According to an FDA warning letter, employees of Columbia University Medical Center’s Kreitchman PET Center repeatedly failed to check the purity of drugs they were injecting into patients before brain scans, and in some cases forged documents to hide the fact that testing showed the drugs to be problematic. The university has temporarily shut down the laboratory that was manufacturing the drugs, but maintain that no injuries have been associated with the substandard drug injections.

The drugs were solutions known as radio tracers injected to help gain good results from a type of brain scan called positron emission tomography (PET). The drugs were experimental and made at a laboratory at the center, but are regulated and must meet certain criteria for impurities and radiation levels. Drugs that fall outside of the acceptable parameters could adversely affect patient health and distort test results.

The brain scans are done as part of research on brain activity of people with mental disorders. The radio tracers are often produced in-house for PET laboratories because they degrade very quickly. The drugs are usually tested for quality before each use, however, the FDA says that the Kreitchman PET Center used poor testing equations and in at least one instance falsified records when a computer test found that there were problems. Columbia University officials say they are restructuring the laboratory as a result of the incidents.

The FDA first discovered problems at the brain imaging center in 2004, and then inspectors found problems again in December 2008. In the December 2008 warning letter, the agency says that the laboratory failed to investigate unacceptable quality control test results and did not reject a batch of PET radiopharmaceutical drugs that did not meet specifications. A January 2010 letter has not yet been posted on FDA’s website, but was first reported Friday by the New York Times.

Inspectors who returned this January found that little had changed, and cited the facility for a number of violations. There were at least 10 batches of drugs that had impurities surpassing the acceptable levels. At least four times, patients were injected with drugs that contained twice the amount of impurities that are deemed acceptable.

One former employee wrote in his 2009 resignation letter that there were “systematic forgeries condoned and approved by the lab director,” according to documents obtained by the New York Times.

Columbia University sent the FDA a letter on July 6 saying it was replacing some management and that the lab that manufactures the drugs would stay closed until it was fully restructured. The PET Center itself remains open.

The FDA issued a public health alert on May 29, warning healthcare professionals not to use certain intravenous bags of the drugs, which are sold under the Claris, Pfizer, Sagent Pharmaceuticals and West-Ward Pharmaceutical labels.

The intravenous drug recall was issued after white matter was found floating in a bag of metronidazole. An analysis of the particles led to the determination that it was Cladosporium, a form of mold. Similar white matter, still under analysis, was later found in a bag of ondansetron. The mold could cause infections in patients, particularly those with compromised immune systems.

All lots of intravenous bags of ciprofloxacin, metronidazole, and ondansetron made by Claris are affected by the recall. Ciprofloxacin and metronidazole are antibiotics. Ondansetron is an antiemetic for the treatment of nausea from surgery and chemotherapy.

All three drugs are sold by Claris, Pfizer and Sagent Pharmaceuticals. West-Ward Pharmaceuticals only sells metronidazole and ondansetron. Sagent also sells its own ciprofloxacin IV drug, which is not affected by the recall.

The FDA and Claris have advised health care professionals and facilities to examine their inventory immediately and quarantine drugs affected by the recall, stop using them, and return them to Claris. Anyone who has distributed the product to other customers are urged to identify the customers that bought it and alert them to the recall.

For more information regarding the recall, customers should visit the Claris Lifesciences website at http://www.clarislifesciences.com/Claris_USA/index.asp. Anyone who experiences an adverse event related to the recalled drugs should contact FDA’s Med Watch Adverse Event Reporting Program at http://www.fda.gov/Safety/MedWatch/default.htm.

The Hylenex recall was announced by Baxter on Monday after the glass-like particulate matter was discovered during stability testing. According to the Baxter press release, there have been no reported injuries or complaints associated with the Hylenex contamination.

Hylenex was approved by FDA in October for use as a means of rehydrating infants and children. Instead of the typical intravenous injection, the drug is delivered subcutaneously, under the skin. Baxter is partnered with Halozyme Therapeutics, which developed the drug delivery technology being used.

On Sunday, Halozyme sent a notice of breach to Baxter, claiming that Baxter’s “manufacturing failures” has led them to be concerned over the company’s capability to provide quality products. If Baxter’s manufacturing problems are not shown to be addressed in 120 days, Halozyme says it can terminate it’s partnership with Baxter.

Baxter has been plagued by a number of major recalls in recent months. Earlier this month, it recalled 200,000 Colleague infusion pumps after federal reviewers found a number of problems with them. In March, Baxter recalled several models of Baxter HomeChoice automated dialysis machines, which were found to overfill patients’ abdominal cavities with fluid. The defective medical devices are believed to have led to the death of at least one patient.

In addition to the recent recalls, Baxter faces a number of lawsuits over a heparin recall issued in January 2008, involving defective batches of the blood thinner that are believed to have killed 81 people and sickened hundreds more in late 2007 and early 2008.

The Baxter heparin recall was issued after a spike in adverse event reports surfaced involving reactions to heparin, an anticoagulant or blood thinner that is critical for a number of medical procedures and conditions. The lawsuits are currently consolidated for pretrial proceedings as part of an MDL, or multidistrict litigation, in the U.S. District Court for the Northern District of Ohio. All of the cases involve similar allegations that tainted lots of heparin distributed by Baxter Healthcare caused severe and potentially life-threatening allergic-type reactions.

At that time, Baxter manufactured about half of the injectable heparin sold in the United States and it was discovered that the blood thinner contained a fake ingredient received from a plant in China that was chemically similar to heparin, yet substantially cheaper.

Investigations by the FDA and a report published in the New England Journal of Medicine in December 2008 found that the heparin reactions were caused by the presence of oversulfated chondroitin sulfate. FDA investigators and researchers believe the fake ingredient was used for fraudulent purposes, to save money.

The GAO report found that the FDA has failed to implement changes to better monitor the side effects of drugs after they have been put on the market. While the agency has begun to take steps in the direction of restructuring to address some concerns, the agency has no timeframe for meeting objectives. The GAO report also suggests there may be too much influence being given to scientists who approve new drugs for the market.

According to the GAO, the FDA needs to develop a plan for transferring some regulatory authority from the Office of New Drugs (OND) to the Office of Surveillance and Epidemiology (OSE), which monitors drugs already on the market. The report indicates that even though the OSE’s role has increased since the GAO’s 2006 recommendations, the office still carries significantly less weight than OND in the FDA’s decision-making process.

Concerns over FDA’s postmarketing surveillance arose after a Vioxx recall was issued for the popular pain medication due to an increased risk of heart attacks and strokes. Following the recall, the GAO and the Institute of Medicine recommended that FDA split authority over determining drug safety equally between the OND and the OSE. The new GAO report says that this has not yet happened.

The FDA says that currently the OND has the more experienced staff, lending it to be the go-to office for drug safety decisions. The FDA has said that it intends to give more power to the OSE once its staff has equivalent experience as those in OND. However, the GAO report says there is no indication of when that would actually happen or how. Currently, the new drugs office has 900 employees, compared to only 200 allocated to OSE.

Senator Charles Grassley, R-Iowa, a frequent critic of the FDA, called for the GAO report. Grassley has said that the agency has had the time it needs and should immediately implement the GAO’s 2006 recommendations.

The report, which was released this week, looks at a group of 90 drugs approved since 1992 through FDA’s accelerated approval process. The GAO found that although pharmaceutical companies often fail to provide FDA-required post-marketing data which shows that the drugs are working, the FDA has never removed any of the drugs from the market.

The accelerated approval process allows critical drugs designed to treat life-threatening or serious illnesses to go through an expedited approval process without years of testing and studies required by normal drugs. To obtain approval, drug makers must show that the drug is likely to work through surrogate endpoints, such as showing that a cancer drug shrinks tumors or an AIDS drug lowers the viral count.

In return for FDA’s expedited approval, the drug makers must provide post-marketing data that demonstrates the drugs are working as predicted. However, the GAO report found that 36% of drugs approved by the FDA under the process do not have the post-marketing data as required. In some cases, the drugs have been available for over a decade and generated hundreds of millions of dollars in revenue for the drug makers without such follow-up studies being completed.

The GAO report recommends that FDA clarify under what conditions it would withdraw one of these drugs off the market, most of which are used to treat cancer or HIV/AIDS. However, the report states that the FDA disagreed with GAO, saying that it did not need to clearly indicate when it would enforce its own rules to remove potentially dangerous or ineffective drugs approved under the accelerated approval process.

FDA officials have said that in many cases, the drugs approved under this process are life-saving drugs for which there are no replacements, and if the drugs are taken off the market, the patients will have no alternatives. However, the GAO report indicates that in some cases the drugs could be harmful to patients, and without the required post-marketing data the FDA may never know.

The GAO noted that the drug makers are under no pressure by the federal drug regulatory agency to provide the data or prove their drugs benefits actually pan out, since the FDA has not acted against a single drug approved under the accelerated approval process since its inception. The GAO found that not only has the FDA never enforced its accelerated approval process rules, but it has no rules or established procedures on how to do so.

The GAO report noted that enforcement of accelerated approval post-marketing requirements does not appear to be a priority for the FDA. “Although FDA has authority to expedite the withdrawal of a drug from the market if a sponsor does not complete a required confirmatory study with due diligence, or if a study fails to confirm a drug’s clinical benefit, it has not specified the conditions that would prompt it to do so,” the report states. “It has never exercised its authority, even when such study requirements have gone unfulfilled for nearly 13 years.”