The US Food and Drug Administration continues the investigation and seizure of the drug class used by millions that began last summer, but there is still "more to find," says the agency's director. Starting in July, separate batches of blood pressure medications from various companies were pulled from the shelves of the pharmacies. The US Food and Drug Administration continues investigating and recalling the drug class used by millions of people who started last summer, but there is still "to be found," says the director of the agency.
Since July, a lot of blood has been removed from the pharmacy shelves, drugs have been withdrawn under pressure from various companies. They are known as angiotensin II receptor blockers or ARBs and contain either valsartan, losartan or irbesartan. The reason? These blood pressure medications contain impurities that pose a risk to cancer for consumers.
"The investigation is not over," said Dr. Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research this week. Working with regulators from around the world, she said she expects more contaminated drugs to be found.
When was the pollution started?
Woodcock said the problem had appeared sometime after 2010 when a Chinese manufacturer made changes
A spokeswoman for the agency later said that based on the information available in the current investigation, the FDA believes that the first possible the emergence of NDMA is in 2014.
But the FDA has not begun to recall. of drugs by July 13, one week after 22 other nations have already pulled the plug of specific manufacturers of valsartan pills to protect patients. Indeed, two months earlier, the European Union's regulatory authorities began a review after reports that valsartan-containing drugs imported from Zhejiang Huahai Pharmaceuticals were stained with impurities known as NDMA (N-nitrosodimethylamine). NDMA is a by-product of the production of certain pesticides, but can also be suddenly introduced by certain chemical reactions. Investigating different ARBs, the FDA found additional batches made by several manufacturers that were infected with NDMA and, in some cases, another nitrosamine known as NDEA (N-Nitrosodiethylamine).
Why are drugs polluted? 19659007] Demand for causes implies that these impurities are generated by specific chemical reactions in the manufacturing process of the active pharmaceutical ingredient, said Woodcock. The FDA believes that pollution may have led, in part, to the reuse of materials, such as solvents, during the process.
It is also possible that some of the source materials may have had some of that in it, added Woodcock. that "this is not something that would be easy to find" because low levels of impurities are measured in parts per million. When the issue was discovered, the FDA had to develop a test capable of identifying nitrosamine in the blood vessel expansion drugs.
There are FDA safeguards to prevent drug contamination, says Maisha Kelly Freeman, professor and director of Samford. University Center for Innovation in Healthcare and Research on Patient Outcomes. Manufacturers are forced, for example, to report on impurities and the agency checks the factories on a risk-based basis. However, there is a catch. "Obviously, if they do not look for it, they do not really know it is happening," Freeman said. And this happened in the case of tainted ARBs. "Before they found this particular compound, they did not even know that there could be a chemical reaction that could produce the compound," she said.
How Many People Use These Drugs?
Losartan is number 9 of the most common drug in the country based on data for 2016. Valsartan is No. 92 and irbesartan is No. 171. For one year 49 million patients were given losartan, 8 million valsartan and 3 million irbesartan, Freeman notes, noting that a total of 60 million American patients do not include hospitals. and VA systems, only patients who buy from pharmacies in the community. These are brick and mortar operations controlled by pharmacists and include chain stores, but not hospital or online pharmacies.
At first glance, the risk of developing cancer in these patients appears to be low. "If 8,000 patients take a contaminated product for four years, only one will develop cancer," Freeman explained. "This is the worst scenario if someone has taken the affected product every time it's filled."
"It is assumed that the impact is relatively small," Freeman said. Of course, if the patient is your favorite person and he or she has developed cancer, you may not think so, she said.
How does the police produce drugs globally?
Woodcock says the FDA is monitoring production processes around the world and noted that the agency found that some manufacturers were "crossing".
"We know well that not all are in the process of being developed," she said, adding that "most of the places the Agency has a number of actions, including warning letters and decrees of consent, to bring manufacturers in line.
Some manufacturers who do not check voluntarily take steps to improve their operations, while others require "official action", such as the FDA's refusal to grant new plant approvals "until it is fixed," said Woodcock. Some local factories are ordered to clear their actions under the supervision of a judge.
"For foreign sites, we can introduce import alerts and they can not import anything into the US," she said. "So we have pretty good hammers for foreign sites if they do something wrong."
Why Factories Not Verified?
In a study published in 2016, Freeman estimates FDA reminders for a period of 30 months December 31, 2014
"There are so many FDA reminders over the course of a year that it is difficult to characterize the causes why they happen, "she said. were analyzed by Freeman and her colleagues. A total of 348 manufacturers were associated with discontinued medicinal products; they found that the most common causes of seizure were contamination, improper labeling, adverse reaction, defective product and proper efficacy. there is a hard time for the FDA to visit every site at regular intervals to make sure it does not happen, "Freeman said.
How often does the FDA check the factories? 19659007] The FDA checks before the start of production, and then, after running in full swing, it checks the risk based on priorities, Woodcock said. How long was the factory checked is at risk and helping the FDA leadership.
Nathan Cortez, a professor and dean of research at the law faculty of SMU Dedman, wrote in an e-mail that "These supply chain issues come periodically to products imported from China – sometimes for medicinal products, sometimes for food products. "
Cortez said that with so many US imports coming from China," it's hard to tell whether periodic problems are inevitable or are the result of negligence. internal oversight there. Either way, the FDA carries out foreign inspections from time to time with the permission of the Chinese government. "
Woodcock said," We are not the only ones in this game. The European Union has inspectors, South Korea has inspectors, Japan has inspectors, Australia, and so on. So there are many people who come and watch these [facilities].
The Chinese government is co-operating and wants to work with the FDA, the agency said. The challenges of accessing a facility in China or elsewhere are usually caused by the particular company involved, but those who refuse an FDA inspection are subject to an import alert.
What some people do not understand is that if manufacturers fail to check or have a problem, it does not always mean "the product is bad," Woodcock says. "This means that they make practices that are not optimal to support the mass production of this product.
How does it affect patients and pharmacists?
"Most patients have to get in and take their medication" to many drugs that have not been affected, Freeman said. Other people get changed prescriptions.
From the point of view of a community pharmacy, this recall was difficult because many pharmacies did not keep the medication number after they were released, Freeman says: "This information is not tracked effectively. She hopes that in the next technologies such as bar codes will be introduced for several years to help identify the affected patients. Freeman belongs to several Facebook groups in which pharmacists complain that ARB's "many reminders" about the past The only pharmacist told Freeman that recall "was awkward." After contacting individuals and basically saying, "Your valsartan is good," that information was changed shortly after a new FDA withdrawal list expanded to include the patient's batch of product. Another pharmacist writes to Freeman: "Tell patients not to come here. We are trying to help.
Are there any additional disabilities? Cortez has not heard of any lawsuits related to the recall – though, of course, he may have, he said. But "production claims are relatively uncommon and difficult to prove," he said. And filing lawsuits against foreign producers may be difficult because it may be more difficult, though impossible, to enforce court decisions.
"The roots of this constantly growing series of reminders seem to be related to at least two foreign production facilities: Zhejiang Huahai Pharmaceutical in China and Hetero Labs in India," according to a letter. "The reports from these two factories show serious problems in both factories even before the carcinogens are found."
Woodcock said, "Once this investigation is stopped, it probably means creating more international standards so that this incident can not happen again."
"We have ideas on how things can be better, "said Woodcock, adding that the FDA has already approved changes in some manufacturing operations.
Pharmaceutical manufacturers would do better with" closed systems, much more automation , "computer control", which is not common in industry and more today, she said.More-advanced production will be "greener" and include fewer, though more skilled employees, including chemical engineers, Woodcock said, to be lower even with initial investment in new machines and such – "but we are in a transitional phase," she said.