July 10, 2019

Supply chain management readiness, Part 4: quality risk management

Note: this post is the last of a four-part series on supply chain planning for personalized therapies such as cell therapies, gene therapies, or neoantigen cancer vaccines. You’ll find links to the other parts of the series below, and you can also download Vineti’s Supply Chain Readiness Checklist.

Previously in this series, we discussed the Strategy, the Operational Ecosystem, and the Processes needed to establish an effective personalized medicine supply chain. Now, we’ll turn our attention to one more essential component — managing risks across the supply chain for cell therapies, gene therapies, and cancer vaccines.

Quality Risk Management is essential for any drug product or therapy, with the key driver being patient safety. A robust Quality Risk Management program delivers other valuable benefits as well, including high-quality drug product, consistent compliance, operational efficiency, and improved decision-making in the event of an issue. Additionally, regulatory agencies expect that product sponsors will use a risk-based approach to product development and implement a program to minimize risk from the product’s use.

The FDA defines Quality Risk Management as “a systematic process for the assessment, control, communication, and review of risks to the quality of the drug product across the product lifecycle.”*  

Every drug product and process has some risk. But because of the complex  — and personalized — nature of advanced therapies, Quality Risk Management has heightened importance and requires a uniquely collaborative approach. The most significant differences in the personalized therapy supply chain are the sheer number of moving parts outside the manufacturing facility, the importance of external stakeholders, and the complexity of the processes for each individual batch of drug product. The patient and the health care providers are part of the process, and a patient (whether the actual patient or a donor) is an essential component of the product. These differences exponentially increase the complexity of the supply chain and create many additional opportunities for deviations and issues to arise — increasing overall risk. 

A systematic, data-driven approach to Quality Risk Management is essential for success. The most commonly used, and proven, industry methodology is the “Failure Mode Effects Analysis,” or FMEA. This tool and process help participants assess the different ways each step, or mode, of the end-to-end value chain, can fail, what the effects of a failure might be, and which risks are the highest priority for avoidance and mitigation strategies. 

Here’s a diagram with a quick definition of FMEA. 

The basic FMEA process is shown in the diagram below:

  • Identify all the steps (modes) of the process and where problems may occur at each step (mode)
  • Assign a “severity number” – how impactful is this to the patient or the business if a failure occurs?
  • Assign the “probability of occurrence” – how likely is this failure to occur?
  • Assign the “detection value” – how likely is this failure to be detected given the controls currently in place?
  • Calculate the risk priority number –  (severity number * probability of occurrence *  detection value)

During risk assessment, the entire value chain should be challenged from every angle., Therefore, it is important that this process is collaborative and cross-functional – and that brainstorming is encouraged. The owner of the risk assessment process can vary from company to company depending on what stage the company is in and the experience of internal staff. It is most common for staff from the Quality or Technical Operations group to be experienced with the FMEA process and take the lead. In more mature companies there could be a dedicated Process Excellence group or a similar function that specializes in assessment and improvement activities.

The result will provide a clear map of what areas need the most attention to reduce overall risk (as seen in the diagram below) and prioritizes what could otherwise seem like an overwhelming amount of work. 

This quantitative process also lays the foundation and provides common ground for the internal and external stakeholders to move forward. The next steps will likely involve developing and implementing operational improvements to remove or reduce risks and creating procedures for situations when a failure or deviation does occur. 

Quality Risk Management is a continuous effort and the risk assessment process should be revisited at various points in product development, clinical trial phases, and pre/post-approval. Information and learnings will grow across the value chain as data is collected from ongoing operations and stakeholders gain more experience with the product, processes, and patients. However, the timing of these reviews may vary from company to company.

An effective Quality Risk Management program will increase patient safety, which is of paramount importance. That is why regulatory agencies expect all pharma companies, including those in the personalized medicine space, to maintain one. An additional advantage to the FMEA or a similar approach is that it provides a useful tool for discussions with regulators and is a resource for them to review during an inspection. Other benefits of a successful Quality Risk Management program include reduced time to correct issues or deviations, increased customer service for patients and health care providers, and lower costs through improved operations and fewer failures.

There are also other types of risk management activities in biopharmaceuticals, such as activities related to product labeling, risk assessment, pharmacovigilance, special studies or interventions, or long-term patient outcomes tracking. We’ll be discussing these topics in later blog posts.

To put this Supply Chain Readiness series into action, you can use a copy of Vineti’s Supply Chain Readiness Checklist

Marc Puich has extensive experience in pharmaceutical manufacturing systems and cell therapy workflows and is Vice President of Business Development at Vineti. If you’d like to see how Vineti’s Personalized Therapy Management (PTM) platform can help you solve your advanced therapy supply chain and workflow challenges, please contact us to schedule a demo.

*FDA/CDER/CBER Guidance for Industry, ICH, June 2006, Q9 Quality Risk Management, IV General Quality Risk Management Process, p.3