1. This project has been funded in whole or in part with Federal funds from the Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract No. HHSN272201200009C, entitled NIAID HIV and Other Infectious Diseases Clinical Research Support Services (CRSS). Testing Facilities Operation Version 5.0 August 2012

2.  Describe why testing facilities are required to have Standard Operating Procedures (SOPs)  List the elements of an SOP  List the elements of an effective document control plan  Describe the elements of an effective SOP distribution plan Objectives 2

3. Which of the following correctly describes why testing facilities are required to have SOPs? A.To ensure the quality and integrity of the data generated B.To guide the auditors in monitoring work performed at a testing facility C.To explain procedures that are to be performed in a laboratory, except for waived or rapid tests Pre-Assessment Question #1 3

4. Information related to the assay’s reportable range would likely be found in which of the following elements of an SOP? A.Principle/purpose B.Specimen C.Procedural steps D.Limitations E.Calculations Pre-Assessment Question #2 4

5. Which of the following should be discussed in a document control plan? A.Reviewing the SOPs periodically and revising them when necessary B.Identifying superseded documents and archiving them to prevent inadvertent use C.Maintaining a master SOP list D.Removing obsolete SOPs E.All of the above Pre-Assessment Question #3 5

6. Pre-Assessment Question #4 6 Which of the following should be considered when developing an effective SOP distribution plan? A.A good document control system B.Encourage staff to have personal copies of SOPs C.Redistribute original and revised versions as needed

7. The Regulations State… A testing facility shall have standard operating procedures in writing setting forth non clinical laboratory study methods that management is satisfied are adequate to insure the quality and integrity of the data generated in the course of a study... 21 CFR § 58.81 – 58.90 7

8. SOP Guidelines Each laboratory should have SOPs for ALL procedures being performed SOPs should be written in a manner and language that is appropriate to the laboratory personnel conducting the procedures SOPs are written for the benefit of the laboratory employees, not auditors Current SOPs must be available in the work areas and accessible to staff 8

9. Document Control Information included in Document Control Names, signatures, and dates of all personnel SOP Number Approval signatures with dates Revision number and date Number of pages 9

10. Signature List Employee Name SignatureInitialsDate Tiri Towindo TT 12-Jul-02 Michael Stirewalt MS 06-Jan-00 Signature and Initial List 10

11. Standard Operating Procedures What should be included in an SOP? 11

12. SOP Title Type of specimen Name of the analyte Title of the Procedure Specific method and/or instrumentation Example: Serum/Plasma Glucose Determination Using the Olympus AU 600 12

13. Standard Operating Procedure Elements Principle and/or Purpose Specimen Recommendation/ Collection Methods Reagents, Standards, Controls, and Media Used InstrumentationProcedural Steps Calculations Quality Control Reporting Results Limitations References Effective Date/Review Schedule Distribution Author 13

14. Principle and/or Purpose Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used InstrumentationProcedural Steps Calculations Quality ControlReporting ResultsLimitations References Effective Date/Review Schedule Distribution Author List in paragraph form the type of reaction and the reasons for performing the test. Example: The glucose method is an adaptation of the hexokinase-glucose-6-phosphate dehydrogenase method, presented as a general clinical laboratory method by Kunst, et al. 1 This method is more specific than general reducing methods and will give results lower than those obtained by such reducing methods 2. Standard Operating Procedure Elements (cont’d) 14

15. Principle and/or Purpose Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media used InstrumentationProcedural Steps Calculations Quality Control Reporting Results Limitations References Effective Date/Review Schedule Distribution Author Conditions for study participant preparation Specific specimen type Handling conditions Rejection Criteria Mislabeled Leaking/broken Hemolysed, lipemic, icteric Example: Normal procedures for collecting and storing serum, plasma, urine, and cerebrospinal fluid may be used for samples to be analyzed by this method. Standard Operating Procedure Elements (cont’d) 15

16. Principle and/or Purpose Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used InstrumentationProcedural Steps Calculations Quality ControlReporting Results Limitations References Effective Date/Review Schedule Distribution Author List reagents, standards, controls, and media employed Indicate directions for preparation List parameters that determine acceptable performance Example: All reagents and materials for this test are stored in the glass door refrigerator (at 2 – 8°C) located in the chemistry department. Overflow reagents are stored in the gray door refrigerator (at 2 – 8°C) located in the chemistry department. Standard Operating Procedure Elements (cont’d) 16

17. Principle and/or Purpose Specimen Recommendation /Collection Methods Reagents, Standards, Controls and Media Used Instrumentation Procedural Steps Calculations Quality ControlReporting Results Limitations References Effective Date/Review Schedule Distribution Author Example: The following information should be considered when calibrating the GLU method: Assay Range: 0–500 mg/dL Reference Material: Primary standards or secondary calibrators such as CHEM I Calibrator (Cat. No. DC18) Suggested Calibration Levels: 0, 250, 425 mg/dL Calibration Scheme: Three levels in triplicate Calibration Frequency: Every new reagent cartridge lot and every 3 months for any one lot Assigned Coefficients: C00.000 C1 0.880 Standard Operating Procedure Elements (cont’d) 17 List equipment used in the procedure Include calibration protocols and schedules

18. Principle and/or Purpose Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used InstrumentationProcedural Steps Calculations Quality ControlReporting ResultsLimitations References Effective Date/Review Schedule Distribution Author Example: Instructions for Processing Samples, Bar Coded Tubes Place bar code labels on tube. 10 mL tubes may be put directly in a segment with the bar code facing the bar code reader. 7 mL and 5 mL tubes must be placed in appropriate adaptors. Brown adaptors are for 7 mL tubes; green adaptors are for 5 mL tubes. Check for sufficient sample volumes using the tube fill gauge. Standard Operating Procedure Elements (cont’d) Detailed Stepwise Appropriate for personnel conducting the procedure 18

19. Principle and/or Purpose Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used InstrumentationProcedural Steps Calculations Quality ControlReporting Results Limitations References Effective Date/Review Schedule Distribution Author Example: To manually calculate Low Density Lipoprotein Cholesterol (LDLC), use the following equation: LDLC = [TC] - [HDLC] - [TG/5] Standard Operating Procedure Elements (cont’d) Give stepwise instructions List any applicable equations Give precise examples 19

20. Principle and/or Purpose Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used InstrumentationProcedural StepsCalculations Quality Control Reporting ResultsLimitations References Effective Date/Review Schedule Distribution Author Identify the control material used List preparation and handling instructions List frequency of analysis Establish and explain tolerance limits and state corrective action for values outside tolerance limits Example: At least once daily, run solutions of a quality control material at two levels with known concentrations Standard Operating Procedure Elements (cont’d) 20

21. Standard Operating Procedure Elements (cont’d) Principle and/or Purpose Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used InstrumentationProcedural StepsCalculations Quality ControlReporting Results Limitations References Effective Date/Review Schedule Distribution Author Example: Serum and Plasma results are reported in mg/dL and are rounded to the nearest tenth Normal range: 72-112 mg/dL Panic values: 350 mg/dL for adults; 350 mg/dL for babies State the reference range Identify procedures for reporting abnormal results Give guidelines on acceptable report format 21

22. Principle and/or Purpose Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used InstrumentationProcedural Steps Calculations Quality ControlReporting Results Limitations References Effective Date/Review Schedule Distribution Author Example: 1.Assay Range: 0–500 mg/dL 2.Hemoglobin of 500 mg/dL falsely depresses GLU results by 20 mg/dL at 131 mg/dL of glucose 3.Bilirubin of 20 mg/dL falsely depresses GLU results by 12 mg/dL at 124 mg/dL glucose 4.Lipemic (triglyceride 600 mg/dL) samples falsely elevate GLU results by 10 mg/dL at 129 mg/dL of glucose Standard Operating Procedure Elements (cont’d) State linearity and/or detection limits State known interferences 22

23. Principle and/or Purpose Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used Instrumentation Procedural StepsCalculations Reporting Results Limitations References Effective Date/Review Schedule Distribution Author Example: 1.Kunst A, Draeger B, and Ziegenhorn J. UV- methods with hexokinase and glucose-6- phosphate dehydrogenase, Methods of Enzymatic Analysis, Vol VI, Bergmeyer HU (ed.) Verlag Chemie, Deerfield, FL 1983:163-172 2.Henry RJ. Clinical Chemistry Principles and Technics, New York: Harper and Row, 1974:1283 Quality Control Standard Operating Procedure Elements (cont’d) List items used as sources of information Literature references Manufacturer product literature Textbooks Written personal communications Standards publications Use Standard Bibliographical format 23

24. Standard Operating Procedure Elements Principle and/or Purpose Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used InstrumentationProcedural Steps Calculations Quality Control Reporting Results Limitations References Effective Date/Review Schedule Distribution Author Example : Review Date Revision Date Signature 24 Performed by authorized personnel Review when changes are made Review annually Document review Remove obsolete or superseded procedures

25. Principle and/or Purpose Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used InstrumentationProcedural Steps Calculations Quality ControlReporting Results Limitations References Effective Date/Review Schedule Author Document control Keeps track of number of copies Example: Distributed ToNumber of Copies Standard Operating Procedure Elements (cont’d) Distribution 25

26. Principle and/or Purpose Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used Instrumentation Procedural StepsCalculations Quality ControlReporting Results Limitations References Effective Date/Review Schedule Distribution Author Take credit for your work Keep track of the number of copies Standard Operating Procedure Elements (cont’d) 26

27. Document Control Plan  The SOPs should be reviewed periodically and revised when necessary  Superseded documents should be identified appropriately and archived to prevent their inadvertent use  Master SOP list  Remove obsolete SOPs 27

28. Authorization Process Establish who has authority to conduct a review May vary based on the administrative structure Document Control Plan (cont’d) 28

29. A.Every two years B.Annually C.Only when changes are made How often should the review of SOPs be documented? Skill Check 29

30. Annual Reviews Ensures Procedures are Current Practice vs. Procedure Document Review Document Control Plan 30

31. Standard Operating Procedure Training  All personnel need to be instructed on new procedures or changes to procedures  Documentation that all personnel are knowledgeable of the contents of the SOP 31

32. Which of the following correctly describes why testing facilities are required to have SOPs? A.To ensure the quality and integrity of the data generated B.To guide the auditors in monitoring work performed at a testing facility C.To explain procedures that are to be performed in a laboratory, except for waived or rapid tests Post-Assessment Question #1 32

33. Information related to the assay’s reportable range would likely be found in which of the following elements of an SOP? A.Principle/purpose B.Specimen C.Procedural steps D.Limitations E.Calculations Post-Assessment Question #2 33

34. Which of the following should be discussed in a document control plan? A.Reviewing the SOPs periodically and revising them when necessary B.Identifying superseded documents and archiving them to prevent inadvertent use C.Maintaining a master SOP list D.Removing obsolete SOPs E.All of the above Post-Assessment Question #3 34

35. Which of the following should be considered when developing an effective SOP distribution plan? A.A good document control system B.Encourage staff to have personal copies of SOPs C.Redistribute original and revised versions as needed Post-Assessment Question #4 35

36.  DAIDS Guidelines for Good Clinical Laboratory Practice Standards.  FDA 42 C.F.R. § 493: Laboratory Requirements (Clinical Laboratory Improvement Amendments, CLIA).  42 CFR § 493.1251  42 CFR § 493.1407  42 CFR § 493.1105  College of American Pathologists Commission on Laboratory Accreditation, Accreditation Checklists, April 2007.  Clinical and Laboratory Standards Institute (CLSI). Laboratory Documents: Development and Control; Approved Guideline-Fifth Edition. GP2-A5 (2006).  NCCLS. Continuous Quality Improvement: Integrating Five Key Quality System Components; Approved Guideline-Second Edition. GP22-A2 (2004). References 36

37. Wrap Up 37