Cytogenetic laboratory management : chromosomal, FISH, and microarray-based best practices and procedures

818 Pages·2016·6.134 MB·English

by  Zneimer, Susan Mahler

CytogenetiC laboratory management
CytogenetiC
laboratory
management
Chromosomal, FiSH and
microarray‐based best Practices
and Procedures
SuSan maHler Zneimer
Adjunct Professor, Moorpark College, California, USA
CEO and Scientific Director, MOSYS Consulting, California, USA
Copyright © 2017 by John Wiley & Sons, Inc. All rights reserved
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Published simultaneously in Canada
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ISBN: 9781119069744
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Set in 10/12pt Times by SPi Global, Pondicherry, India
10 9 8 7 6 5 4 3 2 1
contents
DeDication xi
Preface xiii
acknowleDgments xvii
about the comPanion website xix
section i: best Practices for laboratory oPerations 1
1 guidelines for good clinical laboratory Practice 3
1.1 Physical Facilities 4
1.2 Specimen Transport and Management 5
1.3 Personnel Safety 6
1.4 Laboratory Information System (LIS) 7
1.5 Quality Management 7
1.6 Organization and Personnel 10
1.7 Laboratory Equipment 10
1.8 Testing Operating Procedures 11
1.9 Safety Plan 12
1.10 Biosafety Plan 22
1.11 Chemical Hygiene Plan 31
1.12 Health Insurance Portability and Accountability Act (HIPAA)
Incident Plan 55
Appendix 1.A: OSHA’s Form 300 60
Appendix 1.B: OSHA’s Form 300A 61
Appendix 1.C: Information on HMIS and NFPA Labeling Systems
used in Laboratories 62
v
vi CONTENTS
Further Reading 66
More Resources 69
HIPAA Reference 70
2 Quality management 71
2.1 QC Program 74
2.2 Individualized QC Plan (IQCP) 80
2.3 Standards for Test Records and Reporting 81
2.4 Overview of General Culturing Issues 83
2.5 QI Program 95
2.6 Proficiency Testing 101
2.7 Inspection Preparation 110
2.8 Calibration Verification 112
Further Reading 121
3 Design control of tests and fDa guidelines for laboratory
Developed tests (lDts) 125
3.1 Design Control of Tests 125
3.2 FDA Guideline Summary for LDTs 139
Further Reading 157
4 Preclinical Validation studies 159
4.1 Validation Plans and Protocols 159
4.2 Validation Reports 179
4.3 Example Validation Plan and Report—Analysis of FISH Probes
for Chromosome 5 Deletion and Monosomy 181
4.4 Example Validation Plan and Report for the
FDA‐Approved Vysis ALK FISH Probe 192
Further Reading 206
5 reagents, instruments, and equipment 209
5.1 Reagents 209
5.2 Instruments and Equipment 227
5.3 IQ, OQ, and PQ Procedures 237
5.4 Example Equipment Process Validation Protocol 245
Further Reading 250
section ii: best Practices for staffing anD training 253
6 cost of testing and staffing requirements 255
6.1 Labor Costs 256
6.2 Time and Cost Assessment 260
6.3 Staffing Hiring Needs 260
6.4 Staff Task Requirements 262
Further Reading 267
CONTENTS vii
7 Process improvement: six sigma approach to laboratory improvement 269
7.1 Introduction 269
7.2 DMAIIC Tools 273
7.3 Defining the Project 274
7.4 Measuring Variables 279
7.5 Analyze Data for the Project 282
7.6 Innovate and Improve the Project 287
7.7 Controlling the Results of the Project 289
Appendix 7.A Raw Baseline Data 295
Appendix 7.B Raw Control Data 295
Further Reading 296
8 staff training and competency for a cytogenetics laboratory 299
8.1 Technician (Nonlicensed/Certified Lab Personnel) Training and Competency 300
8.2 Technologist (Licensed/ASCP‐Certified) Training and Competency 303
8.3 General Supervisor/Manager Training and Competency 307
8.4 Cytogenetic Technical Supervisor/Director Training and Competency 310
Further Reading 316
9 training Program for cytogenetic and fish technologists 319
9.1 Training Program Overview and Objectives 320
9.2 Program Content 323
9.3 Practical Component 332
9.4 Lectures, Quizzes, and Assignments 335
9.5 Trainee Competency and Completion of the Program 335
9.6 Trainee Handbook 336
9.7 Logs, Competency Forms, and Evaluation Forms 344
Further Reading 356
10 training Program for molecular genetic technologists 357
10.1 Training Overview and Objectives 358
10.2 Program Content 361
10.3 Practical Component 367
10.4 Lectures, Quizzes, and Assignments 370
10.5 Trainee Competency and Completion of the Training Program 370
10.6 Trainee Handbook 371
10.7 Logs, Competency Forms, and Evaluations Forms 379
Further Reading 383
section iii: stanDarD oPerating ProceDures 385
11 general soP information by test and Preanalytic Procedures 387
11.1 Definition of an SOP 387
11.2 Example Template for Writing an SOP 390
viii CONTENTS
11.3 CAP and ACMG Guidelines for Writing SOPs 393
11.4 Preanalytic Procedures: Accessioning Specimens for all Specimen Types 396
Further Reading 402
12 analytic Procedures: chromosome analysis 405
12.1 Peripheral Blood and Percutaneous Umbilical Blood
Specimen for Constitutional Disorders 410
12.2 Amniotic Fluid Specimens 440
12.3 Chorionic Villus Sampling 479
12.4 Solid Tissue Samples: Tissue Biopsies and Products of Conception 505
12.5 Bone Marrow and Blood for Hematologic Malignancies 534
12.6 Lymph Nodes and Solid Tumors 565
12.7 Breakage Syndromes 592
Appendix 12.A Cytogenetics Blood Culture and Harvest Worksheet 597
Appendix 12.B Daily Harvest Log 598
Appendix 12.C Test Slide Banding Log 599
Appendix 12.D Batch Banding Log 600
Appendix 12.E Analysis Sheet 601
Appendix 12.F Prenatal Culture and Harvest Worksheet 602
Appendix 12.G Culture Failure Log 603
Appendix 12.H Amniotic Fluid Count Guidelines—for Normal and
Extended Studies 604
Appendix 12.I Hematologic Culture Log 605
Appendix 12.J Specimen Setup—Hematologic Malignancies 606
Appendix 12.K Solid Tumor Culture Worksheet 607
Further Reading 608
13 analytic Procedures: fluorescence in situ hybridization (fish) analysis 613
13.1 General Information 613
13.2 CAP and ACMG Guidelines for Performing FISH Analyses 617
13.3 Cell Sorting for Plasma Cell Disorders for FISH Analysis 619
13.4 General Procedure for Direct Labeling of FISH Probes 624
13.5 Prenatal Multicolor Probes 641
13.6 ToTelVysion™ Multicolor DNA Probe Mixtures 654
13.7 Multicolor: Telomere, Centromere, and Paint Probes (Cytocell) 666
13.8 Microscope Analysis for Metaphase Scoring 680
13.9 Microscope Analysis for Interphase Scoring 685
13.10 Formalin‐Fixed Paraffin‐Embedded Procedure for FISH Analysis 693
13.11 HER2/ERBB2 FISH Analysis 700
13.12 UroVysion (Vysis) Bladder Cancer FISH Analysis 711
Appendix 13.Aa Constitutional FISH Probes 722
Appendix 13.Ab Hematologic FISH Assays 723
Appendix 13.B Probe Chart: Panels of Probes 724
Appendix 13.C FISH Direct Harvest Log 725
Appendix 13.D Batch Hybridization Log 726
Appendix 13.E General FISH Probe Analysis Sheet 727
CONTENTS ix
Appendix 13.F FISH Probe Analysis Sheet—AML Panel 728
Appendix 13.G FISH Probe Analysis Sheet—MDS Panel 729
Appendix 13.H FISH Probe Analysis Sheet—CLL Panel 730
Appendix 13.I FISH Probe Analysis Sheet—NHL Panel 731
Appendix 13.J FISH Probe Analysis Sheet—MM Panel 732
Appendix 13.K FISH Probe Analysis Sheet—ALL Panel 733
Appendix 13.L FISH Analysis Sheet—BCR/ABL/ASS Triple Fusion 734
Appendix 13.M HER2 Analysis Sheet 735
Appendix 13.N UroVysion Analysis Sheet 736
Further Reading 736
14 analytic Procedures: chromosomal microarray analysis (cma) 739
14.1 Test Principle 739
14.2 Comparing Conventional Chromosome Analysis, FISH Analysis
and Chromosomal Microarray Analysis 741
14.3 Interpretation 745
14.4 Procedure Overview 747
Further Reading 752
15 Postanalytic Procedures 755
15.1 Reviewing and Reporting Cases for Chromosome Analysis 756
15.2 Reviewing and Reporting Cases for FISH Analysis 762
15.3 Reviewing and Reporting Cases for Microarray Analysis 765
15.4 Procedure for Avoidance and Detection of Clerical Errors Post Reporting 772
15.5 Specimen, Material and Record Retention, and Specimen Disposal 774
Appendix 15.A Record of Results Correspondence Log 778
Further Reading 779
glossary 781
inDex 811
DeDication
I dedicate this book to my daughters, Mira and Alana, who since they were born have
changed my life forever and for the better. They have given me strength, inspired me to do
great things, and have given me abounding love. I hope I have done the same for them.
Mira and Alana, I wish you both a life of good health, happiness, and profound
significance. And may you strive for Tikkun Olam.
And to my dear friend and colleague, Lauren Jenkins, whom I have known for most of my
life. Your time on this earth was much too short. I miss you with all my heart.
Lauren died on Rosh Hashanah 5776 (September 14, 2015).
xi
Preface
For the last 25 years, I have been the director of different cytogenetic laboratories. Like
most directors, I started out in academia for my American Board of Medical Genetics
fellowship, but then moved on to various commercial laboratories for the next 20 years,
and now currently to consulting for different genetic laboratories, both commercial and
academic. After all these years, I realize that my daily work consists of two main tasks,
signing out cytogenetic cases and managing the clinical laboratory. I wrote my first
book, Cytogenetic Abnormalities, Chromosomal, FISH and Microarray‐Based Clinical
Reporting, published by Wiley Publishers in 2014, to reflect all the information that I have
learned in signing out cases throughout my career. In this book I want to focus on the other
aspects of my laboratory duties, namely, laboratory management. Managing or directing a
lab requires vastly different skills than what we learn as scientists who need to perform,
review, and interpret cytogenetic laboratory results. As scientists, we generally receive lit-
tle training in the field of management, let alone laboratory management. As geneticists,
we rely on our scientific knowledge base and experience in genetic procedures to perform
and sign out test results. We acquire those skills after years of working in the laboratory in
graduate school and postdoctoral programs.
However, laboratory management uses other skills that we usually learn “on the job.”
We learn that to be a good director or manager, we need to be good at interpersonal
relations, organization, and time management. We learn to be supportive of the laboratory
staff yet be good disciplinarians when performance is not acceptable. We learn to be inno-
vative and strive to be as productive as possible. We learn to be conscious of interpreting
patient results and performing genetic analyses with complete accuracy, yet to also be
aware of the “bottom line” in order to be within a specific budget. It is a balancing act that
we must perform daily and get right every time. Genetic results require 100% accuracy in
diagnostic testing as well as being business savvy to be always within a budget; otherwise,
our jobs may be in jeopardy.
For these reasons, I decided to write this book on laboratory management. I know what
most lab directors and managers face with regards to “running a lab.” So I want to share as
xiii