2005N-0184 Precursor Preference in Surfactant Synthesis of Newborns
FDA Comment Number : EC3
Submitter : Dr. Satish Kalhan Date & Time: 06/17/2005 10:06:57
Organization : Case Western Reserve University
Category : Health Professional
Issue Areas/Comments
GENERAL
GENERAL
The proposed study will be an important contribution to our understanding of the surfctant metabolism in the premature infant and may lead to development of noval treatment strategies in the future. Dr Hamvas and colleagues have already published few studies exmining the fractional rate of surfactant synthesis in the low birth weight baby using the proposed methodologies; presumably therefore the protocol was previously approved by the local IRB; hence it is not clear why it is being rexamined now.

The use of stable isotopic tracers as proposed here have not been shown to carry any risk in healthy adults, neonates nor in growing embryos. Even when used in very large doses carbon-13 labeled tracers did not show any harmful effects.

The major risk of the proposed studies relates to the preparation of tracer infusion i.e. the risk of contamination of the albumin containing preparation of palmitic acid. The investigators can further minimize it by using appropriate precautions. Although precautions for strility during preparation are described the investigators have not detailed any methods of examining the sterility of the preparation. In addition they should develop some objective measures such as rapid testing for sterility,prior to use and of the assumed 24 hour shelf life of the palmitic acid/albumin preparation. Once such sterility of the preparation can be ensurred and the procedures are established they should be able to do the proposed studies without addig any additional risk to the subjects.
It should be underscored that the infusion solution must be prepared by adequately trained and skilled personale only.
Additionally the investigators should also recognize that if contaminated, the albumin solution forms an excellent medium for bacterial growth and proliferation and hence the need for stringent care.
The committee is certainly aware of the case from Maryland when a contaminated solution of tracer palmitate/albumin was infused into a healthy adult resulting in septic shock etc.