Recombinant DNA Advisory Committee - 12/1-2/94 
autopsy reporting requirements. Mr. Capron said that the RAC should specify required post mortem data for 
individual protocols. Dr. Par km an agreed with Mr. Capron that biologically relevant data can be obtained by 
requesting specific autopsy information for a particular protocol. Dr. Smith suggested that each member of 
the working group should provide a list of required information to be transmitted to the investigators for the 
next data reporting period. Dr. Zallen suggested that the page limitations described in the Points to Consider 
should be modified to allow investigators to provide detailed responses to questions. Dr. Walters said that the 
RAC could include specific autopsy recommendations for a particular protocol, and that these 
recommendations could be included in their NIH approval letter. 
VI. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN GENE TRANSFER 
PROTOCOL ENTITLED: ADENOVIRUS MEDIATED GENE TRANSFER FOR CYSTIC FIBROSIS: 
SAFETY OF SINGLE ADMINISTRATION IN THE LUNG/DRS. DORKIN AND LAPEY 
Review— Drs. Straus and Ginsburg (presented by Dr. Straus) 
Dr. Walters called on Dr. Straus to present his primary review of the protocol submitted by Dr. Henry Dorkin 
of the New England Medical Center, and Dr. Allen Lapey of Massachusetts General Hospital, Boston, 
Massachusetts. In Dr. Ginsburg’s absence. Dr. Straus presented his primary review in combination with Dr. 
Ginsburg’s written comments. Dr. Straus explained that this adenovirus aerosol administration proposal was 
originally submitted in combination with the lobar instillation arm as a request for Accelerated Review. 
Although the primary reviewers approved the lobar instillation arm of the study, the reviewers recommended 
that aerosol administration of the adenovirus vector should be reviewed by the full RAC. 
The adenovirus vector, Ad2/CFTR-2, has been previously approved by the RAC for direct installation 
(Protocol #9212-036). The proposed Phase I study is designed to determine safety of lobar vector followed by 
subsequent aerosol administration 2 months after lobar treatment (same vector dose). A total of 16 subjects 
will be entered over a 10 month period and divided into 8 cohorts. In this dose-escalation study, subjects will 
receive between 8 x 10 6 and 2J5 x 10 10 infectious units (IU). Subjects will be evaluated for clinical responses by 
x-ray and epithelial brushings. Gene expression will be assessed by PCR. Subjects will be monitored for viral 
shedding for 3 days following aerosol administration; outpatient follow-up will continue up to 10 years 
following treatment. The investigators possess extensive experience in the clinical management of CF. Major 
scientific and logistic support is provided by Genzyme Corporation, Cambridge, Massachusetts. The 
investigators have provided adequate written responses to many of the technical issues raised in the primary 
written review. 
This protocol is the first study involving aerosol administration that has been submitted for RAC review. The 
protocol provides a very vague description of the aerosol administration process. The RAC should consider 
the following issues: (1) the mechanics of aerosol administration, (2) performance standards of the aerosol 
devices, (3) possible penetration of the adenovirus vector into the small airways of the lung, (4) the possibility 
of horizontal transmission and subsequent environmental impact, (5) individuals who will be permitted to enter 
the facility during vector administration, (6) necessary protective clothing, (7) nebulizing masks, (8) airflow and 
filtration devices, (9) proposed procedures for environmental decontamination and air sampling, and (10) the 
potential for vector dissemination outside the containment facility. The investigators have provided written 
responses regarding recommended protective equipment and techniques and have noted that experiments are 
currently being conducted to determine the possibility of environmental transmission. 
Dr. Straus described the canopy that the investigators have proposed to place over subjects as a filter. The 
investigators have not provided any data demonstrating the effectiveness of such a canopy, i.e., fluorescein 
labelled vector. Dr. Straus suggested the adoption of some of the techniques developed by Dr. Mark Sawyer 
of the University of California at San Diego who detected environmental spread of varicella zoster virus and 
respiratory syncytial virus. In their written responses, the investigators indicated that health care workers who 
are present during aerosol a dminis tration will be monitored for vector contamination; however, Informed 
Consent will not be requested. 
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