The COVID-19 pandemic was pivotal for governments and the pharmaceutical industry, highlighting critical gaps in global health preparedness. The pandemic revealed severe gaps and weaknesses in the pharmaceutical supply chain strategy used in the pre-pandemic era. In the aftermath, two distinct methods for addressing these weaknesses have emerged: one that emphasizes domestic-only preparedness, focusing on national self-sufficiency and independence, and another that promotes a global approach built on collaboration and equity.

The pandemic specifically underscored the need for rapid vaccine development, scalable manufacturing, and effective distribution strategies. Yet, the debate continues on whether future health crises should be addressed primarily through a national lens or a more cooperative global framework.

Vaccine Development: Speed vs. Collaboration

The domestic-only approach to vaccine development, as demonstrated during COVID-19, focused on achieving rapid vaccine production through intensive government funding and private-sector partnerships. Programs designed to fast-track research, clinical trials, and regulatory approval enabled pharmaceutical companies to bring vaccines to market in record time. This ensured that domestic populations had early access to life-saving vaccines, minimizing the health and economic fallout of the pandemic.

On the global stage, vaccine development has been characterized by collaborative efforts, where countries pool scientific resources and data to accelerate the discovery and deployment of vaccines. Initiatives such as COVAX aimed to ensure that all countries, regardless of income, had access to vaccines. This collaborative approach also prioritized the development of vaccines that could be easily distributed in low-resource settings, addressing challenges like storage and transportation in regions with less infrastructure.

Manufacturing Scalability:

In the domestic-only framework, one key lesson from the pandemic was the need for self-sufficiency in pharmaceutical manufacturing. Supply chain disruptions during COVID-19 exposed the vulnerabilities of relying on international suppliers for critical components like active pharmaceutical ingredients (APIs) and personal protective equipment (PPE). As a result, significant investments were made in domestic manufacturing capacity to ensure that during future health crises, national production would meet the needs of the population without reliance on foreign sources.

In contrast, a global approach advocates for distributed manufacturing networks, where production is spread across multiple countries. This strategy reduces the risk of bottlenecks and supply chain breakdowns, especially during emergencies. By transferring technology and know-how to low- and middle-income countries (LMICs), global initiatives aim to empower these regions to ramp up their manufacturing capabilities during a health crisis, ensuring more equitable and efficient production of vaccines and treatments.

Distribution Strategies:

In certain instances, the domestic-only approach during COVID-19 focused on prioritizing domestic vaccination efforts. Vaccines were distributed rapidly to the national population before international aid or exports were considered. This strategy, though effective in protecting the local population, has been criticized as a form of vaccine nationalism, where wealthier countries secured and administered vaccines while less affluent nations struggled to obtain doses.

On the global side, distribution efforts were grounded in equity and fairness. Global initiatives like COVAX sought to distribute vaccines to all countries, focusing on vulnerable and underserved regions to prevent widening health disparities. The emphasis was not just on vaccinating wealthier nations but ensuring that populations worldwide had equal access to protection, regardless of economic standing.

Access and Affordability:

A major difference between the two approaches lies in the question of vaccine access and affordability. Under a domestic-only model, pharmaceutical companies maintained patent protections on their vaccines, controlling both the manufacturing process and pricing. This allowed for recouping research and development costs but created barriers for LMICs that could not afford to pay market prices for vaccines.

In contrast, a global approach would emphasize solidarity by advocating for patent waivers on life-saving vaccines during global health emergencies. By allowing the production of cheaper generic versions, more countries would have the opportunity to access vaccines, reducing financial barriers and improving global vaccination rates. This approach aims to prioritize public health over intellectual property rights during crises.

Public Health Infrastructure:

A domestic-only model calls for building a robust national public health infrastructure that can detect, respond to, and manage health crises within the country. This includes investing in national stockpiles of medical supplies, bolstering local research institutions, and developing an early-warning system to detect emerging pathogens. The focus is ensuring national preparedness and reducing reliance on international assistance during crises.

Meanwhile, a global approach emphasizes the importance of strengthening public health systems worldwide. By investing in health infrastructure in LMICs, international health organizations aim to prevent future pandemics from spreading unchecked. Efforts focus on improving healthcare access, enhancing diagnostic capabilities, and creating global surveillance systems that can detect and respond to outbreaks anywhere in the world, thus benefitting the entire global population.

Conclusion:

When compared, the domestic-only and global approaches each present a distinct set of strengths and opportunities. Neither approach is without its risks.

The domestic-only approach provides a quick, independent response to national health crises, ensuring that the population is protected without waiting for international aid. It strengthens national manufacturing capacity and supply chains, enhancing self-reliance. However, this approach risks fostering “medical nationalism,” where the focus on national interests comes at the expense of global health, potentially prolonging a pandemic by limiting international cooperation. Sole reliance on national resources could also isolate the country from global innovations.

A global approach fosters equity and collaboration, ensuring that all countries, particularly LMICs, have access to life-saving treatments. It promotes shared research and technology, speeding up vaccine development and manufacturing through international cooperation. The downside to this approach, as was revealed through the pandemic, is that it requires high levels of coordination and funding across borders, which can slow down response times. Success depends heavily on contributions from wealthier nations, and global collaboration may face political or logistical challenges that delay progress.

There are opportunities. A domestic-only approach offers the chance to build a strong domestic pharmaceutical industry, creating jobs and economic growth. This can position a country as a leader in pharmaceutical innovation and rapid response to future health crises. Governments need to be cautious and avoid policies that hoard medical supplies or vaccines, potentially delaying the end of a global pandemic. Future crises may not be confined to national borders, and a lack of cooperation could exacerbate health risks.

The global approach strengthens global health systems, reducing the risk of pandemics spreading uncontrollably. Global collaboration creates opportunities for sharing best practices and resources, and distributed manufacturing can ensure more efficient and equitable vaccine distribution worldwide. The success hinges on sustained commitment from high-income countries. Global efforts could be compromised if funding or political will falter, leaving vulnerable populations without necessary protections. Logistical hurdles in coordinating international efforts may also slow down the response.

Both the domestic-only and global strategies have their advantages, but a balance between national preparedness and international cooperation may offer the best protection against future pandemics. While domestic resilience ensures that a country can act quickly to safeguard its population, global solidarity recognizes that public health is an interconnected challenge. Pandemics do not recognize borders. This challenge can only be fully addressed through shared responsibility.

The US pharmaceutical supply chain is heavily reliant on foreign manufacturing. A significant portion of drugs sold in the US are produced abroad, primarily in China. The numbers speak for themselves:

• Ibuprofen: 95% of imports come from China
• Hydrocortisone: 91% of imports come from China
• Acetaminophen: 70% of imports come from China
• Penicillin: 40–45% of imports come from China
• Heparin: 40% of imports come from China
• Antibiotics: 80% of the US supply is made in China

According to the FDA, 72% of active pharmaceutical ingredient (API) facilities that supply the US market are located overseas. This overreliance on foreign production poses risks to national health security, as supply disruptions due to geopolitical tensions, quality control issues, or global crises like COVID-19 could have serious consequences for American patients. In August of this year, pharmaceutical active ingredients were listed as a critical sector for potential cooperation under the IPEF Supply Chain Agreement.

Why Restoring US Pharmaceutical Manufacturing Is Critical

The pandemic and recent natural disasters exposed vulnerabilities in the global supply chain when several countries limited exports of critical medical supplies to prioritize their populations. A domestic approach to pharmaceutical production would create a more resilient supply chain, ensuring essential medications remain accessible during emergencies. Beyond the supply chain, restoring domestic manufacturing could improve quality control, reduce environmental impacts, and create jobs across various industries.

How Long and How Much It Will Cost to Restore US Pharmaceutical Manufacturing

Restoring pharmaceutical manufacturing in the US is a significant undertaking that involves both time and financial investment. Depending on the scale of the operation and the technology being implemented, estimates for how long it takes and the associated costs can vary widely. Based on industry research and government studies, the following factors influence the timeline and cost of reshoring pharmaceutical production:

1. Timeline for Restoring Pharmaceutical Manufacturing
   • Short-term Goals (2–5 years): Initial steps such as investing in infrastructure for API manufacturing, upgrading existing facilities, and launching workforce training programs can begin immediately. Companies that already have facilities in the US may be able to ramp up production within 2 to 5 years by adopting advanced manufacturing technologies like continuous manufacturing, which streamlines production.
   • Long-term Goals (5–10+ years): Building new, fully operational domestic pharmaceutical manufacturing facilities from the ground up takes longer. Large-scale projects typically require 5 to 10 years, accounting for construction, regulatory approval, workforce development, and technological integration. These timelines could extend further depending on the scale of operations and regulatory hurdles, such as gaining FDA approval for new processes.
2. Cost of Restoring Domestic Manufacturing
   • Infrastructure Investment: Building new API and drug manufacturing facilities is capital-intensive. According to a 2021 study by the Congressional Research Service, constructing a modern pharmaceutical manufacturing facility can cost between $500 million to $2 billion. This includes costs for land, construction, equipment, and technology implementation.

For example, Phlow Corporation’s project in Virginia, part of a government contract to produce essential medicines domestically, was funded with an initial investment of $354 million. The total project cost is expected to surpass $1 billion when fully operational, demonstrating the high cost of building advanced manufacturing infrastructure.

2. Technological Upgrades: Adopting advanced technologies such as continuous manufacturing, AI-driven quality control, and automation can cost an additional $50 million to $200 million depending on the size of the facility. However, these technologies can increase efficiency, reduce waste, and lead to long-term cost savings.
3. R&D Investment: Companies that are reshoring manufacturing will also need to invest in research and development (R&D) to ensure that new manufacturing processes comply with FDA regulations and industry standards. The FDA’s Emerging Technology Program supports companies working on these innovations, but R&D costs typically run in the tens of millions of dollars, depending on the complexity of the products being manufactured.
4. Workforce Training and Development: Developing a skilled workforce for advanced pharmaceutical manufacturing is another significant cost. Companies can expect to spend between $10 million and $50 million on workforce development initiatives, including vocational training programs, education partnerships, and on-the-job training to equip workers with the necessary skills to operate new technologies.
5. Ongoing Operational Costs: Operating a pharmaceutical facility in the US tends to be more expensive than in countries with lower labor costs. Companies will need to account for higher wages, stricter environmental regulations, and energy costs. However, advanced manufacturing techniques can help offset some of these operational costs by improving efficiency and reducing resource consumption.

Steps Toward Restoring Pharmaceutical Manufacturing in the US

1. Federal Assistance and Investment in Domestic API Production One of the key resources available for companies interested in reshoring pharmaceutical manufacturing is financial support through federal programs. For example, the Defense Production Act (DPA) and the CARES Act have been used to fund domestic production of critical health supplies, including APIs. The Department of Health and Human Services (HHS) has partnered with private companies to invest in advanced manufacturing technologies to boost domestic production of essential medicines.

In 2020, the HHS awarded a $354 million contract to Phlow Corporation, a Virginia-based company, to build the infrastructure for domestic API manufacturing. This partnership aims to develop an end-to-end advanced manufacturing process that can reduce costs and improve efficiency, creating a more sustainable supply of essential medicines like antibiotics and generics.

2. Educational Programs and Workforce Development Restoring domestic pharmaceutical manufacturing will require a skilled workforce. Companies can leverage resources from the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), a public-private consortium that supports innovation and workforce development in biopharmaceutical manufacturing. NIIMBL offers funding opportunities and training programs to help companies adopt new technologies and educate the next generation of workers.
3. Public-Private Partnerships Public-private partnerships have been critical to reshoring efforts. In addition to Phlow Corporation, the Biomedical Advanced Research and Development Authority (BARDA) has invested in domestic production of vaccines and APIs. BARDA supports the development of new technologies and facilities that can increase production capacity and reduce reliance on foreign suppliers.
4. Tax Incentives and Policy Support Legislative efforts to provide tax breaks and other financial incentives for reshoring pharmaceutical production have gained momentum. For instance, The Pharmaceutical Supply Chain Review Act, introduced in 2020, called for a comprehensive review of the US pharmaceutical supply chain and proposed policies to incentivize domestic manufacturing.
5. Sustainable Manufacturing and Environmental Considerations Companies can access assistance from agencies like the Environmental Protection Agency (EPA) for implementing sustainable manufacturing practices. The EPA provides guidance on reducing waste and pollution during pharmaceutical production through programs such as Green Chemistry initiatives. These programs aim to support environmentally friendly production methods while maintaining competitiveness.
6. Utilizing Advanced Manufacturing Technologies The shift toward continuous manufacturing, which allows for more efficient production, has been gaining traction in the US. Companies can explore grants and funding opportunities through the National Science Foundation (NSF) for R&D in this area. Continuous manufacturing, when paired with artificial intelligence and automation, can make domestic pharmaceutical production competitive with low-cost manufacturing abroad.

Conclusion: A Collaborative Approach to Restoring Pharmaceutical Manufacturing

Restoring pharmaceutical manufacturing in the US is a significant and costly endeavor, with timelines ranging from 2 to 10 years depending on the scale of investment and infrastructure development. Initial costs can run into the billions of dollars for constructing and upgrading facilities, with additional expenses for workforce development and R&D. However, the long-term benefits—improved drug security, job creation, and reduced dependence on foreign suppliers—make this effort crucial for the nation’s health and economic resilience. Any plan will require coordination between public and private entities and a long-term strategic approach that covers critical need APIs now, and covering future products so that some percentage of the demand is always available from a US-manufacturer.

References:

• U.S. Food & Drug Administration (FDA): Drug Shortages & Supply Chain Information
• Phlow Corporation: HHS Contract for Domestic Pharmaceutical Manufacturing
• Defense Production Act (DPA) and CARES Act
• National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL)
• Biomedical Advanced Research and Development Authority (BARDA)
• American Innovation and Manufacturing Act, CHIPS and Science Act
• Congressional Research Service: Costs of Building Pharmaceutical Manufacturing Facilities

The journey of developing a successful pharmaceutical product is a testament to the power of collaboration, innovation, and shared purpose. It’s a process that not only transforms molecules into life-saving treatments but also brings together diverse minds and talents to solve some of the most pressing health challenges. Being part of such a team is a source of profound joy and pride, rooted in the collective pursuit of making a meaningful impact on the world. At GreenField, we’ve been part of teams in various applications. We’ve seen our share of successes as well as failures. The key feature of every project has been the incredible nature of the teams we’ve been part of.

The Engine of Innovation

Innovation thrives in environments where diverse perspectives converge. In the pharmaceutical industry, this means bringing together scientists, clinicians, engineers, and business experts to tackle complex problems from multiple angles. Each team member contributes unique skills and insights, creating a dynamic synergy that fuels breakthrough discoveries.

The joy of being part of this innovative engine comes from the continuous learning and growth it demands. It’s about staying curious, asking the right questions, and challenging assumptions. It’s about embracing the iterative process of experimentation, where failures are not setbacks but stepping stones to success. The thrill of uncovering new knowledge and pushing the boundaries of what’s possible is a shared experience that binds the team together.

The Power of Purpose

At the heart of our work is a deep sense of purpose. We are not just developing drugs; we are developing solutions that have the potential to save lives and improve the quality of life for millions of people. This purpose is a powerful motivator, driving us to overcome obstacles and stay committed to our goals.

The pride we feel in our achievements is closely linked to this purpose. It’s the knowledge that our efforts contribute to a greater good and that we are making a tangible difference in the world. This sense of purpose fosters a culture of collaboration and mutual support, where every team member is valued for their contributions and united by a joint mission.

The Strength of Collaboration

Effective teamwork is the cornerstone of success in pharmaceutical development. It requires open communication, trust, and a willingness to share knowledge and resources. Collaboration is not just about working together; it’s about leveraging each other’s strengths and compensating for each other’s weaknesses. It’s about building a cohesive unit where the whole is greater than the sum of its parts.

The joy of collaboration lies in the relationships we build along the way. It’s about celebrating each other’s successes, providing support during challenging times, and continuously learning from one another. These relationships create a strong foundation of trust and respect, essential for navigating pharmaceutical development’s uncertainties and complexities.

The Reward of Impact

There’s a unique joy in seeing the tangible impact of our work. When a new pharmaceutical product successfully reaches the market, it culminates years of hard work, perseverance, and collaboration. The ultimate reward is knowing that our efforts have led to a solution that can improve health outcomes and save lives.

This impact is not just measured in numbers or sales but in the stories of patients who benefit from our work. It’s the story of the child who can now lead a normal life because of a new treatment, the story of the family who has more time with their loved one, and the story of the healthcare provider who can offer hope where there was once none. These stories are a powerful reminder of why we do what we do and a source of immense pride.

Conclusion

The joy and pride of being part of a team that develops a successful pharmaceutical product are rooted in the journey of innovation, purpose, collaboration, and impact. This journey requires dedication, resilience, and a relentless pursuit of excellence. It transforms not only the lives of patients but also the lives of those who are part of the process.

As we continue to navigate this journey, let’s remember that our greatest strength lies in our ability to work together, stay curious and innovative, and remain committed to making a positive difference in the world. Together, we can achieve extraordinary things and take pride in the profound impact of our work.

Celebrate the power of innovation. Embrace the sense of purpose. Foster collaboration. Cherish the impact. And always remember, the joy of making a difference is found in the shared journey and the collective achievements of the team.

The narrative of drug development often focuses on the eureka moments in the lab, the tireless research, and the groundbreaking discoveries. But this story’s another, frequently under-appreciated chapter – the crucial interaction with regulatory agencies. These institutions, acting as the gatekeepers of safety and efficacy, ensure the medications we rely on are genuinely beneficial. However, the communication between developers brimming with hope for their innovative treatment and regulators adhering to rigorous protocols can be surprisingly fraught. Misunderstandings and jargon-laden exchanges can create a logjam, delaying the arrival of potentially life-saving drugs to patients eagerly awaiting them.

The good news? The key to unlocking this logjam lies not in a scientific breakthrough but in a communication superpower: clear, concise, and timely communication. This blog post delves into strategies that foster a collaborative dialogue between developers and regulators. By bridging the communication gap between developers and regulators, we can streamline the approval process and accelerate the journey of promising treatments from the lab bench to the hands of those who need them most. This isn’t just about efficiency; it’s about unlocking the full potential of scientific innovation to improve lives.

Demystifying the Maze: A Thinker’s Guide to Regulatory Agencies

Imagine this: you’ve poured years of research into a groundbreaking drug, a potential beacon of hope for countless patients. Now, you stand at the threshold of the final hurdle – regulatory approval. But before the metaphorical ribbon gets cut, you must navigate a complex landscape: the world of regulatory agencies.

Often shrouded in mystery, these institutions play a critical role in ensuring patient safety. They act as gatekeepers, meticulously evaluating drugs for efficacy and weeding out anything that might pose a threat. Understanding these agencies and how to communicate effectively with them is paramount for a successful drug development journey.

Think of regulatory agencies as regional shepherds for drug development. Here are some key players:

• The Food and Drug Administration (FDA): The US giant responsible for ensuring the safety and effectiveness of drugs, medical devices, and even your morning coffee (okay, maybe not the coffee, but you get the idea).
• The European Medicines Agency (EMA): Overseeing drug approval across the European Union, the EMA fosters a harmonized approach for medications reaching a vast market.

But it’s not just about individual agencies. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) deserves a shout-out. This global collaboration sets the stage for a more streamlined process by establishing standard guidelines for drug development. Think of them as the international language of drug development, facilitating communication and reducing roadblocks for multi-region approvals.

Effective communication with regulatory agencies is a dance with two intricate steps:

• Written Submissions: These formal documents, such as Investigational New Drug (IND) applications and New Drug Applications (NDAs), are your detailed narratives. They outline your drug’s development story, detailing its safety profile and the data supporting its potential.
• Meetings: Pre-IND meetings and formal application meetings provide a platform for face-to-face dialogue. They are opportunities to clarify questions and address concerns before a formal submission. These meetings foster a collaborative spirit and iron out potential issues early on.

Speaking the Right Language: Familiarity is Key

Regulatory agencies don’t operate in a vacuum. They have established guidelines, like the FDA’s Good Clinical Practice (GCP) guidelines, that outline their drug development and data presentation expectations. These guidelines are essentially the “rules of the game.” Understanding them ensures your communication is relevant, addresses the agency’s specific requirements, and ultimately increases your chances of a smooth review process.

By demystifying the regulatory landscape, communication channels, and the importance of understanding agency expectations, you can approach regulatory agencies not as adversaries but as partners in the pursuit of safe and effective treatments.

Building the Bridge: Assembling Your A-Team for Regulatory Communication

The road to regulatory approval is complex, demanding a well-equipped team to navigate the twists and turns. Effective communication with regulatory agencies requires a strategic approach. Here’s how to build the bridge for a successful dialogue.

Assembling the A-Team:

Think of your regulatory communication team as your dream collaborators – a diverse group with the expertise to tackle any challenge. This dream team likely includes:

• Scientific Experts: The resident rockstars who understand the intricacies of your drug’s science and data inside-out. They can translate complex scientific jargon into clear regulatory-speak.
• Regulatory Affairs Specialists: These individuals interpret the regulatory landscape and are fluent in the agency’s guidelines and expectations. They ensure your communication aligns with the agency’s specific requirements.
• Communication Experts: The masters of crafting clear and concise messages. They can distill complex information into impactful narratives that resonate with the agency.

A Roadmap for Success: The Communication Strategy

Like any good explorer would only venture into uncharted territory with a map, a well-defined communication strategy serves as your roadmap for interacting with regulatory agencies. This strategy should outline:

• Key Messages: What core points do you want to convey about your drug? What makes it unique, safe, and effective?
• Target Audience: Understanding who you’re communicating with (specific agency personnel) helps tailor your message accordingly.
• Objectives: What do you hope to achieve with each communication? Is it to secure a meeting, address a concern, or provide an update?

A clear communication strategy ensures your team is aligned and your message is focused. It prevents confusion and ensures everyone sings from the same hymn sheet, fostering a more productive dialogue with the agency.

The Point Person: A Pillar of Consistency

Imagine a game of telephone – the message gets muddled with each retelling. Establish a dedicated point of contact within your team to avoid this with regulatory communication. This individual acts as the central hub, ensuring consistent and clear communication with the agency. They coordinate with the team, answer agency inquiries, and ensure all communication aligns with the overall strategy.

By assembling a well-prepared team, developing a clear communication strategy, and establishing a dedicated point of contact, you lay the foundation for effective dialogue with regulatory agencies.

Speaking the Same Language: Strategies for Effective Communication with Regulatory Agencies

The bridge to regulatory approval is built on expertise and effective communication. Here’s the thing – regulatory agencies aren’t bastions of impenetrable jargon. They’re filled with intelligent individuals seeking to understand the science behind your groundbreaking drug. The key? Speaking their language, a language of clarity, data, and a genuine commitment to collaboration.

Imagine wading through a swamp of technical terms. That’s what wading through jargon-laden communication feels like for a regulatory agency. Strive for clear, concise language. Explain complex concepts in a way that is easy to understand, focusing on the core message: why your drug is safe and effective.

Data-Driven Communication: Numbers Speak Louder Than Words

Science, after all, is the bedrock of drug development. Back up your claims with robust scientific data. Don’t just tell the agency your drug works; show them the meticulously organized reports and clinical trial results that prove it. Consider data as persuasive evidence, the facts that paint a compelling picture of your drug’s potential.

Active Listening: It’s Not a Monologue

Communication is a two-way street. Don’t just send information; actively listen to the agency’s feedback. Their questions and concerns are not roadblocks but opportunities for clarification and collaboration. Address their inquiries promptly and thoroughly, demonstrating a genuine interest in fostering a productive dialogue.

Timeliness: Respecting the Clock

Regulatory agencies have tight deadlines, and so should you. Respond to inquiries and requests for information promptly. Don’t let delays in communication snowball into missed opportunities or a tarnished reputation for reliability. Remember, timeliness demonstrates respect for the agency’s process and keeps your drug development journey on track.

Transparency and Honesty: Building Trust

Building trust is paramount in any successful partnership. Maintain a transparent and honest approach throughout all communication with regulatory agencies. If there’s a challenge or a setback, don’t sugarcoat it. Present the facts with a commitment to finding solutions. Transparency fosters trust, the foundation for collaborative and successful drug development.

These communication strategies can transform your interaction with regulatory agencies from a frustrating hurdle into a productive partnership.

Beyond the Approval: Fostering Long-Term Partnerships with Regulatory Agencies

The coveted green light of regulatory approval isn’t the finish line; it’s the beginning of a new chapter. A successful drug development journey hinges on securing approval and building a robust and collaborative relationship with the agencies that granted it.

From Gatekeepers to Collaborators: A Mindset Shift

Think of regulatory agencies not as gatekeepers but collaborators invested in the same goal – bringing safe and effective treatments to patients. By fostering a respectful working relationship built on open communication, you create an environment where both parties can learn and grow.

Proactive Engagement: Addressing Concerns Head-On

Imagine a ticking time bomb – that’s what potential issues can be if left unaddressed. Don’t wait for the agency to raise concerns. Proactively engage with them, schedule meetings to discuss potential roadblocks early on, and demonstrate a willingness to address any questions or uncertainties they might have. This proactive approach fosters trust and positions you as a partner, not just an applicant.

Embracing Constructive Criticism

Not every piece of agency feedback will feel like a bouquet of roses. But remember, even constructive criticism, however thorny it may seem initially, can be a valuable fertilizer for improvement. Be receptive to the agency’s concerns and be willing to address them. This collaborative spirit shows your commitment to continuous improvement and patient safety, strengthening your relationship with the agency.

By developing a collaborative and respectful working relationship with regulatory agencies, you’re not just navigating the approval process but building a foundation for future innovation. The knowledge gained through open communication can inform future drug development efforts, ultimately accelerating the path to bringing life-saving treatments to the patients who need them most.

Here’s the key takeaway: clear, concise, and data-driven communication is the Rosetta Stone for unlocking a smoother and more efficient approval process. Replace jargon-laden exchanges with collaborative dialogue; proactive engagement replaces reactive scrambling. This is the power of effective communication – it fosters trust, streamlines the process, and ultimately accelerates the path of your life-saving drug to patients in need.

Numerous resources are available to equip you with the communication skills needed to navigate the regulatory landscape confidently. The International Council for Harmonisation (ICH) provides a wealth of information on global regulatory guidelines. Regulatory affairs professional organizations offer training programs and workshops specifically designed to hone communication skills for interacting with agencies.

Here’s an excellent map to navigate the path to communication mastery:

• International Council for Harmonisation (ICH): Consider this your Rosetta Stone for deciphering the global language of drug development. The ICH website (https://www.ich.org/) is a treasure trove of information, offering a wealth of resources on global regulatory guidelines. Dive in and equip yourself with the knowledge to communicate effectively across borders.
• Professional Development Opportunities: Sharpen your communication skills like a master swordsman! Consider attending training programs or workshops offered by esteemed organizations like the Regulatory Affairs Professionals Society (RAPS) (https://www.raps.org/) or the American Society for Clinical Pharmacology & Therapeutics (ASCP&T) (https://www.ascpt.org/). These organizations offer practical guidance and insights specifically designed to hone your communication skills for interacting with regulatory agencies.
• Expert Guidance: Don’t hesitate to seek the wisdom of experienced mentors – regulatory consultants or communication specialists. Their expertise can be invaluable. Imagine them as your wise guides, leading you through the complexities of crafting compelling communication strategies and navigating intricate interactions with regulatory agencies.

Remember, effective communication isn’t just about securing approval but building long-term partnerships with regulatory agencies. By fostering a collaborative spirit and embracing constructive criticism, you position yourself as an applicant and a valued partner in the shared mission of bringing safe and effective treatments to the world.

Pharmaceutical companies are constantly seeking ways to enhance efficiency, reduce costs, and ensure the timely delivery of high-quality products. One innovative solution gaining traction is Supply Chain as a Service (SCaaS). This model offers a flexible, scalable, and cost-effective approach to managing supply chains, allowing pharmaceutical companies to focus on their core competencies while leveraging specialized expertise in supply chain management. In this blog, we will explore the value of SCaaS in the pharmaceutical industry and how it is transforming the landscape.

Understanding SCaaS

SCaaS is a comprehensive solution where third-party providers offer businesses end-to-end supply chain management services. These services include procurement, logistics, inventory management, order fulfillment, and data analytics. By outsourcing these functions to specialized providers, pharmaceutical companies can streamline operations, reduce overhead costs, and gain access to advanced technologies and expertise.

Critical Benefits of SCaaS in the Pharmaceutical Industry

1. Cost Efficiency:
   • Reduced Overhead: SCaaS providers offer economies of scale, allowing pharmaceutical companies to benefit from lower operational costs. This includes savings on infrastructure, technology, and personnel.
   • Flexible Pricing Models: SCaaS typically operates on a pay-as-you-go basis, enabling companies to scale services up or down based on demand, reducing the risk of overinvestment.
2. Enhanced Focus on Core Competencies:
   • Concentration on R&D and Innovation: By outsourcing supply chain functions, pharmaceutical companies can allocate more resources to research and development, accelerating the discovery and development of new drugs.
   • Improved Quality and Compliance: SCaaS providers specialize in supply chain management, ensuring that operations adhere to industry regulations and standards, thus maintaining high levels of quality and compliance.
3. Access to Advanced Technology:
   • Digital Transformation: SCaaS providers leverage cutting-edge technologies such as artificial intelligence, machine learning, and blockchain to optimize supply chain processes. This includes predictive analytics for demand forecasting, real-time tracking of shipments, and secure data sharing.
   • Integrated Systems: SCaaS offers integrated supply chain platforms that provide end-to-end visibility and control, enhancing coordination and collaboration across the entire supply chain network.
4. Scalability and Flexibility:
   • Adaptable Solutions: SCaaS can quickly adapt to changes in demand, market conditions, and regulatory requirements. This agility is crucial in the pharmaceutical industry, where product lifecycles and market dynamics can be highly variable.
   • Global Reach: SCaaS providers have established networks and partnerships worldwide, facilitating efficient and reliable international logistics and distribution.
5. Risk Mitigation:
   • Resilient Supply Chains: SCaaS providers implement robust risk management strategies to ensure continuity of supply in the face of disruptions, such as natural disasters, geopolitical issues, or pandemics.
   • Regulatory Compliance: SCaaS providers stay abreast of changing regulations and industry standards, helping pharmaceutical companies navigate complex compliance requirements and avoid potential penalties.

Case Studies and Examples

Several extensive multinational pharmaceutical companies have successfully implemented SCaaS models, reaping significant benefits:

• Pfizer: Pfizer partnered with a SCaaS provider to enhance its global supply chain operations. By leveraging advanced analytics and real-time data, Pfizer improved its demand forecasting accuracy and reduced inventory holding costs.
• Novartis: Novartis utilized SCaaS to streamline its procurement processes, resulting in improved supplier collaboration, reduced procurement cycle times, and significant cost savings.
• GlaxoSmithKline (GSK): GSK adopted SCaaS to enhance logistics and distribution capabilities. The partnership enabled GSK to achieve greater supply chain visibility, reduce lead times, and ensure the timely delivery of critical medications to patients worldwide.

Small, early-phase pharmaceutical companies can gain the same benefit through SCaaS. Many times, these companies are resource—and finance-constrained and lack the ability to bring on all the resources needed to self-sustain a robust supply chain. By utilizing SCaaS, these companies have access to all the features of a large pharma supply chain management team at a manageable cost.

Challenges and Considerations

While SCaaS offers numerous benefits, there are also challenges and considerations to keep in mind:

• Data Security: Pharmaceutical companies must ensure that SCaaS providers have robust data security measures to protect sensitive information.
• Integration: Seamless integration between the pharmaceutical company’s systems and the SCaaS provider’s platform is essential for effective collaboration and communication.
• Trust and Collaboration: Building a solid partnership based on trust and open communication is crucial for the success of SCaaS initiatives.

Conclusion

Supply Chain as a Service (SCaaS) represents a transformative approach to supply chain management in the pharmaceutical industry. By outsourcing supply chain functions to specialized providers, pharmaceutical companies can achieve cost efficiencies, enhance focus on core competencies, access advanced technologies, and build resilient and flexible supply chains. As the industry continues to evolve, SCaaS will play a pivotal role in helping pharmaceutical companies navigate the complexities of modern supply chain management and deliver life-saving medications to patients worldwide.

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Author’s Note: If you have any insights or experiences with SCaaS in the pharmaceutical industry, please share them in the comments below. Let’s continue the conversation on how this innovative model shapes the future of healthcare supply chain management.

The journey from a promising molecule to a life-saving medication is complex. Drug development is a marathon, not a sprint. There are scientific uncertainties, regulatory hurdles, and ever-present financial pressures. Bringing a single drug to market can take over a decade and cost billions of dollars, with only a 10% success rate (references 1 and 2). So, how do pharmaceutical companies navigate this intricate maze and increase their chances of success?

Two powerful tools help manage drug development: the Stage-Gate Process and Integrated Risk Management (IRM). The Stage-Gate Process breaks development into phases with clear goals and decision points, while IRM identifies and mitigates risks throughout. Together, they improve efficiency, minimize risks, and increase the chances of delivering effective treatments.

The Stage-Gate Process

The Stage-Gate Process is a structured project roadmap that divides drug development into stages, each with specific goals and decision points to foster efficiency and ensure informed decision-making.

Stage 1: Scoping and Feasibility

In this stage, the basics of the drug development project are defined. Key questions addressed include:

• Defining the drug product and desired dosage form.
• Assessing manufacturing feasibility.
• Evaluating potential CMC risks (e.g., raw material availability, scalability).
• Developing a preliminary CMC development plan and budget.

A feasibility study evaluates scientific, technical, regulatory, and market feasibility. Based on this, a Go/No-Go decision is made to proceed with development or reconsider the project.

Stage 2: Preclinical Development

This stage focuses on testing the drug’s safety and efficacy in animals. CMC activities include:

• Developing analytical methods to ensure consistency and quality.
• Formulation optimization for stability and delivery.
• Supporting toxicity studies with CMC data.

A Go/No-Go decision is made based on preclinical data and CMC’s contribution to refine or continue development.

Stage 3: Clinical Development

In this stage, the drug is tested in human trials. CMC activities include:

• Scaling up manufacturing processes.
• Producing clinical trial materials under GMP guidelines.
• Conducting stability studies to determine shelf life and storage conditions.

CMC collaborates with clinical teams to ensure quality and compliance, with a Go/No-Go decision based on trial data.

Stage 4: Regulatory Approval

CMC plays a critical role in assembling the CMC package for regulatory agencies, including:

• Detailed manufacturing process descriptions.
• Analytical methods for quality assurance.
• Product characterization and stability studies.
• Quality control procedures.

Successful CMC strategies increase the chances of regulatory approval.

Stage 5: Launch and Post-Marketing Surveillance

With regulatory approval, CMC focuses on:

• Transferring manufacturing processes to commercial sites.
• Implementing quality management systems.
• Monitoring product quality and investigating adverse events.
• Continuous improvement of manufacturing processes and drug products.

CMC ensures ongoing safety and efficacy of the drug post-market.

Conclusion: The Advantages of Stage-Gate for CMC Management

The Stage-Gate Process enhances efficiency, mitigates risks, supports data-driven decision-making, and ensures seamless integration with overall development. It accelerates time to market and improves regulatory compliance, offering a flexible framework for successful drug development. By employing the Stage-Gate Process, CMC teams can navigate drug development more efficiently and confidently, ensuring the delivery of safe and effective medications to patients.

Let’s be real. When you think of “business networking,” you probably picture stale conference rooms, weak coffee, and awkward conversations where you try way too hard to remember the other person’s name without glancing at their badge every two seconds. But hold on, skeptics. Building those business relationships is more than surviving the rubber chicken dinners. In fact, it might just be the secret sauce to success (okay, maybe not as tasty, but equally important).

CONNECTIONS MATTER!!!

Let’s face it: connections matter. Suppliers often become your Fairy Godparents. You know that feeling when everything’s going wrong? The shipment’s delayed, your usual supplier is playing hardball on the price, and that client’s breathing down your neck for an earlier deadline? A good relationship can magically transform a nightmare into a “no problem, we’ve got you covered.” Suddenly, delays disappear, better prices materialize, and deadlines become flexible. It may not be actual magic, but it feels close.

I KNOW A GUY!!!

I can’t tell you how often our clients have a problem, and we respond with the “I Know a Guy” response. Need new software but want to avoid getting fleeced by slick salespeople? Trying to source that incredibly specific widget? A strong network is like having an army of helpful elves. Someone always knows someone who knows someone, connecting you with the right people in record time. The real point is that your network is the most fertile ground for idea generation. Someone else out there has had a similar problem, and they can relay their experiences. Remember! There’s strength in numbers!

TOGETHER, WE’RE MEANT TO DO GREAT THINGS!!!

Newsflash: those other companies in our industry? They’re not the actual enemy. Sure, some healthy competition is motivating. But imagine the power move of joining forces on a project, sharing market insights, or creating something bigger together. No one company is good at everything. By collaborating, we bring our individual strengths together to solve big problems. It’s like the Avengers but with business cards and slightly less awesome suits.

So, take the time to build GOOD Relationships.

Be natural and be yourself. Ditch the elevator pitch. No one enjoys being bombarded with a sales pitch the second you shake hands. Be genuinely interested in people and what they do. You might be surprised by what connections you form, even if they don’t seem immediately relevant to your business. That next new relationship may not solve today’s problem, but they may be an excellent person to know a week, a month, or a year down the road.

Don’t be shy about helping others first. This is a tough one for some people. It’s hard to not think of our business interactions as transactional. Don’t be the person who only shows up when they need something. Offer your expertise, make introductions, and be a valuable resource to people in your network. Karma’s a thing, plus you’ll build a reputation as someone people actually want to help in return. Don’t be afraid to give a little up to help somebody. I have found that this type of investment always pays good dividends.

An in-person, face-to-face meeting is one of the most important things, especially in today’s ZOOM/TEAMS/Mobile Phone world. Way back in the 1990s, that’s how we did ALL our business. Embrace the awkwardness. It’s not so bad! Let’s face it, networking isn’t always natural. Own it! Buy a box of doughnuts or some healthy snack, and go out there and meet somebody new. Tell a joke. A bit of humor and self-deprecation goes a long way. Remember, everyone else probably feels the same, and sometimes, the most unexpected connections blossom out of shared awkward moments.

The bottom line is that while you won’t magically become besties with every contact you meet, building strong business relationships is an investment. So next time you’re agonizing over whether to attend that industry event, ditch the cynicism and go for it. You might just be surprised at the opportunities you’ll enjoy as a result.

The pharmaceutical industry is instrumental in promoting global health, yet it faces increasing scrutiny over its environmental footprint. The dual challenge of ensuring access to essential medications while minimizing ecological impacts makes sustainability a crucial concern. Sustainability in pharmaceutical manufacturing has been an ongoing challenge for decades. Manufacturing managers and scientists work diligently to identify critical challenges, innovative strategies for improvement, and future directions. The industry can advance towards more sustainable practices by integrating green chemistry, waste management, and energy efficiency.

Pharmaceutical manufacturing involves complex processes that consume significant resources and generate substantial waste, leading to environmental pollution and resource depletion. The industry’s reliance on finite resources and the environmental toxicity of its waste products pose significant sustainability challenges. However, the growing awareness of environmental issues among consumers, regulators, and industry stakeholders drives the pharmaceutical sector towards more sustainable practices.

Sustainability Challenges in Pharmaceutical Manufacturing

Regardless of the specific pharmaceutical manufacturing processes, manufacturers have the same general challenges: Environmental Impact, Regulatory Compliance, and Economic Considerations.

Environmental Impact issues can be extensive. In broad-brush strokes, any facility needs to consider energy consumption, water usage, and waste generation/disposal:

• Energy Consumption: Manufacturing processes, sterilization protocols, and controlled environment maintenance rely heavily on energy, leading to substantial greenhouse gas emissions and contributing to climate change. Studies have shown that the pharmaceutical industry can be responsible for a significant portion of a nation’s energy consumption, highlighting the need for immediate action.
• Water Usage: Large volumes of water are utilized for various purposes, including cleaning, dissolving chemicals, and cooling equipment. This can deplete water resources and jeopardize local ecosystems, particularly in water-scarce regions. Research suggests that pharmaceutical manufacturing can significantly contribute to water stress in certain areas, demanding responsible water management strategies.
• Waste Generation: The production of pharmaceuticals generates various types of waste, particularly in manufacturing drug substance intermediates/final products, excipients, and components. These fall into three broad categories:

1. Solid waste: Unused materials, packaging, and equipment contribute to landfill burden, potentially leading to environmental pollution and resource depletion.
2. Liquid waste: Spent solvents, chemicals, and washing waters pose potential risks of water contamination if not managed appropriately. Improper disposal of these wastes can have detrimental effects on aquatic ecosystems and human health.
3. Hazardous waste: Expired drugs, contaminated materials, spent catalysts, chemical waste, and cytotoxic substances require meticulous management to mitigate environmental and health risks. Ineffective disposal of such waste can lead to soil and water contamination, posing serious threats to human health and ecological balance.

• Regulatory Compliance is an ever-changing landscape in almost every aspect of the pharmaceutical industry. In addition to FDA requirements to establish safety and efficacy in the use of the final drug product, the industry is tasked with meeting local, state, national, and global environmental regulations. Compliance with these regulations requires significant investment in cleaner production technologies and waste management systems, posing financial and operational challenges for pharmaceutical companies.
• Economic considerations are another critical concern across any production environment. Let’s face it: the pharmaceutical industry is a for-profit industry. Those profits drive the development of new products. Every manufacturing manager spends time daily or weekly analyzing the production cost variances. This is not to say that sustainability practices are cost-burners. Sustainable practices can ultimately lead to long-term cost savings and risk mitigation. The initial investment in green technologies and process redesigns can be a barrier for many companies, particularly smaller firms with limited capital.

Strategies for Sustainable Pharmaceutical Manufacturing

The pharmaceutical industry acknowledges the need for change and has actively explored many approaches to improve its environmental footprint. Promising strategies include:

• Green Chemistry: This approach prioritizes the utilization of safer reagents, catalysts, and solvents throughout the production process. This reduces the environmental impact, enhances worker safety, and minimizes waste generation. By implementing green chemistry principles, pharmaceutical companies can significantly reduce their reliance on hazardous chemicals and contribute to a cleaner environment. Techniques such as biocatalysis and flow chemistry have shown promise in making pharmaceutical manufacturing more efficient and environmentally friendly.
• Waste Management: Implementing waste minimization strategies like source reduction, segregation, and efficient treatment and disposal of different waste types is essential. Additionally, exploring alternative disposal methods like co-processing or waste-to-energy conversion can further reduce the environmental impact of waste. Effective waste management practices contribute to environmental protection and ensure compliance with relevant regulations. Some pharmaceutical companies have made strides in achieving zero waste to landfill, setting a benchmark for the industry.
• Energy Efficiency: Implementing energy-efficient technologies, including upgrading equipment and utilizing renewable energy sources like solar or wind power, significantly reduces greenhouse gas emissions and dependence on fossil fuels. Investing in energy-efficient infrastructure and exploring renewable energy options can lessen the environmental impact and lead to cost savings in the long run.
• Life Cycle Assessment (LCA): Conducting LCA studies helps identify and quantify a product’s environmental impact throughout its life cycle, from raw material extraction to disposal. This provides valuable insights for optimizing processes and minimizing environmental impact at each stage. By employing LCA, pharmaceutical companies can gain a comprehensive understanding of their environmental footprint and identify areas for improvement across the entire value chain.
• Water Conservation: Optimizing water usage through process redesign, implementing closed-loop systems for water recycling and reuse, and utilizing rainwater harvesting techniques are crucial for water conservation. By adopting these strategies, pharmaceutical companies can significantly reduce their reliance on freshwater resources and contribute to sustainable water management practices.
• Sustainable Packaging: Utilizing recyclable, biodegradable, or reusable materials for packaging minimizes environmental burden and contributes to a circular economy. This approach reduces waste generation and aligns with growing consumer demand for environmentally responsible products.

Collaboration for a Sustainable Future is critical for achieving true sustainability in the pharmaceutical industry. It involves a sustained effort from all stakeholders.

Pharmaceutical companies need to develop and implement sustainable practices within their operations and throughout their supply chains. This involves investing in cleaner technologies, partnering with environmentally responsible suppliers, and adopting transparent reporting on environmental performance. The industry needs to be the driver of these changes or else they risk having changes implemented from outside.

Government regulatory bodies are another key stakeholder. These agencies can implement regulations that incentivize and facilitate pharmaceutical companies’ adoption of sustainable practices. This helps create a cycle of positive change and more willing industry participation.

Consumers are also key stakeholders. Understanding the environmental impact of pharmaceutical production and making informed choices regarding medication use plays a large part in influencing industry practices toward sustainability.

The journey towards a sustainable future for the pharmaceutical industry is complex. However, the potential benefits are undeniable – a greener planet, improved public health, and a more responsible approach to life-saving innovation. Embracing sustainable practices may initially require higher investments and process adjustments, but the long-term benefits, including cost savings through resource efficiency and improved brand image, are immense.

By actively investing in sustainable solutions, fostering collaboration, and adopting transparent communication, the pharmaceutical industry can ensure its continued progress in improving human health without compromising the well-being of the place where we all live. This collective effort paves the way for a future where advancements in medicine coexist with environmental responsibility, creating a healthier tomorrow for all.

NOTE: To learn more about this topic, consider attending the DCAT Sustainability Summit: The Global Bio/Pharmaceutical Sustainability Imperative, May 21 – 22, 2024 in Lugano, Switzerland (https://dcat.org/luganosummit/)

Sickle cell disease (SCD), a genetic and inheritable blood disorder characterized by sickle-shaped red blood cells, impacts approximately 100,000 patients in the US and over 20 million people worldwide. The emergence of CASGEVY™ (exagamglogene autotemcel), the first CRISPR-Cas9-based gene therapy approved for SCD, provides hope for those afflicted with this disorder.

Traditionally, SCD was treated through blood transfusions, bone marrow transplants, and supportive measures (hydroxyurea, OTC NSAIDs, voxelotor, etc.) offering limited relief from chronic pain, fatigue, and organ damage. The quest for a definitive cure led to explorations of gene therapy, initially utilizing lentiviral vectors for β-globin gene correction. However, concerns about insertional mutagenesis prompted a shift towards the precision of CRISPR-Cas9 technology.

Vertex Pharmaceuticals and CRISPR Therapeutics spearheaded the development of CASGEVY™, employing CRISPR-Cas9’s unparalleled accuracy and efficiency. Pre-clinical studies in human hematopoietic stem cells established successful β-globin gene modification, paving the way for clinical trials. These pivotal trials, HITI-186 and HITI-229, provided hope for patients waiting for a permanent solution.

Patients underwent leukapheresis to collect their hematopoietic stem cells, subsequently edited ex vivo using CRISPR-Cas9 to introduce a functional β-globin gene. Reinfusion of these modified cells held the promise of producing healthy red blood cells. The results were transformative, with both trials demonstrating significant reductions in vaso-occlusive crises (VOCs), the hallmark pain episodes of SCD, alongside substantial improvements in patient-reported outcomes (PROs). This resonated deeply within the SCD community, generating widespread anticipation for CASGEVY™’s broader application.

Figure 1: Approaches to CRISPR-Cas9 mediated SCD Gene Therapy (https://www.synthego.com/crispr-sickle-cell-disease)

The path to regulatory approval was complex yet ultimately successful. In December 2023, CASGEVY secured the coveted status of the first FDA-approved CRISPR-based gene therapy, marking a historical turning point in both gene therapy and SCD treatment. Conditional approval by the EMA in November 2023 further solidified its potential, with final authorization eagerly awaited. With its indication restricted to individuals aged 12 and above with recurrent VOCs, CASGEVY™ represents a targeted yet crucial first step towards transforming the lives of countless individuals burdened by SCD.

While CASGEVY™’s approval is a monumental triumph, challenges remain. Long-term safety and efficacy data necessitate continued monitoring and the potential for off-target effects of CRISPR editing demands further investigation. Additionally, the intricate manufacturing process and high cost (projected at $2 million per patient) of CASGEVY pose potential barriers to access for many patients. Addressing these challenges through ongoing research, cost-reduction strategies, and broadened healthcare policies is crucial to ensure this life-altering therapy reaches those most in need.

CASGEVY™ is more than just a gene therapy; it is a beacon of hope for the SCD community. It illuminates a future where genetic modifications may permanently alleviate the suffering caused by SCD, enabling individuals to flourish instead of endure. Continued research, dedicated efforts to ensure accessibility, and unwavering scientific optimism are essential to realizing the transformative potential of CASGEVY™ fully. With each advancement, the shadows cast by SCD will recede further, allowing the light of hope to illuminate a brighter future for those living with this challenging condition.

For more information on this novel therapy, see:

1. https://www.businesswire.com/news/home/20231208951733/en/
2. https://time.com/6343853/fda-crispr-treatment-sickle-cell/
3. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease
4. https://www.sicklecelldisease.org/2023/10/26/scdaa-statement-on-exa-cel-gene-therapy/
5. https://www.scientificamerican.com/article/fda-approves-first-crispr-gene-editing-treatment-for-sickle-cell-disease/
6. https://www.oligotherapeutics.org/exa-cel-a-potential-breakthrough-with-astounding-results/

This month, Science published an article on the open science discovery of noncovalent SARS-C0V-2 main protease inhibitors (https://www.science.org/doi/10.1126/science.abo7201). It’s a fascinating article, and I urge you to read it. Aside from the science, I found it fascinating to read about the genesis of the COVID-19 Moonshot project.

The article shines a light on the COVID-19 vaccine, but there are many other examples of the use of AI and crowdsourcing in pharmaceutical development. Following the theme of COVID-19, there are two examples of marketed products that utilized AI in their development.

Benevolent^AI (founded in 2013) played a crucial role in repurposing the Lilly rheumatoid arthritis drug barcitinib for use in helping hospitalized COVID-19 patients improve and speed recovery. The FDA approved the drug in May 2022 to treat COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Over 1 million patients were treated with OLUMIANT® (barcitinib) worldwide under the original emergency use authorization (https://www.insideprecisionmedicine.com/news-and-features/these-six-biotechs-are-winning-the-race-to-get-ai-designed-drugs-to-the-clinic/).

Pfizer utilized IBM’s supercomputing and AI capabilities as far back as 2020. This led to the development of PAXLOVID®. AI technology reduced computational time by 70 – 80%, allowing them to design the drug in four months. (https://www.pharmaceuticalprocessingworld.com/ai-pharma-drug-development-billion-opportunity/)

The use of crowdsourcing in drug discovery is expanding. Multinational pharmaceutical companies are taking advantage of this in developing new drugs and to discover uses for old compounds:

Eli Lilly’s Open Innovation Drug Discovery Program connects research institutions, academics, and Lilly scientists on a collaborative platform designed to speed up progress in biomedical fields by leveraging distributed innovation. Lilly provides access to its databases, tools, and expertise, including private libraries of chemically diverse compounds and new molecule design tools​​. Since starting in 2011, the program has tested nearly 50,000 crowdsourced compounds, generating over 1.8 million data points, with a success rate comparable to traditional early drug discovery programs​​. (https://d3.harvard.edu/platform-rctom/submission/crowdsourcing-a-pharma-breakthrough-lillys-open-innovation-drug-discovery-program/)

Bayer Healthcare’s Crowdsourcing Platforms: Bayer Healthcare has initiated several crowdsourcing platforms like Grants4Targets (G4T), Grants4Leads, and Grants4Apps (https://www.grants4apps.com/). G4T, for instance, invites external scientists to propose ideas for targets and animal models. Proposals accepted and finding their way into Bayer’s drug pipeline can lead to collaborative agreements. G4T has been notably successful, with more than 1100 applications and contributions to 10 drug discovery projects​​. (https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1499-2)

BioMedX’s Collaboration Model represents a new approach at the interface of crowdsourcing and innovation centers. It includes pharmaceutical companies like AbbVie, Boehringer Ingelheim, Johnson & Johnson, and Merck. Based at Heidelberg University, this model supports interdisciplinary projects by young scientists in fields like oncology, neuroscience, and respiratory diseases. The aim is to translate these research activities into drug development projects​​. (https://bio.mx/)

The use of AI is also taking off in the field of drug discovery. Companies like Atomwise (https://www.atomwise.com/) and Schrödinger (https://www.schrodinger.com/) have created AI-based platforms for various aspects of drug discovery, such as target discovery using knowledge graphs and small-molecule design using generative neural networks. These platforms have enabled large pharma companies to enhance their pipelines through partnerships or software licensing deals. For instance, Roivant Sciences acquired Silicon Therapeutics to integrate distinct platform technologies, and Atomwise formed a joint venture with Schrödinger. As of 2022, AI-first approach companies have as many as 150 small-molecule targets in discovery and more than 15 in clinical trials. The annual expansion rate for this area of research is ~40%. Investment has more than doubled in AI-directed drug discovery programs ($2.4 billion in 2020 up to $5.2 billion in 2021). Combining this approach with CRO-based custom synthesis groups has cut the time to identify pre-clinical candidates from an average of 3 – 5 years, down to 12 – 18 months. (https://www.bcg.com/publications/2022/adopting-ai-in-pharmaceutical-discovery)

This mode of drug discovery is in its infancy. It represents an opportunity to make drug discovery, design, and development more efficient from a time and cost perspective. To pursue this, companies must strategically plan to incorporate this new approach. Management needs to define a specific vision and goals for this technology within their corporate environment and with their collaborative partners. Companies wishing to participate in crowdsourcing ventures must ensure they mesh well with those goals and visions. And, of course, being flexible will be critical to mutual success.

These examples illustrate how AI and crowdsourcing are revolutionizing pharmaceutical development, from drug discovery and design to clinical trials, enabling faster, more efficient, cost-effective, and potentially more successful drug development processes.