The Debate Over Generic Biopharmaceuticals: Which Concerns Are Genuine, and Which Are Fear-Mongering?

This morning, The Wall Street Journal Health Blogger David Armstrong had an interesting post that pertains to generic biopharmaceuticals. Specifically, he writes about Genzyme's (a Boston-area biopharmaceutical company) struggle to produce enough of a promising drug to treat a rare genetic disorder which he believes adds more fuel to the raging debate about generic biotech drugs. Specifically, he notes that Genzyme is having trouble persuading the FDA to sign off on its medicine known as Myozyme made in big batches because the FDA wants to be sure the drug produced in large tanks is the same as the stuff Genzyme made successfully on a smaller scale. Thats a legitimate concern, but its really up to the FDA to inform the drug maker how they are to address those concerns to ensure patient safety.

As I have chronicled on this topic as developments occur, there is now legislation pending in Congress (S. 623/H.R. 1038, the "Access to Life-Saving Medicine Act of 2007") which would not only legalize generic biopharmaceuticals (the FDA prefers the term "follow-on" proteins), but would also outline procedures for the FDA. The key, however, is that the agency would be given considerable leeway to make decisions on a case-by-case basis, which puts more pressure on the people reviewing the medicines and less on the agency itself. For the past 6 years, the FDA has danced around this issue, effectively extending the patents on biopharmaceuticals such as insulin (notably Humulin and Novolin R and N), whose patents expired years ago.

Perhaps I should provide some quick but relevant background. For those of you unfamiliar with the term, unlike regular drugs which are simple, chemical compounds, biologic medicines (or biopharmaceuticals) usually depend on living organisms such as bacteria or yeast to grow and requires maintenance of precise conditions in order to grow. They are not chemical drugs, but more complex proteins and/or peptides. Insulin is one of the first-generation biopharmaceuticals (along with human growth hormone), and has been commercially available for over 2 decades.

As I first wrote in my groundbreaking article on generic insulin back in January 2007, the introduction of generic insulin has been stymied by a variety of political and competitive factors. But whether we like it or not, passing legislation which outlines specific procedures for generics manufacturers to obtain approval from the FDA is critical to the emergence of generic insulin in the U.S. market.

The Genzyme story noted in David Armstrong's posting is a legitimate concern for many of the newer biopharmaceuticals. Think about it this way: just imagine if one bottle of insulin was dramatically different in strength from another, and the same dosage could not be relied upon to have the same blood glucose-lowering effect. One day, it works fine, the next day you plunge into hypoglycemia. To some extent, we have already seen some example of that with synthetic, rDNA-origin insulins, as many patients complain that their dosages do, in fact, not always yield predictable results, but their complaints are routinely written-off by doctors and many diabetes educators as patient error (in carb counting, fat content of meal, etc.). However, its important to note that the FDA relies on the manufacturers to have their own quality-control procedures in place, they do not require them.

This is because insulin is considered by the FDA to be nothing more than a small-molecule chemical drug, which is governed by the Federal Food, Drug & Cosmetic Act. The pending legislation on biogenerics would do nothing to guarantee our insulin strength does not vary from one batch to the next nor does it require batch testing to ensure that. But that isn't stopping fear-mongerers like the Biotechnology Industry Organization (BIO) from implying that only brand-name manufacturers will produce reliable medicines. The only problem with that claim is that they are up against some of the drug industry's biggest and best-prepared companies, such as Israel-based Teva Pharmaceutical Industries Ltd., an $8 billion/year giant in the world of generics, Swiss drugmaker Novartis and its Sandoz unit, and U.S.-based companies such as Barr Pharmaceuticals. None of them are fly-by-night companies, and most have established themselves as leaders because of their price and quality. But unlike smaller startups, these giants are very familiar with the legal tactics employed by brand-name rivals and are very well-prepared to respond in an appropriate manner.

Even more importantly, unlike newer biopharmaceuticals, the genetic structure of insulin (and human growth hormone) is very well-characterized, meaning its genetic structure can easily be verified with fairly simple tests. Another key difference is that few patients take insulin without blood testing to estimate their dosage, and because of that, the concerns differ in some of the more complex medicines like anemia treatments which can mean life-or-death. The system is far from perfect, but we should not allow BIO to use fear-mongering to delay this critical legislation any further!