There are presently two abbreviated approval pathways under the Hatch-Waxman Act. One is section 505(j), which allows the submission of an Abbreviated New Drug Application (ANDA) for generic versions of branded drugs.
The ANDA must establish that the generic version is the same as and bioequivalent to the branded drug, which may be done with limited clinical testing, after which, the applicant may rely on the FDA’s finding of safety and effectiveness for the branded drug.
Once an ANDA is approved, the generic and branded drugs are treated as interchangeable, and a prescription written for the branded drug can be filled with the generic version. Generic versions of certain synthetically produced biologic agents, such as the peptide desmopressin, have received ANDA generic drug approval.
The other abbreviated approval pathway, section 505(b)(2), is more flexible because it does not require bioequivalence to the branded drug. For example, the new version may have a different dosage or rate of absorption than the branded drug. Instead of requiring full preclinical and clinical testing, an applicant must submit testing only as to the differences. The applicant may otherwise rely on information from published scientific literature and on the FDA’s prior finding that the similar branded drug is safe and effective.
Depending on the substitutability rating it receives, an approved 505(b)(2) drug may be treated as interchangeable with the similar branded drug; if not, doctors must write a prescription specifically for the new version. The FDA has permitted very few well-characterized biologics to be regulated as drugs under Section 505.b.2. This limited group includes insulin, growth hormone, glucagon, calcitonin and hyaluronidase.
For several reasons there currently exists no standard approval pathway for generic versions of more complex biologic therapeutics. Of primary concern in limiting the clinical trial requirements for any biologics are unanticipated immunogenic responses such as reactions to unique glycosylation patterns produced by different vector organisms.
Would-be generic biotech drug manufacturers can not simply copy the original process or obtain vector samples for producing the biologic from the original drug application. This is so because, in addition to patent protection, the FDA permits drug manufacturers to maintain confidential business information, including trade secrets, within their drug applications, indefinitely.
Therefore, long after the relevant patents have expired, the manufacturer of a biotech drug can continue to enjoy exclusivity pricing in the market. For each new generic version of a biologic, a complete, new application is currently required for FDA approval, which includes expensive preclinical and clinical testing proving that the biologic is safe, pure, potent, and produced under good manufacturing practices.
Biologics are typically 20 times more expensive per patient per day than a drug counterpart. The biologics market reached an estimated $32.8 billion in 2005 and as the fastest-growing sector of the prescription drug market, is predicted to exceed $60 billion by 2010.
The costs extend beyond individual patients, to insurance companies, health plan providers, and taxpayers. The same need for affordable healthcare that led to the 1984 Hatch-Waxman Act clearly favors the creation of an abbreviated approval pathway for follow-on biologics.
Rep. Henry Waxman’s Access to Life-Saving Medicine Act is the first proposed mechanism to allow the FDA to approve abbreviated applications for generic versions of biotech drugs without repeating expensive and duplicative clinical trials. It would bring desperately needed competition into the biopharmaceutical marketplace and put an end to indefinite monopolies.