February 25, 2020

Quality Management Systems for advanced therapies, Part 1: the essentials

Note: this post is the first 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. This series focuses specifically on Quality issues, and cGMP, in personalized therapy supply chains.

Biopharma risks – big and small – are ever-present, especially for advanced therapies. These unique and complex therapeutics not only share the standard risks associated with any biologic product, but also carry an additional layer of risk due to the use of living cells as raw material and the manufacturing of products tailor-made for specific patients. Every step in the supply chain is affected by the variable, time-sensitive nature of these products. Yet the criticality of delivering safe and efficacious therapies to patients remains the same.

Given this variability and complexity, the pressures on teams are high. One proven way to de-risk an advanced therapy supply chain is with a robust Quality Management System (QMS). This tried and true approach is effective because basic QMS principles apply to any pharmaceutical product – from a white tablet to autologous cell therapy – and form a foundation for consistently delivering safe drug products. And indeed, in the FDA’s recently published guidance for gene therapy INDs, it has re-grounded the industry in basic QMS principles by indicating how to apply them to human gene therapies.¹ This blog, the first of a five-part series, will discuss select aspects of a QMS and how to expand them to de-risk and support advanced therapy supply chains.

Quality Management System (QMS) defined

Before getting into the details, let’s start with a review of what is meant by the term “Quality Management System” (QMS). In order to carry out its mission to ensure patient safety, the FDA requires Quality oversight of all aspects of producing drug products throughout the product lifecycle and recommends that biopharmaceutical companies operate a full QMS.^1,2,3,4,5 The EMA has similar requirements and directs companies to conform to ICH Q10.⁶

At the highest level, a QMS is defined by the FDA as a “Management system to direct and control a pharmaceutical company with regard to quality.”² Or put another way, a QMS is a basket of tools and systems used by an organization and its supply chain stakeholders to ensure that a quality drug product is produced and delivered every time. This includes elements such as quality control testing, training, vendor audits, standardized processes, lot genealogy, and in-process drug product labeling. 

Many of these QMS activities are collectively known as “current Good Manufacturing Practices” (cGMP), which are commonplace in the biopharma industry, but not in healthcare settings and other parts of the ecosystem for advanced therapies. This extension of cGMP into non-traditional settings is one of the key differences involved in implementing a robust QMS for advanced therapies. 

Unique aspects of an advanced therapy supply chain QMS

A critical unique feature of advanced therapies was introduced earlier in this post- the use of living human cells as a raw material. And because this raw material is procured from live patients outside of a GMP manufacturing facility – and is inherently delicate and variable – there is an extra level of complexity in the people, processes, and technologies involved in producing these therapies and safely treating patients. This requires special attention to certain aspects of the QMS and provides an ideal opportunity to utilize modern technology and data management when implementing a QMS.

For example, nothing changes in the nature of GMP when implemented for advanced therapies. GMP is simply propagated more broadly and with more complexity than is typical for a standard tablet or biologic. An effective QMS relies heavily on standardized processes and systems to ensure product safety and consistency. This need for standardization remains the same in advanced therapies, but there are also more processes that can be more complex and sometimes more manual. Therefore, to be successful, it’s important to:

1. Take a quality-minded approach from the earliest stages of product development.
2. Know the product and the processes (including everyone who touches the product and processes — and that can be dozens of individuals).
3. Utilize a risk-based approach to direct focus to the most impactful activities.
4. Employ a collaborative, partner-oriented approach across the ecosystem to maintain standards and consistency, build a continuous feedback loop, and identify and mitigate risks.
5. Implement technology solutions, where appropriate, to maintain Quality as processes scale. Complexity matters more here than volume — even at relatively low volume, a highly complex supply chain will benefit from automation.

Next up in this series on QMS, we’ll look at six key areas of focus for Quality Management Systems in advanced therapies. 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.

Quality management systems for advanced therapies series:
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 critical risks
Part 5: what does a successful QMS look like in advanced therapies?

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)  platform can help you solve your advanced therapy data challenges, please contact us to schedule a demo.

References

1. 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 Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), January 2020. (https://www.fda.gov/media/113760/download)
2. 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. 2,16. (https://www.fda.gov/media/71553/download)
3. Title 21–Food and Drugs, Chapter I–Food and Drug Administration, Department of Health and Human Services, Subchapter C–Drugs: General, Part 211 – Current Good Manufacturing Practice for Finished Pharmaceuticals, Subpart B (All Sections, Section 211.22) (https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=211)
4. Guidance for Industry: Quality Systems Approach to Pharmaceutical cGMP Regulations, 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), Center for Veterinary Medicine (CVM), Office of Regulatory Affairs (ORA), September 2006, Pharmaceutical cGMP Regulations. (https://www.fda.gov/media/71023/download)
5. Title 21–Food and Drugs, Chapter I–Food and Drug Administration, Department of Health and Human Services, Subchapter H–Medical Devices, Part 820 – Quality System Regulation, Subpart B (All Sections, Section 820.20) 
6. 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, Chapter 1 – Pharmaceutical Quality System, European Commission Health and Consumers Directorate-General, Health Systems and Products, Medicinal Products – Quality, safety and efficacy; Deadline 31 January 2013, Brussels, SANCO/AM/sl/ddg1.d.6(2012)860362 (https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-4/vol4-chap1_2013-01_en.pdf)
7. FDA.gov, What We Do. (https://www.fda.gov/about-fda/what-we-do#mission)