The quality by design (QbD) methodology is nothing new for the medical device or life sciences industries, but it has evolved over time. Since the mid-20th century, and in works such as Joseph M Juran’s Quality Planning and Analysis, quality planning has been a core tenet of QbD. The approach has become fundamental to the way medical device companies employ risk-based strategies to make product development quicker, better and more efficient.
QbD is simple in essence. It is a systematic approach to ensuring product quality by building it into the design and development process rather than waiting until the end-product testing stage to evaluate quality. It represents a shift towards a proactive method based on scientific principles, risk assessment and statistical methodologies to create high-quality devices rather than traditional reactive quality control processes. It starts with clearly defined objectives, including the device’s intended use, its desired performance characteristics and the needs of target users. It requires an in-depth understanding of the product’s critical quality attributes (CQAs) and the critical process parameters (CPPs) needed in the manufacturing process. On top of that, it incorporates risk assessment throughout the development process to identify all potential issues that could negatively impact on quality so that manufacturers can implement the necessary controls. The rigorous use of statistical tools further optimises design and manufacturing processes to ensure greater consistency in product quality.
At the end of the process, manufacturers stand to benefit from the higher quality of their products, with fewer iterations and adjustments to the manufacturing process along the way. Rigorous risk management throughout should limit the potential for defects and ultimately product recalls. Not only is patient safety improved, but the enhanced efficiency of the product development process can play a huge role in reducing time to market and keeping manufacturing costs to a minimum without compromising quality in any way. As a result, more flexible regulatory pathways for medical devices may open, as a more proactive, science-based approach to development and manufacturing – and the deeper understanding of product and process interactions that comes along with it – can result in more efficient and adaptable regulatory submissions, potentially reducing the time and resources required for the approval stage.
The many moving parts of QbD
So far, so good, but in practice QbD involves many key steps, starting with defining the CQAs – the characteristics of the medical device that are critical to its safety and efficacy. Next come the CPPs – the manufacturing process parameters that can impact the CQAs. Then there is a risk management process using tools such as failure mode and effects analysis (FMEA) – a systematic and proactive method for identifying potential failures in systems, processes or products.
15%
The quality assurance services segment is projected to attain a fast CAGR growth during a forecast period to 2030.
Grand View Research
But that is by no means the end of it. Design of experiments (DoE) is a statistical method used to plan, conduct, analyse and interpret controlled experiments that evaluate crucial factors that influence a process or product. DoE can shed light on the relationship between CPPs and CQAs and lead to further optimisation of the manufacturing process. Then there is a need to establish process controls to maintain the CPPs within acceptable ranges during manufacturing before the validation phase, which confirms that everything is operating effectively and documents the QbD process. The results of QbD can be transformational, but there is a lot to do here and it begs the question whether this really is an area of core competence for OEMs.
An obvious opportunity for outsourcing
The importance of QbD is something that regulators are keen to emphasise. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are working together to encourage the adoption of QbD frameworks that integrate successful product development processes with the needs of patients and the regulatory requirements they have set down. This is partly because the value of QbD has been frequently demonstrated in real use cases.
During the Covid-19 pandemic, some 3D-printing companies in Belgium and elsewhere rapidly retooled to produce swabs and other devices to help meet shortages. In many cases, they worked with external partners to meet regulatory and quality requirements, showing how outside expertise can be critical when speed and compliance are equally important. So, does something that can contribute so much to successful product development have to be done in-house, with all the complexity and investment that would be required? The answer, it seems, is no.
A growing number of medical device companies are outsourcing QbD to control costs, improve device quality and gain access to specialist expertise. In part, this trend is driven by the everincreasing complexity of the devices they produce. This, coupled with the need to deliver these products to market faster, is putting greater pressure on the design and manufacturing processes. More than ever, OEMs need to get it right the first time.
At the same time, they want to focus on core competencies such as R&D, marketing and sales without investing in the development of in-house QbD expertise. Outsourcing allows companies to leverage the experience and resources of specialised contract manufacturers and design firms, which promise more efficient and higherquality product development.
The industry knows well that outsourcing can significantly reduce the costs associated with manufacturing, quality control and regulatory compliance. Contract manufacturers often utilise advanced technologies for complex manufacturing and invest in keeping their technology infrastructure up to date. Outsourcing has demonstrated its ability to accelerate product development by leveraging specialist expertise and offers the ability to scale up production on demand.
In essence, medical device companies are recognising that QbD is not just about internal processes but also about strategic partnerships that can enhance their overall capabilities and competitiveness. Sure, the industry continues to spend millions on QbD, but it is imperative that those huge investments bring proportionate returns.
Turning data into quality
The heavy cross-functional investment in design quality and manufacturing is meant to result in higher product quality with fewer iterations, but the return on investment in QbD can often fall short of expectations, particularly if the money is spent on developing in-house processes.
The inefficiency may come from the failure of continuous process verification programmes to make best use of manufacturing data. Real-time, transactional manufacturing data has great value in determining how any shortfall in quality has arisen. Understanding it can pay huge dividends down the line, not only when it comes to post-launch issues but also in the development stage before the product is finalised.
Outsourcing a host of QbD services – everything from initial risk management through post-market surveillance, including statistical DoE, risk-based control strategies and validation protocols – can leverage the investment that is being made by software vendors in developing QbD modules within their digital quality management systems (QMS). These systems are optimised to use data from manufacturing and a host of other processes to enable CMOs and OEMs to outsource QbD execution, data capture and regulatory-grade validation with confidence.
The services on offer come under ISO 13485 and FDA design-control frameworks, both of which are crucial for ensuring the quality and safety of medical devices throughout their life cycle. They establish a structured approach to design and development to ensure that devices meet user needs and regulatory requirements. Though they do differ in some respects, they share the same core principles of planning, specification, review and correction.
Software meets science
Software vendors are embedding QbD processes into QMS systems through modules that streamline processes, enhance traceability and facilitate proactive risk management, ultimately improving product quality and compliance. A QMS can be integrated into the entire design process so that key quality parameters are factored in at every stage. It can also identify, assess and mitigate any risks associated with product design and manufacturing, making risk management a proactive process.
Integration with manufacturing execution systems (MES) and ERP systems enables a QMS to provide real-time monitoring and control of production processes and some QMS solutions also offer statistical process control capabilities that allow manufacturers to track and analyse process variations and identify potential issues before major problems arise.
Through document management, change management and workflow automation through to high-end reporting and analytics on quality performance and compliance status, the latest generation of QMS solutions is enabling software vendors to help their clients build quality into their products and processes from the outset.
While traditional approaches to QbD may bring significant value – for a price – a more dynamic, costeffective and flexible approach is close at hand.
