Docket Management
Docket: 99N-4063 - Current Good Manufacturing Practice for Positron Emission Tomography Drug Products;Draft Rule
Comment Number: EC -1

Accepted - Volume 1

Comment Record
Commentor Dr. Joanna Fowler Date/Time 2002-05-14 08:16:26
Organization Brookhaven National Laboratory
Category Individual

Comments for FDA General
Questions
1. General Comments Response to Docket No. 99N-4063 Thank you for the opportunity to respond to “Current Good Manufacturing Practice for Positron Emission Tomography Drug Products: Preliminary Draft Proposed Rule.” We felt that the document was clearly written and very thoughtful and expressed many of the special problems associated with the short-lived PET radiopharmaceuticals. Though we are not confident that we have interpreted the document correctly, we do have the following concern. In our laboratory we do only clinical research and the majority of our radiopharmaceuticals are labeled with carbon-11 (half-life: 20.4 minutes). [We are also developing an N-13 labeled radiopharmaceutical for human studies.] Because of the complexity of the syntheses, some of the C-11 radiopharmaceuticals are produced in fairly low yield and therefore it necessary to inject them within a few minutes of their synthesis in order to have appropriate counting statistics and specific activity. The requirement to complete all of the acceptance testing except sterility testing before the final release of the radiopharmaceutical would be a problem for us because most of our testing (pyrogen testing, radiochemical purity etc) takes at least 30-40 minutes. We do this testing as soon as the radiopharmaceutical is prepared. However, we inject the radiopharmaceutical before the testing is complete. Over the last 20 years we have never had a C-11 radiopharmaceutical that did not meet acceptance criteria except for one failure in sterility. While we agree that it would be ideal to have all of the tests (including sterility) done before release, waiting for the pyrogen testing and the chromatography to be completed before the injection of the C-11 radiopharmaceutical would result in an unacceptable decay of carbon-11 and loss of specific activity. It would largely preclude our doing clinical research with carbon-11. More specifically, waiting 40 minutes would result in a loss of 75% of our product and quadruple the radiation exposure to our staff. The situation is worse with N-13. We suggest that an exception to this requirement that all acceptance tests except sterility be performed before release of the radiotracer be made for carbon-11 and nitrogen-13 radiopharmaceuticals. Based on our long-term experience, we think that the retrospective review of the testing results from prior batches would provide adequate assurance that the quality of a future batch would meet acceptance criteria. We think that this is similar to the exception allowing the testing of one sub-batch when multiple sub-batches are made in one day as was exemplified for N-13 ammonia (see Section K., page 31 and 32, for example). We appreciate the opportunity to comment. Sincerely, Joanna S. Fowler Director, Brookhaven PET Program




EC -1