Quality by Design (QbD)

It is a simplistic analogy, think of formulation and process development in terms of developing the recipe for a cake. The result should mimic a packaged cake mix, which includes or lists all the ingredients required and provides complete yet simple instructions. By using these ingredients and following the directions, you create a cake that has the appearance, texture, and taste described in the product’s literature. The cake mix represents a well-defined formulation, manufacturing process and control strategy that enables a home baker to produce a delicious dessert.

Whether it is a cake or a tablet, capsule, cream or injectable, the formulation development process is the same: Identify the ingredients and their essential properties and quantities. Likewise, with process development: Specify the equipment, and critical processing conditions and times. The result is a formulation and manufacturing process with a defined control strategy which should give you a product that can be manufactured over and over again to its defined quality standard.

Quality Can Be Planned

Quality by Design (QbD) for product development and manufacture is a concept which states that quality can be planned and that most quality problems relate to the way in which quality is planned.: QbD principles have been used to advance product and process quality in many industries. In fact, almost all commercial products outside pharma use manufacturing techniques that ensure product quality by building it into the process by which the product is manufactured.  Very few products are release-tested to ensure that they meet their design specifications prior to commercial distribution. If done properly, this same concept should work with pharmaceutical products. Thus, in last decade or so the FDA has promulgated QbD as part of its 21st Century Initiative as a vehicle for transforming how drug products are developed and manufactured.

The FDA’s 2004 “Guidance for Industry: PAT–A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance” introduced the concept of building quality into the preparation of drug products through the use of Process Analytical Technology (PAT). The goal was to replace end product testing as a means of ensuring that a product met its specifications. The International Committee on Harmonization (ICH) with the help of pharma and global health authorities has issued guidance documents, Q8 through Q11, that describe how QbD concepts apply to the lifecycle of a drug product.

Product and Process Understanding

In short, quality can be designed into products if you follow well-defined development practices. It starts with gaining product and process understanding, followed by identifying, evaluating, and minimizing risk.

To achieve the required safety, efficacy, manufacturability, and stability using QbD, follow these steps:

• Define the QTPP, which describes the design profile of the product and forms the basis for the development of the quality attributes that ensure clinical safety and efficacy. The QTPP also forms the basis for the control strategy.
• Review prior knowledge including the scientific literature and experience with similar dosage forms and/or with APIs that have similar properties.
• Evaluate the physicochemical properties of the API and how potential excipients could affect the dosage form.
• Conduct an assessment to identify, understand, and minimize the potential risks associated with the preparation that may affect manufacturability, safety, or efficacy.
• As needed, conduct studies to facilitate and understand the product’s design and the manufacturing process.
• Develop a control strategy to ensure that the product will have the required quality attributes and be consistently produced. This control strategy will be derived from product and process understanding and should ensure that the process performs as designed and gives the specified product quality.

For more information on how you may be able to use Quality By Design Concepts in your formulation and process development  activities, please fill out the Contact Form on this page.