A Holistic Mindset is Key to Supply Resiliency

Supply resiliency capability is most often utilized in unusual disruptive situations, which makes it generally more difficult to sustain. A back-up plan or redundancy for every organizational, operational, or logistical element of pharmaceutical manufacturing usually presents an untenable business model, both from cost and regulatory complexity perspectives. Lifecycle management and continual improvement of manufacturing processes have been significantly complicated by global, regulatory divergence (e.g., post approval changes taking upwards of 5-7 years for global dossier updates and implementation). These complications have resulted in companies pursuing risk management related to supply resiliency to the degree possible as a best business practice and treading carefully before undertaking any global post approval changes.

Now, in the wake of recent large-scale, high-profile events impacting global supply chains (most notably the COVID pandemic) and an ongoing escalation of shortages, there is increased scrutiny by governments and regulators, and heightened pressure on the pharmaceutical industry to accelerate development of expanded, mature supply resiliency practices. The pressure has resulted in more regulatory requirements related to drug shortage reporting and risk management planning, as well as making some good progress toward regional/global approaches to streamline or accelerate global post approval changes. ISPE has reflected at length on these developments and how to balance supply resiliency needs and the primary challenges of related risk management activity: cost and regulatory complexity. Our current positions and recommendations include:

1. Industry-owned quality maturity, risk management and drug shortage prevention excellence, through application of ISPE’s Advancing Pharmaceutical Quality (APQ)™ program (figure 2) and other complementary ISPE resources such as the ISPE Drug Shortages Prevention Model (figure 3) and upcoming risk management guidance (based on ICH Q9[R1]), is our recommended approach to achieve long-lasting supply resiliency. ISPE also recommends the use of the term quality maturity be used with care or replaced. Stakeholders with limited understanding of manufacturing may incorrectly assume lower quality maturity results in lower quality product. However, all products released by manufacturers for use by patients are held to cGMP standards and tested to ensure appropriate quality. Therefore, a manufacturer with emerging quality maturity is capable of producing product of appropriate quality but may have difficulty with uninterrupted supply of product. A reference, like supply resilience maturity, that will focus our collective discussion on supply reliability rather than potentially generating concern over product quality and possibly patient mistrust is preferred.

2. Sustainable supply resilience begins with prioritization to ensure the highest levels of risk management are directed toward essential products with supply chain vulnerabilities. Essential products are typically sterile injectables that are life-saving, life-sustaining, and used in surgery or critical for public health during a public health emergency, although other dosage forms may be equally important. Prioritization of resources for risk management activities to support essential products with supply chain vulnerabilities is important because the total sum of considerations to ensure product availability is extensive, including risk management for product quality and more (Figure 4).

Additionally, in general, supply resiliency and product availability performance are elevated with:

1. Less-siloed risk management activities
2. Real-time data updates for stakeholders and rapid responses to issues
3. Product quality and product availability risk evaluations at different altitudes (product, operational and organizational levels)
4. Scenario planning of supply challenges in a global market
5. Manufacturing evolution in alignment with developing regulatory expectations for product availability risk management

To avoid an unsustainable business model that would strive to invest in all possible proactive supply resiliency measures when future supply challenges may be unpredictable and mitigation steps may never be needed or needed in the way that was originally anticipated, ISPE continues to recommend striking the right balance between critical patient needs and the business investment for drug shortage prevention measures.

3. A global mindset is essential to success. Health authority mutual reliance or mutual recognition initiatives, and global regulatory harmonization present significant opportunities for supply resiliency. Individual market regulatory requirements that generate regulatory divergence can result in unintended consequences, such as limitations to lifecycle management, continual improvement, sustainability efforts and/or product availability . This is because many manufacturers supply a global market and may not be able to navigate a complex, lengthy, global post-approval change for all products and business situations.

New, rapidly developing market-specific requirements related to drug shortage prevention may also create unintended consequences. As an example and as noted by recent ISPE research on convergence opportunities. Hale article when available), market-specific safety stock or stockpiling requirements may lead to unprecedented inventory levels that constrain or exhausts raw materials, excipients, components, API and/or finished product to meet mandated inventory reserves. Further concerning, without robust supply chain practices material in these reserves could possibly expire without use. A sustainable alternative could be a universal stockpile with an internationally accepted label for equitable, global allocation in times of product shortage and urgent need.

ISPE encourages and is available to provide platforms for discussion regarding any regulator-driven harmonization initiatives that address regulatory or harmonization opportunities for supply resiliency (Figure 4).

4. Pursue responsible transparency. Stakeholder interest in greater transparency of supply chain or quality maturity information has been steadily increasing to support market-wide predictive analytics. Predictive analytics could more rapidly and accurately identify market vulnerabilities to support earlier interventions or set the stage for market incentives for manufacturers to generate more reliable supply. Because of these potential benefits, new regulatory expectations have been developed or are under consideration globally. ISPE has had a longstanding commitment to constructive health authority engagement. ISPE continues to support industry-health authority interactions when appropriate to optimize risk management for product availability and optimize supply disruption mitigation, as needed. However, transparency of the complex pharmaceutical supply chain without sufficient context may be problematic. Therefore, ISPE recommends that pursuit of further data exchange, and in particular any initiative to increase pharmaceutical data publication in public forums, should be carefully considered to ensure unintended consequences such as, panic-buying or hoarding, loss of patient trust, impact to supply chain security, proprietary data infringements or unnecessary administrative burden are avoided.

5. Technical advancement is foundational to supply resiliency. ISPE continues to generate information exchange platforms for advancing expertise and progress in various areas that may be transformational for supply resiliency, including, data analytics, digital solutions, advanced technology, and lifecycle management.

6. Market dynamics and related geo-political considerations are outside the scope of ISPE focus and may have a significant impact on product availability because of the challenging demand fluctuations they may generate. ISPE’s scope includes the technical, quality and regulatory aspects to supply resiliency and drug shortage prevention. ISPE input to the evaluation of potential solutions to drug shortages and supply resiliency challenges beyond these areas of expertise may be limited. However, ISPE does continue to provide guidance and platforms for discussion regarding how industry may improve risk management, overall quality maturity and drug shortage prevention performance, because these capabilities will provide the agility and ability to mitigate the impact of unexpected market dynamics or geo-political generated issues as quickly as possible.

7. Investing in talent is critical to our success. Considering the post-COVID workforce dynamics, ongoing depletion in trained pharmaceutical experts, and focusing on future resources needs, it is evident that a renaissance in how the industry attracts, develops and retains talent is essential for supply resilience. Additionally, the industry needs to consider what new roles may be needed to lead holistic supply resiliency at an enterprise level within manufacturing companies. The ISPE Emerging Leaders program and ISPE Workforce of the Future initiative both support this important evolution.

ISPE’s observation is that supply resiliency is a journey. How a manufacturer may support continued supply throughout a product lifecycle may vary. How manufacturers may support continued supply over time in relation to evolving regulatory requirements may vary. How manufacturers may support continued supply throughout the global marketplace may vary. Furthermore, no one is working in isolation. All global stakeholders noted herein (Figure 1) have an important perspective and contribution to supply resiliency outcomes. Only when all global stakeholders approach supply resiliency with a holistic mindset will we serve every patient to the best of our ability globally.