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Cytogenetic Laboratory Management: Chromosomal, FISH and Microarray-Based Best Practices and Procedures



Cytogenetic Laboratory Management: Chromosomal, FISH and Microarray-Based Best Practices and Procedures

Susan Mahler Zneimer

ISBN: 978-1-119-06977-5 January 2017 Wiley-Blackwell 840 Pages


Cytogenetic Laboratory Management: Chromosomal, FISH and Microarray-Based Best Practices and Procedures is a practical guide that describes how to develop and implement best practice processes and procedures in the genetic laboratory setting. The text first describes good laboratory practices, including quality management, design control of tests and FDA guidelines for laboratory developed tests, and pre-clinical validation study designs. The second focus of the book describes best practices for staffing and training, including cost of testing, staffing requirements, process improvement using Six Sigma techniques, training and competency guidelines and complete training programs for cytogenetic and molecular genetic technologists. The third part of the text provides step-wise standard operating procedures for chromosomal, FISH and microarray-based tests, including pre-analytic, analytic and post-analytic steps in testing, and divided into categories by specimen type, and test-type.

All three sections of the book include example worksheets, procedures, and other illustrative examples that can be downloaded from the Wiley website to be used directly without having to develop prototypes in your laboratory.

Providing both a wealth of information on laboratory management and molecular and cytogenetic testing, Cytogenetic Laboratory Management will be an essential tool for laboratorians world-wide in the field of laboratory testing and genetics testing in particular.

This book gives the essentials of:

  • Developing and implementing good quality management programs in laboratories
  • Understanding design control of tests and pre-clinical validations studies and reports
  • FDA guidelines for laboratory developed tests
  • Use of reagents, instruments and equipment
  • Cost of testing assessment and process improvement using Six Sigma methodology
  • Staffing training and competency objectives
  • Complete training programs for molecular and cytogenetic technologists
  • Standard operating procedures for all components of chromosomal analysis, FISH and microarray testing of different specimen types

This volume is a companion to Cytogenetic Abnormalities: Chromosomal, FISH and Microarray-Based Clinical Reporting. The combined volumes give an expansive approach to performing, reporting and interpreting cytogenetic laboratory testing and the necessary management practices, staff and testing requirements.

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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

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


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

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


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

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

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



"From beginning to end, this book provides relevant concepts, procedures and strategies that give the reader a complete overview of good laboratory practices. In addition to providing an excellent guide for setting up a new clinical lab, Zneimer's book should be considered as a useful guide for any laboratory because it provides a wealth of practical information that can be used on a daily basis. All of the spreadsheets, guides, examples and templates in the book are useful bonus features and represent a valuable legacy of the author's extensive experience." (Phenotype June 2017)