Integration of Emerging Technologies in Drug Substance and Drug Product Development and Manufacturing

1. Can you provide an overview of your understanding of the term "emerging technologies" in the context of drug substance and drug product development and manufacturing?

Emerging technologies are technologies that are in the early stages of adoption in drug substance and drug product development and manufacturing in the biopharmaceutical industry. In some cases, the technology may have been known for several decades; however, its adoption in drug substance and drug product development and manufacturing may still be in the nascent stage. I would include these technologies under the term “emerging technologies” in the context of drug substance and drug product development and manufacturing.

2. What are some specific emerging technologies that you believe hold significant promise for advancing the pharmaceutical industry in terms of efficiency, quality, and innovation?

I think machine learning, robotics, continuous manufacturing, additive manufacturing, new catalysts (organic catalysts, photocatalysts, and enzyme catalysts), click and flow chemistry, drug bioavailability enhancement, drug delivery technologies, and blockchain are emerging technologies that hold a lot of promise in the next 5-10 years.

3. When integrating emerging technologies into drug development and manufacturing, what challenges do you foresee in terms of regulatory compliance and validation? How do you plan to address these challenges?

The typical challenge with regulatory compliance and validation and adoption of emerging technologies is the uncertainty of regulatory acceptance. This lack of guidance can hinder the integration of emerging technologies in the highly regulated environment of the biopharmaceutical industry, as any questions with the emerging technology can extend the timeline for regulatory review and approval of a marketing application.

There are several ways to address such challenges: The firms that promote the technology can form a consortium and engage directly with the regulatory agencies with proposed standards and seek guidance for a process/pathway for implementing their technology in the biopharmaceutical industry in a compliant manner as part of drug development and manufacturing.

From the perspective of someone leading drug development in the biopharmaceutical industry, early engagement with the regulatory agencies through meetings to propose a plan and seek agreement on implementing the new technologies can help avoid surprises. For some new technologies, there may not be an official position or guidance from the agency, and the lack of guidance can delay the implementation of those technologies.

In recent years, regulatory agencies have supported innovation and adoption of emerging technologies. Examples of this support are the new FDA discussion paper and request for feedback on Artificial Intelligence/Machine Learning titled “Proposed Regulatory Framework for Modifications to Artificial Intelligence/Machine Learning (AI/ML) - Based Software as a Medical Device”. The draft guidance “Marketing Submission Recommendations for a Predetermined Change Control Plan for Artificial Intelligence/Machine Learning (AI/ML)-Enabled Device Software Functions.”

4. Could you discuss potential hurdles in terms of workforce readiness and skill development that might arise with the adoption of complex emerging technologies? How do you plan to bridge these skill gaps?

Workforce readiness and skill development are critical issues for complex emerging technologies and some solutions include:

1. Training programs
2. Partnering or collaborating with academic or research institutions,
3. Partnering or contracting with technology or solution providers, and
4. Targeted hiring of skilled talent

5. How do you approach the process of selecting emerging technologies for integration? What criteria do you consider to ensure that the chosen technologies align with your business goals?

Some questions to consider when selecting an emerging technology include:

1. Does the technology support current and future drug development and business goals?
2. Does it provide a sustainable competitive advantage?
3. In which stage of the hype cycle is the technology? It is preferable to choose technologies in the later stages of the trough of disillusionment or in the slope of enlightenment, and to avoid technologies that are still at the peak of inflated expectations,
4. How long would it take to implement the technology, and what is the time needed for it to make a significant difference in an R&D or manufacturing environment?
5. What are the upfront and ongoing resource commitments required to implement the new technology, and what is the return on investment?

6. Maintaining product quality is paramount in pharmaceuticals. How do you plan to implement quality control measures for newly integrated technologies, and what strategies will you employ to minimize associated risks?

The quality impact depends on the technology, the area, and the stage of drug development in which the technology is adopted. For instance, the quality impact in the early stages of drug development is lesser than in later stages. To manage and mitigate risk, a change control process is used, and phased implementation is used, with feasibility testing, use testing, protocol-driven qualification and validation, and comparison of release and stability data for impacted drug substance and drug product batches before and after the change.  

7. How do you stay updated on the evolving regulatory landscape and guidelines related to the integration of emerging technologies in drug development and manufacturing?

There are various regulatory information sources that one can use to stay updated, including Health authority websites (FDA, EMA, etc.), societies such as Regulatory Affairs Professionals Society RAPS, regulatory news publishers, blogs, software vendors, and newsletters such as Dickinson’s FDA review and FDA Aware. The above description is not an endorsement of any of the vendors or services; it is shared as an example of external sources of regulatory information that are available to keep oneself updated on the evolving regulatory guidelines.   

8. Collaboration is often crucial in technology integration. How do you identify potential collaborators, such as technology providers or research institutions, and what factors do you consider when forming these partnerships?

It's very important to choose the right technology partners and collaborators.  Some factors that can help in choosing the right partner/collaborator research institution or technology provider are

1. Does the research institution or technology provider have the level and depth of expertise in the given technology domain?
2. Can they support your department/company’s specific needs and objectives?
3. Are they going to be around 5 to 10 years from now to support the implemented technology at your organization through its lifecycle?
4. Size, scope, capacity and capability of the team - scientists, engineers, and project managers who will support your project after business development has moved on
5. Culture fit - transparency, flexibility, etc.
6. Budget is also a factor so knowing the total cost/expense associated with the implementation of the technology through its lifecycle at your organization - including implementation, troubleshooting, upgrades, training, etc.

9. In your opinion, how do you envision the pharmaceutical landscape evolving over the next 5 to 10 years due to the integration of emerging technologies?

In the next 5 to 10 years, I expect the pharmaceutical landscape to evolve to become more automated, with more environment-friendly processes and more patient-friendly products,

Greater access to large volumes of more reliable curated data sets, the exponentially increasing computing power to process the data, and the sophistication of the machine learning algorithms will drive the increased use of machine learning in drug development and manufacturing. Advances in hardware and software will increasingly drive automation and robotics in manufacturing.

Greater adoption of flow chemistry, click chemistry, organic catalysts, photochemical catalysts, and enzyme catalysts will drive more environmentally friendly processes for drug substance manufacture.  Increasing adoption of continuous manufacturing can lead to more environmentally friendly drug product manufacture closer to the markets where those drugs are needed and the adoption of additive manufacturing can lead to more custom drugs for patient-stratified medicines with distinct release profiles.

Novel drug bioavailability enhancement technologies will allow for the development of more chemical space in drug development, and novel drug delivery technologies will allow for the development of unique delivery of drugs allowing for patient comfort with extended release over a period of time supporting patient medication adherence, Greater adoption of blockchain can allow for more robust drug product supply chains and near real time update to patient drug labels

10. Reflecting on your experiences, could you provide insights into where the integration of an emerging technology did not go as planned? What were the key takeaways and adjustments made from that experience?

Three important lessons learned on the integration of an emerging technology include,

1. It's important to choose the right technology partner who can support your department/company’s specific needs, and match the organization's culture.
2. Don’t overestimate your own capabilities or your organization’s capabilities in the area of an emerging technology i.e., be aware of the risk of the Dunning-Krueger effect and try to be objective about your capabilities and that of your team, your organization, and partners when implementing an emerging technology.
3. Implementing an emerging technology at the local US R&D site is a challenge, but when the same emerging technology is being transferred to other R&D or manufacturing sites globally then even small differences can compound and lead to greater roadblocks, Having the same technology team available to manage the integration of the emerging technology at the site and to trains SMEs capable of troubleshooting any issues on an ongoing basis is critical.

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