Pharmaceutical Sovereignty: The Resilience We Cannot Outsource

By Ajaz S. Hussain, Ph.D., independent pharmaceutical regulatory science expert

Pharmaceutical sovereignty is no longer a theoretical concern but an urgent national imperative. As global supply chains become increasingly fragile and geopolitical tensions rise, the continuous availability of essential medicines can no longer be assumed. Sovereignty in this context does not imply isolation, but rather strategic resilience: building robust national and regional capabilities that ensure security while enabling global collaboration. This article urges policymakers, regulators, and industry leaders to act now by embracing innovation, reinforcing regulatory maturity, and advancing initiatives that restore the public’s trust in the pharmaceutical supply chain.

The Imperative Of Resilience

Resilience — the capacity to withstand disruption and recover with strength — cannot be outsourced. It must be cultivated through coherent policy, transformative innovation, and courageous leadership. It is not simply a function of supply logistics, but a reflection of our national priorities and professional integrity. Within local and global regulatory frameworks, resilience requires moving beyond superficial corrective and preventive actions to address root causes and institutional blind spots. We must convert good intentions into scalable, sustainable systems. ¹

EQUIP-A-Pharma: A Forward-Leaning Initiative

The EQUIP-A-Pharma initiative, led by the Defense Advanced Research Projects Agency (DARPA) in collaboration with the Administration for Strategic Preparedness and Response (ASPR), Division in Health and Human Services (HHS), offers a blueprint for the future. It seeks to establish a digitally integrated, reprogrammable platform capable of manufacturing multiple drug products from locally sourced precursors. Designed for agility and speed, the platform leverages smart manufacturing tools and adaptive control to meet fluctuating demand due to emergency needs or strategic supply disruptions. EQUIP-A-Pharma promises to advance a self-reliant pharmaceutical ecosystem built for the 21st century by embedding quality control into every production stage. ²

Closing The Blind Spots: Continued Assurance Of Therapeutic Equivalence

A persistent challenge in generic drug regulation is ensuring therapeutic equivalence over the product life cycle. As I discussed in a recent column for Pharmaceutical Online, blind spots — especially those tied to formulation differences and cherry-picked bioequivalence studies — continue to erode confidence. ³ True assurance must be integrated, by design, not retrospective. Adaptive digital manufacturing platforms offer the opportunity to embed quality assurance from the outset, delivering consistent quality, safety, and real-world evidence of continued therapeutic equivalency performance at speed and scale. However, such systems must be incentivized and validated with a modern, data-informed regulatory approach, and recognized.

From Subjective Assurance To Patient-Centric Reality

In an era of geopolitical volatility and fractured supply networks, subjective confidence (assurance) in pharmaceutical quality is necessary but insufficient. The shift from abstract regulatory compliance to patient-centered assurance must be deliberate and evidence-driven. This is the defining test of pharmaceutical sovereignty: whether we can turn diffuse legacy-based systems into cohesive structures that are resilient, responsive, and ready to adapt.

Rethinking The Regulatory Landscape: Resilient, Responsive, And Ready

Achieving pharmaceutical sovereignty is impossible without rethinking the regulatory infrastructure that underpins it. Despite the creation of the FDA’s Office of Pharmaceutical Quality (OPQ) and its guiding principle of One Quality Voice,⁴ there remains a need to address systemic inconsistencies and organizational silos further persist.⁵ We must address recurring errors, particularly those stemming from outdated “prior knowledge” and assumptions embedded in legacy approvals.⁶

To this end, the FDA should reinforce its internal quality management system; integrate insights across surveillance, inspection, review, and policy; and enable cross-functional teams to respond with agility and foresight. The agency should embody team science, pay attention to team building and training,⁷ and pursue regulatory system maturity necessary to facilitate transformative programs like EQUIP-A-Pharma.

Tariffs As Incentives For Reshoring Pharmaceutical Manufacturing?

Tariffs have emerged as a potential tool to motivate domestic production of pharmaceutical ingredients and products. Their impact, however, is expected to be mixed:

• For brand-name drugs, tariffs may provide enough economic pressure to encourage domestic investment and reduce foreign dependency.
• Tariffs alone are insufficient for generic drugs, which operate on thin margins and serve as the backbone of public health. ⁸ Without targeted support, these critical products will likely remain embedded in global supply chains, vulnerable to disruption.

Building Lessons Learned: Beyond Tariffs

A broader and more strategic approach is essential to change the trajectory of U.S. pharmaceutical manufacturing. In testimony before Congress, the FDA has consistently highlighted the transformative potential of advanced manufacturing — particularly continuous manufacturing (CM) — as a critical pathway to modernization.⁹ The approval of CM-based NDAs such as Orkambi and Prezista, along with internal assessments demonstrating faster market entry and improved quality outcomes, validate this direction. ¹⁰

Yet, despite this momentum, the adoption of CM remains limited in the generic drug sector. Regulatory uncertainty, insufficient economic incentives, and operational inertia continue to hamper progress, especially in areas like harmonizing the rigor and frequency of cGMP inspections. ¹¹ Without targeted policy, regulatory clarity, and alignment of incentives, generics risk falling further behind, perpetuating the vulnerabilities the modernization agenda seeks to eliminate. To overcome these barriers, the FDA should pursue a trio of targeted actions:

1. Close the “New Prior Knowledge” Gap for Legacy Products
   Beyond mandating effective corrective and preventive actions (CAPA), the FDA should require annual ANDA updates, via Annual Reports, that demonstrate process stability and capability using statistical process control (SPC) indices aligned with its 2011 process validation guidance.¹² These data would provide objective, real-time insights into process performance, forming a robust foundation for continuous improvement.

Public transparency regarding these improvements — or lack thereof — would incentivize manufacturers to prioritize quality, especially in the context of the reputational damage caused by FDA Warning Letters. Such a requirement would also strengthen the structural integrity and coherence of the FDA’s One Quality Voice vision.

Moreover, linking the frequency and intensity of cGMP inspections to measurable performance metrics — leveraging ASTM standards cited in FDA guidance, including E2709-10, E2281-03, E2474-06, and E2476-09 — would enable a more precise, risk-based oversight framework. This approach would enhance the efficient allocation of regulatory resources and reinforce the assurance of consistent, high-quality medicines that patients depend on and deserve.

2. Facilitate Targeted Pre-ANDA Meetings for Advanced Manufacturing based ANDAs
   Advanced manufacturing-based ANDAs deserve priority regulatory engagement to recognize innovation and tailor regulatory considerations, prioritized review, and a life cycle approach that integrates pre- and post-approval oversight. Furthermore, promoting transparency on continued process verification in the context of improved evidence of quality assurance and continued generation of evidence of therapeutic equivalence would reward and incentivize quality by design and continually high-performing facilities while allowing the FDA to focus scrutiny where it is most needed. Such efforts bring to life the promise of a One Quality Voice regulatory ecosystem.

3. Strengthening Policy Incentives Beyond the FDA’s Direct Purview
   The FDA should actively collaborate with other federal agencies to shape economic and other incentives supporting reshoring and modernization. These policies must be aligned with current (not legacy) scientific and regulatory insights to ensure that funds flow toward platforms and practices capable of sustaining high-quality output over time.

Conclusion

Pharmaceutical sovereignty is not a return to isolation but a renewal of responsibility. From API sourcing to process validation to commercial manufacturing, every link in the medicine chain must reflect a commitment to resilience and quality. Regulatory blind spots can no longer be tolerated. Institutional inertia must give way to adaptive learning, intelligent oversight, and transparent assurance systems.

The United States possesses the talent, technology, and scientific foundation to uphold the highest standards of pharmaceutical quality, safety, and real-world effectiveness — and must now reassert its leadership in pharmaceutical manufacturing. To sustain and advance this potential, agencies like the FDA must go beyond aspiration and fully operationalize their commitments, and chief among them is the vision of One Quality Voice. By aligning risk-based resource allocation and incentives with measurable outcomes, and embedding systems thinking into regulatory processes, we can safeguard public health, rebuild public trust, and create a genuinely resilient pharmaceutical ecosystem that is adaptive, reliable, and prepared for the challenges ahead.

References and Notes

1. Hussain, A. S. Intuitively Moving Institutions Towards Global Regulatory Resilience. Guest Lecture, King Saud University, Riyadh. December 2023. Link to slides.
2. DARPA, Biological Technologies Office: EQUIP-A-Pharma: Establishing Qualification Processes for Agile Pharmaceutical Manufacturing. Link to the Program.
3. Hussain, A.S. Addressing Blind Spots In Assuring Therapeutic Equivalence. Pharmaceutical Online, January 14, 2025. Link to the column.
4. FDA White-Paper--FDA-Pharmaceutical-Quality-Oversight: One Quality Voice. 2013. Link to FDA White Paper.
5. Hussain, A.S., Gurvich, V.J. & Morris, K. Pharmaceutical "New Prior Knowledge": Twenty-First Century Assurance of Therapeutic Equivalence. AAPS PharmSciTech 20, 140 (2019). https://doi.org/10.1208/s12249-019-1347-6
6. Shah, S.H., Chaturvedi, K, Morris, K, and Hussain, A.S. Physicochemical failure modes for first-line therapy: Narrow Therapeutic Index (NTI) drugs: a call for attention, NTI risk classification, and New Prior Knowledge. European Pharmaceutical Review, 2 July 2021. Link to the article.
7. Note the importance of team science, common team training, and building across the FDA functions, which are often discounted lessons. The PAT Team's efforts at the FDA at the beginning of the 21st-century initiative remain a helpful reminder: FDA's PAT Team: Shall We Dance? Pharmaceutical Manufacturing. April 6, 2005. Link to the article.
8. Roades, T, Colvill, S and McClellan, M.B. Pharmaceutical Tariffs: Potential Impacts and the Need for Vulnerability Assessments. Health Affairs Forefront. March 26, 2025. Link to the article.
9. Janet Woodcock, FDA Testimony, House Committee on Energy and Commerce, Subcommittee on Health: Safeguarding Pharmaceutical Supply Chains in a Global Economy. October 30, 2019. Link to the FDA website.
10.  An FDA Self-Audit of Continuous Manufacturing for Drug Products. CDER Small Business and Industry Assistance Chronicles. 28 June 2022. Link to the FDA website.
11. U.S. Government Accountability Office: FDA Has Faced Persistent Challenges Overseeing Foreign Drug Manufacturing. Published: Feb 06, 2024. Publicly Released: Feb 05, 2024. Link to GAO-24-107359
12. FDA Guidance for Industry, Process Validation: General Principles and Practices, January 2011. Link to the guidance document.

About The Author:

Ajaz S. Hussain, Ph.D., is a pharmaceutical quality and regulatory science expert with decades of experience across academia, industry, and government. As a former deputy director of the FDA's Office of Pharmaceutical Science, he was pivotal in pioneering initiatives like the process analytical technology (PAT) framework and the Pharmaceutical Quality for the 21st Century Initiative. Hussain also served as president of the National Institute for Pharmaceutical Technology and Education (NIPTE), advancing pharmaceutical technology and regulatory science. Now an independent consultant, he empowers organizations to integrate design thinking with a systems approach to advance innovative technologies that hold high potential for enhancing patient care and operational excellence.