Breaking Open Hermetically Sealed Regulatory Solutions for 2025: Starting with Dissolution Failures

Explore systemic resilience in pharma, tackling dissolution failures with SMART practices and innovative AI-driven solutions.

Pharma Now's “For the Leaders” section seeks to be an indispensable resource for pharmaceutical executives, offering deep insights into industry trends, strategic decision-making, and leadership challenges. Recent articles have explored pivotal topics, including digital transformation in the Indian pharmaceutical sector, strategies to foster innovation in R&D, and the critical role of empathetic leadership in building robust teams.

As a new member of the magazine’s advisory board, I am thrilled to contribute to this vital conversation with my inaugural article, “Pharma Now Cracking Hermetically Sealed Regulatory Solutions for 2025: Beginning with a Solution for Dissolution Failures.” This piece invites readers on a transformative journey—from systemic failure to systemic resilience—through humility, innovation, and collective action. I argue that it is time to crack open the hermetically sealed mindsets of our industry and embrace dissolution—not merely as a test or recurring failure but as a metaphor and pathway for continual development and improvement.

In December 2024, ProPublica spotlighted a troubling reality: when medicines fail to dissolve as intended, patient safety and efficacy become matters of chance ^[1]. The report highlighted Glenmark Pharmaceuticals, an Indian pharmaceutical company, which faced seven recalls due to dissolution failures from the same facility. Such events are not isolated, as I witnessed firsthand during my tenure at the FDA, where dissolution failures jeopardized national security and the survival of major pharmaceutical companies. These experiences, chronicled in my commentary “Past, Present, and Future of Pharmaceutical Dissolution Testing ^[2]” underscore the urgency of addressing these challenges.

Dissolution, as methodology and metaphor, forms the backbone of this article. Beyond the technical test, it symbolizes the necessity of dissolving barriers between disciplines, functions, and ideologies within the pharmaceutical industry for S.M.A.R.T Pharmaceuticals 2021-2030 - Express Pharma. By adopting a holistic, systems-based approach to quality, underpinned by SMART Shepherding Practices ^[3], Process Analytical Technology or PAT ^[4], and Generative AI application as discussed in Pharma Now ( SMART Practices for Responding to FDA Observational Warnings Using Generative AI), we can transcend compliance to achieve excellence.

The systemic failures outlined in the ProPublica article pose a fundamental question: How can we restore trust in pharmaceutical regulatory science? The answer lies in dismantling entrenched assumptions and embracing innovative, data-driven solutions prioritizing patient safety and industry accountability.

From Systemic Failure to Systemic Resilience

To transform the pharmaceutical industry’s approach to quality, we must move from reactive compliance to intuitive proactive resilience ^[5]. This shift requires embracing SMART Shepherding Practices that emphasize:

Specificity: Identifying the root causes of failures through rigorous, holistic AI-enabled search, analytics, and knowledge synthesis across the portfolio of products and their life cycle ^[6].
Measurability: Establishing clear metrics to track and evidence improvements on a path to Quality Management Maturity ^[7].
Achievability: Implement realistic, scalable interventions that provide objective risk management ^[8] within current systems.
Relevance: Ensuring practices align with real-world patient outcomes, improving pharmacovigilance and the reporting of consumer complaints, adverse event reporting, and evolving regulatory expectations ^[9].
Time-Bound Planning: Establishing achievable timelines for systemic changes by adopting a continuous development perspective, integrating annual product and performance reviews, and fostering continual improvement alongside professional development planning.

These principles serve as both theoretical constructions and practical tools for formulating the right questions at the appropriate scale. They encourage the examination of assumptions, dissolving barriers ^[10], and the continuous validation of prior knowledge while also recognizing when it is necessary to gather “new prior knowledge^[11],” especially when addressing complex issues like repeating dissolution failures. These principles empower organizations to align their operations with the FDA's "Pharmaceutical Quality for the 21st Century ^[12]" initiative, which promotes continuous improvement and lifecycle management.

The Role of Generative AI in Dissolution Testing

ML/AI tools present an unparalleled opportunity to leverage valid prior knowledge to improve the effectiveness and efficacy of new drug development ^[13], quality control, and regulatory compliance ^[14]. For instance:

Predictive Modeling: AI can simulate in-vitro and in-vivo relationships and correlations ^[15], identifying potential dissolution issues before they manifest in production.
Data Transparency: AI can identify gaps in data and information and detect fraud ^[16].
Real-Time Analytics: Advanced algorithms can instantly detect anomalies in dissolution ^[17] profiles, enabling swift corrective actions.
Process Optimization: AI-driven insights for PAT applications ^[18] facilitate the continuous refinement of manufacturing processes, ensuring consistency and quality.

Lessons from the Past, Solutions for the Future

Reflecting on historical failures, such as those highlighted by ProPublica and my own experiences at the FDA, reveals a recurring theme: the need for systemic accountability. Dissolution testing is a microcosm of broader industry challenges, where siloed thinking and outdated practices hinder progress.

By integrating SMART Shepherding Practices with lessons learned from past failures, we can address critical gaps in:

Root Cause Analysis: Moving beyond superficial investigations to uncover systemic issues.
Regulatory Alignment: Harmonizing practices with global standards to enhance trust and transparency.
Workforce Development: Investing in experiential learning programs that prepare professionals for the complexities of modern pharmaceutical manufacturing.

Conclusion

The journey from a systemic failure to systemic resilience demands Team Science and collective action ^[19]. It requires us to dissolve the barriers that impede innovation and embrace a culture of continuous improvement. By leveraging SMART Shepherding Practices, advanced technologies, and a commitment to excellence, we can ensure that pharmaceutical quality evolves to meet the demands in 2025 and beyond.

As we crack open our industry's hermetically sealed assumptions, let us not view dissolution failures as mere technical challenges. Instead, let them inspire us to reimagine what is possible in pharmaceutical science and regulatory practice. Together, we can build a future where trust, safety, and efficacy are not aspirations but certainties.