FDA under pressure to 'open the floodgates' for biogenerics
four US states have petitioned the US Food and Drug Administration
(FDA) for clarity in their requirements for the production of
generic versions of insulin and human growth hormone (hGH), the
first step to opening the market up to generic biopharmaceuticals.
It is the first time elected officials in the US have filed a citizen petition, underscoring the significance generic biologics, sometimes referred to as biogenerics or "follow-on" products, carry not just with generic drugmakers, who are eager to see competition in the market, but also with politicians, who see rising healthcare costs tightening their state budgets. According to IMS Health, biologic drug product sales jumped 17.2 per cent in 2005 to $32.8bn (€25.4bn), and with a total value of $20.2bn in global sales, insulin, human growth factor, epoetin, colony stimulating factors, interferon alpha and interferon beta are all now susceptible to competition from biogenerics since they have come off patent. Yet the FDA has so far been reluctant to approve copycat biologics because of the challenges that the sophisticated manufacturing of biogenerics pose and the significant regulatory hurdles. Intriguingly, the fact that a molecule is biologic does not automatically make its generic version a biosimilar - insulin is treated by the FDA as normal drug. As for hGH, when last May the FDA approved a generic version, Omnitrope (somatropin), made by Novartis's Sandoz unit, it stressed that the authorisation "does not establish a pathway for approval of biological follow-on products, nor does it mean that more complex and/or less well understood proteins could be approved as follow-on products." Consequently, most companies find biologics are too complicated to copy and those brave enough to try often get a bloody nose; last month the FDA turned down Nastech's generic version of the nasal spray Miacalcin (calcitonin salmon), refusing to treat the protein-based drug as a normal generic. This regulatory deadlock prompted governors Kathleen Sebelius of Kansas, Jim Doyle of Wisconsin, Tim Pawlenty of Minnesota and James Douglas of Vermont to sign a petition calling for the immediate release of guidelines that would allow more affordable versions of insulin and human growth hormone (HGH) to be sold in America. About 7 per cent of Americans, or nearly 21 million people, have diabetes, with the numbers increasing as obesity in America becomes more prevalent. "More and more of our citizens are finding it increasingly difficult to afford prescription drugs," Douglas said. "We owe these individuals the best medicine science can provide at the most affordable price." According to the citizen petition, American patients spend approximately $1.5bn on insulin products to treat diabetes and approximately $433m on hGH, which is used to treat a variety of conditions, including growth deficiencies in children and adults, chronic renal insufficiency, and AIDS wasting syndrome. Although therapeutic equivalents for insulin and hGH were authorised under the landmark Hatch/Waxman legislation in 1984, standards for manufacturing have never been released. "These products raise complicated scientific issues and we continue to work on them internally," FDA spokeswoman Crystal Rice told In-PharmaTechnologist.com. "The agency will review the governors' concerns carefully and will respond accordingly." Pressure groups claim market competition for insulin and increased market competition for hGH products could save the American health care system hundreds of millions of dollars annually. They point to the actions of the European Medicines Agency (EMEA) which has published a series of guidances that provide a roadmap for the approval of several different types of generic biopharmaceuticals. "It is our position that the 505(b)2 FDCA approval process, in conjunction with FDA's authority under the Public Health Act (PHS), already serves as a foundation for the approval of safe and effective generic biopharmaceuticals," said Kathleen Jaeger, presedent of the Generic Pharmaceutical Association. "The time has come to open the floodgates for generic competition on these and other products and we will continue to call on Congress to codify FDA's authority to approve generic biopharmaceuticals under section 351 of PHS." Naturally, many companies that wish to hold on to their biologics are apprehensive, and the Biotechnology Industry Organization has said that generic versions of biopharmaceuticals should undergo lengthy human trials to prove they are safe and effective, since manufacturing can have a severe impact on their performance.