New York, the state with the highest number of infected and dying people in the country, has experienced peaks in demand for fentanyl and other necessary sedatives for patients with respiratory failure who are placed on respirators for up to ‘at two weeks. The Food and Drug Administration placed another sedative called midazolam on an official list of drug shortages last month.
“Everyone has discussed the requirements for more vents, but no one is discussing the needs of patients when they are on vents, sedatives, anesthetics and paralytics,” said Onisis Stefas, vice president and head of pharmacy at Northwell Health. , a system of 23 hospitals in New York, which has experienced the highest peaks of coronavirus patients in the United States.
Other drug shortages have emerged as unintended consequences of the coronavirus. When doctors avoided nebulizers for respiratory patients in the hopes of preventing the coronavirus from spreading in their facilities, they inadvertently created shortages of daily inhalers for albuterol asthma in hospitals and retail pharmacies.
Shortages highlight US heavy reliance on bulk pharmaceutical ingredients and finished drugs made in China, India and Europe, medical experts say, but also FDA’s limited ability to monitor global supply chains, creating vulnerabilities for the health system in times of crisis.
If supply conditions worsen, particularly in areas like New York with rapid surges in patients, a lack of sedatives and paralyzers necessary to safely intubate patients with severe respiratory failure turn out to be just as critical as a lack of fans, experts said.
“The pharmacy supply chain is really not designed for that,” said Stefas. “They manufacture their product and launch it on the basis of historical data. This makes situations like this, unexpected, very difficult to handle. “
Hospitals need large 50 ml vials of fentanyl to treat humanely ventilated patients, but providers quickly ran out and only had 2 ml vials in warehouses – which did not provide enough medicine to be effectively administered to patients, said Stefas. Northwell has worked with the FDA and the Drug Enforcement Administration to obtain manufacturers’ approval to fill more than 50 ml vials, he said.
The DEA announced Tuesday that it is significantly increasing production quotas for a handful of key sedative drugs used for ventilated patients, including fentanyl and midazolam. Fentanyl was widely abused during the opioid addiction epidemic in the United States, and the DEA last September proposed reducing drug quotas. The agency made it clear that the increase is temporary during the Covid-19 crisis.
“After the withdrawal from the health emergency, the DEA will reassess the request and adjust [quota] as needed, “said the agency.
GlaxoSmithKline, the maker of Ventolin inhalers, said it has increased production to 24 hours, seven days a week in factories in France and North Carolina. He said he chartered jet planes to deliver emergency supplies from its French facilities instead of using shipping containers.
“GSK is experiencing unprecedented demand for Ventolin inhalers in the United States,” said company spokesperson Evan Berland. “We are doing everything we can to provide as much Ventolin to people as possible.”
Pharmacies also request emergency authorization from states to allow pharmacists to exchange therapies equivalent to albuterol inhalers without having to call a doctor for another prescription.
“The doctor doesn’t want to be disturbed when he tries to save a 19-year-old patient,” said Kathleen Jaeger, senior vice president of pharmaceutical care and patient advocacy at the National Association of Chain Drug Stores.
Last month, an explosion in chloroquine and hydroxychloroquine purchases by hospitals, doctors and consumers responded to President Trump’s admonitions that decades-old antimalarials can treat covid-19, a House claim White that has not been proven in rigorous clinical trials. Drug shopping and hoarding almost wiped out US supplies in a matter of weeks.
Drug manufacturers and the FDA do not publicly disclose the sources of raw ingredients and packaged drugs sold in the United States, and critics say the FDA does not have the authority to know where the drugs come from. Last month, Congress gave the FDA new powers to further investigate where drugs and ingredients are made, but the authority doesn’t take effect until September. The agency said it is working with drug manufacturers to respond to shortages caused by the pandemic.
“This communication and the full cooperation of companies providing specific and necessary information is imperative so that we can have a clear understanding of the supply landscape and work to take proactive measures to alleviate shortages,” the agency said in a statement on Thursday. “This is an evolving and dynamic situation and the FDA is actively engaged.”
Generic drugs account for about 90% of all prescriptions filled in the United States. According to industry estimates, about 87% of the factories manufacturing raw pharmaceutical ingredients used in generics are located abroad, including 48% in India and China. China has closed its drug manufacturing facilities during its coronavirus lockout, but some of these facilities are expected to return online in the coming weeks and months.
The shortages show how a lack of basic information is hindering US planning and preparedness for various disasters, said Stephen Schondelmeyer, professor of pharmaceutical economics at the College of Pharmacy at the University of Minnesota.
“What we are experiencing right now is one of the worst scenarios of what could happen,” he said. “We need to be concerned about the security and resilience of our drug supply in terms of market concentration, foreign dependence and lack of transparency about where these drugs come from.”
A New Zealand government website Schondelmeyer and other Minnesota researchers have used provides insight into the origins of the global supply. New Zealand is the only country in the world to have such a public resource, he said.
Although comparisons with the United States are inaccurate, New Zealand data shows that some of the crucial shortage pharmaceuticals in the United States are manufactured in India, Italy and other countries that have been hard-hit affected by the coronavirus and block their populations or block pharmaceutical exports. The University of Minnesota’s supply chain analysis project has identified 156 drugs that may be missing in 90 days, although the list is still preliminary and has not been released.
Schondelmeyer has blamed drug manufacturers for a lack of transparency on impending shortages.
“They say our medicines and supplies are safe and that we have no problems,” he said, “and that suddenly we have shortages in the system. “
Asked to respond, the Association for Accessible Medicines, which represents generic drug manufacturers, said it supports new FDA rules that will give the agency greater ability to monitor foreign and domestic supplies. These figures do not take into account the volumes of ingredients from these factories.
Coronavirus shortages have been caused by the sudden surge in demand for drugs, followed by a delay of just a few days for the industry to fill the gaps, said Erik Komendant, vice president of federal affairs ‘Association for Accessible Medicines.
“Our goal is to continue working with the agency to make sure they have the information they need and that we have the right kind of structures in place to ensure that the global nature of the supply chain can continue.” to meet the needs of patients, “he said. Komendant added that he expects the Trump administration and Congress to consider ways to bring more drug manufacturing to the United States as part of the next federal economic stimulus cycle.
“One potential element is what incentives are in place, what can we do as a country, to attract more investment, more manufacturing, here with us,” said Komendant. “If there is increased demand to respond to a number of crises, we need to make sure that manufacturing in the United States is part of the solution. “
The White House cites shortages as it pushes to increase drug manufacturing in the United States. White House trade advisor Peter Navarro, defender of protectionist trade policies, said in an interview that one option would be to make rules forcing federal agencies and Medicare and Medicaid to “buy American” for essential drugs, from antibiotics to anesthesia. The government could also offer tax incentives and government loans.
Before the coronavirus struck, members of Congress were already concerned about chronic shortages of drugs such as antibiotics, seeing a potential safety threat in the FDA’s limited supply chain information.
Senator Susan Collins (R-Maine) was one of the lawmakers last year who proposed requiring drug manufacturers to disclose to the FDA each year their drugs are made, including their raw materials, called “ingredients” active pharmaceuticals ”.
A weaker version of Collins’ proposal was included in the $ 2 trillion stimulus package adopted by Congress last month. It requires manufacturers to disclose sources of raw materials in the event of a shortage and to maintain emergency plans available for government inspection.
Premier Inc., a large group buying organization for hospitals, urges the FDA to quickly use its new powers to investigate and anticipate drug shortages, said the company’s chief advocacy director, Soumi Saha.
She cited two examples of FDA blind spots. Hurricane Maria paralyzed manufacturing in Puerto Rico in 2017, creating a severe shortage of saline in the United States. The FDA was taken aback that a high level of manufacturing concentration had left the country vulnerable to the disruption of basic medical supplies, Saha said. In July 2018, small amounts of carcinogens were discovered in common generic drugs for high blood pressure made in China and India, resulting in widespread recalls. The contaminants appeared in tablets distributed by several manufacturers until November 2019.
“It took months for the FDA to identify which other final dose products used the same API,” said Saha.
India, which exported nearly $ 6 billion in pharmaceuticals to the United States in the year ending March 2019, has become a crucial bottleneck for the supply of the antimalarial drug hydroxychloroquine that Trump is stimulating to treat coronavirus. Serious shortages have prevented some patients who depend on drugs for approved uses, such as lupus and rheumatoid arthritis, from obtaining their routine supplies.
Faced with a sharp increase in its own cases of coronavirus, India has wavered between the urge to store medicines at home and the need to meet its obligations abroad. In recent weeks, it has restricted the export of a dozen drugs, including paracetamol, several antibiotics and an antiviral medication. It banned the export of hydroxychloroquine “without exception.”
Trump spoke to Indian Prime Minister Narendra Modi on the phone on April 5 and told reporters that he urged Modi to authorize shipments of hydroxychloroquine to the United States. ” Yes [Modi] doesn’t allow him to go out, that would be nice, but of course there can be retaliation “, Trump said, a statement widely regarded in India as a threat.
New Delhi then reversed course, saying it would allow exports of hydroxychloroquine to countries “particularly affected by the pandemic” as well as to neighboring countries. It also removed restrictions on the dozen previous drugs, with the exception of paracetamol. With hydroxychloroquine, the demand for the anti-fever drug will be “continuously monitored,” a spokesman for the Indian foreign ministry said on Tuesday.
Indian drug makers are also fighting to increase production of hydroxychloroquine for use in India and beyond. Zydus Cadila, a leading manufacturer of the drug, has increased production to 10 times its normal capacity and could increase it even more, said Mike Keenley, president of the company’s US subsidiary. Ipca laboratories – which until recently faced an FDA import ban on some of its facilities due to quality control violations – are also increasing production. IPca is a key source of hydroxychloroquine listed by several distributors on the New Zealand medication website. Ajit Kumar Jain, the company’s deputy managing director, did not respond to requests for comment.
The Indian pharmaceutical industry presents a major vulnerability: around 70% of the active ingredients needed to make its medicines are imported from China, said Ashok Kumar Madan, executive director of the Indian Drug Manufacturers ’Association. He said that Indian drug manufacturers had sufficient stocks to cope with the disruption in the supply of raw materials caused by China’s battle with the coronavirus earlier this year and that supplies are coming back to India by air and by sea.