Regulatory Affairs

TARGET HEALTH excels in Regulatory Affairs and works closely with many of its clients performing all FDA submissions. TARGET HEALTH receives daily updates of new developments at FDA. Each week, highlights of what is going on at FDA are shared to assure that new information is expeditiously made available.

Although the disease is usually self-limiting, rotavirus causes about 2.7 million cases of gastroenteritis in US children each year—about 55,000 to 70,000 of those require hospitalization; and between 20 and 60 deaths are attributed to it. Without vaccination, nearly every child in the US would likely be infected at least once with rotavirus by age 5. The FDA announced the approval of Rotarix, the second oral U.S. licensed vaccine for the prevention of rotavirus, an infection that causes gastroenteritis (vomiting and diarrhea) in infants and children. Rotarix is a liquid and given in a two-dose series to infants from 6 to 24 weeks of age. While there are many different strains of rotavirus, the vaccine protects against rotavirus gastroenteritis caused by the G1, G3, G4, and G9 strains. During studies involving more than 24,000 infants, Rotarix was effective in preventing both severe and mild cases of rotavirus-caused gastroenteritis during the first two years of life. The most common adverse reactions reported during clinical trials were fussiness, irritability, cough, runny nose, fever, loss of appetite and vomiting. In 1999, a different rotavirus vaccine from another manufacturer was voluntarily withdrawn from the U.S. market because of an association with an increased risk of intussusception, or intestinal folding, which can lead to potentially life-threatening intestinal blockage. Intussusception can occur in children spontaneously in the absence of vaccination, but to help ensure that Rotarix does not increase the risk of intussusception, its manufacturer conducted a study of more than 63,000 infants. In that study, there was no increase in the risk of intussusception in those who received Rotarix (31,673 infants) compared to those who received placebo (31,552 infants). Increased rates of convulsion and pneumonia-related deaths were observed in the Rotarix recipients in the intussusception study, however these events were not observed in other studies conducted by the manufacturer. Although the FDA has concluded that the available data do not establish that these events are related to the vaccine, the agency has requested the manufacturer to conduct post-marketing safety studies involving more than 40,000 infants to provide additional safety information. Rotarix is manufactured by GlaxoSmithKline Biologicals, Rixensart, Belgium.

For more information about our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.

The Phylum Cnidaria contains species with highly regenerative reproductive potential. A number of cnidarians, including such diverse forms as jellyfish, 1) ___, sea anemones, and corals, can undergo ontogeny reversal, or reverse development, where one or more stages in the life 2) ___ can reactivate genetic programs specific to earlier stages, leading to back-transformation and morph rejuvenation. The switch is achieved by a variable combination of cellular processes, such as transdifferentiation, programmed cell death, and proliferation of interstitial 3) ___. The potential for ontogeny reversal, at this time, has limited ecological meaning and is probably just an extreme example of a more general strategy for withstanding unfavorable periods and allowing temporal persistence of species in the environment, in other words, for 4) ___. Turritopsis nutricula is a hydrozoan (jellyfish) with a life cycle in which the organisms develop through a series of stages leading to mature adults. However, this animal has the ability to revert back to the polyp stage after becoming mature. It is the first case in which a metazoan (animal) is capable of reverting completely to an immature, colonial stage after having reached maturity as a solitary stage. It does this through the cell development process of 5) ___. This cycle then repeats, rendering it effectively immortal. Ontogeny reversal is possible, but it does not occur typically after the onset of reproductive maturity. All stages of the medusa Turritopsis nutricula, from newly liberated to fully mature individuals, can transform back into colonial hydroids, either directly or through a resting period, thus escaping death and achieving potential 6) ___. This is the first metazoan known to revert to a colonial, juvenile morph after having achieved maturity in a solitary stage. Selective excision experiments show that the transformation of medusae into polyps occurs only if differentiated cells of the exumbrellar epidermis and part of the gastrovascular system are present, revealing a transformation potential unparalleled in the animal kingdom. What if we could transfer these “ontogeny reversal” gene(s) to humans? At the end of Arthur C. Clarke’s epic film, 2001: A Space Odyssey, an old man slowly reverses his life until he becomes a fetus, floating in embryonic fluid, about to be reborn. Could it be that Arthur C. Clarke was futuristically thinking of the human ability to switch on the transdifferentiation process?

ANSWERS: 1) hydra; 2) cycle; 3) cells; 4) survival; 5) transdifferentiation; 6) immortality

As Target Health has expanded to a second floor at 261 Madison Avenue. we are looking for a Director of Clinical Research (PhD preferred) and a really few smart CRAs who can integrate monitoring with Target e*CRF. A plus would be both Pharma and CRO experience. You would be working in a fast, no-nonsense and highly stimulating environment. We were directly involved with 4 regulatory submissions last year (1 already approved) and 1 regulatory submission already in 2008 (US and Europe). A 2nd submission will be made in Europe this quarter (47 centers, >1,600 subjects).

If you are still using ring binders and paper documents for your trial master file (TMF), give us a call and we can show you how to go paperless. If you are a CRO and doing regulatory submissions and giving clients paper copies of INDs, give us a call and we can show you how to go paperless. For more information about Target Document of any of our software tools for clinical research, please contact Dr. Jules T. Mitchel or Joyce Hays.