Why A Recent FDA Decision Should Have You Concerned

Today, the Boston Globe reported that the U.S. Food and Drug Administration rejected Genzyme Corp.'s request for permission to sell in the U.S. a version of its Pompe disease (a rare inherited and often fatal disorder that disables the heart and muscles) drug, called Myozyme, the company wanted to make at its Allston, Massachusetts manufacturing plant. Presently, the company can only make this drug at a smaller facility in Framingham, Massachusetts. The FDA ruled that any Myozyme made at the second plant should be considered a different product because of small differences in its chemical structure, and in order to receive FDA approval, the company needs to file another application with new data showing the drug is safe and effective in large numbers of patients. That means costly clinical trials and a lengthy approval process for the company.

But this decision demonstrates that drugs made with biotechnolgy via recombinant DNA manufacturing, even made by the very same company at a different facility, suggests that regulators are reluctant to approve other versions without clinical data proving the drugs are at least as safe and effective as the originals if there are even slight differences in the compounds.

So what does this have to do with diabetes?

Well, since 2005, all of the insulin manufactured for human use in the U.S. is made by recombinant DNA technology (some FDA-approved animal insulin is still sold legally in the U.S. for veterinarians, but it is imported from the Netherlands), so insulin is a biotechnology drug – sort of.

The regulation of insulin is an anomaly even within the FDA. Insulin, along with human growth hormone (HGH) are grandfathered as small-molecule drugs governed by the Federal Food, Drug & Cosmetic Act, while virtually all other biotechnology drugs including vaccines are ruled by the amended Public Health Service Act. The law considers insulin and HGH small-molecule drugs even though their manufacture is covered by the Center for Biologics Evaluation and Research (CBER) within the FDA, which is one of six main centers at the FDA responsible for assuring the safety, purity, potency, and effectiveness of biological and related products. Its primary objective is to ensure that all prescription and over-the-counter (OTC) medications are safe and effective when used as directed.

Some History

Congress enacted the insulin amendment in December 1941. This law served patients very well, had a very marginal cost to manufacturers and also helped to establish insulin as one of the safest drugs regulated by the FDA. A much more complete history of the insulin certification process can be found at the PubMed website.

But in 1997, the geniuses in Congress passed the Food and Drug Administration Modernization Act (FDAMA) of 1997. The FDAMA repealed the statutory provision in the Federal Food, Drug, and Cosmetic Act (the act) under which the FDA certified drugs containing insulin. As a result, in 1998, the FDA repealed virtually all of its regulations governing certification of drugs containing insulin and made amendments to other relevant sections of their regulations. In effect, governance of insulin had to comply with the FDA’s good manufacturing standards, but the batch testing mandated on virtually all other biotechnology drugs became strictly voluntary.

Novo Nordisk: The Manufacture of Insulin Must Be Monitored Closely

Some manufacturers, such as Novo Nordisk continue to adhere to stringent manufacturing standards. On March 26, 2007, Novo Nordisk A/S sent one of its exectutives, Inger Mollerup, Vice President for Regulatory Affairs to testify before Congress. Mollerup said "While some of the best known peptide molecules - like insulin - can be largely characterized with today’s technology, we do not yet have the tools and models that enable us to predict safety and efficacy from that characterization without undertaking human clinical trials."

That admission was important, because it suggests strongly that the FDA’s decision regarding Genzyme Corp.'s request to make Myozyme at its Allston, Massachusetts manufacturing plant was correct. However, not all insulin manufacturers adhere to the same stringent manufacturing standards as Novo Nordisk does. For example, in February, I reported that Indianapolis-based drug giant Eli Lilly and Company has been farming out the manufacture of at least some vials of Humalog and Humulin R to a third-party.

If we are to believe rival Novo Nordisk’s testimony before Congress, then the reality is that while Lilly is not violating any law, it seems clear that the 1998 removal of regulations regarding insulin certification was a dangerous decision which needs to be changed urgently to ensure the safety of patients. Why is it that Genzyme’s manufacture of Myozyme made at a facility other than Framingham, Massachusetts needs trials to prove its the same drug, but Lilly can so easily have Hospira, Inc. manufacture Humalog and Humulin R in Kansas and its considered exactly the same drug? The simple fact is that it is NOT the same drug, and if we’re going to insist that generic biotechnology drug manufacturers must undergo clinical trials, then the same needs to apply to Lilly’s Hospira contract manufacturing.

What Needs to Be Done?

There is a simple way to resolve this issue. Congress must amend the section of the Food and Drug Administration Modernization Act (FDAMA) of 1997 which removed the Regulations Regarding Certification of Drugs Composed Wholly or Partly of Insulin. This will require more intense monitoring of these medicines to ensure consistency in the potency and safety of insulin. Another way is to pass a law mandating that insulin and HGH can no longer be governed by the Federal Food, Drug & Cosmetic Act, but must be governed by the Public Health Services Act like virtually all other biotechnology medicines. But in order for these changes to occur, you must write to your Representatives and Senators in Congress demanding that these changes be made. Tell them why it is important to you personally (they find personal stories very useful in letters they receive because it helps them to address these issues in Congress. If you suspect that your dosage for Humalog differs from one vial to the next, tell them that may be because its made by a different company!) To find your Congressmen/women, visit http://www.contactingthecongress.org/.