Myozyme raises awkward questions for would-be biogenerics manufacturers. Credit: Genzyme

Genzyme ran into a snag in April when the US Food and Drug Administration (FDA) rejected its application to produce Myozyme (alglucosidase alfa, rhGAA) in its 2,000–liter-scale facility under the same approval authorization given for its 160-liter-scale plant. The FDA says the carbohydrate structure of the products manufactured at each scale differs and thus the 2,000-liter product requires a new biologic license application. Myozyme was approved in April 2006 for the treatment of Pompe disease, an autosomal recessive metabolic condition occurring in about one in 40,000 births. The condition, which arises from a mutation in the gene for α-glucosidase, leads to a buildup of glycogen in skeletal muscle, and its effects on heart, liver and the nervous tissue can be fatal. Genzyme, which has preferentially targeted child sufferers, is now maxed out on production, and to meet the growing demand from older patients, including those who would be finishing clinical trials, it has invested $53 million in facilities in Allston Landing, Massachusetts and Geel, Belgium. Although Genzyme still expects to receive approval of its 2,000-liter version of Myozyme by the end of this year and to begin commercial sales in the first quarter of 2009, the FDA's position has sent shudders through the generics industry. If the FDA is not satisfied that a brand-name company, with all its proprietary knowledge about biomanufacture, can replicate its own product, what chance do generics companies have of manufacturing biogenerics? The situation highlights “the difficulty a competitor would have coming into the market with a biosimilar,” says senior biotech analyst Aaron Reames of Wachovia Capital Markets, in Charlotte, North Carolina. “It will be exploited by big brand-name pharmas and biopharmas,” he adds. “They can change a molecule slightly, call it a new drug and evergreen the product with a new term of exclusivity.” The FDA has said repeatedly that it does not have the authority to prescribe a definitive regulatory pathway for biogenerics, and big pharma has been happy to postpone the day when Congress would give FDA the framework and mandate. It would be ironic indeed if brand-name manufacturers find themselves unable to consistently get FDA's approval for scale-up projects.