Two Major Issues of Pharmaceutical Safety and Supply Shortages Challenge Pharmaceutical Companies
Pharmacists and doctors hope that Congress will require manufacturers to pay attention to the signals issued by the FDA's "Sentinel Safety System." Early warnings can help address the serious situation of supply shortages.
Historically, the primary goal of US FDA policy has been to ensure the safety of the national pharmaceutical supply. Recently, a severe adverse event involving Roche/Genentech’s Avastin (bevacizumab) prompted the FDA to reassess the risks and benefits associated with this type of cancer drug, eventually recommending the removal of its indication for breast cancer treatment. This decision sparked strong protests from patients who believed the drug could save their lives.
For patients and doctors, situations like critical drug shortages due to manufacturing difficulties and supply chain regulation are increasingly common. Adverse event reports and databases can help patients avoid risky treatments. In the future, these data analyses will assist healthcare institutions in evaluating the quality of treatment and care, as well as supporting clinical trials for new drugs.
Early Warnings and Publicity Challenges
To obtain pharmaceutical safety information more quickly, the FDA established the "Sentinel Monitoring System" to detect adverse events. In July 2010, the FDA first mined over 25 million patients' drug usage information through this system.
Judith Rucks, Chief Scientific Officer of the FDA's Center for Drug Evaluation and Research (CDER) "Sentinel Program," explained that the program is proceeding according to plan to further test scientific methods for specific drug use. The FDA has also formed partnerships with other federal agencies for drug monitoring, querying these health databases regarding common safety concerns.
As the "Sentinel Program" progresses, pharmaceutical companies are researching how to release early drug safety signals without misleading the public or causing panic. Daniel Troy, General Legal Counsel of GlaxoSmithKline, raised some questions about pilot studies on Avandia and heart events, such as when and how the FDA will make investigation results public.
Rachel, Deputy Director of Medical Policy at CDER, acknowledged that pharmaceutical companies will face greater responsibilities, likely being criticized for not disclosing safety information in a timely manner. The FDA clearly stated to the public that "Sentinel Signals" are based on observed data, which often is insufficient to make correct decisions on medical safety issues.
Profit Margins Leading to Shortages
While early information on drug adverse events can curb unsafe prescriptions, warning signals can also help prevent severe shortages of essential medicines. However, in recent years, the situation of drug shortages in the U.S. has not improved. In 2010, Utah State University's Drug Information Service Center recorded 211 drug shortages, compared to 166 in 2009 and 70 in 2006. The most alarming shortages affect anesthetics and drugs used to treat cancer, pain, and severe infections.
The FDA points out that sterile injectable drugs accounted for nearly half of all drug shortages in 2009 because very few companies can produce these complex products. Any disruption on the production line can affect the production of multiple products, causing long delays.
This situation has led hospitals and doctors to complain that they have to use products never applied clinically before, sometimes resorting to inappropriate substitutes "that may cause dosing errors and jeopardize patient medication safety." The Institute for Safe Medication Practices (ISMP) reported an increase in drug incidents related to alternative drugs. For example, replacing opioid analgesics when various strengths of sedatives and patient monitoring protocols are required can lead to dosage confusion.
Shortages Stem from Multiple Factors
Many of these products are low-profit drugs, with profits insufficient to support product upgrades. FDA inspectors have repeatedly found violations in the production of generic drugs.
FDA Policies Encourage Production
In 2009, quality issues caused a severe shortage of propofol, an anesthetic produced by Hospira and Teva. After receiving multiple warning letters from the FDA, Teva closed its injectable manufacturing plant in Irvine, California, with no clear reopening date.
At a conference hosted by the American Society of Health-System Pharmacists last November, pharmacists and doctors discussed remedies for the shortage crisis. Group discussions acknowledged that manufacturers generally operate production lines at full capacity, making it difficult to respond quickly to increased market demand. Limited sources and storage of active pharmaceutical ingredients (APIs) make it challenging for manufacturers to deal with sudden shortages.
Some existing products may be abandoned if they are not profitable for the company, especially if facility inspections are required to continue production. Products that have been sold for decades without formal FDA approval but have become targets of enforcement actions in recent years are particularly affected. When the FDA began inspecting the manufacturing processes of injectable drugs, several companies faced challenges, as no one wants to sell contaminated products.
Although many of these situations are unavoidable, experts believe that earlier warnings from manufacturers regarding emerging shortages will help them handle severe supply shortages. Pharmacists and doctors hope that Congress will require companies to focus on the FDA's early signals, including the source of active ingredients for a single drug. This suggestion has been submitted to the Senate and may provide further solutions.
In addition to strict management, the US FDA encourages policies such as new applications and tax incentives for manufacturers to expand or upgrade facilities for needed products, addressing the production of short-term supply drugs. This may also help stabilize the process of expanding product supplies. Without some way to alleviate shortages, manufacturers seem to prioritize profit over patients, offering ineffective and even unsafe alternative therapies.
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