If you had read the NDA for human insulin, I think you would be astounded. The technology was AWESOME . . . so much so that at least one (and perhaps other) scientist, I believe, let his AWE outweigh his scientific integrity. This is truly a case where the discovery far outpaced the technology . . . and patients (and doctors who prescribed for them) were TRUSTING that pharma ’science’ and pharma ‘propaganda’ were the same. They were not. So for almost two decades, insulin-using diabetics have relied more on trust (and a willingness or need to embrace myriad add-on protocols/medicines) and achieve no better–only more expensive–outcomes. As you said . . . if technology cannot (yet) prove bioequivalence for this small (non)biotech molecule, I think (if this is to be truly 21st century medicine), research funds need to be spent on improving analytical methodology BEFORE we rush headlong into biotech generics.

Human insulin, porcine insulin and bovine insulin can all be made by rDNA technology (none of the molecules are PATENTABLE.) Let’s compare bioequivalency of these synthetic molecules to cadaver pancreatic extraction and natural animal insulins BEFORE we jump ahead with MORE rDNA discoveries. IOW, let’s start with this small molecule and prove the methodology (not that it can be CREATED, but that it is EQUIVALENT to natural).

(And you thought I was anti-pharma.)

Bottom line: If biological equivalence of insulin cannot be adequately established, there is NO WAY IN HELL that biological equivalence of larger proteins can be established

However, since 2007, rival Eli Lilly and Company has been outsourcing the manufacture of its blockbusters Humalog and Humulin to Hospira, Inc., both of which are biotechnology medicines. But Lilly is not breaking any laws because 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 The FDAMA repealed the statutory provision in the Federal Food, Drug, and Cosmetic Act (the act) under which the FDA certified drugs containing insulin. As a result, in 1998, the FDA repealed virtually all of its regulations governing certification of drugs containing insulin and made amendments to other relevant sections of their regulations. Last week, Lilly announced it was closing a facility in Indianapolis and laying off close to 500 people who worked in the facilities who made Humalog and Humulin as well as for the osteoporisis medicine Forteo. The company plans to increase its use of contract manufacturing, including for biotechnology medicines.

If we are going to require this of generics manufacturers, the same standards need to apply to giants like Eli Lilly and Company, and that means no to contract manufacturing unless it is the ONLY facility making the drug.

Among the scientists involved, it has ALWAYS been known that synthetic human insulin molecules contained in a vial of “insulin” do not necessarily have the same three-dimensional spatial configuration as the human insulin molecule produced by the human body. The resultant molecule produced by a bacterial or yeast process (with later transcription of A and B chain to form the perfect human insulin molecule) relies on undisclosed proprietary information. This is a case where technology lags far behind “discovery.” Five million insulin users will tell you that their medication is NOT identical, vial-to-vial. (But of course, this can be ascribed to anecdotal patient non-compliance.) For two decades, no one has been willing to question the original NDA, and stop the abuse.

Biotech insulins, in today’s FDA formulary (including all of the synthetic analog insulins) are considered small-molecule drugs like aspirin. We now know biotech drugs cannot be compounded with safety, in the same manner as aspirin. All of us should entertain the possibility that because rDNA insulins are never batch-tested, the pharmaceuticals in question have escaped scrutiny. Checking a production plant for cleanliness and procedural methodology does not guarantee ‘what’s in the vial.’

Just an example: Humalog and Humalin are both produced by Eli Lilly and Company. When analyzed by the latest Maldi-Tof method, the results are identical for these two very different products. They both have the same molecular weight (Daltons); only the patient knows whether he gets a peak of action in 45 minutes . . . or in 3 hours. Every vial should be analyzed with a technology adequate to determine the exact STRUCTURE of the compound within each batch. Does being ‘the first in the game’ (as was Lilly and its rDNA insulin) allow a company to both set the rules and exempt themselves from oversight?