Introduction
Contract Development and Manufacturing Organizations (CDMOs) have become indispensable partners for pharmaceutical and biotech companies seeking cost-effective solutions, specialized expertise, and streamlined processes across the drug development and manufacturing lifecycle. As the demand for CDMO services continues to grow, embracing Quality by Design (QbD) principles is essential for CDMOs to differentiate themselves, mitigate risks, and deliver value-added solutions to their clients. QbD has emerged as a fundamental philosophy driving efficiency, reliability, and regulatory compliance.
Quality by Design: A right approach
QbD represents a proactive and systematic approach to ensure quality is built into every aspect of product development and manufacturing processes. It emphasizes a thorough understanding of product and process variables, risk assessment, and the application of scientific principles to achieve desired quality outcomes. QbD applied to process development and scale-up focuses on five main aspects: safety, environment, health, quality, and economics. The goal is to develop a robust and reliable process and transfer it to the manufacturing plant to ensure that quality product is delivered to the customer every time.
Neuland has expanded its capabilities to support a QbD approach to identify the critical quality attributes (CQAs) of active pharmaceutical ingredients (API) and the critical process parameters (CPPs). Our scientists create a robust design space with flexibility built in to maximize accuracy and reproducibility on scale-up and transfer to a manufacturing facility.
Implementing a QbD approach at Neuland
The principal objective underlying a QbD approach to drug manufacturing is developing a comprehensive understanding of the various parameters that can impact the drug candidate and ‘what-if’ scenarios to increase the likelihood of ‘right-at-first-time technology transfer.’
The holistic QbD life cycle implemented at Neuland involves:
- A clear understanding of the quality target product profile (QTPP) – drawn from the knowledge base around the product – identifying and characterizing the CQAs and CPPs and how they might be impacted by the raw materials, reaction and environmental conditions, and other factors.
- Determination of the CQAs, within an appropriate range limit or distribution to ensure the desired product quality, according to the ICH guideline governing
the product. - Design, implementation, and optimization of a process to manufacture the product – including risk assessment to evaluate the impact of raw material attributes and process parameters on the CQAs; development of an experimental method and design space (using DoE); and creation of a process control strategy that makes efficient use of multivariate analysis and feedback systems.
Figure 1. Drug development and manufacturing roadmap.
Figure 2. QbD methodology.
Successful application of a QbD approach can help advance a product and process from the lab to commercial-scale manufacturing and through the stages of regulatory approval more quickly and cost efficiently. Process optimization should not end with product launch, as a QbD approach incorporates continuous process monitoring and improvements to manage the product life cycle.
While identifying the potentially unexpected is a core element of QbD, using the information to reduce the risk of those what-if drug manufacturing scenarios is
equally important.
QbD approach to manufacturing process development
- Systematic evaluation, understanding, and optimization of the manufacturing process based on prior knowledge and data on how material attributes and process parameters affect drug substance CQAs.
- Experiments, simulations, and modelling to identify and confirm the relationships between material attributes and process parameters and drug substance CQAs.
- Analysis and assessment of the data to establish appropriate ranges, including establishment of a design space if desired.
- Apply Design of Experiment (DoE) to support process development studies, with the aim of reducing the number of experiments needed in developmental stage. Use of modern equipment like a parallel reaction station (Radleys Mya 4) and PAT tools (like Mettler Toledo FBRM) to speed up the rich data-driven approach.
Figure 3. Real time monitoring using a Mya 4 station and an FBRM probe.
About Neuland
Established in 1984, Neuland is a leading global Contract Development and Manufacturing Organization (CDMO) specialising in designing and development of complex drugs for biotechnology & pharmaceutical companies. With over 40 years of experience and expertise, Neuland provides an end-to-end continuum of customized services from early-stage drug development through to commercial manufacturing of complex APIs, including process development, process optimization, analytical testing, and regulatory support. Neuland has three world-class regulatory compliant API manufacturing facilities capable of handling complex chemistry reactions.
The company is headquartered in Hyderabad, India and the manufacturing and research facilities are situated near Hyderabad. Neuland is a reliable manufacturing and development partner to over 500 customers in 80 countries across US, Europe, Japan, APAC, India, MENA and LATAM.
Contact Details
marketing@neulandlabs.com
www.neulandlabs.com
