Wednesday, February 13, 2008

Big Pharma Deception

On Monday, I posted that some brand-name insulin manufacturers have been deceiving patients by slapping their brand-names on insulin made by third-party manufacturers. Since 2003 at least, Lilly has had FDA approval to sell Humulin® R (and apparently, Humalog®, too) made by Hospira, Inc.'s "One 2 One Contract Manufacturing Services" (known previously as Abbott Laboratories' One2One Global Pharmaceutical Services which was spun-off as an independent company in 2004).

Do you know this company? Well, if you use Eli Lilly and Company's Humulin R or Humalog, perhaps you should. The fact is that Lilly has been contracting the manufacture of vials of Humulin R and Humalog to Hospira, Inc. (which is headquartered in Lake Forest, IL), but has an FDA-approved manufacturing plant for protein in McPherson, KS. If you don't believe me, try reading what's printed on the insert in your next package of insulin. Below, I have included a relevant excerpt from the current FDA-mandated package insert for Humalog, taken directly from Lilly's website which highlights the third-party manufacturing relationship:



Perhaps the packages should also be updated (I took some Photoshop liberty on a package for Humulin R here):



Of course, this does explain how Lilly was able to shelve plans last year for a new insulin manufacturing plant in Manassas, Virginia. Apparently, it's far cheaper and easier to let someone else make it, and simply slap their label on the product. But a commenter suggested that brand-name manufacturers had higher standards than generics companies.

Gimme a break.

When it comes to recombinant DNA manufacturing, the FDA has outlined standards that all companies must follow, generic or brand-name alike. But thanks to lobbying from the brand-name insulin manufacturers, quality controls are strictly voluntary, not mandated by the FDA, according to a 1998 change in policy entitled "Removal of Regulations Regarding Certification of Drugs Composed Wholly or Partly of Insulin" (also found here) which effectively exempts synthetic insulin manufacturers from batch testing -- the sort which vaccine manufacturers are obliged by FDA policy (and U.S. law) to conduct at regular, periodic intervals. Insulin manufacturers may indeed do this testing voluntarily, but why isn't this mandated policy, or more specifically, if it's so important to patient safety for vaccines and other biopharmaceuticals, why was the rule discontinued for insulin?

I responded to the comment by noting that although Lilly is presently approved to sell Hospira insulin made in Kansas, there is no reason why the company cannot contract with another manufacturer. According to FDA documents, India's Biocon, Ltd. has had the FDA seal of approval since January 27, 2004 to manufacture human insulin in bulk at the company's facility in Bangalore. In addition, since February 5, 2001, another company based in the Netherlands known as Organon BioSciences NV, which as of November 19, 2007, is now part of the American pharmaceutical company Schering-Plough. Schering-Plough also owns Diosynth, another large bulk insulin supplier also based in the Netherlands. Schering-Plough was recently implicated for holding back information about the pivotal, failed clinical trial called Enhance which compared Vytorin (a combination of Zetia and Zocor) with Zocor alone and showed no difference. The company's president, Carrie Cox, is now being investigated for insider trading of stock options by selling her stock before the study results were released to investors. Once again, big pharma and ethics displayed at its finest!

A fair number of people I've met on various diabetes social networks and message boards feel adamantly that drugs coming from India are inherently lower quality. Initially, I shared these concerns, but today, I'm no longer so sure. With the outright deception and greed that has been going on in big pharma, and the clearly unethical management such as at Schering-Plough and others, it makes me honestly wonder if outsourcing to an Indian company is really any worse? I'm starting to think otherwise! After all, Indian companies already have a significantly lower-cost of scientists, manufacturing and intellectual capital, so they have nothing to gain by delivering a low-quality product. In fact, they are trying to establish themselves as viable, global players, so they may be more likely than the big guys to adhere to the letter of the regulations, while big pharma routinely tries to weasel their way out of them with lobbyists and other shady maneuvers. Think about that!

9 comments:

Anne said...

With all due respect, I don't see why it is such a big problem for Lilly to contract out its manufacturing to another company, as long as that company follows its same strict guidelines on quality. Is this such an unusual practice in any business?

I admit that I am biased towards Lilly in part because my brother worked there, and I had a chance to visit their site in Indianapolis. There is greed everywhere and the pharmaceutical industry is no exception, but my guess is that Lilly is contracting some of its manufacturing to Hospira because it couldn't afford the VA plant due to a tight market.

From my brother's experience, the quality of insulin produced by Lilly (wherever it is produced) is exceptional and the company and its employees care about the people behind the diseases they are helping to treat. In fact, there is employee education on diabetes, for example, and what people with diabetes go through. This is so people working on diabetes-related products may have a better sense of purpose in their work.

Just my 2 cents.

Scott said...

To be sure, it is no worse than subcontracting any other type of manufacturing. However, the industry and Lilly in particular (given the company paid some $3 million for lobbyist in 2006 according to the Center for Public Integrity) has in recent years abandoned its sterling reputation and and done things to boost its shareholder interests. But the brand name also carries a promise, in the words of James S. Hirsch (author of the book Cheating Destiny) "Each day, you inject it or pump it into your body, on blind faith that it will keep you alive to do the same tomorrow".

When the company outsources this, the control over the product's manufacture is also lost to some extent. One need not look too far into the distance to see when the company might put the subcontracting up for bid and give the business to an Indian company would could undercut the others on price. I suppose there's nothing inherently wrong with that, indeed, they have a fiduciary responsibility to do it. But the days of having a customer for life are clearly gone, and the company cannot rely on developments from over a decade ago to turn the business around.

BetterCell said...

Scott, I do not mind that India is involved in Insulin Manufacturing. However since Diabetes is so widespread, the overseas manufacturing should be what is supplied to those countries within the same hemisphere.
Here in the USA, there should be Insulin manufactured within our own borders. This provides for a much better quality control means over the product from manufacturing to distribution and supply with a lot less third party people to deal with.
Will this stop Greed and the resulting harm that could be created(inferior/contaminated product)?...............No, but there would still be less people involved.

Anonymous said...

Your conclusion that "quality controls are strictly voluntary" is simply untrue. The FDA audits insulin-making facilities and is strict about QA. The FDA's Good Manufacturing Practices are still enforced. I don't know exactly what the document you reference is repealing, but as Inigo Montoya says, "I do not think it means what you think it means"

Also when a company outsources production the subcontractor must follow the same Quality regulations as the parent company.

Your post kind of implies that you think Hospira isn't a good manufacturer. I can't see any reason to assume this. Also, don't you think Lilly would pick someone they would trust not to hurt their reputation as a subcontractor?

If you think about it, Lilly is actually the first major subcontractor of Insulin. It was invented at the University of Toronto, but they couldn't mass produce it.

Scott said...

The FDA's Good Manufacturing Practices still apply, but those general standards are insufficient for biotechnology medicines. I would add that FDA inspections for U.S. and foreign plants have fallen to a record low as the media has already disclosed.

Keep in mind that insulin IS, according to the FDA, a small-molecule drug which unlike most others, happens to be made via biotechnology processes. Batch testing for potency, contaminants, etc. for example, is required for vaccines and most other biotech drugs, but the 1998 decision no longer obligated manufacturers to do the same for insulin. That doesn't mean that aren't doing it, only that there is no obligation and if the company wanted to cut costs, could reduce the amount of testing required and still be compliant with FDA requirements.

I did not imply Hospira wasn't a good manufacturer, only that they aren't Lilly and Lilly has clearly given up some control over what happens in the manufacturing facility as far as quality control is concerned. As for their reputation, I think doesn't value it as much as you believe they do. To note an example, consider the off-label marketing of Zyprexa as an example of this reputation and where it has gone in recent years.

Anonymous said...

Those who defend 'outsourcing' and think our FDA strictly monitors adherence to guidelines, I would ask you to support your beliefs. My concerns--which, I must admit come from the 'quality' reporting of CNN and other media--are that FDA is underfunded and understaffed; they do not have adequate man-power to oversee adherence. Equally important, they have very little enforcement power!

And, even if Lilly (and its subcontractors) CURRENTLY adhere to guidelines, with the rule of greed that has become the corporate norm, we should expect that when bottom lines falter, rules can be changed or ignored. Cost cutting measures are undertaken for SHAREHOLDERS’ benefit, not for consumers/patients.

Remember MATTEL? They cut corners, outsourced, did whatever was required to maintain profit margins and market dominance. When it was determined that they were harming our children, they PROMISED they were taking remedial actions . . . all the toys on the shelves for Christmas shopping WOULD BE safe! Their mea culpas before Congress were truly astonishing. Strangely, after Christmas shopping season came and went, toys were still found on retailers' shelves that were unsafe! So much for promises made and promises kept. And did our watchdog government agency serve us? The CPSC is a joke! They have neither the manpower, the budget, nor the DESIRE to monitor and hold accountable the corporations that place profit above all.

Anne, I believe your endorsement of Lilly may be well intentioned. Years ago, I would have defended them with the same kind of enthusiasm. I guess the turning point for me (in believing they CARED about their diabetic patients) was when I read about one of their VPs who publicly admitted that NOT ALL DIABETICS CAN USE rDNA INSULIN. He could have then promised to ensure freedom of choice; to maintain a supply of product for those WHO COULD NOT USE rDNA insulin. Instead, the admission was followed by Lilly's swift removal of the final animal-sourced insulin available to U.S. consumers. The sincerity of Lilly’s claims to care about all their diabetic patients was, unarguably, a lie. Why, then, should I trust statements and claims and promises that have been promulgated since that time? Needless to say—I don’t!
--Melody

Anonymous said...

Scott—

Me thinks you must have touched a nerve somewhere. Lilly defenders seem to equate plant inspection, and “Best Manufacturing Guidelines” protocols with final batch testing. First of all, final-product insulin batch testing DOES NOT reflect the same thing that plant inspection is intended to do. Plant inspection (often with pre-notification) have very little to do with the purity, the safety, or the strength of the end product. With the removal of batch testing requirements, there is no longer any guarantee that the product in the vial is actually ‘human insulin.’

In fact, Novo has admitted (Lilly probably doesn’t even KNOW) that there is no technology today that can insure that the human insulin molecules in the bottle is identical to that made by “the human body.” The molecule may have the same atomic weight, but not necessarily the same 3-dimensional structure and/or spatial quality. Even more importantly, there is no way in the world to know whether what is in the bottle from a subcontractor is identical to what they actually produce in their own plant. Again, Novo admitted there was no way for generic manufacturers to guarantee they were making the same product as the original patent-holder.

If you want know just how ethical Lilly is, you might want to check out a lawsuit brought by the courts of India. It seems Lilly was supplying substandard insulin which, it turns out, was manufactured by a subcontractor in another country, but which carried Lilly’s label on the bottle. I wouldn’t place too much credence in “Lilly caring about its diabetic patients.” http://www.telegraphindia.com/1050830/asp/nation/story 5173547.asp


At a time when I was enjoying excellent diabetic “control” (management), A1c’s of 5.5-6.1, no hypoglycemia, and freedom to eat and exercise almost “normally”, Lilly pulled my insulin-of-choice off the market. Lilly’s caring answer to rather significant medical problems I subsequently experienced with their new, latest-and-greatest-rDNA insulin was succinct. “It was just a business decision.” Again, those who point to Lilly’s caring attitude, I suspect, may never have been on the ‘receiving end’ of the problems Lilly so cavalierly created for their patients. As far as I’m concerned, if and when all my choice of insulin is narrowed to ONLY rDNA insulin, I will select a Novo product—at least they tell the truth.

--Brent

Donna said...

Scott,
I think Lilly is like all the other big companies who are outsourcing their work. Unfortunatley, in this case, it could be a problem for us - personally.

I work very close to their headquarters in Indianapolis & I have relatives that work for them. I hate the outsourcing for their sakes, as well.

This is a troubling situation.

International Regulatory Affairs said...

Great post!!!!!!!!!!1