FDA maintains caution, but risk appears to be low

As experience broadens, fears lessen

(Editor’s note: The Food and Drug Administra tion has ultimate regulatory authority over gene therapy research protocols and product licensing. At a recent conference on infection control and gene therapy in Lexington, KY, Anne Pilaro, PhD, an expert toxicologist at the FDA, described the agency’s current view of the field to Hospital Infection Control.)

Q: Does the FDA try to strike a balance between the risks and the rewards of gene therapy in order to let an important scientific field have freedom to advance?

A: Our mission is really to protect the health of the public while promoting the development of new technologies or new agents. Gene therapy is especially relevant to this because it is an intervention frequently for diseases where there is not other treatment. It is something very novel, fast moving, and rapidly developing. We really don’t want to put a roadblock there, but we also understand that there are safety concerns that have to be addressed.

Q. It’s been 10 years or so since the first gene therapy research protocols began. Is the FDA gaining more confidence that the infection control risks — particularly of transmission of an agent to contacts of the patient — are minimal?

A: This has been a learning curve. As we learn more and more about the different classes of vectors, we feel more confident with the safety of the materials and we’ve allowed things to go forward. Initially with the adenovirus, the patients were confined for two weeks in isolation in a hospital. Then it was down to one to two days, and now we’ve been discussing doing this on an outpatient basis. It has actually been approved for a couple of vectors. That’s because we have been provided with data that have shown us that the concerns haven’t been as bad as we thought they were going to be.

A lot of the initial theoretical concerns just haven’t come to pass. There’s a lot going on with the technology, though, because now we are developing more classes of viruses, and we are modifying viruses that we have worked with before. And that takes us back to the beginning, so it is sort of a sliding scale. As you don’t know a lot, you are much more cautious, and as you know more about it, you become a little more confident in the safety of the material. You can drop some of the cautious approach you’ve previously taken, but you are never fully 100% confident that this is zero risk.

Q. What are you currently recommending for infection control measures for gene therapy research patients?

A. What we have basically told people is that standard precautions are in order. Handle the vector as if you are handling biohazard materials, as if it is infectious material. [That means using] masks, gloves, disposable outer clothing. It is our understanding that the patient no longer has to be isolated in a negative-pressure room. But the major issue for protecting the health care workers taking care of the patients is just be cautious, and realize that this is a potentially infectious agent and proceed appropriately.

Q. Do gene therapy patients have to be followed for life?

A. That was [an issue] with the retroviruses, because we know that they are stablely integrating materials, and once they are in a cell they are there for the life of the cell and that cell’s progeny. That is where the initial lifetime monitoring has come along. However, we’ve realized with the past 10 years’ experience with this that maybe lifetime monitoring is too long. We are still kind of open-ended about how long is long enough, but we have gone five to nine years in some of these patients, and we haven’t seen anything in terms of viremia and replicating virus. So we have somewhat relaxed the recommendations for monitoring. Initially they were monitoring every month, and now it is going to every three months for the first year after treatment, and then every year for the rest of the period of monitoring.