As compounds get more complex, so do the variables in development and manufacturing. API derived from biologic processes can be sensitive to aggregation, degradation, or subject to loss activity at any stage along the way. And given the expensive nature of biologic API, a significant quality issue that arises during manufacturing is not something any company wants to face.
Rethinking the concept of quality
Quality by Design (QbD) is a concept that’s important in today’s pharmaceutical industry. QbD is a holistic, proactive, science- and risk-based approach to the development and manufacturing of drugs. The goal is to design a process in which the critical steps that affect quality are identified and their influence measured and defined within an agreed “design space.”
So why is QbD emerging as such an important concept? Because it’s an approach with several potential advantagesto every industry stakeholder:
For drug companies, it enables consistent, robust production of quality products. QbD can help reduce batch failures and stock-outs, as well as enhance ROI by avoiding costly quality issues
For patients, it enhances consistency and quality, and it reduces the risk of recalls. In the case of generic drugs, it helps guarantee therapeutic equivalency to the reference drug
For regulators, it offers the potential for greater confidence in drug quality and may reduce the need for intensive oversight. It also may help reduce approval times and get more needed drugs to market faster
Over the past several years, both the EMA and FDA have issued guidance on the use of a QbD approach. A pilot program was launched, allowing drug companies to submit information for an NDA demonstrating the use of QbD principles. In 2006, Januvia, manufactured by Merck, became the first drug approved using QbD in the application process.
So how does Quality by Design work?
At the heart of the QbD concept is the idea that quality is built into a product based on an in-depth understanding of the product and process by which it is developed and manufactured. Knowledge of the risks involved—and how to mitigate them—is also a critical part.
To achieve that, several detailed steps make up QbD approach:
Basically, the process begins with a Target Product Profile (TPP) that describes the intended use, safety, and efficacy parameters of the product. This along with a target product quality profile is used by formulators and process engineers during product development. Critical Quality Attributes (CQAs), such as sterility or dose accuracy requirements, are then identified based on prior product knowledge or experience with similar compounds. CQAs are those things that must be controlled to achieve the TPP. A manufacturing process is designed to produce a final product having these CQAs.
A control strategy for the entire process is established, accounting for variability in material and process as well as expected changes in scale, etc. Using such a strategy and various In-Process-Control (IPC) and Process Analytical Technology (PAT) tools, the process is monitored and quality assessed in real time.
Vetter can provide Quality by Design
When you work with Vetter, you work with a company that embraces the innovators of manufacturing – which includes QbD. Vetter can support you to develop, monitor, and evaluate the manufacturing process according to QbD principles as well as Design Control of Combination Pruducts. We can optimize processes, as well as assist you in defining robust product specifications.
We can help you better understand the manufacturing process and risks in order to deliver a high quality product. Through development studies done within a QbD approach, we can help to identify potential risks early, allowing you to develop risk mitigation activities and implement a risk-based control strategy to enable consistent quality throughout the life of your compound.
Process Analytical Technology (PAT)
These analytical tools help monitor and control the manufacturing process, including accommodating for variability in material and equipment, in order to ensure consistent quality.
Target Product Profile (TPP)
This key strategic document summarizes the features of an intended drug product. Characteristics may include the dosage form, route of administration, dosage strength, pharmacokinetics, and drug product quality criteria.
Quality by Design (QbD)
This concept involves a holistic, proactive, science- and risk-based approach to the development and manufacturing of drugs. At the heart of QbD is the idea that quality is achieved through in-depth understanding of the product and the process by which it is developed and manufactured.
A New Drug Application (NDA) is the vehicle submitted to the FDA by drug companies in order to gain approval to market a new product. Safety and efficacy data, proposed package labeling, and the drug’s manufacturing methods are typically included in an NDA.
The Food and Drug Administration (FDA) is an agency within the U.S. Department of Health and Human Services. The FDA is responsible for the approval of new pharmaceutical products for sale in the U.S. and performs audits at the companies participating in the manufacture of pharmaceuticals to ensure that they comply with regulations.