Streamlining the Path to Drug Supply Resilience in the US

The good news: we're all pulling in the same direction. The question isn't whether we should strengthen drug supply resilience. It's how we do it in a way that works.

Since 2012, ISPE has actively championed a Drug Shortages Initiative, recognizing the critical importance of the contribution of the pharmaceutical industry in ensuring uninterrupted supply of medicines worldwide. After more than a decade leading this effort and engaging with our 25,000+ members worldwide, ISPE has concluded the path forward should be about working smarter, together. Leveraging what we already knows, focusing our energy on what truly matters, and giving manufacturers the flexibility to do what they do best: solve problems and supply medicines.

The Stakes are Shared

When discussing supply chain resilience for the US, it is important to recognize that it is a multifaceted challenge, shared across multiple stakeholders. Strengthening resilience will require holistic solutions that account for the full range of stakeholder perspectives and support positive outcomes across the system.

For patients, pharmacies and healthcare providers, shortages mean delayed treatments, substituted therapies, added complexity to patient care, potentially increased expense or worse, no options at all. Every improvement in supply resilience translates directly to better health outcomes.

For the US FDA, better supply resilience and actionable market-wide data means increased proactive shortage mitigation, fewer crisis-mode interventions, more predictable workloads, and the ability to focus resources on improving or expanding access to therapies for patients.

For industry, ISPE members are always engaged in risk management, cost optimization and supply resiliency through technical, operational, quality, and regulatory initiatives because sustainable business conditions are essential. What could elevate industry performance further is accountability for resiliency through a risk-based regulatory framework that gives:

• Clear expectations
• Recognition for strong performance
• Flexibility to deliver and innovate

Fundamentally, our interests align. From this vantage, ISPE has reflected extensively and recommends a system that rewards resilient manufacturers, streamlines data collection, and focuses oversight on vulnerabilities to ensure patients have uninterrupted supply of critical medicines. Here's what that could look like:

US FDA Already Has Actionable Data — Let’s Explore Using It

US FDA possesses an enormous amount of information about manufacturers and quality maturity performance signals are embedded in existing data. As a result, the US could data mine institutional knowledge, with digital technology modernization or AI, to assess supply resilience, rather than create new, parallel approaches. What US FDA can already see:

• Shortage history: Which companies have had products in shortage for extended periods, e.g., greater than four months? This is the most direct, outcome-based measure available to reflect a manufacturer’s supply resiliency.
• Manufacturing sites, locations and inspection outcomes: Facility compliance records help paint a clear picture of operational maturity. Companies with consistent, strong inspection histories demonstrate they can sustain successful pharmaceutical quality systems necessary for continuous supply.
• Engagement posture and data quality: How do companies engage with US FDA during inspection interactions or the application review process? Are submissions high-quality? Are responses to queries timely and thorough? Positive outcomes in these areas signal organizational capability, regulatory sophistication and cultural excellence.
• Recall patterns: Analysis of frequency, severity, root causes and general recall data could reveal the health of a company's quality systems in ways that inspections alone cannot.

ISPE suggests exploration and investment in interpreting existing US FDA data to create a tiered recognition system with a well-defined, significant, risk-based regulatory incentive. For example, could companies demonstrating sustained high-performance across the areas listed above earn significantly reduced filing and inspection requirements for a defined period (e.g., Changes Being Effected (CBEs) on file and fewer, quicker Prior Approval Supplements, minimal inspections)? In this potential framework, high-performance would need to be maintained and qualification for the program refreshed periodically. However, for as long as a company holds that high-performance position, they'd benefit from streamlined interactions with the agency, translating to competitive advantage.

This type of disciplined, risk-based regulatory framework is how ISPE envisions creating a race to the top. Everyone has a clear, achievable target. Strong performers get breathing room to focus on continual improvement, ensuring patient supply and expanding access. Resources, both US FDA's and industry's, get directed toward companies and products that genuinely need attention.

A Streamlined Approach to Visibility

There is general agreement that US government offices continue to face limited visibility into market wide supply chain vulnerabilities and that a market-wide lens is an important complement to individual manufacturer supply resiliency performance results. While several calls to action have emerged, one proposal ISPE would like to spotlight has been the recommendation to assist insight to market-wide vulnerabilities by adding manufacturing site information to product labels. This approach would generate duplicate regulatory activity because manufacturing site information for every product registered with the US FDA is currently filed and maintained in the marketing authorization records. ISPE also views public disclosure of manufacturing sites as potentially generating significant harm more so than contributing to helpful transparency. Unintended consequences of increased publicly available siting information could include any, and any combination, of the following: patient confusion or loss of trust, impacts on supply chain security, proprietary data infringements, or significantly increased potential for mislabeling and related supply disruptions when products have multiple sources for finished drugs, drug substances and/or active pharmaceutical ingredients.

As we noted in the ISPE Drug Shortages Prevention Model released in 2023, drug shortages are rarely the result of a single issue. Their causes are multifaceted and interwoven, spanning the entire pharmaceutical supply chain and frequently connected to economics. Against this backdrop, we find that quality risk management and supply resiliency are much like the fit of a T-shirt. One size does not fit all, nor does one size fit an individual over their lifetime. Accordingly, ensuring reliability of supply for patients requires a blend of strategies that must adapt over time. Excessive rigidity in requirements or expectations could result in industry completing actions out of regulatory obligation rather than taking the best steps toward balanced risk management that ensures product availability.

Therefore, ISPE believes patients would benefit best by defining what needs to be achieved and give manufacturers the flexibility to design and evolve the how. Ideal risk management requirements provide sufficient flexibility to accommodate lifecycle evolution, market dynamics, and sustainability, to achieve both business and environmental target conditions.

An alternate, streamlined path that could avoid these concerns may be:

First, define a clear critical and essential medicines list. Ambiguity is the anti-hero to prioritization. When manufacturers don't know which products warrant enhanced attention or too many products are tagged as critical or essential, resources are spread too thin and optimal market-wide resiliency can be inconsistent. A transparent, regularly maintained short list allows everyone to prioritize appropriately.

Second, establish one coordination office for the US market. Decentralized oversight can create gaps, duplicative requests, or conflicting guidance. A single point of contact improves communication, maximizes synergy, and creates clear accountability to drive progress for US patients.

Third, as described above, create a race to the top by investing in analysis of existing US FDA institutional knowledge that reflects the quality maturity and outcomes individual manufacturers need to cultivate for long term supply resiliency. Leveraging this knowledge could be transformational in generating a streamlined, contemporary risk-based regulatory strategy that provides substantial resource relief to both US FDA and high-performers in industry.

Fourth, for market-level visibility, cease redundant data collection and modernize. For example, manufacturing sites on labels discussed above should not be started and the FDA CARES Act manufacturing volumes requirements and current annual report supply chain data collection should be retired. These types of requirements create administrative burden, generate overlapping data and we believe may also impact US FDA resources, without delivering proportionately actionable insight.

Rather than layering on new reporting requirements to generate transparency into market-level vulnerabilities, let’s look to transformational digital and AI opportunities for meaningful improvement and modernize instead. Consider modifying the existing SPL and Drug Listing process or evolve transparency by collecting supply chain data through digital PQ CMC initiatives. This type of design should ensure IDMP-compatible output to align with international standards and could include targeted metrics that meaningfully reflect reliability and resiliency, like OTIF delivery performance. Crucially, this data should be visible only to government, protecting competitive sensitivity while giving regulators the visibility they need. Start with critical medicines and expand methodically, where needed, as systems mature.

Modernizing would consolidate rather than multiply work and is similar to how the European Medicines Agency (EMA) is evolving existing data and digital tool infrastructure where possible, rather than creating parallel systems. It also respects the reality that our members work in a complex, often global environment that mandates digital interoperability and fiscal prudence.

Looking Forward: Sweeping Simplification and Focused Requirements for the Win

Behind the scenes, a lot of careful, sometimes heroic, work prevents many more shortages from ever happening. ISPE members live this reality every day. Holding perspectives as industry professionals, caregivers, and sometimes as patients too, we are vested in success from every angle.

We work in a complex environment with real economic headwinds: operating costs, supply chain footprint changes, gaps in pharmaceutical talent, and civic obligations to sustainability. Financial stakeholders may be hesitant to allocate resources toward resilience goals due to immediate business pressures and the need to maintain competitive pricing. Folding these considerations into policy development will bolster our long-term success.

To better position US drug supply resilience in the face of these challenges and more, ISPE recommends:

• Target regulation on the critical medicines that matter most.
• Centralize US drug supply strategy under one accountable government office.
• Explore assessing supply reliability and resilience by leveraging existing US FDA data.
• Reward strong performers through contemporary risk-based regulation—creating a race to the top that optimizes industry and US FDA resources.
• Modernize and protect data collection to enable reliable, market-wide supply vulnerability visibility.

ISPE and its members are always ready to partner on this journey. ISPE routinely hosts platforms to support the convening of regulators, industry and other stakeholders to advance breakthrough ideas. ISPE invites all interested parties to participate again this year, to further this cause of increased supply resiliency for the US and global markets. ISPE has been at this for over a decade, and the goal has always been the same: reliable medicines for patients who need them. Let's find the path forward, together. 

Learn more about the ISPE's Drug Shortages Initiative and the 2023 Drug Shortages Prevention Model.

Acknowledgements

ISPE Drug Shortages Initiative team