APPENDIX A TO APPENDIX C 
component a proposed protocol , an assessment of the levels of 
physical and biological containment required by the Guidelines, 
an MUA, and a Certification Statement from the institutional 
biohazards committee. The program official in the awarding 
component has the responsibility for reviewing the request 
in light of the Guidelines, for ensuring that the required 
documents are properly executed , and for forwarding to ORDA 
a copy of all the documents along with a recommendation. The 
latter should include the program official's independent assess- 
ment of the levels of physical and biological containment re- 
quired by the NIH Guidelines, and a recommendation as to how 
to proceed. ORDA will review the request, and, v/hen appropriate, 
refer the request to the initial review group, the Recombinant 
Advisory Committee, or ^ hoc consultants. 
VIII. Requests for Lowering of Containment Levels 
Under Characterized clones of DNA recombinants derived from 
shotgun experiments , the Guidelines state: 
before containment conditions lower than the 
ones used to clone the DNA can be adopted, the in- 
vestigator must obtain approval from the granting 
agency. Such approval would be contingent upon data 
concerning: (a) the absence of potentially harmful 
genes (e.g., sequences contained in indigenous tumor 
viruses or which code for toxic substances), (b) the 
relation between the recovered and desired segment 
(e.g., hybridization and. restriction endonuclease 
fragmentation analysis where applicable) , and (c) 
maintenance of the biological properties of the vector. 
This stipulation for NIH approval may be one of the most difficult 
sections of the Guidelines to implement. This is because of the 
technical nature of the data to be evaluated and because of the 
volume of requests which can be anticipated. Therefore, the follow- 
ing proposed procedures are especially viewed as a feasibility 
trial. 
An investigator who wishes to use lower levels of containment 
for characterized clones derived from shotgun experiments must 
state, in writing, the justification for the request to the pro- 
gram official of the NIH awarding component. Such justification 
will provide data on (a), (b) and (c) as stated above. The pro- 
gram official will retain the original request in the awarding 
component's file, and forward a copy to ORDA which will submit 
the request to- the Recombinant Advisory Committee or to a sub- 
committee thereof for evaluation, or, if a precedent has been 
Appendix C — 11 
