March 18, 2020

Quality Management Systems for advanced therapies, Part 5: what does a successful QMS look like in advanced therapies?

Posted in Commercial Scale by Heidi Hagen, Subbu Viswanathan

Note: this post is the fifth, and final post, in a five-part series on Quality Management Systems (including cGMP and Quality Risk Management) for personalized therapies, such as cell therapies, gene therapies, or neoantigen cancer vaccines. You can find the previous post in the series here.

Advanced therapy supply chains, while challenging and complex, can be de-risked by employing proven Quality Management System practices. This blog series has taken a practical approach to discuss the essential components of QMS (Part #1) that benefit from special attention (Part #2), what a risk-based approach means (Part #3), and identifying and tackling the critical advanced therapy supply chain risks (Part #4).

Now, to wrap things up, we’ll turn our attention to understanding what success looks like, and some strategies for ensuring the development of a successful QMS.

How to achieve success

A successful QMS is the result of continual and intentional efforts throughout the drug developer’s organization and across the ecosystem. Quality is a mindset and a way of working that influences everything done individually and collectively. It is a combination of people + process + technology — effectively three legs of a stool that cannot stand without the other two “legs.”

QMS success requires integration of people, process, and technology

The advanced therapy ecosystem is a complex, interdependent web of people, process and technology. By carefully and intentionally deploying each type of resource across the ecosystem, the advanced therapy supply chain can be successfully de-risked.

The key is finding the right balance of each. An organization has limited resources available for operations and risk control efforts and the supply chain is a dynamic system. Determining the right mix of people, process, and technology requires consideration of the following:

How much of each resource is available in total and for this particular effort?
What is the most effective and appropriate solution for controlling this particular risk given its level of criticality?
If one particular type of resource and approach is used in one place, what might be sacrificed somewhere else?
How are other activities and risks (upstream or downstream) impacted by the implementation of a “solution” or risk control effort at a particular point?

Identifying and deploying the right risk control efforts takes careful consideration and should involve looking ahead. Here are six strategies used by industry veterans to approach risk control and determine how to integrate people, processes, and technology to ensure Quality and de-risk the advanced therapy supply chain.

Keep the patient front and center

The patient is the reason for everything a drug developer does. And treating patients safely and effectively with consistent, high-quality drug products is the only way to advance through the development lifecycle and receive product licensure. The FDA uses product quality-related data to evaluate IND applications and potential patient risk.⁵ Continually assessing and linking each activity back to this objective will help every participant, internally and across the ecosystem, stay focused.

Begin with the end in mind

Design a comprehensive QMS from a strategic point of view, with an eye toward efficient scaling (up and out), ultimate commercialization of the product, and supporting traceability requirements for the life-time of the patients. Both the FDA and EMA stress the importance of traceability and avoiding product mix-ups in recent guidance for advanced therapies. Involve ecosystem partners from the beginning. Collaboration and good communication from the outset will build trust and gain buy-in – and provide valuable information – thus providing a better result and reducing resistance and change management needs. And finally, leverage modern technology (such as Vineti) as early as possible to establish simple, cost effective, and error free processes from the start.

Support from senior management

Quality is a “way of working” and thinking, and when successful, it is an inherent part of the company culture. It starts at the top with commitment from senior management and incorporation of Quality (and Quality Management Systems) as a key business strategy. The FDA recognizes this foundational concept in the guidance and by placing the ultimate responsibility for senior management.^1,4 This commitment will be demonstrated through adequate resourcing and training, a “patient first” approach, continuous improvement and innovation, a focus on value-added tools and activities, and periodic management reviews.¹ Key performance indicators (KPIs) are one feedback mechanism that leadership can utilize when reviewing the QMS performance.

Stay grounded in data-driven decision making

With such a complex supply chain and so many moving parts, it can be hard to understand what is really happening and why. The key here is to focus on insights from the data and the science, base risk evaluation on scientific knowledge, and link it to the protection of the patient.²

This is sometimes easier said than done, given the volume of data generated in such a complex ecosystem and the number of participants, all of whom have thoughts and opinions. Additionally, paper based processes and multiple disconnected systems remain a challenging reality.

Automating processes and data collection (including integrating systems) early on will ensure that the right information is available at the right time to support data-driven decisions and a risk-based approach – and ensure compliance with FDA safety monitoring requirements.

For more information on the benefits of standardizing and automating data collection and how to approach it, you may also want to download our whitepaper: From Complex to Controlled – Proven Data Management strategies

Strive for standardization and simplicity

Advanced therapies have complexities in the processes and ecosystems not seen with other drug products. Therefore, the need for focusing on standardization as a QMS fundamental is paramount. The more simple and standardized the processes and systems are across the ecosystem, the lower the risk in the supply chain and the higher degree of success for the product. This is a place where automation can have maximum impact by eliminating manual processes and enforcing the correct steps in every process every time. Clarity and ease of use improve adherence and satisfaction on the part of the people involved in the processes as well, raising the level of overall compliance.

Continually monitor for effectiveness and new opportunities

We can’t say it enough — Quality and de-risking the supply chain are not one-time activities. The guidance states that “Risk management should be an ongoing part of the quality management process. A mechanism to review or monitor events should be implemented.¹ And for authorized advanced therapies, the EMA recommends annual quality reviews to “verify the adequacy and consistency of the existing processes, and to highlight any trends and identify opportunities for product and/or process improvement.⁶ More experience with the product and process will yield new learnings and insights. The successful organization will constantly be looking for ways to uncover insights and capitalize on them in the pursuit of higher Quality, lower supply chain risk, and patient safety.

Looking ahead – why it’s important to get this right from the beginning

Advanced therapies are a new frontier in the treatment of disease and the long-term implications are still unclear. Considering that patients are receiving live cells, modified genes and/or customized vaccine formulas, the regulatory agencies are requiring drug developers to monitor recipients for safety and efficacy well into the future. This can be in the form of post approval studies and/or programs, called “REMS” – Risk Evaluation and Mitigation Strategies, which are simply an extension of the risk management approach to the post-treatment time period and aim to enable drug developers to supply “novel drug therapies while ensuring the highest level of patient protection.”³ These therapies, in essence, become part of the healthcare system and part of the patient. Drug developers may need to maintain traceability for the lifetime of the patient, including multiple doses and multiple therapies. As more patients are treated with a single therapy (as a therapy scales in its target markets) and the number of advanced therapies available to patients increases, there must be solid, proven systems in place to provide clear information, not only for traceability but also to help healthcare providers and scientists understand the overall dynamics and impact of the therapies – and to carefully manage the risk profile of advanced therapies. One key foundational piece of this is a Quality Management system accompanied by Quality Risk Management.

Download the Guide

Six benefits of a successful QMS (and a de-risked supply chain)

Patient safety – zero mix-ups or near misses
Consistent product quality – high rate of “right first time” and ultimate product licensure
Satisfied “customers” – from healthcare providers, to vendors, to patients
Low error rates and costs – mistakes and deviations with activities large and small are rare, keeping costs down
Scalability – the QMS is flexible and will grow with the supply chain instead of being a hindrance
Real-time transparency – into product journey status, QMS activities (investigations, CAPA effectiveness, etc.), and other insights for internal stakeholders, regulatory agencies, and ecosystem partners

Conclusion

A successful Quality Management System provides significant benefits to the drug developer and the patient – and is required by the regulatory agencies. The six strategies outlined in this blog combine people + process + technology to provide a practical, incremental approach to QMS implementation and patient safety. Implementing fundamentals early and revisiting them often, will ensure the appropriateness of a QMS now and for the future of the product lifecycle.

Quality management systems for advanced therapies series:
Part 1: the essentials
Part 2: six areas of focus
Part 3: a risk based approach – what does this mean for advanced therapies?
Part 4: practical tips for de-risking the critical risks in the advanced therapy supply chain

If you have Quality-related supply chain questions for us in the meantime, please contact us. We’ve focused this blog series specifically on supply chain issues. If you have questions about other aspects of Quality in advanced therapies, such as rapid microbial testing, the Standards Coordinating Body is a helpful resource.

Heidi Hagen is the Chief Strategy Officer and a Co-founder of Vineti. Over the course of her career, she has overseen the operations and delivery for more than 100,000 doses of cell therapy. Subbu Viswanathan is Vineti’s Vice President of Quality, Security, and Compliance, with 20 years of experience in life sciences. If you’d like to see how Vineti’s Personalized Therapy Management (PTM)

Vineti PTM icon - PTM only clear.png platform can help you solve your advanced therapy data challenges, please contact us to schedule a demo.

References

Guidance for Industry Q10 Pharmaceutical Quality System, US Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), April 2009, ICH, P. 3-14. (https://www.fda.gov/media/71553/download)
Guidance for Industry Q9 Quality Risk Management, US Department of Health and Human Services Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), June 2006, ICH, P. 3,6. (https://www.fda.gov/media/71543/download)
New FDA Regulation to Improve Safety Reporting in Clinical Trials; Rachel Behrman Sherman, M.D., M.P.H., Janet Woodcock, M.D., Janet Norden, M.S.N., R.N., Cheryl Grandinetti, Pharm.D., and Robert J. Temple, M.D; July 7, 2011; N Engl J Med 2011; 365:3-5; DOI: 10.1056/NEJMp1103464 (https://www.nejm.org/doi/full/10.1056/NEJMp1103464)
Pharmaceutical Quality System (Chapter 1), EudraLex, The Rules Governing Medicinal Products in the European Union, Volume 4, EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use, 2012, P. 2. (https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/vol4-chap1_2013-01_en.pdf)
Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs), Guidance for Industry, US Department of Health and Human Services Food and Drug Administration, Center for Biologics Evaluation and Research (CBER), January 2020, P. 5. (https://www.fda.gov/media/113760/download)
Guidelines on Good Manufacturing Practice specific to Advanced Therapy Medicinal Products, EudraLex, The Rules Governing Medicinal Products in the European Union, Volume 4, Good Manufacturing Practice, November 2017, P. 8. (https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/2017_11_22_guidelines_gmp_for_atmps.pdf)