Penicillin G Sodium

"We're about to open up our manufacturing plant this week, where we will be releasing sterile injectables for generics that are in short supply. We're going to start shipping sterile injectables and pediatric cancer drugs in about two months," Mark Cuban said. Mark Cuban Cost Plus Drug Company will begin manufacturing its own generic medications this week, starting with sterile injectables, founder and CEO Alex Oshmyansky, M.D., Ph.D., said Monday during a White House roundtable on lowering healthcare costs. The company, which launched just two years ago, will first manufacture commercial batches of epinephrine and norepinephrine for patients in the intensive care unit, Oshmyansky said. "And we, shortly after that, will be making pediatric chemotherapy, limited only by our capacity to make these products," he said. Cost Plus Drugs built a 22,000-square-foot, $11 million fill-and-finish facility in Dallas. The manufacturing facility will help address drug shortages, Oshmyanksy said. "Cost Plus Drugs is proudly bringing pharmaceutical manufacturing back to the U.S. with advanced robotic and AI computer vision technology that allows us to pivot from making one drug type to another very rapidly, in principle within four hours, that way whatever product is in shortage we can start making that product," he said. Oshmyansky, a practicing radiologist, noted that the current pharmaceutical supply chain for generic drugs is an "extremely brittle supply chain." "Only a few companies make a given drug, and they are prone to either being shut down by the FDA for unsafe practices or having their manufacturing lines physically break. The drive to lower costs also pushes drug manufacturing to China," he said. According to Oshmyansky, currently, a single vial of Penicillin G benzathine costs $600. "Penicillin-based antibiotics are required to be made in dedicated plants by the FDA, which makes it more difficult to set up alternative manufacturing in times of shortage. We at Cost Plus are aiming to work with the FDA to import Penicillin G benzathine at a price of about $3 a vial," he said.   "Bypassing [pharmacy benefit managers (PBMS)] and source programs allows us to directly sell our products in times of need without being blocked by middlemen. We are pledging to be transparent in our pricing, publishing our true manufacturing cost of operating and adding a flat markup. That way we are profitable and sustainable but never extortionate," he said, adding, "No parent should be told the chemotherapy their child needs is not available. Nobody should not get the lifesaving ICU medications they need or have to postpone their surgery because the common cheap medications are just not available in united in the United States in the year 2024. These shortages are driven by the PBMs and the wholesalers and our dysfunctional model of drug distribution." Both Oshmyansky and Cuban, who initially joined the company as an investor, attended the White House roundtable on Monday. The billionaire entrepreneur and "Shark Tank" star told CNBC reporter Morgan Brennan during an interview Monday that the company's biggest challenge was keeping up with volume. "We have got millions of scrips that we have delivered, probably a couple million patients now. I mean, our numbers, we're setting records almost every single week," he said. Cost Plus Drugs currently offers about 2,500 generic medications, he noted. "The goal is to get every single drug we're legally allowed to sell. We have probably 10 different brand manufacturers that we're working with, but it's hard to add the brands because those big three PBMs are telling the brands, don't work with CostPlusDrugs.com. So that's our biggest challenge." Cost Plus Drug Company works directly with drug manufacturers to bypass middlemen and lower prices. For consumers, the price of each drug includes a 15% markup as a profit margin, a $3 pharmacy handling fee and a $5 shipping fee. Cost Plus also transparently displays what it pays for its medicines. "We're about to open up our manufacturing plant this week, where we will be releasing sterile injectables for generics that are in short supply. We're going to start shipping sterile injectables and pediatric cancer drugs in about two months," he said. Standing up the production line was a hefty investment, Cuban noted, but has been part of Cost Plus Drugs' vision to address drug shortages. "We don't have unlimited capacity, so once we can get this up and running, then we will look at ways that we can expand it. If we do this right, over the next five years, there will no longer be any more shortages in sterile injectables," he said. When asked about Cost Plus Drugs' financial operations, Cuban said the company is "not making money yet." "But that's OK. We're changing an industry, we're saving patients. I can give you example after example. A drug like Imatinib, where you might have to walk into a CVS and they will charge you $2,000 or $2,500, and, depending on the strength, you can get for $21 from Cost Plus Drugs. A drug like Droxidopa, same type of story, $10,000 for three months down to $30 a month from CostPlusDrugs.com. So I may not be making money yet. I will be. This will be self-sustaining, but the impact we're having is just incredible," Cuban said. Cuban had harsh words for the three dominant PBMs, pointing the finger at their business practices and lack of transparency for driving up drug prices. "The dominant three PBMs put stock price over health," he told the White House roundtable panel. The three biggest players in the PBM market are CVS Health's Caremark, Cigna's Evernoth/Express Scripts and UnitedHealth's OptumRx. "The craziest part is, and the message really that I wanted to get across, these big three pharmacy benefit managers, there's nothing unique about them. There is nothing that they do that so many of the independent and small transaction-based, rebate-free PBMs that couldn't do the same thing," he said during the CNBC interview. In just two years, Mark Cuban Cost Plus Drugs has become a major disruptor in generic drug pricing and has built up notable partnerships. The company now works with at least four PBMs, including Rightway, EmsanaRx, RxPreferred Benefits and PCA Rx. RELATED Fierce 50: Health Equity honorees It made waves when it inked a partnership with Coherus BioSciences to sell a biosimilar version of AbbVie’s blockbuster rheumatoid arthritis drug Humira. Cost Plus also is poised to shake up the drug benefits market. In August, Blue Shield of California, one of the state’s largest health insurers, announced it would drop CVS’ Caremark as its main PBM in favor of a new model for drug benefits. The insurer plans to partner with Cost Plus Drug Company along with Amazon Pharmacy, Abarca and Prime Therapeutics. It marked the second insurer to sign with Cost Plus, following Harrisburg, Pennsylvania-based Capital Blue last fall. Bayer also is working with the online pharmacy to provide access to Yaz birth control pills and Climara, a hormone patch for menopause. Cuban sold his majority stake in the Dallas Mavericks NBA team, and this is reportedly his last season on "Shark Tank." Asked during the CNBC interview what's next for him, Cuban replied, "Healthcare, healthcare, healthcare. It's the only company I've ever put my name on."

Pictured: Pill Collage/Taylor Tieden for BioSpace The FDA continues to face challenges in its oversight of drug manufacturing plants overseas due to disruptions related to the COVID-19 pandemic and staff vacancies, according to a report from the U.S. Government Accountability Office published Tuesday. “GAO has had long-standing concerns about FDA’s ability to oversee the increasingly global drug supply chain,” read the report summary, which acknowledged that the FDA is working to address the issues. It’s not the first time the GAO has raised the issue. The concern reiterated in this week’s report comes as the healthcare industry is still grappling with significant drug shortages, many of which were triggered or exacerbated by issues with international manufacturing facilities. The situation is also still on the minds of those in Congress as the House Ways and Means Committee held a hearing on Tuesday examining drug shortages in the U.S. Chairman Rep. Jason Smith (R-MO) said that active drug shortages are at the “highest levels” since 2014 and that over half of the drugs that are in shortage have been limited in their availability for at least two years. Michael Ganio, senior director of pharmacy practice and quality at the American Society of Health-System Pharmacists (ASHP), told BioSpace that the organization is currently tracking over 300 drug shortages—close to a 10-year high. While new manufacturers are coming online and President Biden has made clear his intentions to fortify the supply chains through government action, experts agree that shortages may persist for some time. “The generics market is in crisis, and it would not be surprising to see more shortages due to product discontinuations caused by bankruptcies, plant closures and individual company decisions that they can no longer afford to supply a drug,” Vimala Raghavendran, the vice president of Informatics Product Development at US Pharmacopeia (USP), told BioSpace. What Drugs Are in Shortage Now? According to the FDA’s drug shortages database, medicines that are in shortage as of press time include antibiotics such as amoxicillin and penicillin G, chemotherapy drugs cisplatin and carboplatin, albuterol, blood pressure and heart medication quinapril and the weight loss and diabetes medication semaglutide. “Everybody talks about cisplatin and carboplatin because that’s what affected so many of the adult patients with cancer, but we talked about methotrexate and decarbazine and . . . on and on,” Yoram Unguru, an associate professor at the Johns Hopkins University School of Medicine and a pediatric hematologist and oncologist, told BioSpace. An ASHP report detailed more than 300 active shortages at the end of 2023, the highest number in nearly a decade. According to an ASHP survey, 99% of pharmacists, pharmacy technicians and others in the industry had experienced drug shortages, with 32% stating the shortages were “crucially impactful.” A significant catalyst to these shortages is manufacturing issues. The FDA must oversee more than 4,800 manufacturing facilities that provide drugs for the U.S. market, according to the GAO report, and as of October 2022, 58% of these were overseas. But in March 2020, the agency postponed most inspections as COVID-19 began to circulate the globe. When the FDA did resume international inspections, it recorded some concerning observations. For example, an Indian plant belonging to Intas Pharmaceuticals, a maker of a wide array of generic drugs, had several quality issues at one of its sites, including disposal of acetic acid into a trash bin containing current good manufacturing practice (CGMP) records and the destruction of balance printouts and titration curves. These inspections led to a halt of U.S. imports of drugs produced there, including cisplatin. Compounding the situation was Lupin Pharmaceuticals, another generics manufacturer based in India, which had to issue a recall of the birth control drug Tydemy. Meanwhile, Akorn Pharmaceuticals, a U.S.-based generics manufacturer, filed for Chapter 7 bankruptcy in February 2023, closing all of its manufacturing facilities in the U.S. and Switzerland and halting the production of all medicines. The situation has prompted action at the federal level. In November 2023, President Joe Biden announced 30 actions to strengthen supply chains, and both chambers of Congress have held several hearings to determine the root causes and find solutions to the shortage issue. There is also some proposed legislation being considered, including a bill that would require drug manufacturers to notify the FDA if there is increased demand for a certain drug and another that would allow the Secretary of the Department of Health and Human Services to establish and maintain a list of essential medicines and maintain a database of supply chain vulnerabilities. Regulators have also been trying to improve the situation by allowing the importation of certain drugs. At the beginning of 2024, for example, the FDA gave its okay to the Florida Agency for Health Care’s drug importation program to bring in prescription drugs from Canada, although this decision has faced some resistance from industry groups. What to Expect This Year Erin Fox, a professor at Utah University’s School of Medicine who testified in front of Congress last year on drug shortage solutions, told BioSpace that one of the reasons these shortages are still pervasive is that health systems are often trying to get their hands on more product than they need to prepare for the possibility of a future shortage, meaning wholesalers don’t know how much product a health system really needs. Lacking an accurate baseline idea of how much drug to make can lead to more confusion and exacerbate the situation. Fox said that she is a bit cynical about the situation, noting that some of the issues around drug shortages are “systemic.” But she added that she does see some hope in newer companies looking to enter the market and start manufacturing products that Akorn used to make, for example. As for any government action, Fox said she does not expect Congress will make any decisions on the situation this year but is encouraged that legislation is being proposed. ASHP’s Ganio noted that the FDA would continue to work on importing medicines that are in shortage but for now said he sees the future as “more of the same,” with pharmacies and hospitals continuing as they have been for the last 20 years in evaluating inventory and ordering what they can. The GAO report noted that staff vacancies for FDA investigators who can do foreign inspections has been another challenge. These include staff at the agency’s foreign offices in India and China. The report did note that the FDA has made progress in putting strategies in place to alleviate the situation, but the GAO is recommending that the agency start to form “tailored strategies” to make sure it has the foreign workforce necessary to run efficiently. Unguru agreed that shortages are here to stay and said medical centers that have not already established a drug shortage committee would be “well advised” to do so. Raghavendran, too, was skeptical of quick improvement, noting that change will be slow without coordinated actions from regulators, the industry and policymakers. “To adequately solve drug shortages, we also need to look more broadly at the resiliency of the medicine supply chain to understand vulnerabilities and risks better," she said. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.