Testing Facilities Operation

1. Testing Facilities Operation Version 5.0 August 2012

2. Objectives • 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

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

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

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 • Reviewing the SOPs periodically and revising them when necessary • Identifying superseded documents and archiving them to prevent inadvertent use • Maintaining a master SOP list • Removing obsolete SOPs • All of the above

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

7. The Regulations State… 21 CFR § 58.81 – 58.90 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...

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

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

10. Signature List Signature and Initial List

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

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

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

14. Standard Operating Procedure Elements (cont’d) Reagents, Standards, Controls and Media Used Specimen Recommendation/ Collection Methods Principle and/or Purpose • 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 methods2. Instrumentation Procedural Steps Calculations Quality Control Reporting Results Limitations Effective Date/Review Schedule References Distribution Author

15. Standard Operating Procedure Elements (cont’d) Reagents, Standards, Controls and Media used Specimen Recommendation/ Collection Methods Principle and/or Purpose • 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. Instrumentation Procedural Steps Calculations Quality Control Reporting Results Limitations Effective Date/Review Schedule References Distribution Author

16. Standard Operating Procedure Elements (cont’d) Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used Principle and/or Purpose • 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. Instrumentation Procedural Steps Calculations Quality Control Reporting Results Limitations Effective Date/Review Schedule References Distribution Author

17. Standard Operating Procedure Elements (cont’d) • List equipment used in the procedure • Include calibration protocols and schedules Specimen Recommendation /Collection Methods Reagents, Standards, Controls and Media Used Principle and/or Purpose Procedural Steps Instrumentation Calculations • 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 C10.880 Quality Control Reporting Results Limitations Effective Date/Review Schedule Distribution References Author

18. Standard Operating Procedure Elements (cont’d) • Detailed • Stepwise • Appropriate for personnel conducting the procedure Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used Principle and/or Purpose Instrumentation Procedural Steps Calculations 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. Quality Control Reporting Results Limitations Effective Date/Review Schedule References Distribution Author

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

20. Standard Operating Procedure Elements (cont’d) • 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 Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used Principle and/or Purpose Instrumentation Procedural Steps Calculations Reporting Results Limitations Quality Control Effective Date/Review Schedule Distribution References Author

21. Standard Operating Procedure Elements (cont’d) Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used Principle and/or Purpose • State the reference range • Identify procedures for reporting abnormal results • Give guidelines on acceptable report format Instrumentation Procedural Steps Calculations Quality Control Reporting Results Limitations Effective Date/Review Schedule References 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: <50 or >350 mg/dL for adults; <40 or >350 mg/dL for babies

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

23. 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 Specimen Recommendation/ Collection Methods Reagents, Standards, Controls and Media Used Principle and/or Purpose Instrumentation Procedural Steps Calculations Quality Control Reporting Results Limitations • Example: • 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 • Henry RJ. Clinical Chemistry Principles and Technics, New York: Harper and Row, 1974:1283 Effective Date/Review Schedule Distribution References Author

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

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

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

27. 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 Document Control Plan

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

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

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

31. 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 Standard Operating Procedure Training

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

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

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

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

36. References • 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).

37. Wrap Up