Tuesday, March 27, 2007

FDA: Simple generic biologics may require less data

Continuing the ongoing coverage I have given to the issue of legislation to support the introduction of generic insulin (including my original post, a follow-up based on NYT coverage, the news that legislators had finally introduced a bill that would force the FDA to permit generic biopharmaceuticals where patents had already expired, as well as a few relevant follow-ups, including a story that a coalition of businesses' (including the largest U.S. employer, General Motors) Congressional testimony that generic biotech drugs would be safe while cutting costs, and another story that outlined the estimated savings that generic insulin could have on the nation's healthcare budget.

On Monday, there was a follow-up story published by Reuters that indiated that some generic biologics would require more data than others. This tends to apply more to newer, more complex treatments such as those for cancer, anemia and other conditions. By comparison, insulin and human growth hormone, both of which have lengthy histories in clinical usage are also structurally fairly simple proteins to begin with, therefore, these likely require less data. The bottom line, however, is that the pending legislation would enable the FDA to make those calls on a case-by-case basis, thus ensuring that the agency can make informed approval or decline decisions. But without legislation to enable this, we will continue to be denied healthy competition in the insulin market, as well as many newer biologic medicines.

However, another article published by the Associated Press (I caught it in the Philadelphia Inquirer) warned that it could be a decade or more before science is available to safely approve generic versions of biotech drugs in the way the agency now approves knockoffs of traditional medicines. FDA deputy commissioner Janet Woodcock testified before Congress saying that while the FDA now could establish the safety of new versions of simple protein-based drugs (such as insulin or human growth hormone), it would likely "be a stepwise progression over a decade or so" before the agency could scientifically verify that a knockoff version of a complex biotech drug was similar to the original. This suggests that insulin and human growth hormone are likely to be among the first to see guidelines, ones that incidentally, the FDA did not release as they were supposed to back in 2001.

In a less-than-surprising response, Inger Mollerup, a Vice President from Novo Nordisk said that if Congress created a system to approve cheaper protein-based drugs, it should be similar to one already used by the European Union. Under the EU process, generic biotech companies still must conduct extensive studies to show the safety of their versions. Even after these studies are completed and the product is approved, knockoff biotech drugs are not considered "interchangeable" with the original product, meaning a patient must get doctor approval before switching from the original drug to a generic. The FDA calls these "follow-on protein products".

Critics, including myself, think that the EU process is unncessarily complex and costly for simple follow-on protein products, and that the process being outlined by Congress enables (OK, maybe it forces them) to outline its own requirements for what types of clinical trials will be required, and how extensive these will be. The FDA has been dragging its heels on this for far too long. Effectively, well-characterized products like insulin and human growth hormone may not require the same extent of clinical trials to be undertaken by generics manufacturers as complex protein-based medicines. If it needs a model of how to proceed, I would argue that the EU is not who the U.S. should be following. The FDA need look no further than the recent application for Novartis-Sandoz's Omnitrope (a follow-on form of Pfizer's Genotropin human growth hormone), which was submitted with preclinical, clinical, and comparability data, as well as literature references to the FDA's original decision on the original manufacturer's product.

Although I don't want to be over-optimistic, increasingly, its finally starting to look like this legislation may finally move forward in the U.S.!

Complex generic biologics need more data: FDA
Mon Mar 26, 2007 2:48PM EDT
By Susan Heavey

WASHINGTON (Reuters) - Cheaper, generic versions of more complex protein-based drugs will need more data than simpler compounds to prove their safety and effectiveness, a U.S. Food and Drug Administration official said on Monday.

"The amount of assurance and the amount of data that would be needed is really based on how complex something is and how well it can be characterized," FDA Deputy Commissioner for Operations and Chief Medical Officer Dr. Janet Woodcock told lawmakers.

Other factors, including whether a drug would be used long-term for chronic diseases, will also impact what kind of testing will be needed, she added during a hearing of the U.S. House of Representatives Committee on Oversight and Government Reform.

Her comments come as Congress weighs legislation to give the FDA authority to approve generic versions of biological medicines such as Genentech Inc.'s cancer drugs Herceptin and Avastin, as well as anemia drugs such as Amgen Inc.'s Epogen and Aranesp and Johnson & Johnson's Procrit.

Unlike conventional, chemical-based drugs, biologics are derived from living cells and are usually injected or infused.

At issue is whether generics could be considered either interchangeable or similar to their more expensive counterparts, and how Congress should set standards.

The FDA already has the power to clear generic versions of traditional medicines. More than 9,000 such products are already on the U.S. market and make up 60 percent of all prescriptions, according to the agency.

Committee Chairman Henry Waxman, the California Democrat who convened the panel, has introduced legislation that would allow the FDA to review generic biologics. A similar bill has been introduced in the Senate.

Brand name drugmakers and other opponents say biologics are too difficult to duplicate and even small differences can affect safety and efficacy. But supporters, including insurers and patient groups, argue competition would make them more affordable than branded versions that can cost tens of thousands of dollars a year.

At the hearing, Woodcock said the FDA has the expertise to evaluate such generics, also known as follow-on biologics, but the ability to compare them to original products will depend on the molecule's complexity.

Some biologics, such as insulin or human growth hormone, are considered simpler than other proteins used to treat cancer, anemia and other conditions.

"Although this may be currently possible for some relatively simple protein products, technology is not yet sufficiently advanced to allow this type of comparison for complex protein products," she said in her testimony.

When asked how long it would take technology to catch up, Woodcock said it would be an ongoing process.

"It's going to be a step-wise progression over a decade or so," she said.

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