The Food and Drug Administration (FDA)- Part I of a II Part Series

Because of the fact that news items continue to come on almost a daily basis on the FDA, we have created a 2nd article effective November 15, 2008. Henceforth the new items in this series will be posted under the title "The Food and Drug Administration (FDA)- Part II"

(11/20/08)- The FDA has issued an Import Alert on dairy products from China that will detain candy, snacks, bakery products and other Chinese products that contain milk until tests prove that they are not contaminated with the toxic chemical melamine. It was discovered in that country in infant formula in September, and has sickened more than 50, 000 infants there, and killed at least 4.

Secretary of Health and Human Services Michael O. Leavitt and Dr. Andrew C. von Eschenbach, commissioner of the FDA will be in China to open agency offices in Beijing, Guangzhou and Shanghai at the end of the month.

Incidentally, former Senator Tom Daschle, who was the Democratic Senate minority leader, and from January 3 through January 21, 2001 the Senate Majority Leader from South Dakota, is being nominated to become the Secretary of Health and Human Services in President-elect Barack Obama's cabinet.

(11/12/08)- A recent report from the Government Accountability Office indicated that the FDA does not have accurate data about foreign drug facilities that it is supposed to oversee, and often does not follow up warning letters with inspections.

The House Energy and Commerce Committee has been investigating the FDA's handling of problems at two plants in India run by Ranbaxy Laboratories Ltd, one of the world's largest generic drug companies. In September, the FDA had banned the import of 30 generic drugs from two plants in India, several years after the agency first found quality problems at one of the plants.

Although the FDA has issued 15 warning letters to foreign companies from fiscal year 2002 through 2007, the agency only re-inspected four of the companies, and those inspections did not take place untill several years later.

The FDA expects to open its first office in China before the end of the year, and also plans to open offices in India and Latin America next year.

(11/9/08)- The U.S. Supreme Court heard oral arguments recently in an important case that involves the legal question as to whether or not a drug's label, as decided by the FDA, pre-empts a state court from in effect overruling this decision.

The case in question arose in Vermont where the plaintiff, Diana Levine, had won a $6.8 million judgment against Wyeth after the misadministration of the company's drug Phenergan caused Ms. Levine to lose her right forearm because gangrene had set in. Phenergan is an antinausea drug normally injected into the muscle, but the label also provided directions for intravenous use.

The jury that heard the case found that the drug's label should have warned against administering the drug through an intravenous injection, known as "IV push." Wyeth contended that it was immune from being sued because the federal agency (FDA) had approved the drug's label.

In February of this year, in an 8-1 decision, the U.S. Supreme Court found that federal law, explicitly pre-empted state regulation of medical devices, and therefore blocked any private negligence lawsuit.

The Vermont Supreme Court upheld the lower court decision and allowed the $6.8 million verdict to stand in 2006.

For more on this matter please see our item dated 3/16/08 below.

(11/2/08)- Public Citizens, a consumer oriented nonprofit organization, has petitioned the FDA to ban GlaxoSmithKline PLC's diabetes drug Avandia, which the agency approved for sale in 1999. The petition cited the increased risk that patients who take the drug are exposed to for coronary incidents and/or liver failure.

Updated guidelines from the American Diabetes Association and the European Association for the Study of Diabetes also advised against using the drug.

The FDA said that is would carefully consider the matter. The drug already has a "black box" warning about the increased risk for heart attacks.

Avandia sales have fallen sharply since May 2007, when the New England Journal of Medicine had an article containing an analysis of the drug's risk from Steven Nissen of the Cleveland Clinic. His analysis found that people on Avandia had a 43% higher risk of suffering a heart attack.

About 20 million Americans suffer from Type 2 diabetes.

The U.S. Food and Drug Administration (FDA) has increased inspections and product testing efforts in response to the melamine contamination problem which originated in Chinese dairy products. As a result of the FDA's on-going testing program, the agency has detected melamine contamination in Blue Cat Flavor Drinks.

The distributor of the product, Tristar Food Wholesale Co. Inc., initiated a recall of several flavors of Blue Cat Flavor Drink, based on the FDAs findings. The FDA advises the public not to consume this product and recommends that retailers and food service operators remove the product from sale or service.

Alert from the FDA

During the last 3 years, 9 surgical mesh manufacturers have submitted more than 1000 reports of complications that have included erosion through vaginal epithelium, infection, pain, urinary problems, and recurrence of prolapse and/or incontinence.

Additional information regarding this alert may be obtained from the Office of Surveillance and Biometrics (HFZ-510) by mail at 1350 Piccard Drive, Rockville, Maryland, 20850; by fax at 240-276-3356; or by e-mail at Voicemail messages left at 240-276-3357 will be returned as soon as possible.

Mesh-related adverse events should be reported to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787 

(10/12/08)- The FDA held a public hearing on October 2nd to solicit opinions about changing federal regulations governing how over-the-counter cold and cough medications are marketed to children. It is expected that the changing of the rules will take many years before coming to fruition.

An estimated 95 million packages of children's over-the-counter cold and cough medications are sold each year in the U.S. according to industry estimates.

John Jenkins, the agency's director of new drugs office, said the system that currently governs over-the-counter cold and cough products was really designed to grandfather these medications that were on the market in the 1960s. That system allowed certain active ingredients to be marketed without obtaining prior FDA approval for each individual product.

The studies done to establish safety of those ingredients were mostly done on adults. Cutting approved amounts for adults to proportionate levels for younger children arrived at proper dosage figures.

The U.S. Food and Drug Administration announced on Sept. 5, 2008 that it has posted on its Web site its first quarterly report that lists certain drugs that are being evaluated for potential safety issues. The drugs have been identified based on a review of reports in FDA's Adverse Event Reporting System (AERS).

The FDA takes an average of seven months to issue warnings to pharmaceutical companies that market medications for off-label uses, and those companies take an average of four months to address the violations, according to a draft report compiled by the Government Accountability Office (AP/Minneapolis Star Tribune report) 

(7/12/08)- Effective this coming August 11th "approval" or "non-approval" letters regarding applications from the drug companies and medical equipment manufacturers for their products will be a thing of the past. The FDA will send "complete response letters" when drugs are not cleared for sale.

The agency first proposed the switch to "complete response letters" in July 2004, and is already using this format for medications made through biotechnology.

The " complete response letter" will describe what is missing from an application and, when possible, give advice on how to fix it, according to the FDA.

Under this new system the drug makers will be responsible to its shareholders and the community as a whole to advise the world as to what the problem may be with a new drug. The "complete response letter" will not be revealed to the public, which was not the case for the "approval", " non-approval' system.

The new rules include standards for how long review cycles will be extended when companies file amendments to applications or re-submissions.

(7/9/08)- New drug applications submitted to the FDA dropped 33% in 2006, which according to Dr. Janet Woodcock, is the reason why the agency approved fewer new drugs in 2007. "You can't approve drugs you don't get applications for," she said

The FDA  approved 19 new medications in 2007 -- 17 "new molecular entities" and two biotechnology medications -- a decrease from 22 in 2006 and the lowest number since 1983, when the agency approved 14 new treatments. The agency also approved 65 new drug applications, or 64% of the applications it received, down from 73% in 2006, according to data released by BioMedTracker.

According to Schering-Plough's Chief Executive Fred Hassan the reason for the fewer approvals is the agency's intensifying focus on safety and diminished tolerance for side effects. What will it take to get new drugs approved?" Mr. Hassan asks. "The point is we don't know."

Thus we have two different viewpoints as to why there are fewer new drugs coming to market in this country. Certainly, if we look at the increased expenditures by the drug companies on their advertising campaigns we can plainly see that the percentage of advertising growth expenditure is increasing at a far greater rate than is the expenditure for research and development by these companies.

The FDA does not restrict physician prescription for off-label indications. It does regulate the manufacturer's promotion for such use. Current law prohibits any promotion of a drug for unapproved uses. (JAMA 2008;299(14): 1949-1951.) This article further reports that "[I]n a recent study of 160 frequently prescribed drugs, off-label use represented 21% of drug mentions and 73% of these off-label uses had little or no scientific support."

(6/21/08)- House Democrats have held 14 hearings over the past 17 months in connection with some of the shortcomings of the FDA. In spite of repeated requests at these hearings to see how much money was needed to repair these problems, the agency and the administration refused to "name an amount".

Two days after announcing a large-scale recall of raw tomatoes, the Bush administration asked Congress to give the FDA an additional $275 million in next year's budget to help improve the agency. Please see our item dated 5/19/08 below for additional information on this matter.

With the added money, the agency would open offices in China, India and Central America and provide more inspections of food and medical products. The FDA also hopes for legislative authorization to enable the agency to accredit third parties to perform food inspections in its stead.

The new request for $275 million would be in addition to the increase of $50.7 million in the president's original budget request of $1.77 billion for the agency. In addition to this amount the agency would also have available about $700 million from user fees paid by the pharmaceutical industry. About one third of all products imported into the U.S. fall under FDA regulation.

The FDA would be able to hire an additional 490 people with this additional funding.

The number of FDA warning letters sent to companies dropped by half in the past 10 years, and several members of Congress want to know why this has happened. In 2002, the agency changed its policies and required that all warning letters go through the agency's chief counsel's office, even though the funding and staffing for the FDA has increased since then.

In fiscal 2001, the agency issued 1,032 warning letters. In 2006, it sent 538 letters and in 2007 it sent 471 letters according to FDA data. Compliance with the warning letter is voluntary, but companies usually try and comply with it.

FDA data also showed that from 1996 to 2000, the agency recalled an average of 3,500 products annually. From 2001 to 2006, that average rose to 4,700. The same data showed that the agency conducted 22,543 foreign and domestic plant inspection in 2003. In 2004, that figure fell to 21,805, with it becoming 19,803 in 2005 and 17,641 in 2006.

(5/25/08)- Mike Leavitt, secretary of the Department of Health and Human Services, said that China is still in the process of approving diplomatic visas for the 13 FDA employees, who would work there to help increase safety monitoring of food and medicine exported to the U.S.

The FDA wants to establish foreign offices in three Chinese cities-Beijing, Shanghai and Guangzhou, but Chinese bureaucracy has been slow in its effort to approve the visas for the newly designated employees of the FDA. Mr. Leavitt said that he expected approval of their paperwork shortly, so that they could be leaving soon for their appointed Chinese cities.

(5/19/08)- In a response, dated May 5, 2008, to Senator Arlen Specter's (Rep-Pa) letter dated May 1, 2008, FDA Commissioner Andrew von Eschenbach wrote that the agency needs an immediate infusion of $275 million to ensure that imported drugs, foods and medical devices are safe. As indicated in our item dated 5/10/08 Dr. von Eschenbach had previously refused to be pinned down with an exact dollar amount that he felt was needed.

He stated that the amount in his budget request was "without regard to the competing priorities that the agency, the president, and their advisors must consider as budget submissions to the Congress are developed."

In February,the president asked Congress to provide the agency with an allocated budget for the fiscal year 2009 of $1.77 billion, which included an increase of $50.7 million over the prior year.

Dr. von Eschenbach had repeatedly refused to give Congress an exact number that he felt the agency needed but he did say that the agency could not absorb $375 million, because money was not the only consideration involved in the matter.

Last week, Senator Herb Kohl (Dem-Wis), who is chairman of the Senate appropriations subcommittee with jurisdiction over the FDA, sponsored a measure that would provide the agency with an additional $275 million this year as part of an emergency supplemental appropriations bill largely intended to finance the war in Iraq.

Both Senator Kohl's measure and Dr. von Eschenbach's letter call for $125 million to finance food safety activities; $100 million for medical product and drug safety activities; $40 million for modernizing the FDA's science and work force; and $10 milliion to upgrade the agency facilities and labs.

(5/10/08)- Recent Congressional hearings in which FDA Commissioner Andrew von Eschenbach has testified has brought to the forefront the differences between Congressional representatives' desire to infuse the agency with funding to better be able to examine foreign drug plants, and the commissioner's avoidance of setting a monetary figure on how much is needed to properly do so.

Our items dated 3/23/08; 2/19/08 and 1/28/08 below discuss this issue, and how it has become such a contentious matter. The Government Accountability Office (GAO) found that the FDA could inspect only about 7% of the foreign plants, and on average inspected such facilities at a rate of once every 13 years. The agency is supposed to conduct these inspections every two years.

Before the FDA approves a new drug or medical device made in a foreign facility it is supposed to examine that facility. The GAO estimated that the agency would need about $70 million in additional funding to inspect the more than 3,000 foreign facilities every two years. That is more than six times the $11 million budgeted in the current fiscal year for foreign-facility inspections

Mr. Von Eschenbach has however stated that it is not a matter of just funding that is required to rectify the problem. He agreed that more inspections were needed, but not to the extent that the Democrats suggested, which is to inspect those plants every two or three years.

"I don't believe that's the solution to the problem," he said. "It's much more complex and the solution needs to be much more comprehensive than simply inspecting a facility."

(4/23/08)- The Bush administration has proposed increasing the FDA's allocated budget next year by 3%, to about $1.8 billion, not enough to pay even for increased costs. The commissioner of the agency, Dr. Andrew C. von Eschenbach, spoke recently about plans to hire up to 700 new employees. At the same time he acknowledged that the FDA did not have the money to do any hiring next year if Congress adopted the president's budget without any changes.

At a hearing before a Senate Appropriations subcommittee Senator Herb Kohl (Dem-Wis) who heads the committee stated, "To us, it's clear that they're (the FDA) seriously underfunded." This committee oversees the FDA's spending.

Senator Robert F. Bennett, (Rep-Utah) the ranking minority member of the committee agreed with Mr. Kohl's assessment.

The Senate passed a resolution last month that would make the FDA's allocated budget-that part of its spending that comes from taxpayer revenue, as opposed to user fees from the drug and medical device companies- $375 million greater in 2009 that this year. That would be a 20% increase, and Dr. von Eschenbach said he did not believe that the agency could absorb so large an increase in one year.

Dr. von Eschenbach said the agency planned to open three new offices this year in the Chinese cities of Beijing, Shanghai and Gaungzhou. The combined staff there is to total 13 people, 5 of them to be hired locally.

(3/23/08)- The recent heparin scare has once again brought to the forefront the inability of the FDA to inspect foreign plants for defective drug ingredients that are being brought into the U.S. from foreign countries. About 80% of the active ingredients for drugs consumed in this country are manufactured abroad. Of this 80% about 40% comes from China and India. Recently released figures show that there were only 341 inspectors for the agency checking on these imports, down from 391 in 2000.

The Senate passed a budget resolution recently that increased the amount allocated for the FDA by 20%. This is a far greater amount than what the administration proposed in the president's budget which called for only a 3% increase..

The House has yet to act on this resolution. Representative Henry A. Waxman (Dem.-CA) chairman of the House oversight committee said: "(the) FDA needs a serious infusion of resources and strong leadership dedicated to reforming the agency."

President Bush has threatened to veto appropriations that go beyond his requests, and there are many that feel that it is not just a matter of increasing funding for the agency to resolve its problems. Among the skeptics is Representative Rose DeLauro, Democrat of Connecticut, who chairs the House appropriations committee. "I don't want to throw money at an agency that doesn't have the infrastructure to carry out is mission."

The administration's budget calls for a 3 % increase in allocated funds for the FDA next fiscal year. That percentage is even lower than the estimated rate of inflation for next year, which is at about the 3.3% level.

(3/16/08)- Does approval by the FDA of a prescription drug, or a piece of medical equipment preclude a product liability lawsuit based on a state law in the absence of fraud in obtaining the approval? That question will be the crux of the matter in a case that is scheduled to be heard by the U.S. Supreme Court this fall concerning Wyeth's challenge to a $6.8 million judgment awarded to a Vermont woman over complications from its anti nausea drug.

Wyeth will use the argument in the case that since the FDA approved the drug, the Vermont law on which the plaintiff based her product liability suit is illegal.

A recent order from a divided Supreme Court gave us an indication as to exactly how difficult this question is. In the ruling the court split down the middle in a 4-4 vote and thus allowed a Michigan product liability lawsuit to proceed to trial. The Michigan law conflicted with the fact that the diabetes drug, Rezulin that was manufactured by the Warner-Lambert subsidiary of Pfizer Inc. had been approved by the FDA.

The lower court had allowed the plaintiff to proceed with the case, and Pfizer had appealed that decision. Chief Justice John Roberts, Jr. had recused himself from the case, because he owns Pfizer stock, according to his most recent financial disclosure filing.

Rezulin had been removed from the market in 2000 after it was linked to nearly 400 deaths and hundreds of cases of liver failure. The plaintiffs in the case allege that Warner-Lambert misled the FDA about the risks of Rezulin.

In a state court trial in Alaska, the state is suing Eli Lilly & Company in connection with its $4.8 billion best-selling schizophrenia medication Zyprexia. The state is claiming that the company had ample evidence that the drug increased the risk of diabetes for anyone taking the drug, and failed to act on that knowledge.

Medical regulators in Japan required Pfizer to include a black box warning in the drug's label in 2002, only 10 months after the drug went on sale in that country. The State of Alaska is suing Pfizer to recover its costs for treating Medicaid patient who developed diabetes after taking Zyprexia.

(2/26/08)- One of our readers recently asked about the drug safety program and how it works. It stimulated this writer to take a look at the history of drug safety. We know that many safety systems usually develop in wake of some scandal. In the case of the FDA, it was the thalidomide scandal in 1962. The Kefauer-Harris amendment to the Food, Drug, and Cosmetic Act required the drug company to provide "substantial evidence" in the area of safety and efficacacy during a premarket evaluation. A multistage approval process was put into place that, in general, improved the evidence base for decision making about new drugs. This step did not consider the postapproval environment where drug sponsors were relatively free of requirements for additional evaluations.

Joseph Famulare, deputy director at the FDA's Center for Drug Evaluation and Research stated that confusion over two Chinese factories with similar names led to the agency's failure to inspect that made an ingredient for Baxter International Inc.'s blood-thinning drug Heparin. Please see our item dated 2/17/08 below. 

(2/17/08)- Dr. Steven Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic said that the proposed new rule from the FDA in regards to off-label usage of drugs is: "I'm astonished that this rule would even be considered." We at therubins are in total agreement with Dr. Nissen's comment.

The new rule proposed by the FDA would allow drug and medical device manufacturers to provide doctors with copies of medical journal articles that discuss product uses that have not been approved by the FDA. There would not be any requirement that the drug companies or medical device manufacturers would have to conduct tests to validate their claims. In other words, the proposal would validate off-label usage of drugs.

If you want to see how this tactic has been abused all you have to do is read about the penalties imposed on these companies that appear in our articles Prescription Drugs and the Cost of Advertising Them-Part I and Research and Marketing of Drugs: A Challenge-Part II

Representative Henry Waxman, Democrat of California, said the proposed rule "caters to the industry's desire to market their products without adequate testing or review." The FDA will accept comments from the public on the proposal and take it up for final consideration in 60 days.

At the same time that Congress allowed direct-to-consumer advertising by the drug and medical equipment industry, it also allowed them to distribute the results from studies published in medical journals as long as reprints were given to the FDA beforehand. The companies had to promise that they would perform clinical trials that would validate the claim made in the medical journal.

These requirements lapsed in 2006. Under the new proposal neither or these requirements is included in the rule.

The articles in the medical journals had to be peer reviewed and have an expert editorial board. The article had to have a prominent warning that the use described was not approved or cleared by the FDA

The FDA admitted that it had erred in granting approval to Baxter International to sell its crucial blood thinning drug heparin, without first having inspected a plant in China that produced some of the drug's active ingredients.

Baxter has temporarily stopped production of heparin because of about 350 bad reactions, including 4 fatalities, tied to the drug that is used primarily in kidney dialysis and heart surgery. Adverse reactions to the drug ranged from stomach pain to vomiting and diarrhea, low blood pressure, speeding heartbeat and fainting.

For more on the failure of the FDA to inspect foreign drug and medical equipment manufacturing facilities, see our items dated 2/9/08 and 1/28/08 below.

Baxter said that the active ingredient for its heparin was supplied by Scientific Protein Laboratories LLC, a Waunakee, Wis., company, with a manufacturing facility there, and a joint venture operation called Changzhou SPL in Changzhou, China.

Scientific Protein is in turn majority owned by American Capital Strategies Ltd of Bethesda, Md. Changzhou Techpool Pharmaceutical Co., of China also owns the manufacturing facility for the drug.

These cross ownership plants gives you an idea of the complexity of trying to determine who is in charge of many of the foreign drugs being brought into the U.S. Scientific Protein said that it had been making the heparin active ingredient at the Chinese facility since 2004

FDA in 2007 approved 19 new medications -- 17 "new molecular entities" and two biotechnology medications -- a decrease from 22 in 2006 and the lowest number since 1983, when the agency approved 14 new treatments. The agency also approved 65 new drug applications, or 64% of the applications it received, down from 73% in 2006, according to data released by BioMedTracker.

(2/9/08)- In testimony that was delivered to a House Energy and Commerce subcommittee, the Government Accountability Office (GAO)testified that the FDA can not keep up with the requirement to inspect domestic makers of medical devices to assure manufacturing quality, and that the agency rarely inspects foreign facilities making this equipment.

According to FDA officials' own estimates, overseas makers of the riskiest products, such as pacemakers were examined only every six years, and moderate risk device manufacturers on average were examined 27 years between FDA inspections.

A report from the FDA's outside Science Board that included members and advisers from industry and academia said the agency "can not even keep up with the advances in science." An appendix to the report said the FDA conducted twice as many inspections of food facilities in 1973 as it did of all facilities in 2006.

The money appropriated for the agency in 2008, which ends on September 30, 2008, is up more than 9% from the prior year, but there are many experts who feel that this is still not enough to help the agency meet its legal requirements. Experts estimate that U.S. makers of the highest-risk products are examined, on average, once every three years, while makers of moderate risk devices are examined once every five years. Both are supposed to be examined every two years.

In 1987, the Centers for Disease Control and Prevention (CDC) were allocated the same amount of money as was the FDA under the federal budget for that year. Last year the CDC received nearly four times the amount given to the FDA.

In the last 14 years, the drug agency has lost 1,311 in employees and nearly $300 million in appropriations to inflation, while Congress has passed more than 100 laws defining or explaining its regulatory responsibilities.

In 1973 the agency undertook 34,919 food inspections, while in 2006 that number dropped to 7,783. The number of food inspectors has plunged to 380 in 2006 from 531 in 2003. Its inspectors inspected only 30 or the more than 3,000 foreign drug plants, and only 100 of the 190,000 foreign food plants last year.

(1/28/08)- Dr. Andrew C von Eschenbach, commissioner of the FDA, said that the agency was working on a plan to post inspectors to embassies and consulates throughout the developing world in the hope of improving the quality of the food and medicines produced overseas and flowing into this country.

The agency already does send inspectors to dozens of countries to inspect pharmaceutical plants and clinical trial sites, but under the plan, permanent inspectors would be stationed overseas in countries that request their being there.

Dr. von Eschenbach said that the inspectors would " build capacity and bring others in to do inspections that are certified". Funding for this plan would come from within the agency's budget, or Dr. von Eschenbach said he would request additional funding from Congress for the operation.

In December, the U.S. and China agreed to a greater American role in certifying and inspecting Chinese food products, including having Americans officials at Chinese production facilities.

(12/20/07)- Representatives Dan Burton, Michael H. Michaud and Tim Ryan called for hearings to investigate the FDA's rejection of the application of Dendreon Corp.'s experimental prostate cancer drug Provenge. The agency rejected approval of the drug in May even though the advisory panel had recommended acceptance of the drug by a 13-to-4 vote in March.

The agency said that it would require the company to produce results from another study in order to win the approval. The Congressmen cited the fact that the inquiry would be centered on the fact that two members of the advisory panel who had argued against approval of the drug had potential conflict -of- interest issues in the matter.

The two members who had the potential conflict-of-interest were Dr. Howard I. Scher of Memorial Sloan-Kettring Center in New York, and Dr. Maha Hussain of the University of Michigan. Dr. Scher is the lead investigator for a trial for a competing experimental drug made by Novacea and advises a venture capital firm that invests in that company.

(11/17/07)- The FDA announced proposed rules that it hopes would reduce potential conflicts of interest among the experts on its various advisory panels. The proposed rules will be open for public comment for 60 days before the agency makes its final decision to revise or adopt them.

Under the proposed new rules, experts on the advisory panels would have to fill out a form disclosing the potential conflicts and explaining why they should still be able to advise the agency.

If the FDA agreed to a waiver, the disclosure form would be posted on the agency's Web site, at least 15 days before the committee meets. Under present rules the agency is not required to release the disclosure documents.

(11/13/07)- From the beginning of this year through October 31, the FDA has approved 15 drugs classified as "new molecular entities", which means the active ingredient hadn't been used before in an FDA-approved therapy. This figure does not include vaccines, or existing drugs approved for new uses.

There were 22 new drug approvals in 2006 and 2005 of them approved in 2005. In 2004 there were 36 new drug approvals making that the highest number of approvals for several years.

Among the new drugs approved this year are two new HIV treatments, Merck's Isentress and Pfizer's Selzentry, and three new cancer drugs: Wyeth's Torisel, GlaxoSmithKline's Tykerb and Novartis' Tasigna.

Senator Edward M.Kennedy (D-Mass.) and Representatives Henry A. Waxman (D-CA.)k and Tom Allen (D-Maine) have introduced legislation that would give the FDA power to quickly ban marketing of over-the-counter products linked to safety risks.

During a hearing being held by the House Energy and Commerce investigation subcommittee, which was chaired by Michigan Democratic Senator Bart Stupak, a report from the Government Accountability Office revealed that the FDA has inspection records for only about one-third of the foreign manufacturers that may be making drugs for the U.S. consumers.

The GAO found that the FDA "could not identify a previous inspection for 2,133 facilities out of 3,249 on a list that the agency used to set its inspection priorities. At its typical pace of 241 annual examinations, the agency would only check 7% of the manufacturers each year.

The FDA is supposed to inspect domestic drug makers every two years, but there is no such requirement for foreign suppliers. "More than nine years after we issued our last report on this topic, FDA's effectiveness in managing the foreign drug inspection program continues to be hindered by weakness in its data systems," Marcia Crosse, director of health care for the GAO said in a statement to the committee.

Other witnesses testified to the fact that the FDA gives foreign drug makers advance notice of inspections, in contrast to the unannounced inspections in the US. In many of the inspections, the FDA has to rely on foreign translators.

The seriousness of this problem comes to the forefront when the question of the importation of foreign drugs is brought up to help reduce the cost of drugs to Americans. It is one of the areas that must be improved on before you can allow the importation of these drugs. In looking at the Canadian situation, the facilities are approved of by the Canadian authorities, and are inspected by inspectors from states that want to legalize the importation of these drugs for its residents.

(10/10/07)- The FDA announced that it would begin to hold hearings on November 14th to explore "the public health benefit of drugs being available without a prescription but only after intervention by a pharmacist."

The pharmacist would be required to ensure that the customer meets certain criteria to get a particular drug, and to instruct that customer on how to properly use the drug. The FDA noted that many countries allow their pharmacists to sell "behind-the-counter" drugs. Included in a list of countries that allow such a practice are Australia, Canada, New Zealand, Denmark, Germany, Italy, the Netherlands, Sweden and Switzerland.

In addition to the public meeting that will be held on November 14th, the agency is also seeking written or electronic comments on the issue until November 28. The agency said certain logistical questions would need to be addressed, including pharmacy storage and dispensing of the drugs along with questions about whether, and how pharmacists might be reimbursed for the additional effort being put forth by them.

(9/26/07)- Both houses of Congress have passed compromise legislation that is the "mother of all FDA reauthorization bills" according to Dan Troy, a former general counsel for the drug agency who represents drug makers. The House and Senate both passed previous versions of the legislation, which is built around a five-year renewal of user fees the FDA charges pharmaceutical and medical equipment manufacturers. For more on the fee structure of the bill please see our item dated 7/19/07 below.

Under the bill, the FDA would be able to take various actions if it believes a drug carries a potential safety concern, including the ability to require new studies, limit distribution or order label changes. The agency would get funding for following up on the monitoring of drugs after they have been approved for sale. The bill would also force the companies to make public some of the results of their studies of their approved drugs.

One of the key items in the bill is the provision regarding the liability of the pharmaceutical and medical equipment companies. The Bush administration had backed the idea that FDA-approved drug labels preempt state law. The drug companies had used that as a shield in legal cases, arguing they were not required to warn consumers about a potential risk if the FDA did not warrant inclusion in the label.

The new bill includes language that says the companies have a responsibility to maintain their labels, thus leaving the manufacturer potentially liable if they fail to make changes even without explicit FDA approval. The FDA will get new power to require drug companies to submit TV ads for review before they run, but it can only recommend changes, not require them. The bill lets the agency levy fines for false and misleading ads.

The new bill also includes a provision that grants pharmaceutical companies and additional 6 months of patent protection if they conduct a study to see the effects of the drug on children under 14 years of age. The bill would give the agency the power to limit the distribution of certain drugs. It would also require that the agency reduce the number of conflict-of-interest waivers it grants to experts who serve on its advisory boards.

(8/9/07)- A Senate panel took the first step toward federal regulation of cigarettes. The bill, which was approved by the Health, Education, Labor and Pensions Committee by a vote of 13-8, would require the FDA to restrict tobacco advertising and regulate the warning labels.

The bill would allow the FDA to require the reduction of nicotine in cigarettes by not to ban them. Those who oppose the bill argue that the FDA should not regulate a product proven to be unhealthy.

(8/3/07)- The FDA announced that it had suspended plans to close more than half the agency's field laboratories. The commissioner, Dr. Andrew C.von Eschenbach said that he would await the recommendations from a presidential panel about how to better guarantee the safety of imported food and other products.

President Bush established the Import Safety Working Group on July 18 and asked for recommendations in 60 days. The FDA had previously announced that it wanted to consolidate its lab network to modernize its food safety protection system.

In a letter sent to Dr. von Eschenbach John D. Dingell and Bart Stupak, both Democrats House representatives from Michigan asked if the purpose of the lab closings was to privatize the testing of imported foods. They cited a pilot program to assess doing just that.

(7/19/07)- The House voted on July 11th, by a 403 to 16 margin, to reauthorize the FDA drug and device user fees that expire on September 30th 2007. For some background on this matter see our item dated 6/29/07. The House and the Senate will meet shortly to negotiate a final compromise to the legislation.

Under the schedule that was voted on in both the House and Senate bills, the drug user fees for fiscal 2008 would be increased to $392.8 million from $305.4 million. This figure was retained from the original agreement struck by the FDA and the pharmaceutical industry. Both chambers would add an additional user fee to enhance post-market drug safety measurements. That amount is about $225 million over 5 years.

The user fees currently finance over 50% of the process for reviewing new drug applications and around 220% of the process for reviewing new device applications. The Senate version of the bill allows for generic copies of biotech drugs whereas the House version contained no such provision.

FDA commissioner Andrew C. Eschenbach testified yesterday before the Subcommittee on Oversight and Investigations of the House Energy and Commerce Committee that the agency would be closing 7 of its 13 labs that test imported foods for safety. He claimed that in doing so, the agency could become more efficient in this area.

The Department of Agriculture has authority to visit overseas facilities and limits imports to 10 ports. The FDA has no authority to inspect overseas facilities and it has inspectors at only 90 of the more than 300 American ports from which imported foods arrive.

Representative Bart Stupik (Dem-Mich) who is chairman of the subcommittee said the closings "would likely expose Americans to even more danger from unsafe food, particularly imports."

Representative John D. Dingell (Dem-Mich) who chairs the committee has put a stop to the labs' closings until the General Accountability Office issues a report on the closings.

The Agriculture Department inspects 16% of all imported meats while the FDA inspects only 1% of the food over which it has jurisdiction. So far we have been unable to ascertain the percentage of imported drugs that the agency has inspected.

(6/29/07)- The current federal law that allows the FDA to impose user fees expires September 30, 2007. Thus it is imperative that Congress pass renewal legislation before the law expires. The agency and the pharmaceutical and medical equipment companies have negotiated these fees ever since 1992 when the original law went into effect. It is a piece of legislation that is renewable every 5 years.

User fees fund part of the FDA's budget, while Congress must appropriate financing to fund the rest of the agency's budget. The FDA had proposed collecting $393 million from drug companies next year. Drug companies would pay an additional $50 million under the Senate bill and an additional $225 million under the House bill over 5 years.

Much of the extra money would be used to fund drug safety monitoring programs. Both the House and Senate bills would also authorize the FDA to collect about $287 million in fees over the next five years from medical-device companies.

(6/14/07)- The FDA announced that it would appoint a panel of outside experts to advise the agency on now to tell the public about the risks and benefits of medicines and medical devices.

There will be 15 voting members on the panel, which would include experts on risk communication, social marketing, health literacy, journalism bioethics and other relevant fields.

A House committee held hearings on Wednesday, June 6 about the FDA's handling of GlaxoSmithKline's diabetes drug that we discussed in our item dated 6/1/07. The hearing is expected to highlight the internal dissension at the FDA between officials who approve drugs and those who track the safety of the drugs after they have been approved.

Congressional investigators said that the safety group recommended months ago that the drug agency put its severest warning on Avandia. The safety group did not believe that such a warning level was warranted.

Senator Charles Grassley, Republican of Iowa proposed a bill recently to separate the agency into different parts but the bill was defeated by a margin of a single vote. The new user fee legislation that must be enacted to replace the expiring user fee arrangement between the FDA and the drug companies has a provision for expanding the power of the tracking and follow-up reporting of drugs after they have come onto the market.

In its quest for transparency, balanced by its need for qualified experts, the FDA has issued guidelines to beef up its conflict of interest for experts issue. The guidelines would bar experts with stock or other financial interests worth more than $50,000 in a particular company from reviewing that manufacturer's product and ban voting by those who receive or own less than $50,000. These guidelines were posted on the FDA Web site on March 21, 2007. The next step is to have the guidelines published in the Federal Register, which opens them up to public comment for 60 days. The suggestions are incorporated into the guidelines and then become final guidelines

(6/1/07)- Senator Charles Grassley, Republican of Iowa said in a statement released by his office, that some FDA staff members had concluded that the label for Avandia, GlaxoSmithKline's popular diabetes drug Avandia should have included a warning framed by a black box, that it increased the risk of heart attacks.

Lawmakers have raised questions about the FDA's handling of Avandia since May 21, when an analysis by Dr. Steven Nissen, of the Cleveland Clinic indicated a 43% higher risk for patients taking the drug in having a heart attack.

Avandia was approved for sale in the U.S. in 1999, and was the company's second most popular selling drug last year with over $3 billion in sales. Advair, its asthma medication, was Glaxo's best selling drug last year.

Incidentally Dr. Nissen found the material that became the basis for his conclusion through a Google search on Glaxo own site. The absolute risk of heart attacks and death was still low with Dr. Nissen finding that the rate of heart attack was between 0.43% and 1.85%, while the cardiovascular death rate was between 0.14% and 0.51%.

About 7 million people worldwide have taken Avandia, and about 1 million Americans are currently using it.

As part of its efforts to make crucial health information easily available to consumers, FDA has launched two new online features:

Web page called "Consumer Health Information for You and Your Family," the page presents important public health developments in easy-to-read language. It also links to other government health information and online Spanish-language publications.View the new page:

E-newsletter -- "FDA Consumer Health Information" replaces the agency's print publication, FDA Consumer. Published monthly free of charge it includes the latest health news, safety warnings and product approvals.

Subscribe to the new e-newsletter:

(5/13/07)- The Senate by a vote of 93-1 approved legislation containing a schedule of new user fees for the FDA, and expanded regulatory powers for the agency. The law would also allow prescription drugs to be imported, but only if the secretary of health and human services first certifies that the imported drugs "pose no additional risk to the public's health and safety," and that they will significantly reduce costs to consumers.

This latter provision in affect means that since the Secretary of Health and Human Services has refused to make such a certification, it is unlikely that you will see the new proposed law change anything.

The new legislation entitled the Food and Drug Administration Revitalization Act of 2007 is a must pass legislation type law since it contains the FDA user fees that the pharmaceutical companies will pay through 2012.

These fees provides the financing for the agency to operate. Included in the provisions of the act is a law to encourage pediatric drug studies.

The House has yet to pass its version of the act, but Representative Henry Waxman (D.-Ca.) has introduced a bill that is very similar to the one passed by the Senate. The Senate bill was sponsored by Sen. Edward Kennedy (D.-Mass.) and Michael Enzi (R.-Wyo.).

The proposed Senate bill would require the FDA to monitor drugs after they go on the market and would provide new funding for that job. The bill would also require drug companies to make public the results from many of their studies. The bill would also expand the regulatory power of the agency

 Pfizer Inc. began posting an online status report on follow-up studies the FDA has required for company drugs already on the market. Many critics of the FDA feel that pursing follow up studies is a particularly weak area for the agency. 

(5/5/07)- The FDA is examining whether Eli Lilly & Co. provided it with accurate data about the side effects of the anti-psychotic drug Zyprexa. One of the key documents that was not presented to the agency when the company sought approval for the drug was a Feb.21, 2000 memo in which Lilly scientists discussed whether Zyprexa's label should be changed to alert doctors of the risk of high blood sugar or hyperglycemia.

The paper showed that 154 of 4,234 patients, or 3.6%, who took the drug in the trial developed high blood sugar. This compared with only 1.1% in the placebo group who developed the problem. This document was not presented to the FDA, but a few months later Lilly provided data that showed almost no difference in blood sugar between patients who took Zyprexia and those who did not.

Lilly is facing federal and state investigations into the way it marketed and promoted Zyprexia. The company has already agreed to pay $1.2 billion to settle 28,500 lawsuits from people who contend that they develop diabetes and other diseases after taking the drug. At least 1,200 more lawsuits are pending against Lilly in connection with Zyprexia.

(4/22/07)- The Senate Health Committee approved the FDA user fee that had been negotiated by the pharmaceutical industry and the agency that we discussed below. The proposed legislation now goes to the full Senate for consideration. The proposal did not contain the amendment to create an expedited process for approving generic versions of biotech drugs as proposed by Senator Hillary Clinton of New York.

The legislation would enable the agency to increase its revenue target for drug user fees by nearly 45% to $442.8 million fiscal year 2008 up from $395.4 million in 2007.

The bill also authorizes $30 million to be appropriated by Congress for the use of a database and other resources to monitor drugs for adverse events once they reach the market. This money would need approval. by Congress in a separate spending bill process that annually funds the agency.

One of the items in our article on Research and Marketing of Drugs: A Challenge-Part II states- (1/15/07)- The FDA and the pharmaceutical industry have reached an agreement on the schedule for the new user fees that we discussed below in the item on 12/2/06. Congress must approve the five-year deal before it can take effect, so there probably will be some major changes before it is enacted. The FDA will start to hold public hearings on the new fee schedule next month.

Under the plan, pharmaceutical companies would pay the FDA a one-time fee on top of charges for each television ad submitted for review totaling $6.25 million in fiscal year 2008. The deal accompanies proposed legislation to renew other industry funding for FDA drug reviews through 2012. It includes about $392.8 million in fees for fiscal year 2008, but the charges for the following years were not immediately clear.

About $29.3 million of those fees would target the agency's drug safety system. The 2008 fees include an additional $4 million for technology that would eventually allow drug manufacturers to submit products electronically.

This is the process that has been in place since 1992, and there are many that question the wisdom of the FDA being funded in part by the industry that it oversees. The ad fees would allow for 27 additional staff reviewers who would evaluate the ads within 45 days

There are many who question the wisdom in the fact that the financing of the FDA comes from the industry that they regulate. 

(3/30/07)- The FDA has announced a set of proposed new rules aimed at limiting the potential for conflict of interest among panel members sitting on the advisory panels for the agency. The proposed new rules will not become final until the end of a 60-day comment period.

Under the new draft rules, panelists would not be allowed to vote if they hold $50,000 or more in financial interest in a company who is appearing before their panel. This applies to both drug companies and medical equipment companies. In connection with the medical equipment companies, the proposed $50,000 limitation would apply if the panel were evaluating a competitor's product.

Under present rules, panelists are screened before each meeting under two sets of federal regulations that are designed to limit conflicts of interest.

(3/10/07)- Based on a recently released report from the Breckenridge Institute, a research and consulting firm in Breckenridge, Colo., the FDA's software system for keeping track of the safety of drugs is in a mess. The system, which is supposed to detect the side effects of medicines after they go on the market, has been delayed in implementation by at least 4 years.

The situation is "frustrating and undermining-the post-marketing drug safety work" of its staff. The FDA's drug-tracking system is called the Adverse Event Reporting System (AERS).

The report went on to state that the current system is overwhelmed by the growing volume of adverse-event reports, which currently exceeds 400,000 a year. The agency has been seeking to upgrade its system since 2003 with AERS II, but has thoroughly failed at the task. The report estimated that the agency has wasted about $25 million so far, and that it would not have an effective new system in place until the year 2009 at best.

The report went on to blame a "lack of effective leadership and management" by the agency's Office of Information Technology, which the report stated mishandled the initiative through bureaucratic infighting, flawed planning and duplicative work performed by outside contractors.

(3/03/07)- The FDA announced that it would hold an advisory committee meeting on April 12 to consider Merck's request for approval to market Arcoxia, the latest in the company's line of pain killing drugs similar to Vioxx.

The former commissioner of the FDA was ordered to pay about $90,000 in fines for lying about stock he owned in companies regulated by the agency. Lester M. Crawford was also given three years supervised probation and ordered to perform 50 hours of community service.

Dr. Crawford pleaded guilty in federal court last October to having a conflict of interest and false reporting of information about stock that he and his wife owned.

(9/9/06)- The FDA and the pharmaceutical industry are presently negotiating the fees that the industry will pay to the agency as required under the Prescription Drug User Fee Act of 1992 (PDUFA). This strange practice of having an industry negotiate with the agency that oversees its operation, because the industry wanted to speed up the whole approval time for new drugs.

Pharmaceutical companies pay fees when they file drug applications. They also pay fees based on how many drug-manufacturing facilities they own, and the number of medicines they sell in this country.

In the first year of operating under the act in 1993 the industry paid $8.9 million in user-fees, which represented about 7% of the agency's drug-review budget for the year. The fee schedule has been renegotiated two previous times under the terms of the act, with fees increasing both times. The user fee of $232 million in fiscal 2004 represented about 53% of the total drug-review budget.

The agency is seeking about a $100 million increase in the user-fee for the budget that commences in October 2007.


By Allan Rubin
updated November 20, 2008

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