FDA hikes GDUFA fees
The Food and Drug Administration is raising the fees that generic drug companies will have to pay when filing for regulatory approval for new products or supplemental applications for existing products, the agency said last month.
The fee increase is the latest development in the implementation of the Generic Drug User Fee Amendments to the Prescription Drug User Fee Act, which Congress passed last year. The generic drug industry had pushed hard for the amendments, known as GDUFA, amid a long-standing backlog of regulatory applications for generic drugs that the agency lacked the financial or staffing resources to review in a timely fashion.
As of July, the agency said it had reviewed more than 30% of the backlogged applications and streamlined the hiring process to recruit new staff, with the expectation that it would meet its year-one GDUFA hiring goal by bringing on at least 25% of new hires by Oct. 1 of this year.
According to the Federal Register, the FDA raised rates for abbreviated new drug applications, the applications companies submit when filing for new generic product approvals; prior approval supplements to approved ANDAs; drug master files; generic drug active pharmaceutical ingredients; and finished dosage form facility user fees. The ANDA fee will be $63,860, compared with $5l,520 this year, an increase of 24%. The prior-approval supplement fee also will be raised by 24%, to $31,930. The domestic finished dosage form facility fee will be increased by 25%, to $220,152, and the drug master file fee will increase by 48%, to $31,460. Meanwhile, the active pharmaceutical ingredient fee will be set at $34,515. For foreign finished dosage form and active pharmaceutical ingredient facilities, the fees will be $235,152 and $49,515, respectively. The new rates become effective Oct. 1, 2013, and remain in effect through Sept. 30, 2014.
The new rates were issued amid news that the program has raised more than a quarter of a billion dollars in its first year. In a memo sent in June to staff members of the FDA’s Center for Drug Evaluation and Research, CDER director Janet Woodcock wrote that the agency had collected more than $255 million under GDUFA, and that it intends to collect $299 million in fiscal year 2013. During that time, it hired 165 new CDER staff members, helped to make it easier to accurately calculate fees and made "significant strides" in reducing the backlog of generic drug approval applications. Woodcock wrote that the program would transition to a new project and governance structure similar to PDUFA, led by a steering committee and focused on enhancing the program and transforming the review process. The committee includes people from CDER, the Office of Regulatory Affairs and FDA commissioner Margaret Hamburg’s office.
But the process has not necessarily gone smoothly. In March, FDA Office of Generic Drugs director Greg Geba resigned over differences related to a reorganization of the office. In his letter, he wrote that the office had issued nearly 600 complete response letters—which the FDA issues when it has finished reviewing an application but is unable to approve it in its present form—since the Oct. 1, 2012, implementation of GDUFA. The Generic Pharmaceutical Association, an industry trade group, expressed concern at the time that Geba’s departure would lead to "further disruption" at the OGD in the wake of the office lacking a leader between 2010 And 2012.
"As of July, the agency said it had reviewed more than 30% of the back-logged applications and streamlined the hiring process to recruit new staff."
Biosimilars score a win
The country’s embryonic biosimilars industry scored a victory last month as the organization that runs the pension fund for California state employees announced its opposition to a state Senate bill provision that would impose special requirements on pharmacists who dispense follow-on biologics.
Last month, the board of the California Public Employees’ Retirement System, also known as CalPERS, voted to oppose a provision in Senate Bill 598 that would require pharmacists to notify prescribers and patients if they have substituted a biosimilar, and also forbid them to substitute biosimilars if prescribers indicate "Do not substitute" on prescriptions. However, the bill contains a sunset clause and only applies to prescriptions made before 2017; at press time, both houses of the state legislature had passed it, and it was awaiting reconciliation and a signature or veto by Gov. Jerry Brown.
The provision, sponsored by Amgen and Genentech, is similar to legislation that has popped up in several states around the country as the Food and Drug Administration works on regulations on biosimilars, as mandated by amendments to the Patient Protection and Affordable Care Act of 2010. The Illinois state legislature defeated a similar bill in June, while Virginia Gov. Bob McDonnell signed that state’s bill into law in March.
Looking ahead: Steer clear of the patent cliff
One trend that generic companies and pharmacy retailers alike should keep an eye on is the patent cliff. One of the reasons why generic prescriptions will likely peak at 86% to 87%, Long said, is that after the patent on Crestor expires In 2016, there simply won’t be a lot of top-selling branded drugs.
Typically, when a generic drug maker is the first to file an abbreviated new drug application with the Food and Drug Administration to market a generic drug, it is entitled to 180 days of market exclusivity upon FDA approval in which to compete directly with the branded version. For generic companies, opportunities like this are what gold veins are to mining companies. As soon as a cheaper generic becomes available for a drug, many payers will automatically switch from the branded to the generic, and a generic drug maker could stand to rake in billions.
Take India-based Ranbaxy Labs, for example. In November 2011, Pfizer’s patent for the cholesterol treatment Lipitor (atorvastatin) expired, and Ranbaxy launched its generic version. At the time, according to Ranbaxy financial reports, Lipitor had sales in the United States of $7.9 billion. But at the peak of its 180-day exclusivity period, Ranbaxy captured 50% of market share in the United States. Generic atorvastatin ranked 21st on the list of the top 25 drugs for 2012, with $2.3 billion in sales, while branded Lipitor had disappeared. Pfizer’s Alzheimer’s disease drug Arlcept (donepezil) is another example. Ranbaxy launched the first generic version in 2010, capturing 36% of Aricept’s $2.6 billion market share. In 2012, its generic captured 30% of the market share for Takeda’s $2.7 billion diabetes drug Actos (pioglitazone).
About $13 billion in drugs will lose patent protection in 2013, Including Purdue Pharma’s Oxycontin (oxycodone); Eisai and Johnson & Johnson’s Aciphex (rabeprazole sodium); Novartis’ Zometa (zoledronic acid); Genentech’s Xeloda (capeticabine); Endo’s Opana ER (oxymorphone); and Warner Chilcott’s Asacol (mesalamine), according to IMS. Drugs that will lose protection next year include AstraZeneca’s Nexium (esomeprazole); Eli Lilly’s Cymbalta (duloxetine); Pfizer’s Celebrex (celecoxlb); AstraZeneca’s Symbicort (budesonide; formoterol fumarate dihydrate); Sunovion’s Lunesta (eszopiclone); Allergan’s Restasis (cyclosporine); E11 Lilly’s Evista (raloxifene); Novartis’ Sandostatin LAR (octreotide acetate); and Warner Chilcott’s Actonel (risedronate sodium).
According to IMS, drugs losing patent protection between 2008 and 2012 had total pre-expiration sales of about $101 billion. But between 2013 and 2017, that total will drop to $86 billion. That’s still a significant figure, but the Lipitor-sized opportunities won’t be appearing again for a while, at least until generic drug makers master the art of manufacturing biosimilars, particularly versions of the biotech drugs with the highest sales.
The opportunity there could be enormous. According to IMS, of the top 25 drugs in the United States as measured by sales, seven are biotech drugs. AbbVie’s autoimmune disease treatment Humira (adalimumab) is in sixth place, with $4.6 billion in sales in 2012, followed by Pfizer’s and Amgen’s Enbrel (etanercept), also used for autoimmune diseases, with $4.3 billion. Remicade (Infliximab), another autoimmune disease drug made by Johnson & Johnson, ranks eighth with sales of $3.9 billion, followed by Teva Pharmaceutical Industries’ multiple sclerosis treatment Copaxone (glatiramer acetate) — officially a pharmaceutical drug, but sometimes considered a biologic due to Its molecular complexity — and Amgen’s Neulasta (pegfilgrastim), used to improve immune system function in patients on chemotherapy.
But there’s a potential threat to biosimilars in the form of state-level, carve-out laws supported by biotech companies whose products are at risk from biosimilar competition. The laws generally require pharmacists to inform physicians and patients if they swap out a branded biotech drug for a biosimilar, and also allow the physician to present substitution by writing "Do not substitute" on the prescription. As of last month, California’s state legislature had passed such a bill, which was awaiting a decision by the governor. (For more on biosimilars, see page 20.)