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When it comes to the safety assessment of biotech products, we enter an Alice in Wonderland world where words mean exactly what corporations choose them to mean, as the following article on genetically engineered pharmaceuticals makes clear.

In the case of food safety, for instance, the biotech industry argues that if the chemical composition of their genetically engineered products appears to even imprecisely resemble that of existing foods, then they should be judged as being 'substantially equivalent' and no further safety consideration is required.

'Substantial equivalence' is a completely vague concept which has not actually been defined anywhere! This vagueness is, of course, extremely helpful to industry, allowing a wide range of difference to be encompassed without any safety or toxicology tests being required.

Yet when it comes to protecting their patents, the corporations are all too eager to emphasize the totally novel and unique nature of their products. Indeed in the case of their pharmaceutical patents, the biotech industry's line of argument is the exact reverse of its claims in regard to food safety. The industry argues:

*living things cannot be easily standardized

*even slight differences can have a big impact on safety

This leads them on to challenge the regulators:

*should we jeopardize public safety by assuming those minor differences are irrelevant to the impact of the product?

The joke is that the production of GM food plants is *invariably* haphazard, involving as it does the random insertion of transgenes into plants with all the unpredictable consequences that are known to follow, i.e. the plant's host genes can be silenced (inactivated) or inappropriately switched on, resulting in either a deficiency in a given protein or the presence of the wrong protein in the wrong place or in the wrong quantity, and, in addition, the introduced gene may not behave in exactly the same way in its new host as in the organism from which it was drawn.

Yet there is normally no testing to see if the inevitable disturbance in the plant's biochemical function, resulting from genetic engineering, has unexpectedly produced novel toxins, allergens or reduced the nutritional value of the food. Any differences introduced into the plant's functioning are simply assumed to have no significance for safety. In other words, public safety is jeopardized to suit the needs of the biotech industry!

However, the biotech industry's apparently more cautious and sensible rationale in relation to genetically engineered pharmaceuticals, should not lead one to imagine that the corporate Humpty Dumpties are actually guided in their own production of GE pharmaceuticals by such caution - far from it!

For all their apparent concern about how even slight changes in production can make a critical difference to the safety of a biotech product, thus making it impossible, they say, for other producers to simply replicate their products, when it comes to their own production activities the biotech companies, according to the article, want to be able to use new pharmaceutical production facilities without undergoing new trials for the resulting products. And, needless to say, the regulators generally allow them to do just that -- even though it totally contradicts the same companies' defence of their patented products from replication by others.

Thus the FDA apparently approved Avonex, Biogen's beta interferon, even though in the clinical trials Biogen used a protein produced by another  company!

For more on these issues in relation to GM foods see:

Breaking the chain -- Dr Michael Antoniou http://members.tripod.com/~ngin/article5.htm

Beyond "substantial equivalence" -- Dr Erik Millstone et al http://members.tripod.com/~ngin/se.htm

The Morton-Pusztai debate on GM food safety http://members.tripod.com/~ngin/pusztaidebate.htm

In relation to safety concerns and biotech insulin see: http://www.btinternet.com/~clairejr/Insulin/insul_1.html
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Biotechnology Companies Try to Ward Off Generic Drugs
New York Times, Thursday 29th December 2000
http://www.nytimes.com/2000/12/28/business/28GENE.html

Most lucrative brand-name drugs eventually lose their patent protection, opening the market to generic products with lower prices. But one class of drugs, which includes some of the most expensive products in the world, is insulated from such generic competition.

These drugs are made using genetic engineering, and at present there are no regulations allowing for generic versions.

But, with patents on many of the biotechnology industry's best-selling drugs set to expire in the next few years, companies that make generic drugs are pushing to change that, hoping to invade new turf.

Generic drugs can sell for a fraction of the price of the equivalent brand-name drugs. Their low prices stem in part from the fact that generic drugs can be approved for sale without lengthy clinical trials to show they are safe and effective. Drug makers need show only that generics are the same chemical and act the same in the body as the brand-name equivalent.

But this applies only to drugs made using chemistry ”” most of the pills sold by big drug companies. There is no procedure for quickly approving generic versions of so- called biologics ”” drugs made from living cells, like vaccines, blood factors and genetically engineered proteins ”” because these drugs are regulated under a different law.

"What we need to do is get a regulatory pathway for generic biologic approval," said William H. Nixon, president of the Generic Pharmaceutical Association, which has about 150 members.

The timing could be right. Senator Orrin Hatch, the Utah Republican, has indicated an interest in updating the Hatch-Waxman Act, the 1984 statute he helped draft that governs generic drugs. Moreover, surging drug prices have provoked a public outcry.

"Some of the most expensive drugs in the world are biologics," said Abbey Meyers, president of the National Organization for Rare Disorders, which represents patients and also supports new regulations for generic biotechnology drugs.

Cerezyme, for example, a drug made by Genzyme for a rare disorder called Gaucher's disease, can cost more than $200,000 a year. The blood-clotting proteins for hemophilia, produced by Bayer and Baxter, can cost more than $100,000 a year, while some of the interferons for cancer can cost tens of thousands of dollars, she said.

An anemia drug, erythropoietin, or EPO, made by Amgen and given to patients undergoing kidney dialysis, sells for millions of dollars an ounce and is one of Medicare's biggest pharmaceutical expenses.

But biotechnology companies plan to fight any new rules. The industry maintains that its products, mainly proteins made by implanting genes into bacteria or hamster cells, are hundreds or thousands of times larger and more complex than chemical drugs. This makes it virtually impossible for a generic drug maker to show that its product is the same as another biotechnology drug.

Living things cannot be easily standardized like chemical processes, the industry argues. What is more, even slight differences among drugs can have a big impact on their safety and effectiveness. The Food and Drug Administration has approved two versions of beta interferon, used to treat multiple sclerosis, because slight changes mean that one has fewer side effects than the other.

"Do we jeopardize public safety by assuming those minor differences are irrelevant to the clinical impact of the product?" said Lisa Raines, Genzyme's representative in Washington.

The F.D.A. also has reservations.

"There are significant unresolved scientific issues about how to show `sameness' between complex biological macromolecules so that F.D.A. can be assured that any generic biologic is safe, pure and potent as well as `equivalent' to an innovator product," Margaret M. Dotzel, associate commissioner for policy, said in a statement.

Some agency officials cite an incident in the 1950's when a slight change in the production process led to a failure to inactivate completely the virus used in the Salk polio vaccine. Some people contracted the disease from the vaccine.

But the F.D.A. has in effect already approved one generic biologic. Because of quirks in drug regulation, hormones are regulated as chemical drugs, not biologics. And in 1997, the F.D.A. approved the Ferring Pharmaceuticals generic version of Pergonal, an infertility treatment sold by Serono that consists of two hormones isolated from the urine of post-menopausal women.

Serono sued to block the approval, citing slight differences between its drug and the drug made by Ferring, a unit of Ferring B.V. Group Holding of the Netherlands. But an appeals court sided with the F.D.A., saying that the drugs do not have to be chemically identical, only identical in terms of their clinical effects.

The market for generic biologics could be sizable. EPO has sales exceeding $4 billion a year by Amgen and its licensee, Johnson & Johnson.

Other drugs that could lose patent protection in the next few years include human insulin for diabetes, beta interferon for multiple sclerosis, alpha interferon for hepatitis and cancer, and growth hormone for dwarfism and other conditions. Each of these drugs has worldwide sales exceeding $1 billion.

Some generic drug companies are linking up with biotechnology companies to acquire the expertise they need.

...Moreover, for all their talk about how even slight manufacturing changes can make a big difference in drugs, biotechnology companies themselves want to be able to build new factories without undergoing new clinical trials. They can generally do this. Indeed, the F.D.A. approved Avonex, Biogen's beta interferon, even though the company used a protein produced by another company in Germany in its clinical trials. The F.D.A. concluded the drugs were comparable and prevailed in court.

That could provide an opening for the generic companies. "If it's good enough for the branded industry to show comparability, it's good enough for us," said Bruce L. Downey, chairman and chief executive of Barr Laboratories in Pomona, N.Y.

With hundreds of new biotechnology drugs under development, some executives think cost pressures will eventually force changes to allow generic biologics.

"It's not reasonable to expect a company should have a lifelong monopoly just because the molecule is larger," said George S. Barrett, president of Teva Pharmaceuticals U.S.A. "I think the clamor on the consumer side is going to force it to happen."