FDA Encourages Development of Novel Drug Delivery Systems

May 01, 2006


Jill Wechsler
Manufacturers, regulators, and public health officials are establishing new policies and expanding research initiatives to improve drug formulations and delivery systems. The US Food and Drug Administration recently approved many new products with novel delivery methods such as inhaled insulin and a depression drug transdermal patch. The agency also bolstered its staff with experts in pharmaceutical engineering and formulation to assess these challenging products.

The Critical Path Opportunities List unveiled by FDA officials in March cites "manufacturing novel dosage forms" as an area in which collaboration with industry and academia could remove roadblocks to new drug development. And, new drug formulations may eliminate complications related to managing temperature-sensitive drugs and vaccines through the distribution chain.




In providing products that are easier for patients to use, new drugs can improve patient compliance and enhance safety and efficacy, observes Moheb Nasr, director of the Office of New Drug Quality Assessment (ONDQA) in the Center for Drug Evaluation and Research (CDER). Some local inhalation products are absorbed better, thus resulting in smaller dosages that lead to a reduction of undesirable side effects.

FDA approved the first inhaled form of insulin earlier this year, a breakthrough with the potential for improving compliance to prescribed treatment for millions of diabetics. Pfizer's "Exubera" (inhaled powder form of recombinant human insulin) offers a fast-acting alternative to injections or pills for adults with types 1 or 2 diabetes.

Although there have been many notable successes in this area, developing new formulations and delivery systems has its perils. Teva recently announced that it was halting clinical trials for an oral version of its injectable multiple sclerosis drug "Copaxone" (glatiramer) because of poor efficacy results. Separately, FDA recently issued a safety alert regarding cracks in prefilled applicators that can cause inadequate delivery of a rectal diazepam gel that prevents acute seizures. Concerns about the safety of some innovative delivery systems are prompting a closer review of how these products work and the need for new methods to ensure their quality and safety. FDA also is examining bioequivalence issues for generic versions of different delivery systems such as nasal sprays and topical treatments.

Push for patches

New patches and other transdermal drug delivery products have received much attention in the news. Patches are popular because they usually require smaller doses to be effective and are convenient for patients to use, thus improving compliance.

More than 30 patch products are now on the market, including those for birth control and pain relief. In February, FDA approved Somerset Pharmaceuticals's "Emsam" (selegiline), the first patch product for treating major depression. A prime advantage of this treatment is that patients using the lowest dose patch may not have to follow the dietary restrictions needed for oral monoamine oxidase inhibitors. FDA also gave final approval of the first patch treatment for attention deficit–hyperactivity disorder (ADHD), Shire's "Daytrana" (methylphenidate).


Product improvement wins little praise
Liquid reservoir patches release a medicine through a membrane into the skin, while matrix patches permit a drug to pass directly through the skin. Recent evidence that heat or other factors may increase drug absorption rates with patches, however, has prompted FDA to launch a more detailed review of these products. Johnson & Johnson studies indicate a possible increased risk of blood clots for women using the "Ortho Evra" birth control patch, possibly related to higher estrogen levels in the blood. And, FDA is examining reports of deaths related to fentanyl patches to treat chronic pain. Product labeling for "Emsam" warns that direct heat may result in increased drug absorption and patients should avoid exposing the patch to heating pads, electric blankets, heat lamps, saunas, hot tubs, or prolonged sunlight.