Pharma manufacturing control strategy starts with the patient

Global Technology Partner, NNE

Line Lundsberg-Nielsen

Global Technology Partner, 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 programmes, 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 organisation, 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 programme, and a well-recognised speaker at international conferences and events.

A robust control strategy is non-negotiable. Not only is it vital for making products, it is a key driver for equipment qualification, process validation, and life cycle management. It is also a good manufacturing practice "must" in the pharma manufacturing process.

Aptly named, a control strategy is a planned set of controls that are taken from a current product and process understanding. It makes sure a process performs as it should and maintains the quality of the product. It must also comprehensively consider the patient and product, while showing how the controls ensure product safety, efficacy and quality.

You can establish a control strategy by using enhanced Quality by Design principles or by using a more traditional minimal development approach. Whichever you choose, it must be implemented early on and considered throughout all cyclical phases, starting at the foundation for all pharmaceutical manufacturing – the patient.

Below is an outline of the steps you need to take to establish a control strategy with the patient in mind.

The development of a control strategy requires a structured process and a multi-disciplinary team of experts to link pharmaceutical development to the manufacturing process and engineering controls of process equipment.

Line Lundsberg-Nielsen, Global Technology Partner

From patient to product - outline the Quality Target Product Profile (QTPP)

Patients or healthcare professionals will give their input on how the product should ideally be designed. These patient needs are outlined in the QTPP under quality characteristics, and include administration form, dosage, purity and container closure system.

From product to process -  identify the Critical Quality Attributes (CQAs)

Once the QTPP is defined, you must identify the CQAs and rate them by severity, with an emphasis on the product safety, efficacy and quality. In other words, what is the consequence to the patient if the CQA varies?

There is then an evaluation of the proposed manufacturing process steps and the material used in relation to their impact on the different CQAs.

From process to production - an evaluation using scientific and risk-based prinicples

Each identified process step (where the process parameter could have a potential impact on a CQA) is then evaluated using scientific and risk-based principles. Variations in the CQA are also evaluated depending on differences in the process parameters and material quality. This can occur, for example, when there is a failure in the process, or a difference in raw material quality.

To determine the risk, you combine this with a facility-dependent evaluation of the likelihood of failure, and the probability of detecting the failure mode. The outcome of the process risk assessment, such as a Process FMECA or FMEA, shapes the control strategy, including the identified risk control measures and monitoring setup.

From equipment to process to product - what are the critical aspects?

Aspects of equipment that have an influence on a CQA are often referred to as critical aspects (CAs). A CA might be a critical process parameter and its control system, or a design feature of the equipment. These CAs must be identified during the process risk assessment.

This is to ensure that the equipment qualification plan and equipment maintenance plan can be integrated into the overall control strategy.

An interdisciplinary approach

To develop a control strategy you need structure - but you also need to involve a multi-disciplinary team of experts. In doing so, you link pharmaceutical development to the manufacturing process and the engineering controls of process equipment. Since both the process and the solutions overlap and are interdisciplinary, the control strategy must reflect that.

TechTalk

Recording: Manage the challenges of pharma 4.0

Control strategy is hot right now - it's a requirement, and it's good business. It is also a focus point for the FDA, issuing 5 warning letters in August and September alone. Get up to speed on control strategy with this webinar.

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