Quality by Design (QbD) is not a new concept. For more than a decade, QbD principles – which, according to a presentation to ICH, is the “integration of patient needs, science and quality requirements during the development of a pharmaceutical product and its manufacturing process” – have been used to improve the quality of products and processes in the automobile industry and others.
Given the success of QbD in industry, the U.S. Food and Drug Administration (FDA) decided to get into the act, and has been nudging QbD implementation for the discovery, development, and manufacture of drugs. The FDA began these efforts more than a decade ago, citing these reasons:
More recently, the FDA provided more detailed guidance on implementing QbD for pharmaceutical product design, process understanding, and lifecycle management. A major focus is on performing in-process testing in order for adjustments to be made prior to any failures. As well, confirmation – of product quality and process changes–is deemed important.
Similarly, the European Medicines Agency (EMA) promotes QbD as an approach that aims to ensure the quality of medicines by employing statistical, analytical and risk-management methodology in the design, development and manufacturing of medicines.
One of the goals of Quality by Design initiatives is to ensure that all sources of variability affecting a process are identified, explained and managed appropriately. This enables the finished drug product to consistently meet its predefined characteristics from the start – so that it is “right first time.”
The core message from regulatory bodies is that quality should be built into a pharmaceutical product from the beginning based on knowledge of its characteristics and a thorough understanding of the process by which the product is manufactured.
The thinking is that QbD will produce a high quality drug product that is free from contamination and that reliably delivers the therapeutic benefit promised in the label to the patient. This article provides an overview of QbD and how PCI Synthesis uses QbD.
In a nutshell, QbD is about communicating meaningful and relevant science up front to establish post-regulatory approval opportunities that will also guide subsequent manufacturing improvements.
Why implement? There are numerous benefits for industry. Chief among them is that indicating QbD principles in regulatory submissions ensures less hassle during review. Fewer deficiencies can result in quicker approvals.
Other benefits include fewer manufacturing problems, reduced number of post-market manufacturing supplements, and the ability to implement new technology that improves manufacturing without regulatory scrutiny.
QbD, despite its many benefits all around – for sponsors as well as regulatory bodies –is not a bed of roses. It still presents challenges. According to the FDA, the devil is in the details:
At PCI Synthesis, QbD is a systemic approach that begins by identifying the quality attributes of the product based on scientific rationale, as opposed to attempting to fit the proverbial square peg into a round hole through a trial-and-error approach.
This rational design approach goes further to identify the limiting factors of each step in a synthesis process and provides the means of attempting to correlate how each step of the process affects the final product quality attributes.
In other words, QbD principles are applied at every step of the development of a synthesis process.
To apply QbD as a systemic approach, the company starts by understanding, step by step:
This approach allows the establishment of priorities and flexible boundaries in the process.
QbD is one of the behind-the-scenes approaches that we use to improve our processes to meet our sponsors’ needs and FDA’s requirements. Please also check out other related articles, including “Internal Auditing: A Sound Business Practice to Ensure Successful Outcomes in cGMP Manufacturing” and “Shedding Light on Quality Investigations in Chemical Manufacturing: Getting to the Root Cause of Process Deviations and Quality Excursions to Ensure cGMP Compliance.”