Project to reformulate children's medicine launched

A Cambridge nonprofit formed to improve medical products for children is introducing a new program today to develop safer pediatric medicines, naming the former dean of Dartmouth Medical School to lead the initiative.

The Institute for Pediatric Innovation, founded by former Children's Hospital Boston technology-transfer executive Donald Lombardi, has appointed Dr. Stephen Spielberg (left) principal investigator of the five-year Pediatric Pharmaceutical Reformulation Program. Spielberg, who will remain on the Dartmouth faculty, has experience in industry as well as academic medicine.

The reformulation project builds on the growing recognition that children are not just a smaller version of adults who can safely take reduced doses of drugs. Extrapolating by size and weight runs the risk of delivering doses that are so high they are dangerous or so low they are ineffective. Children metabolize drugs differently, and their growth can be affected in ways not detected in tests on adults. Many drugs are not tested separately in children.

"Children deserve the same kind of information on safe, effective use of medications as do adults," Spielberg, 63, said. "Children also deserve the same validated products."

Pharmacists inside and outside hospitals often use mortar and pestle to grind adult tablets into a powder that can be suspended in liquid for children under 6 to swallow, a process that can be time-consuming and imprecise, Lombardi said. Parents are sometimes sent home to do their own kind of compounding when they are told to give their children a quarter tablet, for example.

The institute is stepping in where economics have left pharmaceutical companies out, Lombardi and Spielberg said. Antibiotics and other common medicines for conditions such as asthma make up half the children's drug market, which accounts for 5 to 10 percent of drug sales, said Christopher Milne, associate director of the Tufts Center for the Study of Drug Development. Those drugs are available in children's formulations, but medicines for less common illnesses are not.

Children present a mixture of challenges, he said.

"It's not just kids, but preterm kids, newborns, infants, preschoolers, school-age kids and then adolescents," Milne said. "Their needs just within that 18 years can change by 100-fold in terms of concentrations. Just within kids you may need two or three different formulations depending on the age and other things going on."

And then there's the taste. Getting children to take their medicines comes down to taste and sometimes texture.

"It's important to know that 80 percent of drugs that we prescribe to children have never been adequately tested in children so that we don't even know if we are giving them in the proper doses," said Dr. Michael Shannon, a pediatric emergency physician and toxicologist at Children's who is also a member of the institute's advisory board. "I think an equally important issue is that some proportion of medications we give to children aren't available in kid-friendly preparations. They exist only as tablets or capsules or foul-tasting liquids that children will not take."

The reformulation project will choose generic drugs that the US Food and Drug Administration has approved for use in children. The group will develop formulations that are stable and easily absorbed by children, and that manufacturers can make, so that pharmacists won't have to compound them each time they are needed, which can lead to errors. The next step would be to find a company that would then manufacture and distribute the resulting product.

Spielberg, who once worked for Johnson & Johnson and represented the pharmaceutical industry to the FDA, also has his eye on international needs.

"There is no good preparation of anti-tuberculosis drugs for kids," he said. "If we could develop a product like that, it would be usable in the rest of the world but also for kids here in the US."

The institute, which also hopes to improve medical devices for children, is funded by Children's Mercy Hospitals and Clinics of Kansas City, Mo., the Ewing Marion Kauffman Foundation, Children's Medical Ventures Inc., AGA Medical, and Oxford Bioscience Partners. Lombardi said the institute would also look for support from foundations devoted to single diseases to hep finance product development.

Last year it said it had raised $1 million from those sources but declined to disclose last week how far it had come toward its five-year goal of $10 million.