Remarque Systems

Quality Management in Clinical Trials, Part 2: Quality by Design

The success of a clinical trial is strongly correlated to its quality — but opinions are shifting on how best to ensure that quality. Traditionally, pharmaceutical companies have emphasized quality by test, a reactive approach that involves testing the quality of end products, then iterating the entire process to make improvements. This can be cumbersome, costly, and time-consuming — including the costs of failure and/or revalidation.

In today’s drug development landscape — where, on average, it takes 12 years and billions of dollars to bring a new pharmaceutical drug to market[1] and only 1 out of 10 drugs manage to move from the early stages of clinical trials to FDA approval[2] — companies are interested in proactive quality management.  Quality by Design (QbD) delivers.

Through careful study design and ongoing risk monitoring, QbD can prospectively identify important errors — thus increasing both patient safety and the ability of sponsors to obtain reliable data from the trial. Its use enables a “quality” clinical trial to be defined as an absence of meaningful errors. This not only helps speed results but also helps sponsors meet important regulatory criteria, including the recent ICH-GDP E6(R2) addendum.

What Is the Quality by Design Approach?

QbD is a systematic approach to clinical trial development that starts with predetermined objectives. It emphasizes process control and product and process understanding, all stemming from quality risk management and sound science.

An effective QbD plan includes:

  • The development of a target product profile that clearly defines the efficacy, use, and safety of the product
  • The creation of a target product quality profile that process engineers and formulators will use to ensure efficacy and clinical safety during the process of developing the product
  • The collection of relevant information about the drug substance, process operations, and potential excipients. Use risk assessment to determine areas of study that should be investigated further
  • The design of a formulation and the identification of the critical quality attributes of the product. These attributes need to be controlled in order to fulfill the established target product profile
  • The design of a manufacturing process to create a product that possesses these material attributes
  • The design of the clinical trial to control risks associated with patient safety and data quality. Identify critical aspects of the trial that could threaten patient safety and/or the integrity of trial data. Develop and implement a plan to monitor those aspects and to take immediate corrective action as needed
  • The establishment of a control strategy for processes associated with data quality, patient safety, and site performance. Identify and explain all critical sources of variability, then monitor them through ongoing risk assessment
  • The continuous monitoring and updating of the process to ensure consistency of quality

What Are the Advantages of Quality by Design?

The advent of precision medicine has led to more complex pharmaceuticals — and an increasingly complex drug development process and regulatory environment. By harnessing QbD throughout the entire development process sponsors not only ensure the safety of patients, they ensure that the results of their trials are reliable and meaningful with metrics that speak to clinicians, payers — and regulators.

Key regulatory authorities like the EMA and FDA have expressed their approval for the implementation of QbD principles in clinical trials. In fact, the recent ICH Quality Guidance documents Q8 to Q11 address QbD specifically. It is becoming a foundational approach to drug development.

Fortunately, it is also becoming more cost-effective. Previously, only big pharmaceutical companies adopted QbD due to the substantial resources required for implementation, especially in relation to frequent on-site monitoring visits. Now, QbD is more readily accessible thanks to new tools, technology, and information. For instance, the Remarque Quality Management System is the first that allows sponsors and CROs of all sizes to implement risk-based monitoring (RBM) methodology at scale, allowing you to continuously monitor and update processes to minimize risk and maximize the value of your clinical trials. This video demo explains how.

That clinical trial success rests on quality is indisputable. Fortunately, the methods to ensure that quality are now not only legally necessary, they are financially feasible. For more information on quality management in clinical trials, register for our upcoming webinar on June 29.

[1] Fusi, L. Timeline of a Pharmaceutical Drug Development—From an Idea to the Market. Scientifist. Published March 12, 2017. Available at

[2] Huss, R. The High Price of Failed Clinical Trials: Time To Rethink The Model. Clinical Leader. Published October 3, 2016. Available at

Read the previous posts in our series here:

Quality Management in Clinical Trials, Part 1: Stick to the Plan