The Supremes protect generic drug producers- but what about patients?

The US has increasingly turned to generic drugs as a key tool in constraining its outlandish health care costs. However, are these drugs as safe and effective as brand name medications? The Supreme Court apparently thinks so since in a recent decision (Mutual Pharmaceutical co. v. Bartlett) it ruled that makers of generic drugs cannot be sued under state law for adverse reactions to their products. The underlying concept is that since the original branded drug has been approved by the FDA and since the generic manufacturer is providing a product that is ‘equivalent’ to the original drug it cannot be held responsible for harm caused by the drug.

Generic drugs now account for 80% of prescriptions and are often 80-90% less expensive than the original branded drug (1).  Generics entered the US market under the 1984 Hatch-Waxman Act that provides a rapid approval process (Abbreviated New Drug Application, ANDA) that is far less demanding than the process for approval of the original drug. The generic has to demonstrate ‘bioequivalence’ which is usually interpreted as attaining comparable blood levels to the original drug. However, it is important to realize that the FDA essentially depends on the generic drug producers to provide the data used in the evaluation. Currently the FDA lacks the resources to extensively test all submitted drugs or to inspect all of the factories that produce these agents. Thus, if a generic drug company manipulates the data submitted for approval, or if its manufacturing practices deviate from accepted standards, these problems may not be discovered for a long time. This may be particularly a problem with foreign generic producers, who now account for a substantial share of the US market, but whose operations are difficult for the FDA to monitor. There is a long history of issues with generic drugs due to the lack of efficacy because of insufficient or degraded active ingredient or due to the presence of harmful contaminants. An especially egregious situation involved Ranbaxy Laboratories, an Indian firm that is one of the largest generic manufacturers. Over a period of decades Ranbaxy engaged in outright fraud to obtain approval for its drugs both in the US and especially in many less developed countries with weak pharmaceutical regulations (2).

In this light the Mutual decision seems very problematic. One of the key constraints that keep pharmaceutical companies on the straight and narrow is the fear of litigation. Thus the Supreme Court seems to be opening the door to allowing generic manufacturers to cut back on monitoring the quality of their products and their manufacturing processes. Inevitably this will have harmful effects on patients.

(1)  http://www.fda.gov/drugs/resourcesforyou/consumers/buyingusingmedicinesafely/understandinggenericdrugs/ucm167991.htm

(2)  http://features.blogs.fortune.cnn.com/2013/05/15/ranbaxy-fraud-lipitor/

Promising Changes in Cancer Drug Clinical Trials

A recent news article in NATURE describes a novel thrust in cancer drug development. An organization called Friends of Cancer Research has convinced the US National Cancer Institute and the US Food and Drug Administration (FDA) to support a new model for late stage clinical trials. Based on the previous success of the pioneering I-SPY-2 and BATTLE trials, the idea is to streamline the drug-approval process by bringing pharmaceutical companies together to test multiple experimental drugs under a combined ‘master protocol’. While this concept makes a huge amount of sense, it had previously been resisted by pharmaceutical companies who were concerned about loss of intellectual property. Now, however, frustrations with and escalating costs of drug development are bringing companies to consider new models such as this one.

See also http://scienceforthefuture.blogspot.com/2013/05/horns-of-dilemma-value-to-cancer.html. 

http://www.nature.com/news/master-protocol-aims-to-revamp-cancer-trials-1.13176 

The Vain Pursuit of ‘Significant’ Research

An excellent editorial in SCIENCE by Marc Kirschner describes how granting agencies and universities are placing undue emphasis on the projected ‘significance’ and ‘impact’ of biomedical research. This is usually interpreted as having the potential for rapid translation to the clinic. However, as Kirschner points out, many of the most important advances have come from basic research that did not seem ’significant’ at the time. Witness early work on restriction enzymes, initially of interest only to a few basic scientists, but now the basis of all molecular biology and genomics. The over-emphasis on ‘significance’ is another manifestation of the increasing ‘corporatization’ of research that leads universities to unduly focus on work that has short-term practical and commercial potential. This topic has been discussed previously on this blog: see  “Making academic research pay off- is that really the point?"

http://www.sciencemag.org/content/340/6138/1265.full 

DNA and the Supreme Court

Today the Supreme Court unanimously ruled that the BRCA gene patents held by Myriad Genetics are invalid.  This seems to negate a great deal of intellectual property on gene technology going back to the Diamond v. Chakrabarty, 447 U.S. 303 (1980) decision. The key element of the new ruling seems to lie in the phrase “A naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated, but cDNA is patent eligible because it is not naturally occurring. “ As a biologist I find this perplexing since the cDNA still derives from a natural (RNA) sequence.

However, the major issue now is how today’s ruling will impact the future evolution of the commercialization of genetic technology. In simplest form the decision should prevent companies like Myriad from monopolizing genetic tests thus lowering cost and accessibility. Clearly this would be a very good thing.  However, the ruling is likely to have many ramifications that may not be easily anticipated and that may have a chilling effect on some forms of translational research. Not being a lawyer I may be naïve about the legal intricacies. However, a few cautionary examples readily come to mind. For example, there is a lot of interest in using short sequences of RNA (siRNAs, miRNAs) to regulate disease genes. Since these are based on naturally occurring base sequences, does the new ruling undermine the patentability of this approach? I would imaging that there will be a lot of work for patent lawyers in processing the full ramifications of today’s decision!