Federal law requires the FDA to maintain an up-to-date list of drugs experiencing a shortage in the United States. This list has significant implications for the activities of compounding pharmacies, especially those categorized as 503A and 503B facilities. However, reliance on this list creates several challenges that can negatively impact both patients and these facilities.
503A pharmacies are traditional compounding pharmacies that create customized medications for individual patients based on prescriptions from licensed healthcare providers. They are allowed to compound medications listed on the FDA drug shortage list but only when fulfilling a valid prescription for an individual.
503B, outsourcing facilities operate on a larger scale and are authorized to compound sterile drugs in bulk without needing individual patient prescriptions. They can also prepare "essentially copies" of commercially available drugs, but only if those drugs are on the FDA's drug shortage list when they are compounded, distributed, and dispensed. 503B facilities face stricter regulatory oversight from the FDA and adhere to manufacturing standards similar to those required of major drug manufacturers.
Problems With the Drug Shortage List
While the drug shortage list aims to help ensure patient access to essential medications, its dependence on self-reporting by pharmaceutical manufacturers creates several issues.
- Underreporting: Manufacturers may be hesitant to report shortages for fear of negative publicity or potential regulatory scrutiny. They might also see an advantage in not reporting shortages to prevent competitors, including compounding pharmacies, from filling the gap.Underreporting: Manufacturers may be hesitant to report shortages for fear of negative publicity or potential regulatory scrutiny. They might also see an advantage in not reporting shortages to prevent competitors, including compounding pharmacies, from filling the gap.
- Delays: Time lags between the onset of a shortage and its reporting by the manufacturer can lead to a delayed response from the FDA in recognizing and addressing the problem.
- Inaccurate Reflection of Demand: Manufacturer reporting may focus on production capacity without fully considering spikes in demand experienced by healthcare providers and patients. Additionally, the national-level reporting may not capture localized or regional shortages, which can significantly impact specific areas and hospitals.
These factors, collectively, create a system where the drug shortage list may not accurately or timely reflect the reality of shortages on the ground.
Impact of the Drug Shortage List on 503A and 503B Facilities
The limitations of the current drug shortage list system have significant consequences for 503A and 503B facilities, often creating obstacles to their ability to respond to shortages and serve patients effectively.
Delays and Inaccuracies Impact Responsiveness
The list's delayed and inaccurate nature directly hinders these facilities' capacity to respond to shortages effectively. 503B facilities face challenges due to the time required to begin producing a shortage drug. They must comply with the FDA's Current Good Manufacturing Practice (cGMP) regulations, which can result in a 3-to-9-month delay from the time a shortage is recognized to when they can start production. This timeline doesn't even factor in the lag between when hospitals identify a shortage and when manufacturers report it to the FDA, creating an even longer delay in response.
Financial Disincentives and Risk
503B facilities face significant financial disincentives and risk when investing in the production of a shortage drug. Once a drug is removed from the FDA shortage list, 503B facilities must stop distributing it within 60 days. This limited window creates a substantial risk for facilities that have invested heavily in production, as they may not have sufficient time to recoup their investment before being forced to halt distribution. This short timeframe also creates a risk of continued shortages even after a drug is officially removed from the list, as existing supplies may take longer than 60 days to reach hospitals and patients.
The Case of Tirzepatide
The case of Tirzepatide illustrates the challenges associated with drug shortages and the impact of the FDA's shortage list management on 503A and 503B facilities. Tirzepatide, the active ingredient in medications used to treat type 2 diabetes and obesity, experienced a shortage beginning in December 2022. Despite evidence of an ongoing shortage, the FDA abruptly removed Tirzepatide from the shortage list in October 2024. This decision, made without prior notice or public comment, was based solely on claims made by the drug's manufacturer that they could meet current and projected demand.
This situation led to legal action from the Outsourcing Facilities Association and FarmaKeio Custom Compounding against the FDA. The lawsuit alleges that the FDA's decision to delist Tirzepatide was arbitrary, capricious, and unlawful, highlighting the lack of reasoned decision-making and procedural irregularities in the FDA's actions. The plaintiffs argued that the FDA's statements acknowledged the continuation of supply chain disruptions that would likely continue to prevent patients from accessing the medication.
The U.S. Food and Drug Administration (FDA) has announced that the shortage of tirzepatide, the active ingredient in medications like MounjaroÒ and ZepboundÒ, has been resolved. As a result, compounding pharmacies must cease the compounding of tirzepatide within specified grace periods to ensure a smooth patient transition. For state-licensed pharmacies operating under Section 503A of the Federal Food, Drug, and Cosmetic Act, the FDA has provided a 60-day grace period from the date of the shortage resolution. For outsourcing facilities operating under Section 503B, a 90-day grace period has been granted.
Potential Solutions
The challenges posed by the drug shortage list system and its impact on compounding pharmacies highlight the need for reform. Several potential solutions have been proposed to improve the accuracy and effectiveness of the shortage list and to better support the vital role played by 503A and 503B facilities:
- Diversify Information Sources for Shortage Reporting: Instead of relying solely on manufacturers, the FDA could gather data from various stakeholders, including healthcare providers, hospitals, pharmacies, and patient advocacy groups. This would provide a more comprehensive and realistic view of drug availability and shortages.
- Incentivize Accurate and Timely Shortage Reporting: Implementing policies to encourage manufacturers to report potential and actual shortages promptly and accurately, such as financial incentives or stricter penalties for non-compliance, could improve the reliability of the shortage list.
- Increase Flexibility for 503B Facilities: Extending the 60-day cutoff for 503B facilities to stop distributing a delisted drug to 180 days would give these facilities greater financial security and incentive to invest in producing shortage drugs.
- Enhance Transparency and Communication: Establishing a centralized platform to share real-time information on shortages among stakeholders would improve communication and coordination within the healthcare system.
Addressing these issues is crucial to ensuring that patients have continued access to essential medications and to support the critical work of compounding pharmacies in mitigating the impact of drug shortages.
At MediZap, we're not just participants—we're pioneers. Proudly aligned with industry powerhouses like the PDA (Parenteral Drug Association) and OFA (Outsourcing Facility Association), we actively advocate for expanding FDA guidance and forward-thinking legislative policies. Our mission? To empower 503A and 503B compounders to elevate their role as indispensable players in the pharmaceutical industry.
By pushing for regulatory advancements, we ensure compounding remains a vital solution, bridging critical gaps in drug availability and delivering life-changing treatments to millions of Americans when they need it most. At MediZap, we're not just shaping the future of pharmacy—we're defining it.