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Review Criteria for Assessment of Cytogenetic Analysis Using Automated and Semi-Automated Chromosome Analyzers (Text Only)

This guidance was written prior to the February 27, 1997 implementation of FDA’s Good Guidance Practices, GGP’s. It does not create or confer rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both. This guidance will be updated in the next revision to include the standard elements of GGP’s.


                         DRAFT DOCUMENT
                        FOR MANUFACTURERS

                                             VERSION:  Original
                                             DATE:     7/15/91

     REVIEW CRITERIA FOR ASSESSMENT OF CYTOGENETIC ANALYSIS

    USING AUTOMATED AND SEMI-AUTOMATED CHROMOSOME ANALYZERS.



This is a flexible draft document representing the current major
concerns and suggestions regarding in vitro automated and
semi-automated chromosome analyzers for cytogenetic analysis.  It
is based on 1) current basic science, 2) clinical experience, 3)
current standard laboratory practice, and 4) previous submissions
by manufacturers to the FDA.  As advances are made in science and
medicine, these review criteria will be re-evaluated and revised
as necessary to accommodate new knowledge.


PURPOSE:            The purpose of this document is to provide
                    guidance on information to present to the
                    Food and Drug Administration (FDA) before a
                    device for chromosome analysis may be cleared
                    for marketing.  This information enables FDA
                    to make better informed decisions based on a
                    uniform data base.


DEFINITION:         The generic type device is intended for use
                    in the cytogenetics laboratory to aid
                    laboratory personnel in performing certain
                    procedures used in karyotyping human
                    metaphase/prometaphase cells for in vitro
                    cytogenetic analysis.


PRODUCT CODE:       LNJ - 88


REGULATION
NUMBER:             CFR ~ 864.5260  Automated cell-locating
                    device.

PANEL:              PATHOLOGY 


CLASS:              II

REVIEW REQUIRED:  510(k)

REGULATORY ISSUES:

Manufacturers are encouraged to develop devices that will be
compatible with guidelines of laboratory regulatory
organizations.

Most cytogenetics laboratories subscribe to certain proficiency
testing and accreditation agencies or are state regulated.  The
College oœ American Pathologist (CAP) and the Council of Regional
Genetics Networks (CORN) offer voluntary proficiency testing.  In
New York State, the Department of Health is responsible for
laboratory testing and certification; the State of Oregon
licenses cytogenetics laboratories.

In New York State, cytogenetics laboratories that use image
analysis computer systems must develop a system for record
retention and retrieval that meets laboratory licensure quality
control standards.


I.   Background

     A.   Cytogenetics in Clinical Practice

          Cytogenetic analysis is an in vitro clinical laboratory
          procedure that evaluates the chromosomes of a cell. 
          Clinical cytogenetics is the study of chromosomes and
          their correlation to the phenotype (observable clinical
          characteristics).  Certain clinical characteristics
          occur consistently in association with a particular
          chromosome abnormality.  This phenotype-karyotype
          correlation is useful to the clinician in making a
          clinical genetic diagnosis and prognosis.

          There are two basic classes of chromosome aberrations: 
          numeric and structural.  Common abnormalities of
          chromosome number include aneuploidy, mosaicism, and
          polyploidy.  Structural abnormalities include
          duplications, deletions, inversions, shifts, fragile
          sites, etc.

          Chromosome aberrations are found in association with
          many anomalies of sexual development such as the Turner
          syndrome (XO) and the Kleinfelter syndrome (XXY);
          mental retardation (Trisomy 21 in the Down syndrome and
          fragile X in the Fragile X syndrome); complex
          malformation syndromes (Trisomy 13); spontaneous
          abortions; and malignant disorders (chromosome
          translocation between chromosome 9 and 22 in chronic
          myeloid leukemia).

          In addition to studies for detection of classic
          chromosome abnormalities, more recent biotechnologies
          add a new dimension to traditional cytogenetic
          analysis.  Cytogenetic procedures may be used to study
          cell cycle associated phenomenon, gene amplification
          (homogeneous staining regions and double minutes),
          clastogen challenge, chromosome breakage syndromes,
          chromosome fragile sites, and polymorphisms to monitor
          organ/tissue transplantation.  DNA probes that are site
          specific are used for identification of chromosome
          abnormalities by in situ hybridization using chromosome
          specific DNA probes and for purposes of gene mapping.

          Clinicians request cytogenetic analysis for individuals
          with clinical findings or a medical or family history
          indicative of a chromosome abnormality.  Requests for
          cytogenetic studies have increased in the last decade
          due to the demand for prenatal chromosome testing and
          because of the widespread use of chromosome analysis in
          cancel diagnosis and monitoring.

          An accurate cytogenetics analysis is essential for the
          clinician to make an accurate clinical genetic
          diagnosis and prognosis for patient management,
          pregnancy planning and prenatal diagnosis.

          An incorrect diagnosis, both false positive and false
          negative, will have far reaching medical and legal
          implications. Therefore it is imperative that any
          device used for purposes of cytogenetic analysis is
          sensitive, specific, safe, and effective.


B.   Historical Background

     The correct chromosome number in humans, 46, was determined
     in 1956 by Tjio and Levan2.  Prior to this date the normal
     human chromosome number was considered to be 48.  With this
     new knowledge came the recognition that certain chromosome
     abnormalities were associated with specific congenital
     defects.

     Improved techniques for handling mitotic chromosomes
     awakened interest in human cytogenetics.  In 1959 Lejeune,
     et al., described the first chromosome abnormality
     associated with a clinical syndrome, trisomy 21 in the Down
     syndrome3.  With the advent of chromosome banding techniques
     in the 1970s, it was possible to identify with certainty all
     chromosome pairs and to characterize more accurately
     abnormalities of chromosome number and structure.   For a
     given banding technique, each chromosome pair exhibits a
     unique pattern of differential staining along the length of
     the chromosome.

     The traditional method for analyzing chromosomes is labor
     intensive.  By the early 1960s, development of instruments
     for 4 automated analysis of metaphase chromosomes was well
     under way. The primary objective was to develop automated
     systems which perform as well as a cytogeneticist using
     conventional techniques and are faster and more cost
     effective.

     Because of the rapid increase in the work load of the
     cytogenetics laboratory and the improved computer
     capabilities for image processing, these devices are being
     used with increased frequency to automate parts of the
     manual procedure.5,6  Various computer hardware and software
     features are available which are designed to assist in one
     or more steps of the process outlined in II.C.


C.   Basic Steps in Routine Cytogenetic Analysis7,8,9

     1.   Specimen Types and Cell Preparation.  (Automated
          chromosome analyzers are not involved in this step.)

          a.   Obtain a specimen with a large population of
               cycling (dividing) cells

          Specimens that contain rapidly dividing cells (e g ,
          bone marrow, solid tumors and  chorionic villus) may be
          harvested without culturing (direct method).  Other
          types of issue (e g., peripheral blood lymphocytes,
          skin fibroblasts and amniotic fluid cells) must be
          cultured in a nutritive media and controlled
          environment before harvesting.  

          b.   Harvest the cells

          Arrest cell division at the metaphase stage of the cell
          cycle by adding colcemid or a similar agent that
          inhibits spindle fiber formation.  Treat the cells with
          a hypotonic agent to swell the cells and to facilitate
          a better spread of the metaphase chromosomes when they
          are dropped onto a microscope slide or are grown on
          coverslips.  Treat them with a fixative to kill the
          cells, clarify the chromosome morphology, and enhance
          the basophilic property of the chromosomes.

          c.   Prepare the slides and stain the cells

     2.   Selection and Analysis of cell with Metaphase
          Chromosomes (Automated Chromosome Analyzers may modify
          or aid in one or more of these processes.)

          a.   Select a predetermined number of metaphase spreads
               of suitable quality for study and count the
               chromosomes to determine the modal chromosome
               number.

          b.   Select several representative spreads for detailed
               analysis. The number of cells selected varies
               depending on individual laboratory practices and
               the clinical indication for testing.

          c.   Photograph the representative metaphase spreads
               and make an appropriate number of photographic
               prints.

          d.   Cut individual chromosomes from the prints.  Pair
               and arrange them in a standard format following
               the International System for Human Cytogenetic
               Nomenclature (ISCN), 1985 guidelines10.

          e.   Prepare a final report using standard nomenclature
               that includes a summary and interpretation of the
               reservations and the number of cells counted and
               analyzed.  Send the report to the referring
               clinician.  Keep permanent records including a
               copy of the final report, the original metaphase
               images and karyotypes, and the microscope slides
               on file for a period of time determined by the
               individual institution or other regulatory agency.





II. Device Description

     A.   General Principles and Features

          Key issues in the review of these devices center on
          specific intended use statements and claims dependent
          on the type of device manufactured.

          The following features/capabilities are representative 
          of devices currently marketed or being developed in the
          United States for clinical use.  Describe fully these
          and any other features for which claims are made in the
          labeling section of the 51OK submission.

               Work Station 
               Hardware/Software 
               Electronic camera with automatic focusing 
               Monitor (color, monochrome) 
               Word Processor 
               Special Decision Making Features 
                    Automatic karyotyping 
                    Metaphase finding 
                    Chromosome finding 
                    Satellite analysis 
                    in situ hybridization analysis 
                    Sister chromatin exchange (SCE) analysis
                    Automatic cutting and/or separation of
                         chromosomes 
                    Image manipulation 
                    Positioning 
                    Rotating 
                    Moving 
                    Eliminating artifact (dodging) 
                    Enlarging selected metaphases, chromosome
                         pairs, or individual chromosomes
                    Enhancing 
                    Contrasting 
                    Image capturing process by a TV camera
                    Resolving gray scale (levels of grayness)
                    Printer interface 
                    Microscope interface 
                    Capacity for networking 
                    Data storage mechanism and capacity 
                    Ability to recognize and analyze prophase 
                         chromosomes 
                    Staining methods the instrument can utilize
                    Chromosome recognition capability 
                    Training feature

     B.   Description of Specific Features:

          1.  Metaphase Finders/Scanners aid the
               cytotechnologist to locate rapidly suitable
               metaphases for analysis.  These instruments
               automatically scan the microscope slide to locate
               likely metaphase spreads.  The instrument may rank
               the metaphase cells according to quality and store
               their microscope slide coordinates in the
               computer's data base. Metaphase finding/scanning
               instruments are not always accurate.  In some
               cases their use is limited to specific types of
               staining and they may not be appropriate for use
               with certain types of disorders.

          2.   Chromosome Counters determine the chromosome
               number by automatically counting the number of
               chromosomes in a given metaphase spread.

          3.  Photomicroscopy and Photographic Dark Room
               Processes eliminate the need for photomicroscopy,
               photographic dark room work and cutting and
               pasting chromosomes when performing karyotyping. 
               The process uses digital image processing to
               digitize the metaphase images by dividing the
               picture into a grid of pixels.  The resolution and
               detail is determined by the number of pixels in
               the image and the range in the level of contrast
               (grayness).  The level of grayness may
               theoretically range from 0 to 256. Optical
               information about each pixel as well as its
               location may be processed and stored in the
               computer data base.  The metaphase chromosomes are
               manipulated (cut) and arranged (pasted) in pairs
               on the karyotype card (projected onto the computer
               monitor).  Some instruments are designed to do the
               "cutting and pasting" automatically (see section,
               B.4.b., below) - others require the operator to
               manipulate the images (see section B.4.a., below).

          4.   Interactive and Automatic Karyotyping

               a.   Interactive systems have no decision making
                    ability and depend on the operator to
                    classify the chromosomes from the computer
                    screen and arrange them on the computerized
                    karyotype sheet.


               b.   Automatic karyotyping systems exist with
                    varying amounts of decision making ability. 
                    Chromosomes are classified on the basis of
                    chromosome dimension (e.g., ratio of short
                    arm to long arm) and banding pattern profile.

          5.   Enhancement, Alteration and Manipulative Features.
               Some instruments have features that enhance or
               contrast chromosome images in metaphases and/or
               individual chromosomes to improve the banding
               characteristics of the chromosome(s).  Other
               features alter or allow the operator to alter
               chromosome morphology and/or other cellular
               characteristics. These features include:
               straightening, enlarging, trimming,
               "mirror-image", "enhancement" (selectively
               altering staining pattern within a metaphase
               spread or within a chromosome region), and
               dodging/lifting the cytoplasmic background.

          6.   Specialized Analysis (in development)  A few
               instruments have the ability to perform analysis
               of specialized studies such as chromosome
               satellites, in situ hybridization and sister
               chromatid exchange (SCE).  Some chromosome
               analyzers automatically count the number of
               satellites or SCEs per metaphase cell or the
               number of hybridized probe sites per interphase or
               metaphase cell. Although this feature is currently
               being used for research purposes, it has not been
               cleared by the FDA for clinical use.

          7.   Hard Copy Prints.  Most systems are capable of
               producing near photographic quality, printer
               generated hard copy of the metaphase images and
               karyotypes.

          8.   Generating Reports.  Many instruments have
               capabilities of generating (preparation &
               printing) a final summary for the referring
               clinician and of handling the billing process and
               other bookkeeping.

          9.   Computerized Patient Data Storage, Retrieval and
               Archival Systems.   A data base may include
               metaphase images and karyotypes, patient
               identifying information, and final reports.


          10.  Training Feature (in development).  This feature
               permits the operator to teach the system to
               recognize the chromosomes preparations particular
               to a given laboratory.  It allows the operator to
               "train" the instrument to recognize different
               staining preparations. Although this feature is
               currently being used for research purposes, it has
               not been cleared by the FDA for clinical use.

          11.  Telecommunication Features allows for site-to-site
               image transmission.

          12.  Networking features provide networking between
               workstations and local areas.


III. Specific Performance Characteristics

     Support specific parameters of importance to the operation
     of the instrument by data generated with the device. 
     Demonstrate that the device is substantially equivalent to a
     legally marketed predicate device.  Conduct performance
     studies to demonstrate that the device is safe and effective
     by comparing the device's performance to the manual
     reference method of chromosome analysis.  See section II.B.,
     "Device Description" for details of performance
     characteristics required for specific feature.

     Address all aspects of performance characteristics as stated
     in section III.C. in the Performance Characteristics section
     of the Labeling.  Provide the following specific information
     on reproducibility/precision and accuracy for instruments
     with features that warrant such studies.  Include a detailed
     study protocol, generated data and statistical analysis of
     the data in any submission to the include a summary of the
     performance data in the Performance Characteristics section
     of the Labeling

     A.   Analytical/Laboratory/in vitro Studies

          1.   Reproducibility Studies

               Study a sufficient number of control specimens and
               test specimens with the types of chromosome
               abnormalities or characteristics for which claims
               are made (e.g., normal, aneuploidies, structural
               rearrangements, fragile sites, sister chromatin
               exchange, etc.) to demonstrate: 

               a.   Within Sample Reproducibility

                    Does the device give the same results on
                    repeated trials (analysis) of a given
                    procedure?  e.g., does it locate the same
                    cells on a given slide, rank cells in the
                    same manner, give the same chromosome count
                    on a given cell, generate the same karyotype
                    for a given cell, etc.

                b.  Between Instrument Reproducibility

                    Do different devices give the same results
                    for a given procedure?  e.g. do they locate
                    the same cells on a given slide, rank the
                    cells in the same manner, give the same
                    chromosome count on a given cell, generate
                    the same karyotype for a given cell, etc.

          2.   Comparison Studies

               Comparison studies provide data on the ability of
               the instrument to determine accurately specific
               results as compared to the manual method for
               chromosome analysis.  (If a method other than the
               manual method is used justify the choice of the
               method and include pertinent references.)

               Perform the test on a sufficient number of
               specimens with and without chromosome aberrations
               and calculate the following parameters:

               a.   Relative Diagnostic Sensitivity: the
                    probability that the instrument will
                    correctly identify an abnormality determined
                    to be abnormal by the reference method.

               b.   Relative Diagnostic Specificity: the
                    probability that the instrument will
                    correctly identify as normal a specimen
                    determined to be normal by the reference
                    method.

          3.   Specifications

               Describe the relative quality:  Does the
               instrument achieve the same (or better band
               resolution compared to the reference method
               according to the ISCM (1985) guidelines10?

     B.   Software Documentation

          All computer software should comply with the FDA's
          Policy for Regulation of Computer Products.  For
          general information contact the FDA Division of Small
          Manufacturers (phone, 800-638-2041).  For specific
          information contact the Division of Product
          Surveillance (phone, 301-427-8156).

     C.   Special Considerations for Specific Features Described
          in II.B.

          All devices that have any decision making features
          should also have a feature which allows the operator to
          interact, edit and override the work generated by the
          device.

          Several features of imaging analysis computer systems
          need special consideration which are addressed below.

          For each of the following features, provide
          reproducibility and comparison studies, specifications,
          and software documentation unless otherwise specified.

          Incorporate the following considerations as appropriate
          in the Labeling (e.g., Intended Use, Methods,
          Limitations, etc.).

          1.   Metaphase Finders

               a.   State which staining methods may be used with
                    the device.  State what types of preparations
                    may be analyzed (e.g., air dried, grown on
                    coverslips, primary colonies, etc.)

               b.   Provide data to demonstrate that the device
                    does not introduce bias in selection of
                    metaphases with respect to chromosome number
                    (e.g., aneuploidy, polyploidy),
                    endoreduplication, poor chromosome morphology
                    as in some malignant cells, structural
                    chromosome abnormality (e.g., translocations,
                    dicentrics, fragments, etc.), or chromosome
                    staining factors.

               c.   Provide data to demonstrate the performance
                    of the metaphase ranking feature.  State in
                    the Labeling whether metaphase finders will
                    or will not detect certain cellular
                    abnormalities such as micronuclei, nucleolar
                    organizing region (NOR) alterations and other
                    abnormalities of the cytoplasm or nucleus
                    which would be noted by an astute observer.

               d.   Since these instruments are not always
                    accurate for finding and ranking metaphases,
                    place the following or (similar) statement in
                    the Limitations Section of the Labeling.

                         "The cytogenetic technologist/
                         cytogeneticist should always review
                         slides independently of the metaphase
                         scanner/finders."

               e.   State whether or not it is appropriate to use
                    the metaphase finder for studies such as drug
                    sensitivity, tumor hard tissue, etc.  State
                    any limitations in the Limitations section of
                    the Labeling.


          2.   Chromosome Counters

               a.   State which staining methods may be used with
                    the device.

               b.   State limitations imposed by how well the
                    chromosomes are spread (e.g., overlapping
                    chromosomes, too much spread, broken cells,
                    too many metaphases in one location, etc.).

               c.   Provide data to demonstrate that bias is not
                    introduced into chromosome counts by
                    aneuploidy, polyploidy, endoreduplication,
                    radial formations, chromosome pulverization,
                    poor chromosome morphology as in some
                    malignant cells, and structural chromosome
                    abnormality (dicentrics, fragments, etc.). 
                    If any incorrect chromosome counts result,
                    this should be declared in the limitations
                    section of the package insert.


               d.   Include the following or similar statement in
                    the Limitations Section of the Labeling:

                         "In general there will be one or more
                         errors in determining the correct
                         chromosome number for the population of
                         cells studied.  It is the responsibility
                         of the operator to determine the correct
                         modal chromosome number."

          3.   Interactive Karyotyping Systems (no decision
               making ability)

               Reproducibility and comparison studies are not
               required since this feature has no decision making
               ability.

          4.   Automated Karyotyping

               Reproducibility and comparison studies are
               required only for the decision making features of
               the device.

               Include the following or similar statement in the
               Limitations section of the Labeling:

                    "In general, there will be one or more errors
                    in the computer-generated karyotype  
                    Therefore, it must always be examined and
                    edited as a final interactive manual
                    operation by a qualified cytogeneticist or
                    cytogenetic technologist."

          5.   Enhancement, Alteration and Manipulation Features

               Altering chromosome morphology in any way (aside
               from improving culturing and staining techniques)
               is not an accepted standard of professional
               practice in cytogenetic analysis.

               a.   Comparison data are not required for
                    enhancement, alteration or manipulation
                    features.

               b.   Any device with features that in any way
                    alter chromosome morphology should also have
                    a built-in feature that automatically and
                    permanently marks/designates these
                    alterations in the karyotype.

               c.   Digitized straightening of chromosomes will
                    often artificially induce extra bands and
                    thus make it impossible to determine,
                    unequivocally, whether the straightened
                    chromosome is, indeed, normal.  Designate any
                    straightened chromosomes as stat.

               d.   Assure that the device does not have the
                    capacity to induce artifacts.

               e.   Features that "lift" cellular background
                    should not be automatic and should have a
                    built-in feature that requires operator
                    activation.  Such a feature should not be
                    used unless the operator has already examined
                    the cell to assure that the material to be
                    lifted is true artifact and not chromatin
                    material such as double minutes.

               f.   Include a statement about the potential for
                    misuse of each feature under the Limitations
                    section of the Labeling and elsewhere in the
                    operators manual whenever use of these
                    features are described.  Use the following or
                    a similar statement about features listed in
                    this section:

                         "It is the responsibility of the
                         cytogenetics technician and/or the
                         cytogeneticist to utilize all features
                         in compliance with standard laboratory
                         practice and regulatory guidelines."

          6.   Photomicroscopy and Dark Room Process

               a.   Reproducibility and comparison data are not
                    required.

               b.   Compare the resolution of the digitized
                    images to standard microscopic resolution in
                    terms of the resolution standards (400, 500
                    and 850 bands) of the ISCN, 1985 guidelines10.


               c.   For devices that have no decision making
                    ability, include the following or similar
                    statement in the Intended Use section of the
                    Labeling:

                         "The device does not locate metaphase
                         spreads; it does not rank the given
                         cells according to quality; it does not
                         automatically classify chromosomes; it
                         does require and relies completely on
                         the operator to manipulate the digitized
                         microscope images."

          7.   Hard Copy Prints

               a.   Reproducibility and comparison data are not
                    required.

               b.   Describe the quality and resolution of the
                    hard copy print in the Principle of the
                    Procedure  section of the Labeling.  State
                    whether the quality/resolution of the
                    computer generated print is equivalent to (as
                    good as) standard photomicroscopy (levels of
                    gray) and whether the device meets the
                    minimum resolution standard set by the ISCN,
                    1985 guidelines.

               c.   Describe the composition, quality and
                    durability of the photo image paper and
                    whether contrast deteriorates with age.

                    i.   A precaution/warning statement in the
                         Precautions section of the Labeling will
                         be required for paper containing mercury
                         or other toxic substances.

                    ii.  State how long the prints will remain of
                         archival quality.  The durability of
                         these hard copy prints is important
                         since some proficiency/licensing
                         agencies require long term storage of
                         metaphase images (up to 25 years for New
                         York State).

          8.   Computerized Patient Data Storage, Retrieval and
               Archival System.

               a.   Reproducibility and comparison data are not
                    required.

               b.   This feature should comply with section
                    III.B. of this document.  The following
                    issues are of special concern and should be
                    addressed in the Principles of Procedure
                    section of the labeling:

                    i.   adequate security control which may
                         require several levels of "password"
                         security to assure protection and
                         confidentially of patient information;

                    ii.  adequate safe guards to protect against
                         accidental or virus generated deletion
                         of the data

                    iii. an explanation of where and how the data
                         are stored; and 

                    iv.  a recommendation of multiple identifying
                         codes (e.g., for patient identifying
                         data, metaphases, karyotypes, final
                         report, etc.) to assure correct and
                         usable storage and retrieval of
                         information from the data base and
                         archival system.


IV.  Labeling Considerations

     The Labeling (Operator's Manual or Package Insert) should
     include all information listed in the in vitro diagnostic
     Labeling regulations 21 CFR ~ 809.10(b)(6) plus additional
     pertinent headings found under 21 CFR ~ 809.10(b):

     A.   Intended Use Statement

          Describe concisely the functions/features of the
          device. State clearly that a qualified cytogenetic
          technologist and/or cytogeneticist must edit and/or
          confirm all computer-generated data/results and make
          the final judgment/decision.

          For devices that have no decision making ability,
          include the following or similar statement in this
          section:


               "The device does not locate metaphase spreads; it
               does not rank the given cells according to
               quality; it does not automatically classify
               chromosomes; it does require and relies completely
               on the operator to manipulate the digitized
               microscope images."

     B.   Limitations of the Device

          Include the following:

          1.   a statement that decision making capabilities of
               the instrument do not relieve the
               cytogeneticist/cytogenetics technologist of the
               responsibility to review and edit all work
               generated by the device and that the final
               decision must be made by a qualified
               cytogeneticist;

          2.   appropriate statements of precaution outlined for
               each feature in the Performance Characteristics
               section (III-C). In some cases, limitation
               statements for more than one features may be
               combined; and

          3.   these general statements for all devices that have
               features with decision making ability:

                    "In general, there will be one or more errors
                    in the computer-generated data/karyotypes.
                    Therefore, it must always be examined and
                    edited as a final interactive manual
                    operation by qualified cytogenetic
                    personnel."

                    "The final clinical diagnosis must be made by
                    qualified medical personnel."


C.   Performance Characteristics

     Provide a summary of all reproducibility and comparison
     studies (sensitivity and specificity) when performed as
     requested by Section III.

     Also address other performance characteristics that relate
     to specific features (as described in section III-C).


V.  Bibliography

     1.   Letter. September 1989 Cytogenetic Proficiency Test,
          General Comments. New York State Department of Health.

     2.   Tjio, JH and Levan, A: The chromosome number in man.
          Hereditas, 42:1, 1956.

     3.   Lejeune, J, Gautier, M, and Turpin, MR: Etude dais
          chromosomes somatiques de neut enfants mongoliens. 
          C.R. Acad. Sci. (Paris) 248, 1721-1722, 1959.

     4.   Lubs, HA and Ledley, RS: Automated analysis of
          differentially stained human chromosomes.  Nobel.
          23:61-76, 1973.]

     5.   Lifshitz, MS and DeCresce, RP:  Genetiscan Digital
          Karyotype System. Lab Med, 18(6):402-403, 1987.

     6.   Bender MK: Karyotyping System with Special Reference to
          the KARYOTEC 100. Presentation: 34th Annual Scientific
          Meeting of The Royal College of Pathologists of
          Australia. Hong Kong, 1989.

     7.   Rooney DE and Czepulkowski BH: Human Cytogenetics: A
          Practical Approach. Oxford, England: ILR Press; 1986.

     8.   Verma RS and Buba A. Chromosomes: A manual of Basic
          Techniques.  New York, NY: Pergamon; 1989.

     9.   Priest JH: Medical Cytogenetics and Cell Culture. 2nd
          ed. Philadelphia, PA: Lea and Fabiger; 1977.

     10.  Harden DG and Klinger HP: An International System for
          Human Cytogenetic Nomenclature (1985).  Basel,
          Switzerland: S Karger; 1985.

 

 

This document was still considered current as of July 1997.
It will be reviewed again in July 1998.