In 2013, the US Food and Drug Administration (FDA) launched a new webpage seemingly intended to shame companies into meeting their pediatric study commitments under the Pediatric Research Equity Act (PREA).

But after an initial deluge of postings, FDA's updates to the page have all but halted, with just five letters posted to the page after its launch, and none within the last six months. Now FDA has posted its first letter to the page in more than half a year detailing the failure of a pharmaceutical company to meet its PREA obligations.

Background

Historically, many companies seeking product approval in the US avoided clinical studies involving children, wary of the ethical problems, the lack of incentives, and the potential consequences if the testing brought up new problems. As a result, many products lacked adequate dosing or safety information for children.

This, as regulators will tell you, is a problem. "We all know that children are not just small adults," wrote Lynne Yao, associate director of Pediatric and Maternal Health Staff in FDA’s Center for Drug Evaluation and Research’s (CDER) Office of New Drugs (OND). Some drugs may be super-potent in children relative to adults, while others may not work at all. In either case, there are inherent safety risks.

To remedy this situation, the US Congress passed into law two critical pieces of legislation: The Best Pharmaceutical for Children Act (BPCA) and the Pediatric Research Equity Act (PREA), which combined had the effect of providing new exclusivity-based incentives to conduct studies (additional six months for pediatric written requests by FDA), as well as the ability for FDA to require companies to conduct pediatric studies as a condition of approval.

The effects of this legislation have been substantial. "Before BPCA and PREA became law, more than 80% of the drugs approved for adult use were being used in children, even though the safety and effectiveness had not been established in children," Yao wrote. "Today that number has been reduced to about 50%."

But despite the law's requirement that some drug manufacturers must conduct studies as a condition of marketing approval, some have failed to do so. In August 2013, FDA announced that rather than simply pressure these companies privately, it would begin posting its letters to the offending companies on a public webpage along with the companies' responses to FDA.

The initial batch of letters included five to three manufacturers: Genzyme (3), Amedra Pharmaceuticals (1) and The Medicines Company (1), and a second batch released in September 2013 included letters to Pfizer (2) and Sunovion Pharmaceuticals (1). Two other letters have been sent since then as well (Tris Pharma and Nautilus Neurosciences).

New Letter

But as we wrote earlier, FDA had a six-month period during which it apparently sent no noncompliance letters to companies. Its last letter to Tris Pharma had been sent in October 2013.

But now FDA's long period of silence has ended, with the agency posting a new noncompliance letter issued in April 2014 to its website, along with the company's letter of response.

The letter, issued to Braintree Laboratories, refers to the company's supplemental new drug application (sNDA) for HalfLytely and Bisacodyl Tablet Bowel Prep Kit, a colonoscopy preparation product. FDA's letter alleges that the company failed to complete its PREA-mandated study by the required date of February 28, 2014.

While the company had reportedly requested an extension for the testing in January 2013, FDA said it determined that the company's request did "not qualify for an extension."

In a response to FDA, Braintree said the company had good reason not to complete the PREA studies: It has discontinued commercial distribution of the HalfLytely product since July 2013, and does not "at this time" intend to reintroduce it.

"For this reason, Braintree does not intend to pursue execution of the outstanding PREA studies, the company wrote.

The product, however, still appears on the company's websites—www.halflytely.com and www.braintreelabs.com—as being actively marketed. It's unclear if the websites have been actively updated since July 2013, however.

FDA Noncompliance Letter

Braintree Response to FDA