Ronald H. Laessig, Ph.D. and Sharon S. Ehrmeyer, Ph.D.*
Note:
This Procedure Manual module is taken from The New Poor Man's (Person's) Guide to the Regulations (CLIA '88, JCAHO, CAP & COLA) written by Ronald H. Laessig, Ph.D. and Sharon S. Ehrmeyer, Ph.D., University of Wisconsin, Madison, WI. The Guide was updated in July 1997 and is divided into two parts. The first part provides a general view and specific requirements of the regulations--Understanding the Regulations; Personnel; Procedure Manuals; Quality Control; Proficiency Testing; Method Validation, Calibration and Calibration Verification; and Quality Assurance. The second part provides successful strategies and specific applications of the regulations -- Point of Care Testing, Qualitative Tests with Built-in Process Controls, Quantitative Tests (automated), and Urinalysis Test.The 220 page Guide is available for $38 (includes postage and handling) from R & S Consultants, 629 Chatham Terrace, Madison, WI 53711.
[Please do not reproduce without permission.]
1)describe the components that are required for an acceptable procedure manual.
2)describe the rules governing the approval process of the procedure manual.
3)describe the role that the manufacturer's insert information has in the procedure manual.
CLIA '88 and Procedure Manuals
All of the CLIA '88 final rules (Subpart
K) 493.1211 (1, 2) make the Health Care Financing
Administration's (HCFA) approach to developing and implementing its
inspection program quite clear. A major focus of the inspection
process is on the laboratory's procedure manual. While Section
493.1211 draws very heavily on the National
Committee on Clinical Laboratory Standards' (NCCLS) guideline for
writing laboratory procedure manuals, the Clinical Laboratory Technical Procedure Manuals (GP2-A3), it also adds
some new wrinkles. An excellent in-house procedure manual that
clearly identifies laboratory policies and philosophies along with
the necessary quality control and quality assurance components will
facilitate the inspection process and encompass a very significant
portion of the inspection. In addition, all inspecting agencies allow
manufacturers to supply customers with most of the necessary
procedure manual components for their reagents/instrumentation.
Regardless of the inspection agency, all laboratories are required to have procedure manuals. No laboratory will ever be far from full regulatory compliance by using the NCCLS's procedure manual guideline, since the College of American Pathologists (CAP), HCFA, the Centers for Disease Control (CDC), and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) as well as many others were a part of the development and recommend its use. Later we will state the specific CLIA'88 procedure manual requirements. Basically, the CLIA '88 and NCCLS approaches to the laboratory procedure manual include the following general points:
1.The procedure manual must include the quality assurance plan for the laboratory with a specific version of the quality assurance plan for each laboratory section.
2.The procedure manual must include detailed instructions on how to perform and report each test. This means that a competent person, already familiar with and oriented to the laboratory, should be able to understand the manual and able to perform the test by following the instructions.
3.The procedure manual must be available at the bench (not on a shelf in the director's office). It can be in electronic form.
4.The procedure manual "cookbook" and the quality assurance philosophy must be in sync.
The place where the regulations come together--the philosophy, the strategy, the tactics, and the implementation--is the procedure manual. In this module on procedure manuals--which applies to both MODERATE and HIGH COMPLEXITY tests for laboratories inspected by HCFA and COLA (4), we attempt to give you a simple, straightforward approach to meeting the requirements and satisfying the inspector. The procedure manual requirements for JCAHO and CAP apply to all testing complexities. (5, 6)
Note:
CAP specifically requires laboratories to follow the NCCLS GP2-A3
Procedure Manual document.
Some useful information
Every laboratory product sold in the U.S. must have information as
follows in its labeling, which can be used as part of the procedure
manual, see 493.1211(c).
Labeling regulations
Every reagent used for in-vitro diagnostic tests and sold in the U.S.
must meet basic FDA labeling regulations. These determine the format
and content of the information that accompanies reagents, controls,
instruments, and laboratory supplies, including (as applicable) data
such as expiration date, calibration process, interferences,
reference range, etc.
510K and PMA (Pre-market approval)
Every test reagent system or product must be registered with the FDA
under a process called "510K" or pre-market approval (PMA). These
processes basically require the manufacturer to demonstrate to the
FDA that the products perform as claimed. This is not trivial, but
rather an comprehensive and expensive process which requires
extensive data on accuracy, precision, interferences, dynamic range,
reference range, control practices, calibration protocols, etc.
Manufacturers create these data during their field trials of new
products.
July 31, 1998 and beyond
It was HCFA's original intent that by 9/1/94 manufacturers were to
submit additional information, including materials for procedure
manuals, to the FDA for meeting the CLIA '88 quality control
requirements. With FDA approval, the product would be labeled as
meeting CLIA '88 quality control requirements and the user would just
need to follow the manufacturer's directions for being in compliance
with most of subpart K, including the procedure manual requirement.
The 9/1/94 deadline for manufacturers submission was extended to
9/1/96 and then again to 7/31/98. (7,8) Many feel that this provision
will never be implemented.
EXCERPTS FROM CLIA RELATED TO PROCEDURE MANUALS
Unmodified moderately complex tests only (until
7/31/98)
493.1251(c)(2):
Have a procedure manual describing the process for testing and
reporting patient test results. The specific requirements in 493.1211
technically only apply to high complexity testing under CLIA '88.
However, most laboratories will recognize that the majority, if not
all, the information listed in this section is essential for good
laboratory practice. We recommend including all the information that
is appropriate.
Modified moderately complex tests, highly complex tests, and tests developed in-house (Under CLIA '88 all of these are considered to highly complex tests and laboratories must have a procedure manual that follows 493.1251.)
493.1211 says:
(a) A written procedure manual for the performance of all analytical
methods used by the laboratory must be readily available and followed
by laboratory personnel. Textbooks may be used as supplements to
these written descriptions but may not be used in lieu of the
laboratory's written procedures for testing and examining specimens.
(b) The procedure manual must include, when applicable to the test procedure:
(c) Manufacturers' package inserts or operator manuals may be used, when applicable, to meet the requirements of paragraphs (b)(1) through (b)(13) of this section...any items... not provided by the manufacturer must be provided by the laboratory.
(d) Procedures must be approved, signed, and dated by the director.
(e) Procedures must be re-approved, signed, and dated if the directorship of the laboratory changes.
(f) Each change in a procedure must be approved, signed, and dated by the current director of the laboratory.
(g) The laboratory must maintain a copy of each procedure with the dates of initial use and discontinuance. These records must be retained for two years after a procedure has been discontinued.
What the CLIA '88 rules really say...:
1.When preparing the procedure manual, follow the steps outlined in
the February 28, 1992 Federal Register.
2.Manufacturers of tests can supply a substantial part of the needed information. This even can be a procedure manual with blanks for the laboratory to "fill-in."
3.Have a procedure manual for each test. The inspector will pick one test and ask to follow the procedure from test requisition to final report. The procedure manual will tell the inspector how to do this.
4.The procedure manual is a laboratory document and the directions should be written at a level that someone familiar with the laboratory can understand.
5.The procedure manual must be current, available to testing personnel, and initially signed by the director. After the initial review and signing by the director, only changes need the director's signature (CAP, however, requires a yearly signature by the director). It should look like it is being used, not something that just remains on the director's shelf.Electronic procedure manuals are acceptable.
NCCLS GUIDELINE GP2-A3
Clinical laboratory technical procedure manuals
Each technical procedure should include explicit information and
unequivocal instruction in the following areas wherever they apply.
(The procedure manual should be easy to follow and contain all
necessary information.) The NCCLS guideline contains several examples
of procedure manuals for specific tests.
1.Test name, substance, or analyte tested.
2.Principle and/or purpose of test, which can be a short paragraph outlining the principle of analysis and the clinical reasons for performing the test.
3.Specimen requirements and collection and handling for the test. This includes any required patient preparation along with potential interferences from drugs and medications. Identify specific specimen requirements--type of collection container, amount needed, and criteria for unacceptable specimens. Timing considerations, transport/storage/preservation, and any special precautions must be identified.Procedures for submission of specimen to referral laboratory need to be included.
4.Reagents, standards, controls, and media used. Include source or supply company, directions for any preparation, and specific storage requirements.Label testing materials with name, lot number, concentration/titer, precautions, date prepared, and expiration date.
5.Instrumentation, including calibration protocols and schedules. Describe calibration protocols. This may mean following the manufacturer's instructions or following specific criteria established by the laboratory. If manufacturer's directions are NOT followed, state stepwise instructions including number, type, concentration of calibrators, acceptable limits, frequency, and reportable range for patient results.
6.Step-by-step directions including result reporting and troubleshooting and corrective actions.
7.Step-by-step instructions for any calculations. Show any equations in basic forms and show how to use each with specific examples. Identify how to handle variations such as dilutions.
8.Specific quality control materials to use. Give instructions for preparation and handling of the materials and identify the number and how frequently the controls are analyzed. For CLIA '88, the minimum requirement for most tests is two different concentrations every 24 hours. Analyte, manufacturer and/or laboratory quality control requirements can differ and each must be identified. State the tolerance limits for acceptable control values and corrective action to taken when the tolerance limits are exceeded. Describe how to record and store quality control data.
9.Expected values (normal range) and whether the range is age or sex dependent. List critical (panic) values that are life-threatening and a protocol for reporting these results.
10.Procedure notes, e.g., linearity or detection limits (reportable range).
11.Limitations of the method, e.g., interfering substances and/or pitfalls and precautions. Provide helpful hints, possible sources of error, alternate clinical applications, alternative procedures, etc. Include telephone numbers for technical service and reference pages from operator's manual for troubleshooting. Describe the action to be taken when the system is not operational.
12.Include references that can be from journal articles, textbooks, manufacturer product literature, technical/professional publications, research and validation data, and written personal communications.
13.Effective date and schedule for review.
14.Distribution.
15.Author.
Preparing the procedure manual
a.Electronic preparation and storage is OK. A computer template can
be purchased from NCCLS.
b.Manufacturer's literature (package inserts/operator manuals) may be used, provided the instructions are followed in the unmodified form. When items are missing from the manufacturer, the laboratory must provide the information.
c.The date the procedure was put in place must be noted.
d.The current director must approve procedures and his/her signature or designee's signature may be on the cover of the document.
e.With a change in directorship, the procedures must be reapproved, signed, and dated
f.Changes in a procedure must be approved by the director, signed, and dated.
g.CAP requires annual review, even when no changes occurred. HCFA, COLA and JCAHO do not require annual review as long as no changes took place.
h.Retain records that include the dates of initial use and discontinuance for two years after the procedure is discontinued.
References
1.U.S. Department of Health and Human Services. Medicare, Medicaid
and CLIA programs: Regulations implementing the Clinical Laboratory
Improvement Amendments of 1988 (CLIA '88). Final rule. Fed Regist
1992; 57:7002-186.
2.Survey Procedures and Interpretive Guidelines for Laboratories and Laboratory Services, Appendix C, US Department of Commerce, National Technical Information Service, Springfield, VA, 1992, p. C-122.
3.Clinical Laboratory Technical Procedure Manuals -- Third Edition. Approved Guideline (GP2-A3). National Committee on Clinical Laboratory Standards. Wayne, PA, 1996. (NCCLS also has the procedure manual format available, for purchase, on computer disk).
4.Accreditation Manual. Commission on Office Accreditation (COLA). Columbia, MD, 1996.
5.Accreditation Manual for Pathology and Clinical laboratory Services. Joint Commission on Accreditation of Healthcare Organizations (JCAHO). Oakbrook Terrace, IL, 1996.
6.Laboratory Accreditation Program. College of American Pathologists (CAP). Northfield, IL, 1997.
7.U.S. Department of Health and Human Services. Medicare, Medicaid and CLIA Programs: Extension of Certain Effective Dates for Clinical laboratory Requirements and Personnel Requirements for Cytologists. Fed Regist 1994;59:62606-9.
8.U.S. Department of Health and Human Services. Medicare, Medicaid and CLIA Programs: Extension of Certain Effective Dates for Clinical Laboratory Requirements Under CLIA. Fed Regist 1997;62:25855-58.