Risk-based process design and advanced control technologies are key to cost-efficient sterile injectable manufacturing

4-Jul-2022

The industry generally understands that creating and maintaining aseptic sterile injectable (SI) processing environments is technically and financially challenging — even for the most adept contract development and manufacturing organisations (CDMOs), reports Fabio Stevanon, Director, Global Injectables Platform, CordenPharma International

Perhaps what could be better understood by all stakeholders, though, is how the quality of available aseptic SI capacity has never been more enabled. During the last decade, process design and quality control systems have seen vast improvements and advances in reliability and capabilities.

As a result, the industry now has aseptic capacity that can handle monumental challenges — such as those presented by the COVID-19 pandemic — when 14 billion doses of vaccines were processed, finished and dispensed.

Demand for control and capacity has expanded

The variety of drug products that require aseptic processing is vast and growing. From gallons of sterile water-for-injection to flu vaccines measured in microlitres, sterile processes are required to fill and finish them all. Strict environmental control is a mandatory prerequisite of aseptic processing.

The biopharmaceutical era has only increased pharma’s demands on the SI capacity remit of contractors. Many biologics are temperature sensitive and add another layer of complexity to aseptic processing. Lyophilisation capabilities and adequate controlled storage is also required.

On top of this, it is essential to unequivocally demonstrate to regulators that the environmental and quality controls implemented are compliant. Maintaining SI quality comes at a price and, for many producers, the costs simply became financially unsustainable.

Risk to quality, like the product, must be contained

Operationally, finishing sterile injectable drug products is no simple task. Processes demand containment, special equipment and cleaning procedures, plus constant environmental and people monitoring to ensure sterility even when the line is not in use. If any aspect of the aseptic process is compromised, the risk to product integrity and quality can have a negative, expensive and far-reaching impact on patients.

Sterility is sustained by effective containment, environmental control capabilities, proper people training in operating SI and monitoring all. To support cGMP operations, institutionalising Quality by Design (QbD) and Process Analytical Technologies (PAT) have become priorities for the Center for Drug Evaluation and Research (CDER) at the US FDA.

A systematic approach to development that begins with predefined objectives and emphasises product and process understanding, QbD is based on sound science and quality risk management. PAT is an important tool for the implementation of QbD because it can be used to monitor and control the manufacturing process with appropriate feedback and feed-forward controls.

Key lessons

Technology has and will continue to play an enormous role in establishing and sustaining conditions within controlled spaces. Aseptic sterile manufacturers, aided by their equipment and technology vendors, are increasingly able to better manage and sustain all aspects of sterility in process. Robust automated data collection, smart, high-speed inspection technologies and PAT in train all help to manage process risk and ensure product quality.

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The worldwide SI capacity right now just keeps up with demand. The industry has learned a lot about SI manufacturing quality in the past two decades and the lessons for CDMOs are clear: a greater emphasis on operational excellence, combined with the strategic application of QbD principles and PAT, are the keys to providing the cost-efficient, sterile manufacturing capacity the world needs — without compromising product quality or operator safety.

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