# Presentation: 244962

## Standard Controls and Best Practice Development for 

**Standard Controls and Best Practice Development for **
**Genomic Technologies**
**Janet A. Warrington, Ph.D.**
**January 4, 2007**

## Standard Controls and Best Practice Initiatives 

- External RNA Controls Consortium
- Clinical and Laboratory Standards Institute MM16, MM17
- Clinical and Laboratory Genomic and Genetic
- 	Standards Group
- Organization for Economic Cooperation and Development (OECD) Biotechnology Industry Advisory Committee,
-     Working Party on Biotechnology
- MicroArray Quality Control Project
- EU Project EMERALD
- MGED

## The External RNA Controls Consortium

- 175 members, 92 organizations, 14 countries
- Government, regulatory, academic laboratories and
- 	biotechnology, pharmaceutical and diagnostic companies
- Ways of working
- Volunteer organization
- Open to anyone with an interest in working together
- Consensus based decision making
- Publish final results as a group by the group
- Goals
- Develop well-characterized standard controls for multiple genomic
- 	technology platforms e.g. microarray, RT-PCR
- Develop protocols for multiple applications, research and clinical laboratory
- First deliverable, August 2006
- (MM16) Use of External RNA Controls published by CLSI

## Nature Methods  2005 (October) 2:731-734

***Nature Methods*****  2005 (October) 2:731-734**

## Global
Nonprofit
Consensus process
Promotes development and use of voluntary consensus standards and guidelines within the healthcare community
Recognized worldwide
Harmonized terminology database – open access
www.clsi.org

- Nonprofit
- Consensus process
- Promotes development and use of voluntary consensus standards and guidelines within the healthcare community
- Recognized worldwide
- Harmonized terminology database – open access
- www.clsi.org

**Clinical and Laboratory Standards Institute**

## CLSI Molecular Methods 

- Gene Expression Profiling in Clinical Applications
- Using Control Materials to Assess Technical and
- 	Clinical Performance
- Technical Performance Metrics
- External RNA Controls for Microarrays
- External RNA Controls for QRT-PCR

**MM16. Guideline for Use of External RNA Controls in Gene Expression Assays**

- Published Aug 2006

## CLSI Molecular Methods 

**MM17-P.Verification and Validation of Multiplex**
**Nucleic Acid Assays: Proposed Guideline**

-    Approaches for defining assay performance characteristics;
-      sensitivity, specificity, accuracy, reproducibility, and methods of
-      statistical analysis
-    Reporting results when one or more of the multiplex assays may
-     be invalid or wrong
-    Intended for manufacturers, laboratory professionals, clinicians,
-     regulatory agencies

- In Progress

## Clinical and Laboratory Genomic and Genetic Standards

- Volunteer organization, 70 participants, 50 organizations, 19 countries
- Public and private sectors; government, industry, academic
- Goals
- Recommendations for qualification of performance controls for microarray-based DNA genetic tests
- Develop forum for driving consensus on characteristics
- 	and output of algorithms for microarray DNA-based genomic tests
- Ways of working
- Volunteer organization, consensus based
- Open to anyone interested in working together
- Publish recommendations, all information made public

## Recent projects of the OECD Biotechnology Working Group 

- International pharmacogenomics standards meeting Rome, 2005
- Guideline for quality assurance in molecular genetic testing
- Best practices guideline for genetic testing
- Expert meeting on evaluation of clinical validity and utility of genetic tests

**Organization of Economic Cooperation and Development**

## Microarray Quality Control Project  (MAQC)

- Initiated and led by Dr. Leming Shi, NCTR, FDA
- 137 participants, public and private
- Test intra and inter-lab reproducibility of microarray based expression assays
- Report, Nature Biotechnology Sept 8, 2006.
- Develop recommendations and best practices for methods of signature extraction.
- In progress

## EU Project EMERALD

- Martin Kuiper Flanders Interuniversity, Belgium

- Sixth EU Framework Programme Coordination Action
- to promote development of standards
-  and quality metrics for microarray technology

**EU Project EMERALD**

## AIMS 

- Establishing metrics for quality control.
- Consensus on best laboratory practices for quality assurance.
- Structuring of communication and information exchange.
- Dissemination of the results to the microarray community.
- Extrapolation and application to new technology development

## Planned Workshops

- 2. The development of QA/QC, pilot - Sep ’07 (MGED)
- 3. Ontology Workshop - Sep ’07 (MGED)
- 4. Dissemination of QA/QC results - April ’08
- 5. Quality metrics tutorial / training - Sep ’08 (MGED)
- 6. Certification of standards - Sep ’08 (MGED)
- 7. Implications for new technologies - Fall ‘08
- 8. Data quality and Systems Biology - Summer ’09 (ECCB)
- 9. Dissemination to larger community - Sep ’09 (MGED)

**Planned Workshops**

## Microarray Gene Expression Data Society - MGED 

- International organization of biologists, computer scientists, and data analysts
- Aims to facilitate sharing of microarray data generated by functional genomics and proteomics experiments
- Currently focused on establishing standards for microarray data annotation and exchange, facilitating the creation of microarray databases and related software implementing these standards, and promoting the sharing of high quality, well annotated data within the life sciences community.
- A long-term goal for the future is to extend the mission to other functional genomics and proteomics
- www.mged.org

## Summary

**Summary**

- Stakeholders from public and private sectors are working together to  establish standard controls and best practice guidelines to advance genomic technology into healthcare
- International harmonization benefits patients, physicians, test and drug developers, regulatory bodies, trade and commerce.
- Standards accelerate development work.
- Development dollars are more efficiently spent when standards are in place.