

3. QA chief will be designated in writing. Responsible for management of QA program

c. Participate in the Armed Forces Medical Examiner System (AFMES) QA inspection and proficiency programs

1. AFMES Blind Program

i. Quarterly percentage of false negative results must not exceed 5%

ii. No false positives

2. AFMES Open Program

1. Analysis is unacceptable when two analyte results quantify greater than 20% from group mean in two consecutive months

11. Analysis is unacceptable when three or more analyte results quantify greater than 20% from group mean in one month

Reporting and Records:

a. Any specimen that fails to meet required quantity or quality criteria for determination as positive shall be reported as negative

b. All results must be reviewed and certified by at least two LCOs. All reviews will be documented in the FTDTL information management system (LIMS). LCOs will annotate results on reporting forms required by Military Departments

c. All discrepancies will be documented on original CoC

d. Report to submitting unit shall only specify which specimens were ( + ), (-), or not tested.

No analytical information on negative specimens shall be reported to the submitting unit, unless there are exceptions (see DODI 1010.16)

e. Negative results I. Should be reported within 4 working days (monthly average)

2. Any specimen with a valid initial, adjunct, or confirmation test that is (-) will be reported (-) for that drug

3. Final LCO shall ensure results have been reviewed and certified prior to reporting

4. All testing and CoC documentation for specimens will be maintained for 1 year

f. Positive results

1. Should be reported within 6 working days (monthly average)

2. Any specimen with a valid initial, adjunct, and confirmation test that is ( +) will be reported ( +) for that drug

3. Final LCO shall ensure results have been reviewed and certified, an LCO has verified information on bottle and CoC, and this information is accurately reflected in LIMS prior to reporting

4. Positive specimens will be placed in secured freezer storage as soon as practical

5. All testing and CoC documentation for specimens will be maintained for 3 years

Disposition of Specimens:

a. Negative specimens

1. May be discarded after transmission of (-) report. Discard date must be documented in LIMS

b. Positive specimens

1. All ( +) specimens will be kept frozen for 1 year

2. Upon expiration ofretention period,(+) specimens may be discarded

Retesting of Specimens:

a. Specimen retest requires a C-MS procedure to confirm the presence of the reported drug.

On retest, drug does not need to quantify above DoD cutoff, rather quantitation above the

FTDTLLOD

b. Documentation of specimen handling must be documented

Document and Information Requests:

a. Complete laboratory records packets must include at a minimum

1. Copies of all CoCs

2. All accepted printouts, and analysis of all calibrators, standards, and controls associated with specimen

3. Packet will include a statement of business records certification

b. A summary packet will include at a minimum

1. Summary sheet that includes tests performed

2. Dates of tests

3. Test results

Computer Requirements:

a. System security ofLIMS will comply with DODD 8500.0lE

b. Each specimen received will be tracked within the LIMS

c. LIMS will maintain a forensic record of each action taken on a specimen

d. LIMS will be capable of verifying SSN on CoC matches SSN on bottle

e. LIMS will maintain an audit trail of changes to records

f. Record ofLCOs who review and approve data will be retrievable from the LIMS

Laboratory Equipment:

a. Major equipment (IA screening and confirmation analysis) must be maintained and inspected at least semi-annually by original equipment manufacturer (OEM)

b. Maintenance must be done by OEM trained technicians

c. Centrifuges must be certified annually

d. Minor equipment (balances, pipettes) will be certified at least annually

e. Weights used to certify balances must be NIST traceable

f. Maintenance records must be retained for a minimum of 3 years

Enclosure 6 MS/MS Instrument Standards:

1. A full autotune shall be performed in accordance with manufacturer' s specifications

2. Instrument performance shall be evaluated daily by injecting system verification sample. It must be analyzed prior to member specimens. Evaluation criteria and corrective actions shall be documented in maintenance files. Evaluation criteria can be established by analyzing multiple system verification samples to determine historical values. Criteria must include:

1. Retention time within± 3%

2. Area counts for quantitative transition shall be > 50% historical value

3. MRM transition ratios shall be within± 20% of historical value

4. Mass assignment for transition should be within± 0.2 amu. This can be accomplished in the following ways:

1. Perform a product ion scan for each compound and evaluate mass assignment

2. Evaluate are counts for compounds, if counts have fallen outside acceptance criteria or MRM transition ratios are unacceptable, mass axis may have shifted or atmospheric pressure ionization source may require cleaning

5. System verification sample shall have concentration within working range of assay

6. System verification sample shall contain analytes that cover both the retention time and molecular mass range of the assay

Minimum Quality Assurance Requirements. QA program makes recommendations to the Command for quality improvement I process improvement based on results from work product audits, work process audits, non-conforming events (NCE) reviews and training records reviews.

The FTDTL must have OP manuals that describe the QA Program and define the documentation used by the FTDTL to manage the Program. FTDTL documentation must include the use and tracking ofNCEs and Memoranda for Record (MFR) for any occurrence that does not follow the strict guidelines of the FTDTL' s OP manual.

The following are requirements listed by the Laboratory sections I processes

QA Officer (QAO):

a. Will be designated in writing by the FTDTL Commander

b. Responsible for overall management of the QA Program

c. Must be independent of the Laboratory Technical Director I Operations Director

d. Must be qualified and certified at the positive LCO level within 6 months of employment

e. Shall dedicate a minimum of 50% of time to QA duties

f. Should seek continuing education on NCEs and other quality processes, such as Lean Six

Sigma

g. Should be available during all technical inspections as a partner in the inspection process.

Quality Assurance Meetings:

a. Shall be held monthly and occur by the 15th of the following month

b. Minutes for the meeting must be documented

c. A member of laboratory' s leadership must attend meetings

d. Shall necessarily include review of work process and work product audits, old and new business, and open and closed items.

NCEs and MFRs:

a. The QAO is responsible for ensuring the investigation of all NCEs for both technical and operational issues and for ensuring the proper use and tracking of MFRs

1. NCEs shall be used to document all situations in which requirements are not fulfilled. Requirements include all those items codified in laboratory operating procedures (LOPs), standard operating procedures (SOPs), operating instructions (Ols), DODis, and other instructions and pertain to circumstances associated with the forensic integrity of the specimens, which necessarily includes data control (including Information Management I Information Technology) and physical security.

2. NCEs shall be classified as either Category A, B or C, depending on the severity of the event:

NCE Category A- Critical Events: These events cause an immediate and significant risk to maintaining DoD certification. They directly affect the integrity of the laboratory's drug test results. This category will also be used for the repetition of serious (Category B) events, indicating a failure of the laboratory technical or administrative procedures.

NCE Category B - Serious Events: These events negatively impact the integrity of the laboratory's drug test results but do not cause an immediate risk to maintaining DoD certification. These events could have resulted in a Category A - Critical Event but did not, due to chance or timely intervention. This category will also be used for the repetition of minor (Category C) events indicating discernible trends.

NCE Category C - Minor Events: These events occur outside normal laboratory practice and are documented to maintain forensic data integrity and may be used to monitor trends.

3. MFRs shall be used to explain situations that are not described in an LOP, SOP, 01 or DODI. While a MFR may be required to clarify a NCE, there are situations in which a MFR will be required when no NCE category is assigned:

Technical MFRs shall be used to document procedures not explicit in any LOP, SOP, 01 or DOD instruction. These are not NCEs as they are not deviations from written instructions, rather they explain extraordinary circumstances not described in any procedures manuals or instructions

Administrative MFRs shall be used to document administrative matters

b. NCE Report Contents:

1. Incident Description

2. Categorization (A, B or C)

3. Incident Investigation including event classification as

i. System - simple human error

ii. Knowledge - lack of training and/or supervision

iii. Behavior - willful recklessness

4. Immediate actions taken

5. Conclusions

6. Corrective and Preventive Actions Recommendations

7. Supporting documentation for all corrective action(s)

i. Training Records

11. OP manual changes, if applicable

11i. Copies of purchase orders, if applicable

iv. MFRs, if applicable '

c. NCE reports must represent a "closed-loop" product that includes the signature and date of the Commander/CO that documents their review of all NCE supporting material, QAO recommendations, and corrective actions taken

Laboratory Work…