Reasons In Support

Following are the reasons and rationale in support of the Petition to Congress, including an explanation of terms used. The reasons below correspond to the same sections in the petition.

1. PREMARKET TESTING OF DRUGS AND BIOLOGICS BY IMPARTIAL ENTITY.

After a drug company has completed its preliminary studies on a drug or biologic (made from living organisms or products), in order to commence clinical (human) studies, it is necessary to file an Investigational New Drug (IND) application with the FDA. Included within the application are clinical protocols, which are the guidelines and designs of the proposed studies, to be used by the clinical investigators. Clinical investigators are physicians who have been hand-picked by the pharmaceutical company to administer the drug during the clinical trials. It is at this stage that the FDA becomes involved for the first time in the overall process to evaluate the safety and effectiveness of drugs destined to be marketed throughout the nation.

Since the FDA was formed in 1938, the drug company has always conducted its own premarket clinical studies, the results of which will ultimately determine whether the drug is approved for marketing. They are usually conducted in three stages or phases and on average last about 7 years. By the time a pharmaceutical company has completed all of the necessary studies, and is prepared to submit the drug to the FDA for approval, it will have invested hundreds of millions of dollars in the research and development needed to get it to market. The studies thus involve a huge conflict of interest for the company.

Although clinical investigators maintain their own set of records created during a study, they usually transfer information onto forms supplied by the drug company, which are sent to the company along with copies of the investigators’ records. As the company gathers these medical charts, laboratory studies and forms of the patients treated with the drug under study, it begins compiling the data onto its computers, which it later summarizes and submits to the FDA, along with its interpretation and conclusions. It is during this compilation stage that the company is in a position to alter, destroy or discard records reporting on unfavorable adverse reactions that might stand in the way of approval or dictate a strong warning that could impact sales.

Any alteration, destruction or discarding thus takes place before the records are forwarded to the FDA as part of the IND. At this point they are also easily excluded from the compilation of data and statistics. Should a company choose to discard or destroy such adverse reaction reports, there is no way an FDA medical review officer could detect such actions, short of securing records directly from each and every investigator – which is virtually never done.

2. ELIMINATION OF ARBITRARY DEADLINES ON NDAS AND BLAS UNDER THE PDUFA.

The Prescription Drug User Fee Act (PDUFA) was enacted in 1992 for the purpose of allowing the FDA to collect user fees from drug companies in exchange for meeting specific deadlines for reaching decisions on New Drug Applications (NDAs). The same laws applied to a New Biological Application (BLA). An NDA or BLA filing generally occurs following the completion of clinical studies pursuant to an IND. The drug company is essentially stating that it has done its homework and completed its exams, and now wants to graduate to the market. Medical officers within the FDA then review the thousands of pages of records from the clinical studies, make a determination on the safety and effectiveness of the drug or biologic under study, and ultimately make recommendations to senior management within the FDA. Before passage of the PDUFA, the average review time for an NDA or BLA was about 2½ years.

The act has a “sunset” clause that terminates the legislation after five years unless renewed. Renewals were enacted by Congress in 1997, 2002 and 2007. In 1997 (PDUFA II), the current time for completing a review and making a decision on the NDA or BLA was established. The review of 90% of standard NDA/BLA submissions had to be completed within 10 months and priority NDA/BLA submissions within 6 months.

With the increased emphasis on speed, the FDA is less effective at screening out dangerous drugs during the NDA review process. Interviewed FDA employees have stated that not only is there an increased emphasis on completing reviews quickly; there is also a great deal of pressure to approve new drugs. In a survey of FDA reviewers by the Office of Inspector General for the Department of Health and Human Services,  at least 40% indicated that the review process had worsened due to the PDUFA in terms of allowing for in-depth, scientific-based reviews; that a large percentage believed that these pressures inhibited the raising of disputes, as reviewers were reluctant to slow down the process; that 21% of the reviewers indicated that the PDUFA work environment was such that there was little room for expressing differing scientific opinions; and that 18% “indicated that they have felt pressure to approve or recommend approval for a drug, despite reservations about its safety, efficacy or quality.”

Following an earlier two-year investigation into the same subject, the Los Angeles Times reported on 7 drugs – Lotronex, Redux, Raxar, Posicar, Duract, Rezulin and Propulsid – five of which had been withdrawn from the market in less than 24 months after their approval by the FDA, and each associated with a series of deaths before their removal. With 4 of the drugs, medical experts warned against approving the NDA. During interviews, FDA medical reviewers described a work environment in which they were continuously pressured not only to meet deadlines, but to approve the drug under review. “People feel swamped,” said one of them. “People are pressured to go along with what the agency wants.” Another commented, “If you raise concern about a drug, it triggers a whole internal process that is difficult and painful. You have to defend why you are holding up the drug to your bosses….You cannot imagine how much pressure is put on the reviewers.” Still another noted, “The people in charge don’t say, ‘Should we approve this drug?’ They say, ‘Hey, how can we get this drug approved?’”

Currently, user fees comprise approximately 55% of the entire budget of the Center for Drug Evaluation and Research (CDER) – the drug division of the FDA. Due to its dependence upon user fees to meet the FDA’s budget for CDER, the industry it is to be policing holds the agency within its economic fist. Considered along with the “sunset” clause and a need for renewal every five years, the FDA is faced with the prospect of the industry pulling its funding should the agency not meet its performance goals or in any way make decisions having a significant negative impact on industry’s financial picture. Not only is upper management at the FDA faced with the prospect of losing a substantial part of its budget – and a corresponding need to substantially cut its personnel – individual reviewers in the Office of New Drugs (and other offices) see the same picture; namely, the risk of losing their jobs if they are not consistently approving drugs for marketing.

In reality, the FDA has effectively formed a partnership with the drug industry. In fact, upper management at the FDA in many ways sees industry as a client that covers much of the agency’s overhead and must be kept happy. This view was echoed by the FDA’s Dr. David Graham in an interview with Fraud Magazine:

“FDA is inherently biased in favor of the pharmaceutical industry. It views industry as its client, whose interests it must represent and advance. It views its primary mission as approving as many drugs as it can, regardless of whether the drugs are safe or needed.”

Dr. Graham is the Associate Director for Science and Medicine in the FDA’s Office of Surveillance and Epidemiology – the department that oversees the safety of drugs once they are on the market. He is also an outspoken critic of his employer and blew the whistle on Vioxx when his superiors refused to take any action.

Of course, there is nothing wrong with user fees per se; they are very much a part of our governmental system of sharing costs, including their use within our judicial system. It is tying them in with arbitrary deadlines and the “sunset clause” of the PDUFA that has created another conflict of interest in the way we test, evaluate and monitor drugs.

Finally, the primary reason for expediting the review time for NDAs and BLAs relates to the declining patent life of the drug or biologic.  In the United States the patent life of a drug is 20 years from the date the patent is issued. For obvious protective reasons, drug companies generally file the patent application well before initiating clinical trials. Thus, by the time the drug hits the marketplace, the patent may only have between 8 and 10 years left. This is why drug companies aggressively sought shorter review times following NDA/BLA filings. Every month saved is one more month of exclusive sales, and saving just one year could add hundreds of millions of dollars of income or, for some drugs, into the billions. It no doubt was the driving force behind the enactment of the PDUFA.

The 20-year patent life on drugs should be tolled during the period between the filing of an NDA/BLA and its approval for marketing. The clock should stop running during the review process. No matter how long it takes the FDA to make its decision, the pharmaceutical company would not lose one hour of market exclusivity. Drug manufacturers should not be penalized as a consequence of a thorough and efficient NDA review by the FDA.

This would also eliminate the primary reason for drug companies insisting on a short deadline to complete NDA/BLA reviews, and would remove a major argument for opposing the changes. Indeed, drug companies will no doubt see that the patent lives of their drugs would be extended by 10 months on a standard review and 6 months on a priority drug review – a win/win for industry and consumer alike.