In statehouses around the country, some of the nation's biggest biotechnology companies are lobbying intensively to limit generic competition to their blockbuster drugs, potentially cutting into the billions of dollars in savings on drug costs contemplated in the federal health care overhaul law.
The complex drugs, made in living cells instead of chemical factories, account for roughly one-quarter of the nation's $320 billion in spending on drugs, according to IMS Health. And that percentage is growing.
They include some of the world's best-selling drugs, like the rheumatoid arthritis and psoriasis drugs Humira and Enbrel and the cancer treatments Herceptin, Avastin and Rituxan. The drugs now cost patients -- or their insurers -- tens or even hundreds of thousands of dollars a year.
Two companies, Amgen and Genentech, are proposing bills that would restrict the ability of pharmacists to substitute generic versions of biological drugs for brand name products. Bills have been introduced in at least eight states since the new legislative sessions began this month. Others are pending.
The Virginia House of Delegates already passed one such bill last week, by a 91-to-6 vote.
The companies and other proponents say such measures are needed to protect patient safety because the generic versions of biological drugs are not identical to the originals. For that reason, they are usually called biosimilars rather than generics.
Generic drug companies and insurers are taking their own steps to oppose or amend the state bills, which they characterize as pre-emptive moves to deter the use of biosimilars, even before any get to market.
"All of these things are put in there for a chilling effect on these biosimilars," said Brynna M. Clark, director of state affairs for the Generic Pharmaceutical Association. The limits, she said, "don't sound too onerous but undermine confidence in these drugs and are burdensome."
Genentech, which is owned by Roche, makes Rituxan, Herceptin and Avastin, the best-selling cancer drugs in the world. Amgen makes Enbrel, the anemia drugs Epogen and Aranesp, and the drugs Neupogen and Neulasta for protecting chemotherapy patients from infections. All have billions of dollars in annual sales and, with the possible exception of Enbrel, are expected to lose patent protection in the next several years.
The trench fighting at the state level is the latest phase in a battle over the rules for adding competition to the biotechnology drug market as called for in the Patient Protection and Affordable Care Act of 2010.
A related battle on the federal level is whether biosimilars will have the same generic name as the brand name product. If they did not, pharmacists could not substitute the biosimilar for the original, even if states allowed it.
Biosimilars are unlikely to be available in the United States for at least two more years, though they have been on the market in Europe for several years. And the regulatory uncertainty appears to be diminishing enthusiasm among some companies for developing such drugs.
"We're still dealing with chaos," said Craig A. Wheeler, the chief executive of Momenta Pharmaceuticals, which is developing biosimilars. "This is a pathway that neither industry nor the FDA knows how to use."
Biotech drugs, known as biologics, are typically proteins made in living cells. They are much more complex than pills like Lipitor or Prozac, which are made in chemical factories.
That makes it extremely difficult to tell if a copy of a biologic drug is identical to the original. And even slight changes in the cells used to produce the proteins can change the characteristics of the drug, with possible effects on patients.
The 1984 law governing generics does not cover biologics, which barely existed then. One reason generic pills are so inexpensive is that state laws generally allow pharmacists to substitute a generic for a brand-name drug unless the doctor explicitly requests them not to. That means generic drug manufacturers do not have to spend money on sales and marketing.
The bills being proposed in state legislatures would expand state substitution laws to include biosimilars. So Amgen and Genentech say the bills support the development of biosimilars.
But the bills would impose some restrictions that do not apply to chemically produced pills. For a substitution to occur, they say, the Food and Drug Administration must find a biosimilar to be "interchangeable" with the branded product. The FDA has said interchangeability will be a higher standard than merely being similar to the branded product.
Some of the bills would also require patient consent for the substitution, for the pharmacist to notify the doctor if a switch is made and for the pharmacist and doctor to maintain records of the switch for years.
Backers of these bills say these safeguards are necessary to enable any problems to be traced that might arise if a biosimilar turns out to have a safety problem.
"These are really complex, highly sensitive molecules," said state Sen. Patricia Vance of Pennsylvania, who is planning to introduce a bill. "We want to make sure we are not hurting people."
The generic drug association and insurers do not object to limiting substitution to drugs declared "interchangeable" by the FDA.
But they say that once the FDA makes that determination, the other restrictions are unnecessary and are there merely to deter substitution.
Gillian Woollett, who tracks biosimilars for Avalere Health, a Washington advisory firm, said extra restrictions on substitution could put the state bills into conflict with the federal law, which defines interchangeability as meaning that a biosimilar can be substituted without the involvement of the prescribing doctor.
Woollett said the lobbying efforts by the biotech companies, which she characterized as "putting a few more tree trunks on the road," might not make much difference as long as insurers have policies encouraging use of the biosimilars.
For one thing, she noted, only a small percentage of biologics are dispensed through retail pharmacies. Most are infused or injected in a hospital or doctor's office.
Still, that has not reduced the intensity of the skirmishes in state houses.
Dr. John O'Bannon III, a Republican delegate who introduced the bill in the Virginia House, said he did so because as a practicing neurologist, he was familiar with biologics.
Then he added, "The Amgen folks actually did come and talk to me."
Amgen contributed $22,000 to Virginia state legislators in both 2011 and 2012, more than double the $11,000 it contributed in 2010, according to the Virginia Public Access Project. O'Bannon received a total of $1,500 in the last two years.
In North Dakota, a bill has cleared a committee in the state Senate, though it was amended to remove some restrictions on substitutions.
"Genentech was the one that brought the bill to me," said state Sen. Dick Dever, R-N.D., who introduced the bill. "I understand they are proposing it in several states."
In Indiana on Monday, the House Public Health Committee approved a bill, but lawmakers, responding to objections from the generic association, removed the requirement that patients consent to any substitution.
Ed Clere, chairman of the committee and author of the bill, said the bill "doesn't do anything to prevent or discourage the use of biosimilars." He said the bill had been brought to him by Genentech and supported by Eli Lilly, which is based in Indiana.
Also supporting the push for such legislation is the Alliance for Safe Biologic Medicines, a coalition of companies, medical societies and patient groups that includes Amgen and Genentech on its steering committee. It has held forums in various states to discuss the complexity of biologic drugs.
It is also pressing on the federal level for biosimilars to have names distinct from those of the original products.
This is not the first time drug companies have turned to states to try to blunt generic competition.
In the late 1990s, the DuPont Merck Pharmaceutical Co. pushed for laws that would restrict substitution for its blood-thinning drug Coumadin on the grounds that the drug was extremely difficult to use safely. The effort probably did slow the use of the generic, known as warfarin, for at least a while, industry executives say.