What is Quality by Design (QbD)?

Quality by Design (QdB) was first developed and coined by the American-Roman engineer and management consultant, Dr. Joseph M. Juran. He believed that quality should be built into the product from the beginning and that most quality crises and problems relate back to the ways in which the product was originally planned.

Although Quality by Design is largely used to advance product and process qualities across various industries, this concept has been applied particularly to the automotive and pharmaceutical industries.

In general, there are two key aspects to the word ‘Quality’ in Quality by Design:

1. The existence of features that bring customer satisfaction
2. The reliability of those features

There are two simple ways of improving quality:

1. Eliminating failures in features that lower customer satisfaction
2. Increasing the reliability and the number of features that bring customer satisfaction

The key takeaway here is that Quality by Design begins with the customer and ends with the customer. It is a customer-focused optimization, hence the focus on improving features that increase customer satisfaction.

1. Define the product’s design targets and goals
2. Define the ideal market and customers
3. Research the needs of the market and customers
4. Develop features of the product that will meet those needs
5. Produce those features
6. Develop process controls to transfer the new designs to operations

Quality by Design is prevalently used in the Pharmaceutical space. QbD defines a systemic approach to predefining objectives and process management in drug manufacturing rooted in science and research.

This enhances the safety and efficacy of the drug being delivered to the consumer.

In order to ensure that there is an industry standard for safety and efficacy, the International Conference on Harmonization has several guidelines that outline the Quality by Design process.

The International Conference on Harmonization is a collection of the world’s leading regulatory authorities. Traditionally, the ICH has provided guidelines that support GMP and marketing applications for new products.

The ICH Q8, in particular, is the guideline where Quality by Design is described.

It is the pharmaceutical development stage at which the company may experiment to better understand the new product and test the finished product specifications at a great level of flexibility.

1. Define the Quality Target Product Profile (QTPP) that identifies the Critical Quality Attributes (CQAs) of the drug
2. Initial product design and research identifying the Critical Material Attributes (CMAs)
3. Process design and research identifying the Critical Process Parameters (CPPs)
4. Understanding how the CQAs, CMAs, and CPPs all tie in together
5. A control strategy that includes specifications for the drug substance(s), excipient(s), and drug product as well as controls for each step of the manufacturing process
6. Process capability and continual improvement

QTPP is the quality characteristics of a drug product that is pre-defined and pre-designed during the development phases of the product. Some of these characteristics include:

• Dosage Strength and Dosage Form
• Dosage Delivery Mechanism
• Container Closure System
• Intended Use in Clinical Setting
• Drug quality criteria appropriate for the intended product (sterility, purity, stability, and drug release)

CQA is the physical, chemical, biological, or microbiological property or characteristic of an output material including finished drug products that should be within an appropriate limit, range, or distribution to ensure the desired product quality. The quality attributes of a drug product may include:

• Identity
• Assay
• Content Uniformity
• Degradation Products
• Residual Solvents
• Drug Release or Dissolution
• Moisture Content
• Microbial Limits
• Physical Attributes: Color, Shape, Size, Odor, Score Configuration, and Friability

Critical Process Parameters (CPPs) are identified by determining the extent to which any process variation can affect the quality of the product. Actual experimental data, product experience, or literature guidance can be used to define the extremes of the parameter sets to be refined.