EPA Risk Assessment Review Process

Process Steps




Receipt and Administrative Preparation


Focus Meeting


Preliminary Report Preparation


Work-Plan Meeting


Risk\Benefit Analysis and Science Review


Mid-Course Meeting


Report Finalization and Integration of Findings


Final Reports Meeting


Final Report:  Hazard\Risk


Options Meeting


Brief Division Directors

Biosafety Science
Estimate Hazard
Estimate Exposure
Risk Assessment and Characterization
Risk Management
Protocols and Procedures
EPA Risk Assessment Review Process

Focus Meeting
Timeline:  Day 5

Purpose and scope of meeting

All reviewing groups are represented. Each group has studied the application. However, discussion centers on hazard and exposure information derived from th application. Issues raised by the application are discussed and the need for additional reviewers resolved. An Integrator responsible for technical progress is selected. The integarators role is as liason to the company and maintaining timely progress on the review. Following the meeting, initial Risk Assessment Activity begins. Specialists within the branches (chemists, biologists, and engineers) scope and prepare preliminary assessments. These assessments will be the basis for reports from each branch at the Workplan meeting

Science Aspects of Review, Example of Outcome

Scientific aspects (chemistry, molecular biology, engineering, exposure assessment)are reviewed by the Risk Assessment and the Economics, Exposure, and Technology branches. The initial emphasis is on identifying the hazard involved and defining the exposure element, the primary elements in a Risk Assessment. The focus meeting objective is to identify issues associated with the submitted organism based on the characteristics of the host organism in conjunction with the inserted genes, as presented in the submission.

The output of the focus meeting is a document describing the application in general terms, and decision as to the level of review.

Example of Information Presented/Outcome of Focus Meeting


This and all example material to follow, is based on PMN 95-1601, an application to field test a strain of Pseudomonas fluorescens, (PF) containing a naphthalene degradative plasmid that was  modified by transposon mutagenesis (TN4431) to create a lux gene transcriptional fusion with the gene for salicylatehydroxylose.

Example of findings

 The potential hazard issues identified include the use of tetracycline resistance gene; potential effects from the lux gene; potential for toxic metabolite formation; and the possibility that PF may be a pathogen. This transposon has been incorporated into another PF strain through an intrageneric transfer. The resulting recombinant organism (HK44) has the ability to degrade naphthalene, phenanthrene and anthracene. In addition, HK44 exhibits a visible bioluminescence in the presence of naphthalene.

 The submission sought to test this organism in a lysimeter at a restricted location away from a residential community.  In the initial submission, the submitters proposed mixing the organisms with the soil in a cement mixer and pouring the soil/microbe mixture into the lysimeters.  Upon development of the process the submitters determined that the process proposed in the initial submission was impractical.  The submitters proposed a modification to the method of application. Instead of mixing the soil in a cement mixer, the submitters propose using hand-held sprayers to apply the organisms to soil.  Concerns about spread of the antibiotic resistance genes were seen as  limited by the fact that the resistance genes are linked to the lux gene.  Movement of this gene to an indigenous organism would presumably place a metabolic burden on the recipient, thereby diminishing its potential to survive.

Example of decisions reached:

P95-1601 will be placed in Standard Review.  Issues that will need to be addressed include:

1) Whether the size of the gene is 7.5 Kb. or 5.7 Kb.? 

2) What are the characteristics of the main plasmid, and how does it relate to concerns for mobility, naphthalene degradation, and soil use? 

3) What hazards do the metabolites and daughter products represent?

4) Will there be tetracyclene resistance and how may it be transferred to natural populations?

5) Will spreadable dust be generated, and how can it be controlled?

6) What documenting support is there for the identity of the Pseudomonas organism?

 The reviewers may require advice from individual outside experts or create panels to examine specific issues.

In this case the application was approved with no restrictions.

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Last Modified: May 21, 2001
Bionomics International
12231 Parklawn Drive
Rockville, Md. 20852