3 key approaches to control strategy in pharma manufacturing

Managing Consultant, Compliance Consulting, NNE

Line Lundsberg-Nielsen

Managing Consultant, Compliance Consulting, NNE

Line has worked in the pharmaceutical industry, both in pharmaceutical development and product manufacturing, for the last 20 years. Her background is in physics and she holds a PhD in Process Analytical Technology.

Line is experienced in pharmaceutical development using a science and risk-based QbD approach. She has worked with different innovator and generic clients implementing QbD strategies, QbD programs, QbD tools, advanced control strategies based on real time release and QbD-based regulatory submissions of new product applications (MAA). She has also been part of a team developing, submitting and gaining approval for an oral solid dosage formulation based on QbD, design space, PAT and full real-time-release testing.

Line was one of the pioneers who, together with the FDA, EMA and the ASTM standard organization, helped to develop the science and risk-based framework - the new foundation for product development and manufacturing in the pharmaceutical and biotech industry. She is active in ISPE, a member of the global PAT & Lifecycle Control Strategy Community of Practice, a global trainer in QbD and process validation, advisor for De Montfort University and their QbD program, and a well-recognized speaker at international conferences and events.

To achieve consistent product quality, having a control strategy in place is non-negotiable. But with considerations such as the patient, GMP compliance and future production, where do you begin when outlining a strategy for pharma manufacturing?

The key to manufacturing a product of consistent quality is control strategy. Yet if you want maximum value, you need to understand the overall process - ultimately preventing many manufacturing issues that plague the industry today.

A lack of understanding means supply delays, drug shortages, GMP issues and pre-approval inspections failures – all of which cause a delay in product launch. So control strategy, in a multitude of different ways, can significantly improve manufacturing and save costs. Here are three key approaches to help you make sure your develop a strong, patient-centric control strategy:

1. Put the patient first

Control strategy starts with the patient and should always be established during development with the patient in mind. A Quality by Design (QbD) system should:

  • Establish the quality target product profile with related critical quality attributes.
  • Identify the critical process parameters and material attributes.
  • Outline how the process should be operated and controlled to make sure the product is of the right quality, the intended quality target and critical attributes.
  • And finally, the control strategy used for commercial production must be approved by healthcare authorities and reflected in the master batch records and standard operating procedures.

A patient-centric control strategy is the foundation for designing a manufacturing facility and production line. This is true for: conceptual process and facility design studies, defining user requirement specifications, equipment and facility qualification, process performance qualification, process validation, continued (ongoing) process verification program, as well as the daily manufacturing and control program.

When is a patient-centric control strategy defined?

You must define the patient centric control strategy during product development and process design. It  should focus on achieving the right critical quality attributes by controlling critical process parameters and material critical quality attributes, often done on a lab scale.

As soon as the process is scaled-up and transferred to a commercial site, you should expand it into an operational-oriented production control strategy using a cross-functional team, including subject matter experts in development, production, technical support, quality assurance, engineering and automation and IT.

2. Combine control strategy with GMP

Control strategy can also be combined with the GMP design strategy for front-end studies. This builds the foundation for the conceptual design of a new expansion or improvement of a production line or facility.

In fact, it is difficult to propose a proper design without a control strategy. This is because it provides a systematic and structured approach to the design, including GMP aspects and regulatory expectations. Additionally (circling back to the patient) it provides a more solid base for customer decisions and reduces the risk of having to invest significantly more at a later stage - particularly when it becomes clear which products will be manufactured in the facility or at the new line, and how.

A control strategy evolves throughout the product lifecycle. It is product-specific during submission, but after scale-up and technology transfer and just before process performance qualification or process validation, it embraces facility, equipment, utility, process automation controls and other GMP controls.

It even encompasses business-oriented controls, including yield, production lead-time, overall equipment effectiveness, energy consumption, waste water, operator protection, and environmental controls. Often, this control kind of strategy is known as, ‘Production Control Strategy’ or ’Manufacturing Control Strategy.’

3. Focus on production in control strategy

Production control strategy is highly complex as it reflects process understanding. However, if it is established using a systematic science and risk based approach, you are able to utilize its full potential for other activities when ramping up the facility and making it ready to produce products.

Production control strategy serves as an input and definition for the master batch records, the process control system and the batch execution system. However it is also useful to define the continued ongoing process verification, for process automation projects, for smarter and leaner qualification and validation programs, and finally, for continual improvement activities.

A robust production control strategy, based on process understanding, implemented in commercial operation minimizes the risk of compromising product quality and process robustness. It helps to address deviations, improve overall management, and means continuous improvement can be proactively proposed. And improvement opportunities drive lifecycle management activities - benefiting both the patient and the business.