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By Dafni Bika

Dafni Bika-finalA key challenge of manufacturing is variability. Variability is caused by many operational and human factors including human error, environment, wear and tear, variability in raw materials and active ingredients, and unclear procedures. It could also result from product and process design, for example, due to insufficient raw material controls and poorly defined processes. Lack of knowledge and risk understanding could also lead to unacceptable residual risks. Through the product life cycle, these risks may compromise the ability to supply the market and add significantly to operating costs. Historically, the pharmaceutical industry has responded by correcting and resolving issues of variability rather than focusing on systems designed to prevent these issues before they happen. This article describes a preventive and holistic strategy to reduce variability and ensure product quality and supply, which started several years ago as a remediation project for legacy products.

The realization that manufacturing issues can be prevented provided the impetus for a global program we today call Product Robustness. Product Robustness is a comprehensive, end-to-end program that seeks to continually reduce variability in processes, products, and supply. It is a strategic imperative and focuses on product (not just process) and effective capability throughout the value chain. Therefore, Product Robustness is the certainty and ability that any product, at any time, in any place, from any company-owned manufacturing facility or allied manufacturer, is of expected quality and available when, where, and how it is intended.

The Product Robustness program has senior management sponsorship and support because:

  • It is viewed as a quality improvement initiative that reduces deviations and eliminates recalls.
  • It is applied as the life cycle extension of quality by design into manufacturing. It provides the data and mechanisms to continue to build process and product understanding, improve our control strategies, and predict future product quality performance.
  • In development, it helps quantify risks, inform risk-based decisions, select robust specifications, define readiness for process performance qualification (PPQ), launch, and address residual risks postlaunch.
  • It provides the framework and approach to demonstrate ongoing process control and reproducibility in compliance with the Food and Drug Administration’s Continued Process Verification and other agencies’ equivalent expectations.
  • It helps anticipate and mitigate risks to supply continuity, prevent drug shortages, and ensure that network and low inventory strategies are successful.
  • It helps reduce the cost of poor quality (COPQ) by preventing deviations and thus reduce the number of investigations and reoccurring events/problems via awareness and directing the right preventive actions to low capability areas.

The Product Robustness framework focuses on four functional areas: supplier, equipment and facilities, process, and packaging and distribution. The four enablers are people and culture, ways of working, business processes, and technology. The cover article in the August issue of the AAPS Newsmagazine explores the scope and purpose of the four enablers of Product Robustness. Read Product Robustness: A Comprehensive Product Quality Strategy, from the MSE section, and then participate in the discussion point below.

What are the current challenges or approaches to instill a preventive mindset in pharmaceutical manufacturing?

Dafni Bika, Ph.D., is head of global pharmaceutical manufacturing science and technology at Bristol-Myers Squibb, which provides technical expertise and innovative technology solutions for API and drug product manufacturing and packaging operations worldwide.