As Congress tussles over two separate bills, each intended to clear the path for the FDA to approve follow-on biologics, or biosimilars, there are a number of growing misconceptions regarding the benefits of this eventuality spoon-fed by their political proponents, industry leaders and lobbyists, and regurgitated by the news media at the feet of the American public.

Few can deny the necessity for lower cost drugs with the possible exception of drug innovators whose patents (and profits) are about to expire. But lower cost biologicals are only one head of the Hydra that is Healthcare Reform and the savings realized from knock-off biologics will likely fall far short of most expectations. Longer-term consequences such as substitutability and interchangeability of follow-on biologics are untried and untested and there is compelling debate as to whether shorter-term drug patents will discourage drug development, and jeopardize innovation of new medicines.

There are several key differences between the two bills. Central to the debate are primarily related to exclusivity issues including length of patents, data confidentiality, and extensions for new indications, in addition to the need for, and extent of, clinical trials. But before those differences are outlined, I think it is important to clarify the term “generic” and what it implies, how it’s inferred, and what it truly means when it is used as an adjective to describe medicine.

Perception is everything. The word “generic,” as it applies to drugs, conjures up a certain perception in the mind of the American public: identical copies of a name-brand drug, that work as well, but at a fraction of the cost. There is no argument that the pathway for generic drug manufacture introduced 25 years ago with the passing of the Hatch-Waxman Act was a good thing overall. It increased drug accessibility, spurred competition in the marketplace, and lowered costs to patients and consumers of chemically synthesized, small-molecule drugs. Wal-mart, for example, has built an entire marketing campaign around generic medicines with its $4 Prescription Program, where more than 350 prescriptions (all of them generics) can be purchased for $4 each. The fine print (available on Wal-mart’s website), excludes certain forms of specific drugs and only includes what they define as “common dosages” and there are 10 paragraphs of detail explaining eligibility, applicability and exceptions. Hey, but it’s great marketing!

Over-the-counter drugs whose generic equivalents sit side-by-side with their nationally branded big brothers on the shelves of our pharmacies, grocers and department stores provide the most obvious examples. A recent trip to my neighborhood Walgreens for some much-needed allergy medicine had me grabbing for the Wal-dryl over the Benadryl. Each contained 25 mg of Diphenhydramine HCl, but the Walgreens “brand” was 35% less expensive than Warner-Lambert’s. It doesn’t take a giant leap of reasoning to be led to believe that the same should or might apply when referring to a “biogeneric” drug. And there’s the rub. There is no such thing as a biogeneric. You can’t simply make a Bud Light vs. Miller Light comparison when it comes to small molecule organic compounded drugs such as acetaminophen, and large molecule therapies like biologics made from living cells or organisms whose molecular complexity cannot be duplicated with current technology. By comparison and complexity, small molecule drugs are to large molecule drugs as Pinewood Derby is to Formula One racing. Even the FDA recognizes that an exact biological copy cannot be made. Therefore, we should not casually define biologic copy-cat drugs as generics in the traditional sense of the word. Similar? Sure. Follow-on? Absolutely. Generic? No way.

The two separate bills recently introduced in Congress for establishing a legal framework by which the FDA can approve the marketing and sale of biosimilars are working their way through the House of Representatives. I have heard them repeatedly described by the media as being akin to the original Hatch-Waxman “generics” bill of 1984, and news accounts have alluded to the same expectations for access, choice, and above all, savings. This is grossly misleading. It is important to point out that nowhere in the text of either proposed piece of legislation is the term “generic” ever used. My concern: if there is this much ignorance, misrepresentation and misconception surrounding the proposed biologics bills, how can we expect to educate those downstream in the supply chain on the critical commonality of all biologics – which has been completely overlooked – proper storage and transport? After all, biological drugs require refrigeration, and follow-on biologics are no exception . . .

Here is a brief explanation of the major differences between the two bills introduced in Congress this past March:

The first bill, HR 1427, with the very urgent sounding title, Promoting Innovation and Access to Life Saving Medicine Act, was introduced on March 11, 2009 by Reps. Henry Waxman (D-CA), Frank Pallone (D-NJ), Nathan Deal (R-GA), and Jo Ann Emerson (R-MO).

A second bill, H.R. 1548, has a much more restrained and practical sounding name: Pathway to BioSimilars Act; it was introduced the following week, March 17, by Reps. Anna Eshoo (D-CA), Jay Inslee (D-WA), and Joe Barton (R-TX).

What are the key elements of each of the bills? According to the HR 1427 Bill Summary, highlights include:

• FDA authority to approve biosimilars;
• approval process will require showing that (1) there are no clinically meaningful differences between the two products and (2) that the two products are highly similar in molecular structure and share the same mechanisms of action;
• a biosimilar may establish that it is “interchangeable” with the original product, and the first such biosimilar able to make such a showing will receive six months of exclusive marketing;
• an original product with a novel molecular structure is entitled to five years of exclusive marketing, and a modification of a previously approved product is entitled to three years of exclusive marketing. These periods can be extended by up to one year if it can be established that the product can be used for a new disease or if the marketer conducts pediatric studies; and
• a new procedure is established to resolve patent disputes prior to approval of the biosimilar, and penalties are put in place for failure to timely litigate such disputes.

In contrast, the highlights of HR 1548:

• establishes safety standards for establishing interchangeability;
• establishes exclusivity for the first product found to be “interchangeable” for a period of 24 months after the product has either been deemed to be interchangeable or goes on sale;
• the reference product receives 12 years exclusivity, and that period of exclusivity will extend to 14 years in the event that a new indication is found for the product in the first 8 years after licensure;
• an additional exclusivity period is also established for pediatric studies and use of product;

Which bill has been more widely received by the biotech industry? The voice of the biotech industry, via the Biotechnology Industry Organization (BIO), has indicated its preference for the second bill in several published reports. The Generic Pharmaceutical Association’s point of view, not surprisingly, is in favor of what’s behind door number one: the Waxman bill.

While both sides have compelling arguments, there is a fair amount of smoke-and-mirror politicking involved as both are seeking separate means to the same end: a healthy biosimilars market that will increase access to biologic treatments by lowering costs and increasing choice. But it is a slippery slope and Congress should proceed with caution. Much of the original Hatch-Waxman “generics” bill of the 1980’s isn’t applicable today. Congress must understand: there are no shortcuts in the manufacture of biological medicines. We cannot run the risk of putting profits and political pressure ahead of patient safety.

The same holds true for distribution. The complexity of the supply chain for these extremely temperature-fragile medications mirrors the drugs themselves. There can be no shortcuts on the use of qualified packaging, which comes at a considerably higher cost than most other transport packaging. For all the work Congress and the FDA will have done to insure safe biosimilar product, there is additional responsibility on behalf of those packaging, storing, shipping, and distributing these miracles of medicine. The world awaits the promise, the potential and the quality of life these follow-on biologics are sure to unleash. What an exciting time it is!

This discussion will continue in the next issue of Contract Pharma. Our next Advanced Degrees column will look downstream at qualified packaging vs. “generic” packaging, and validated distribution processes vs. “generic” distribution.

Kevin O’Donnell is director and chief technical advisor to industry at Tegrant Corp., ThermoSafe Brands. He blogs at Where Cooler Heads Prevail.