Washington Editor

WASHINGTON - The United States Pharmacopeia (USP) countered assertions that its newly developed monographs on somatropin, or human growth hormone (HGH), provide a boost to those seeking an approval pathway for follow-on biologics.

But when the standards first were released, the Generic Pharmaceutical Association (GPhA) used the opportunity to say that the somatropin monographs validate the science underlying generic biopharmaceuticals. By showing that they can be characterized, GPhA said, the USP's action further supports the establishment of an abbreviated approval process for follow-on biologics.

But Roger Dabbah, a senior fellow in the USP's department of standards development, argued that such characterizations fall short of establishing the kind of outright equivalence that is recognized for small-molecule compounds.

"A lot of biotechnology-derived products are very well characterized, meaning that you can characterize them using physical and chemical methodologies," said Dabbah. "But it doesn't tell you if the product is biologically active."

He added that since the USP only deals with quality parameters, not safety and efficacy, its establishment of product standards should not be misinterpreted to also represent a means of circumventing regulatory pathways. The FDA has yet to issue guidance on an approval pathway for follow-on biologics, and the GPhA and other interested groups have been eager for a decision.

"A biological is a complex molecule," Dabbah told BioWorld Today, "and small changes, let's say, in manufacturing, will give you a molecule that is different."

The USP's monographs represent published accounts or standards of analytical methods for any entity - in this case, somatropin. Established as standards for manufacturers to comply with for products legally marketed in the U.S., the monographs address quality, identification, labeling, purity and potency, among other tests. Those written accounts provide standards for active ingredients and official substances that are incorporated in drugs, biologics, dietary supplements and devices.

HGH, a protein hormone made up of 191 amino acids and produced by recombinant DNA technology, has a structure that corresponds to the major component of growth hormone extracted from human pituitary glands. It is used to treat children with pathologically short stature.

"In order to get a monograph developed, we talk to an innovator [company]," Dabbah said, which is crucial. "By the time we started working on somatropin, there were about six different products on the market, all from different companies. So in this case, we felt it was fair to discuss that monograph with all the manufacturers, and that's the way we did it."

Multiple meetings included representatives from those U.S. and international companies and from the FDA, as well as outside committee members who weigh in on USP matters.

All somatropin products must fulfill the requirements of the USP monographs, at a minimum. Generic companies can use the newly established public standards to ensure that their follow-on products are identical to pioneer products, as well as to gain FDA approval. The monographs will facilitate the FDA's determination of compliance of the marketed products to those public standards.

"This probably should be a model," Dabbah said, "for the USP to follow for biotechnology-derived products in which there are several manufacturers."

The USP's official somatropin monographs, issued in the First Supplement of the U.S. Pharmacopeia 28 and National Formulary 23, became official April 1.

And while the somatropin monographs have drawn attention from groups such as the GPhA, which is based in Arlington, Va., they are not the only standards for recombinant products in the USP. Others include human insulin, in six different dosages and combinations, sargramostim and altaplase. The USP also has published its proposal to develop a monograph for apotinin, and soon plans to issue a proposal for recombinant glucagon.

"We're looking at all biotechnology-derived products," Dabbah said. "And as such, we're trying to work with innovators to develop them, because our mission is to get monographs for all products on the market."

The USP, a nonprofit, non-governmental, standards-setting organization based in Rockville, Md., has about 4,000 monographs to ensure product quality and consistency. Its standards are developed through public involvement and contributions from pharmacy, medicine and other health care professions, as well as science, academia, government, the pharmaceutical industry and consumer organizations.