Testing Facilities Operation
Version 5.0 August 2012
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).
Objectives
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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
Pre-Assessment Question #1
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
3
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?
A.
B.
C.
D.
E.
4
Principle/purpose
Specimen
Procedural steps
Limitations
Calculations
Pre-Assessment Question #3
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B. Identifying superseded documents and archiving them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
5
Pre-Assessment Question #4
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
6
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
SOP Guidelines
8
Each laboratory should
have SOPs for ALL
procedures 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
Document Control
Information included in Document Control
SOP Number
Number of pages
Approval signatures
with dates
Names, signatures, and
dates of all personnel
Revision number and
date
9
Signature List
Signature and Initial List
10
Employee
Name
Signature
Initials
Date
Tiri Towindo
Tiri Towindo
TT
12-Jul-02
Michael Stirewalt
Michael Stirewalt
MS
06-Jan-00
Standard Operating Procedures
What should be
included in an
SOP?
11
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
12
Standard Operating Procedure Elements
Principle and/or Purpose
Instrumentation
Quality Control
References
Author
13
Specimen Recommendation/
Collection Methods
Reagents, Standards,
Controls, and Media Used
Procedural Steps
Calculations
Reporting Results
Limitations
Effective Date/Review
Schedule
Distribution
Standard Operating Procedure Elements
(cont’d)
Principle and/or Purpose
Specimen Recommendation/
Collection Methods
Reagents, Standards,
Controls and Media Used
List
in paragraph form the
typeSteps
of reaction and the
Instrumentation
Procedural
Calculations
reasons for performing the test.
Quality Control
Reporting Results
Limitations
Example: The glucose method is an adaptation of the
hexokinase-glucose-6-phosphate dehydrogenase method,
presented
as a general
clinical
laboratory method
by
Effective
Date/Review
References
Distribution
Kunst, et al.1 This methodSchedule
is more specific than general
reducing methods and will give results lower than those
Authorby such reducing methods2.
obtained
14
Standard Operating Procedure Elements
(cont’d)
Principle and/or Purpose
Specimen Recommendation/
Collection Methods
Reagents, Standards,
Controls and Media used
• Conditions
for study participant
preparation
Instrumentation
Procedural Steps
• Specific specimen type
• Handling conditions
Quality
Control Criteria
Reporting Results
Rejection
• Mislabeled
• Leaking/broken Effective Date/Review
References
• Hemolysed, lipemic,Schedule
icteric
Calculations
Limitations
Distribution
Example:
Normal procedures for collecting and storing
Author
serum, plasma, urine, and cerebrospinal fluid may be
used for samples to be analyzed by this method.
15
Standard Operating Procedure Elements
(cont’d)
Principle and/or Purpose
Specimen Recommendation/
Collection Methods
Reagents, Standards,
Controls and Media Used
• Instrumentation
List reagents, standards,
controls,
and mediaCalculations
employed
Procedural
Steps
• Indicate directions for preparation
• List parameters that determine acceptable performance
Quality Control
Reporting Results
Limitations
Example: All reagents and materials for this test are stored
in the
glass door refrigerator
(at 2 – 8°C) located in the
Effective Date/Review
References
Distribution
Schedule
chemistry department. Overflow reagents are stored in the
gray door refrigerator (at 2 – 8°C) located in the chemistry
department.
Author
16
Standard Operating Procedure Elements
(cont’d)
Principle and/or Purpose
Instrumentation
17
Specimen
Recommendation
Standards,
• List equipment
used inReagents,
the procedure
/Collection Methods
Controls and Media Used
• Include calibration protocols and
schedules
Procedural Steps
Calculations
Example: The following information should be considered
Quality
Control
Reporting
Results
when
calibrating
the GLU
method:
Limitations
• Assay Range: 0–500 mg/dL
• Reference Material: Primary standards or secondary
Effective Date/Review
References
calibrators such as CHEM
I Calibrator (Cat.Distribution
No. DC18)
Schedule
• Suggested Calibration Levels: 0, 250, 425 mg/dL
• Calibration Scheme: Three levels in triplicate
Author
• 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)
• Detailed
Specimen Recommendation/
Reagents, Standards,
• Stepwise
Principle
and/or Purpose
Collection Methods
Controls and Media Used
• Appropriate for personnel conducting the procedure
Instrumentation
Procedural Steps
Calculations
Example:
Instructions for
Processing
Samples, Bar
Coded
Quality Control
Reporting
Results
Limitations
Tubes
Place bar code labels on tube. 10 mL tubes may be put
Effective Date/Review
References
Distribution
directly
in a segment with Schedule
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
Author
adaptors are for 5 mL tubes. Check for sufficient sample
volumes using the tube fill gauge.
18
Standard Operating Procedure Elements
(cont’d)
Principle and/or Purpose
Specimen Recommendation/
Collection Methods
• Give stepwise instructions
Instrumentation
Procedural Steps
• List
any applicable equations
• Give precise examples
Quality Control
Reporting Results
Reagents, Standards,
Controls and Media Used
Calculations
Limitations
Date/Review
References
Distribution
Example:
To manuallyEffective
calculate
Low Density Lipoprotein
Schedule
Cholesterol (LDLC), use the following equation:
LDLC = [TC] - [HDLC] - [TG/5]
Author
19
Standard Operating Procedure Elements
(cont’d)
Principle and/or Purpose
Instrumentation
Quality Control
References
Author
20
Reagents,
Standards,
• Identify the control material
used
Controls and Media Used
• List preparation and handling
instructions
Procedural Steps
Calculations
• List frequency of analysis
• Establish and explain tolerance limits
and
state
corrective actionLimitations
for values
Reporting
Results
outside tolerance limits
Specimen Recommendation/
Collection Methods
Effective Date/Review
Distribution
Example:
At least once daily,
run
Schedule
solutions of a quality control material at
two levels with known concentrations
Standard Operating Procedure Elements
(cont’d)
Principle and/or Purpose
Specimen Recommendation/
Collection Methods
Reagents, Standards,
Controls and Media Used
• State the reference range
• Identify
procedures for reporting
abnormal results
Instrumentation
Procedural Steps
Calculations
• Give guidelines on acceptable report format
Quality Control
Reporting Results
Limitations
Example:
Serum and Plasma
results are reported
in mg/dL
Effective Date/Review
References
Distribution
Schedule
and are rounded to the nearest
tenth
Normal range: 72-112 mg/dL
PanicAuthor
values: <50 or >350 mg/dL for adults; <40 or >350
mg/dL for babies
21
Standard Operating Procedure Elements
(cont’d)
•
Example:
Specimen Recommendation/
Principle and/or Purpose
Collection Methods
1. Assay Range: 0–500
mg/dL
2. Hemoglobin of 500 mg/dL
•
Instrumentation
Procedural
Steps
falsely depresses GLU
results
by 20 mg/dL at 131 mg/dL of
glucose
Quality Control
Reporting Results
3. Bilirubin of 20 mg/dL falsely
depresses GLU results by 12
Effective
Date/Review
mg/dL
at 124 mg/dL
glucose
References
Schedule
4. Lipemic (triglyceride 600 mg/dL)
samples falsely elevate GLU
Author
results
by 10 mg/dL at 129
mg/dL of glucose
22
State linearity
Reagents, Standards,
and/or
detection
Controls
and Media Used
limits
State known
Calculations
interferences
Limitations
Distribution
Standard Operating Procedure Elements
(cont’d)
List items used as sources
of information
Specimen Recommendation/
Principle
and/or references
Purpose
• Literature
Collection Methods
• Manufacturer product literature
• Textbooks
Instrumentation
Procedural Steps
• Written
personal communications
• Standards publications
Use Standard Bibliographical format
Quality Control
References
Author
23
Reporting Results
Reagents, Standards,
Controls and Media Used
Calculations
Limitations
Example:
1.Kunst A, Draeger B, and Ziegenhorn J. UVEffective Date/Review
methods
with hexokinase and glucose-6Distribution
Schedule
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
Standard Operating Procedure Elements
• Performed by authorized
Specimen Recommendation/
Reagents, Standards,
Example
:
Principle
and/or Purpose
personnel
Collection Methods
Controls and Media Used
Review
Revision Signature
• Review when changes
Date
Date
are made
Instrumentation
Procedural Steps
Calculations
• Review annually
• Document review
• Remove
obsolete or Reporting Results
Limitations
Quality Control
superseded procedures
References
Author
24
Effective Date/Review
Schedule
Distribution
Standard Operating Procedure Elements
(cont’d)
Specimen Recommendation/
• Document control
Collection Methods
• Keeps track of number of copies
Principle and/or Purpose
Instrumentation
Procedural Steps
Distributed
To
Quality Control
Reporting Results
Limitations
Effective Date/Review
Schedule
Distribution
Example:
References
Author
25
Reagents, Standards,
Controls and Media Used
Number of Calculations
Copies
Standard Operating Procedure Elements
(cont’d)
Principle and/or Purpose
Specimen Recommendation/
Collection Methods
Reagents, Standards,
Controls and Media Used
Instrumentation
Procedural Steps
Calculations
Reporting Results
• Quality
TakeControl
credit for your work
• Keep track of the number of copies
References
Author
26
Effective Date/Review
Schedule
Limitations
Distribution
Document Control Plan
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 (cont’d)
Authorization Process
Establish who has
authority to
conduct a review
28
May vary based
on the
administrative
structure
Skill Check
How often should the review of SOPs be documented?
A.
B.
C.
29
Every two years
Annually
Only when changes are made
Document Control Plan
Annual
Reviews
Ensures
Procedures
are Current
Document
Review
Practice vs.
Procedure
30
Standard Operating Procedure Training
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
Post-Assessment Question #1
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
32
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?
A.
B.
C.
D.
E.
33
Principle/purpose
Specimen
Procedural steps
Limitations
Calculations
Post-Assessment Question #3
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
34
Post-Assessment Question #4
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
35
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
36

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).
Wrap Up
37