Testing Facilities Operation

Testing Facilities OperationVersion 5.0 August 2012This 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).

1Describe why testing facilities are required to have Standard Operating Procedures (SOPs)List the elements of an SOPList the elements of an effective document control planDescribe the elements of an effective SOP distribution planObjectives22Which of the following correctly describes why testing facilities are required to have SOPs?

To ensure the quality and integrity of the data generatedTo guide the auditors in monitoring work performed at a testing facilityTo explain procedures that are to be performed in a laboratory, except for waived or rapid tests Pre-Assessment Question #13Remember to pick the best answer.

The correct answer is: A. To ensure the quality and integrity of the data generated

3Information related to the assays reportable range would likely be found in which of the following elements of an SOP?

Principle/purposeSpecimenProcedural stepsLimitationsCalculationsPre-Assessment Question #24Remember to pick the best answer.

The correct answer is: D. Limitations

4Which of the following should be discussed in a document control plan?

Reviewing the SOPs periodically and revising them when necessaryIdentifying superseded documents and archiving them to prevent inadvertent useMaintaining a master SOP listRemoving obsolete SOPsAll of the abovePre-Assessment Question #35Remember to pick the best answer.

The correct answer is: E. All of the above.

5Pre-Assessment Question #46Which of the following should be considered when developing an effective SOP distribution plan?

A good document control systemEncourage staff to have personal copies of SOPs Redistribute original and revised versions as needed

Remember to pick the best answer.

The correct answer is: A A good document control system.

6The Regulations StateA 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 58.907The regulations state [Read from slide.]

This means we should have SOPs for tasks we perform within the laboratory; and to add, they should be written in a manner and language that is appropriate for the laboratory personnel conducting the procedures.SOPs should be user-friendly, written for the benefit of the staff, and readily available to all staff.7SOP GuidelinesEach laboratory should have SOPs for ALL procedures being performedSOPs should be written in a manner and language that is appropriate to the laboratory personnel conducting the proceduresSOPs are written for the benefit of the laboratory employees, not auditorsCurrent SOPs must be available in the work areas and accessible to staff8All procedures, even waived or rapid tests which appear simple to perform, must have an associated SOP.8Document Control

Information included in Document ControlNames, signatures, and dates of all personnel

SOP NumberApproval signatures with datesRevision number and dateNumber of pages9Additional information useful in document control:

SOP numberApproval signatures with datesRevision number and dateNumber of pagesNames, signatures, and dates of all personnel involved in the procedure, who have read and understood the SOP

9Signature ListEmployee NameSignatureInitialsDateTiri TowindoTiri TowindoTT12-Jul-02Michael StirewaltMichael StirewaltMS06-Jan-00Signature and Initial List10The signature list allows tracking for who has not read/signed for understanding procedure; also acts as master signature interpretative guide for other signed or initialed items, such as maintenance documents, or collection containers.Standard Operating ProceduresWhat should be included in an SOP?11

Now we will review the elements that should be included in an SOP.11SOP TitleType of specimen Name of the analyte

Title of the ProcedureSpecific method and/or instrumentationExample: Serum/Plasma Glucose Determination Using the Olympus AU 6001212Standard Operating Procedure ElementsPrinciple and/or PurposeSpecimen Recommendation/Collection MethodsReagents, Standards, Controls, and Media UsedInstrumentationProcedural StepsCalculationsQuality ControlReporting ResultsLimitationsReferencesEffective Date/Review ScheduleDistributionAuthor13The body of the SOP should contain these elements. [Read from slide]

Over the next few slides we will review each of these elements, what they should contain, and an example for each.As we discuss, please note where the information provided in the example is useful, could be improved, or other comments as needed.Principle and/or PurposeSpecimen Recommendation/ Collection MethodsReagents, Standards, Controls and Media UsedInstrumentationProcedural StepsCalculationsQuality ControlReporting ResultsLimitationsReferencesEffective Date/Review ScheduleDistributionAuthorList 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.Standard Operating Procedure Elements (contd)14Fewer sentences are better; make the principle as clear and concise (to the point) as possible.

This could even be shorterleaving out the more specific than general.

Principle and/or PurposeSpecimen Recommendation/ Collection MethodsReagents, Standards, Controls and Media usedInstrumentationProcedural StepsCalculationsQuality ControlReporting ResultsLimitationsReferencesEffective Date/Review ScheduleDistributionAuthor Conditions for study participant preparation Specific specimen type Handling conditionsRejection 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 (contd)15Give an example of conditions for study participant prep; participant must be fasting for 12 hours.

Specimen type: Sodium Heparin PlasmaHandling conditions: Must be protected from light

Principle and/or PurposeSpecimen Recommendation/ Collection MethodsReagents, Standards, Controls and Media UsedInstrumentationProcedural StepsCalculationsQuality ControlReporting ResultsLimitationsReferencesEffective Date/Review ScheduleDistributionAuthorList reagents, standards, controls, and media employedIndicate directions for preparationList parameters that determine acceptable performance

Example: All reagents and materials for this test are stored in the glass door refrigerator (at 2 8C) located in the chemistry department. Overflow reagents are stored in the gray door refrigerator (at 2 8C) located in the chemistry department.

Standard Operating Procedure Elements (contd)16You can list catalog numbers, vendors, storage requirements, and actual storage locations. Some even use this section to state nominal inventory recommendations.

Principle and/or PurposeSpecimen Recommendation /Collection MethodsReagents, Standards, Controls and Media UsedInstrumentationProcedural StepsCalculationsQuality ControlReporting ResultsLimitationsReferencesEffective Date/Review ScheduleDistributionAuthorExample: The following information should be considered when calibrating the GLU method:Assay Range: 0500 mg/dLReference 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 triplicateCalibration Frequency: Every new reagent cartridge lot and every 3 months for any one lotAssigned Coefficients: C00.000 C1 0.880Standard Operating Procedure Elements (contd)17List equipment used in the procedure Include calibration protocols and schedulesAgain, vendor, catalog number, version, and model information is good to have here; contact information for service calls is appropriate for this section, too.

Principle and/or PurposeSpecimen Recommendation/ Collection MethodsReagents, Standards, Controls and Media UsedInstrumentationProcedural StepsCalculationsQuality ControlReporting ResultsLimitationsReferencesEffective Date/Review ScheduleDistributionAuthorExample: Instructions for Processing Samples, Bar Coded TubesPlace 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 (contd)DetailedStepwiseAppropriate for personnel conducting the procedure18Broken down into movement by movementdo not assume any component of a procedure is understood.

Principle and/or PurposeSpecimen Recommendation/ Collection MethodsReagents, Standards, Controls and Media UsedInstrumentationProcedural StepsCalculationsQuality ControlReporting ResultsLimitationsReferencesEffective Date/Review ScheduleDistributionAuthorExample: To manually calculate Low Density Lipoprotein Cholesterol (LDLC), use the following equation: LDLC = [TC] - [HDLC] - [TG/5] Standard Operating Procedure Elements (contd)Give stepwise instructionsList any applicable equationsGive precise examples19Give stepwise instructionsList any applicable equationsGive precise examples

Again, do not assume, and give explanations between steps, if calculation is multi-step.

It is a good idea to define what each abbreviation stands for the sample calculation could go something like, total Cholesterol result is 205 mg/dL, HDLC result is 40 mg/dL, and Triglyceride result is 300 mg/dL, then the Low Density Lipoprotein equals 205-40-(300/5) = 105 mg/dL.

Principle and/or PurposeSpecimen Recommendation/ Collection MethodsReagents, Standards, Controls and Media UsedInstrumentationProcedural StepsCalculationsQuality ControlReporting ResultsLimitationsReferencesEffective Date/Review ScheduleDistributionAuthorIdentify the control material usedList preparation and handling instructionsList frequency of analysisEstablish 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 concentrationsStandard Operating Procedure Elements (contd)20Vendor, catalog number, and storage information is also good to include. Lot numbers and tolerance limits are frequently changed, so you must determine if this is something you want to include in this section. The frequency of analyses, as we will talk about in another module, should be determined and recorded here, based on the control material, the assay and its complexity. Corrective actions here usually include notation referring to a general QC policy, stating that out-of-control situations do not allow for release of participant results derived from the run.

Standard Operating Procedure Elements (contd)Principle and/or PurposeSpecimen Recommendation/ Collection MethodsReagents, Standards, Controls and Media UsedInstrumentationProcedural StepsCalculationsQuality ControlReporting ResultsLimitationsReferencesEffective Date/Review ScheduleDistributionAuthorExample: Serum and Plasma results are reported in mg/dL and are rounded to the nearest tenthNormal range: 72-112 mg/dLPanic 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 format21Reference ranges are almost always applicable; if you expect a negative result, then the reference range is NEGATIVE, if you expect None Detected, etc. Results must always be reported with measurement units, such as mg/dL, if applicable. Each facility must determine the protocols for abnormal results and critical results follow-up. Report format refers to the number of decimal points, > and < guidelines, correct qualitative result entry, and any interpretive comments that may be recommended, for instance, Males: 0.3 - 1.2 ng/mL, Females: Follicular phase 0.2 - 1.4 ng/mL,Luteal phase 3.3 - 25.0 ng/mL,Mid-luteal phase 4.4 - 28.0 ng/mL,Postmenopausal less than 0.7 ng/mL.Principle and/or PurposeSpecimen Recommendation/ Collection MethodsReagents, Standards, Controls and Media UsedInstrumentationProcedural StepsCalculationsQuality ControlReporting ResultsLimitationsReferencesEffective Date/Review ScheduleDistributionAuthorExample: Assay Range: 0500 mg/dL Hemoglobin of 500 mg/dL falsely depresses GLU results by 20 mg/dL at 131 mg/dL of glucoseBilirubin of 20 mg/dL falsely depresses GLU results by 12 mg/dL at 124 mg/dL glucoseLipemic (triglyceride 600 mg/dL) samples falsely elevate GLU results by 10 mg/dL at 129 mg/dL of glucose

Standard Operating Procedure Elements (contd)State linearity and/or detection limitsState known interferences22Again, the SOP should state the > and < guidelines for reporting; with interferences, the SOP can include actions to take with specimens with obvious interferents, such as lipemia or hemolysis, and state any related reporting comments that should accompany a specimens results.

Principle and/or PurposeSpecimen Recommendation/ Collection MethodsReagents, Standards, Controls and Media UsedInstrumentationProcedural StepsCalculationsReporting ResultsLimitationsReferencesEffective Date/Review ScheduleDistributionAuthorExample: 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 1983:163-172Henry RJ. Clinical Chemistry Principles and Technics, New York: Harper and Row, 1974:1283

Quality ControlStandard Operating Procedure Elements (contd)List items used as sources of informationLiterature referencesManufacturer product literatureTextbooksWritten personal communicationsStandards publicationsUse Standard Bibliographical format23Standard Operating Procedure ElementsPrinciple and/or PurposeSpecimen Recommendation/ Collection MethodsReagents, Standards, Controls and Media UsedInstrumentationProcedural StepsCalculationsQuality ControlReporting ResultsLimitationsReferencesEffective Date/Review ScheduleDistributionAuthorExample:

Review DateRevision DateSignature24Performed by authorized personnelReview when changes are madeReview annuallyDocument reviewRemove obsolete or superseded proceduresThis portion can be automated; may also include indication of revision.Principle and/or PurposeSpecimen Recommendation/ Collection MethodsReagents, Standards, Controls and Media UsedInstrumentationProcedural StepsCalculationsQuality ControlReporting ResultsLimitationsReferencesEffective Date/Review ScheduleAuthor Document control Keeps track of number of copies

Example:Distributed ToNumber of CopiesStandard Operating Procedure Elements (contd)Distribution25When edits are made or when SOPs are retired, we must be able to collect all SOPs that are in circulation, and replace them with the newest version. There is a balance to be achieved with accessibility and the number of documents that have been placed in different areas of a laboratory or at different sites. Best to distribute on a need to know basis. Be careful of copies of old SOPs made by staff.

Ensure all copies are the official copies; discourage and limit access to personal copies of SOPs potential hazard when multiple versions of SOPs are in circulation.Need a good system for document controlRetrieve and redistribute new versions as needed.

Principle and/or PurposeSpecimen Recommendation/ Collection MethodsReagents, Standards, Controls and Media UsedInstrumentationProcedural StepsCalculationsQuality ControlReporting ResultsLimitationsReferencesEffective Date/Review ScheduleDistributionAuthor Take credit for your work Keep track of the number of copiesStandard Operating Procedure Elements (contd)26Often, the author is the resource person for a specific procedure/protocol. As we tend to say, that individual owns that procedure. Note: Often promotes job satisfaction with employee responsible for authoring procedure.

Document Control PlanThe SOPs should be reviewed periodically and revised when necessarySuperseded documents should be identified appropriately and archived to prevent their inadvertent useMaster SOP listRemove obsolete SOPs

27How frequently do you review your SOPs?GCLP recommends annual reviewHow do you archive superseded and/or retired SOPs? Should be appropriate labeled and otherwise clearly identified (Obsolete, Do Not Use, etc.)Store obsolete SOPS in retired procedure fileHistorical Liability

27Authorization ProcessEstablish who has authority to conduct a review

May vary based on the administrative structureDocument Control Plan (contd)28Who has the authority and responsibility to review and approve SOPs?And how does the authorization process take place? What are the steps?28Every two yearsAnnuallyOnly when changes are madeHow often should the review of SOPs be documented?Skill Check29Remember to pick the best answer.The correct answer is: B. Annually29Annual ReviewsEnsures Procedures are CurrentPractice vs. ProcedureDocument ReviewDocument Control Plan3030Standard Operating Procedure TrainingAll personnel need to be instructed on new procedures or changes to procedures

Documentation that all personnel are knowledgeable of the contents of the SOP31

31Which of the following correctly describes why testing facilities are required to have SOPs?

To ensure the quality and integrity of the data generatedTo guide the auditors in monitoring work performed at a testing facilityTo explain procedures that are to be performed in a laboratory, except for waived or rapid tests Post-Assessment Question #132Remember to pick the best answer.

The correct answer is: A. To ensure the quality and integrity of the data generated

32Information related to the assays reportable range would likely be found in which of the following elements of an SOP?

Principle/purposeSpecimenProcedural stepsLimitationsCalculationsPost-Assessment Question #233Remember to pick the best answer.

The correct answer is: D. Limitations

33Which of the following should be discussed in a document control plan?

Reviewing the SOPs periodically and revising them when necessaryIdentifying superseded documents and archiving them to prevent inadvertent useMaintaining a master SOP listRemoving obsolete SOPsAll of the abovePost-Assessment Question #334Remember to pick the best answer.

The correct answer is: E. All of the above.

34Which of the following should be considered when developing an effective SOP distribution plan?

A good document control systemEncourage staff to have personal copies of SOPs Redistribute original and revised versions as neededPost-Assessment Question #435Remember to pick the best answer.

The correct answer is: A A good document control system.

35DAIDS Guidelines for Good Clinical Laboratory Practice Standards.FDA 42 C.F.R. 493: Laboratory Requirements (Clinical Laboratory Improvement Amendments, CLIA).42 CFR 493.125142 CFR 493.140742 CFR 493.1105College 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).References3636Wrap Up

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