Talking about: Application of QbD in Drug Development (Part 1)

Text | Johnson

Inscription

From “quality is tested”, to “quality is produced”, and then to “quality is designed”, the industry’s understanding of drug quality is constantly advancing with the times; in this process, there are Happiness also has pain.

The origin of QbD

Quality comes from design~QbD.

For the pharmaceutical industry, after people have generally accepted that the quality of drugs is produced, not the quality concept that is tested, the US pharmaceutical industry has begun to explore QbD in depth.

According to the concept of QbD, the quality of the final product must be considered from the beginning of drug development.

From a technical point of view, the main content of QbD application includes: designing drugs that meet the needs of patients; designing processes that always meet key quality attributes; integrating product and process knowledge acquired in the development process through the quality system; understanding the effects of prescription ingredients and process parameters The impact of product quality; identify and control key process variables; continuously monitor and update the process to ensure quality consistency.

Figure 1 Continuous upgrading of quality concept

The origin of FDA and QbD

The US FDA's proposal of QbD is definitely not a whim.

In the early 1940s, in order to deal with a large number of deaths caused by drugs, GMPs standards were established, and the main method of GMP to control quality was that quality comes from testing, that is, QbT; in the early 1960s, the response to drug "thalidomide" caused 10,000 In the event of multiple infant malformations, the "Kefauver-Harris Drug Amendment" was issued to ensure the safety and effectiveness of the drug; in 2002, the FDA issued cGMP; in 2004, the FDA once again upgraded cGMP and published the "Kefauver-Harris Drug Amendment Act".

FDA’s promotion of QbD mainly includes the establishment of a risk-based pharmaceutical quality assessment system (PQAS) by the FDA’s New Drug Quality Review Office based on the application of product and process understanding and the approval of allowing pharmaceutical companies to submit applications that include QbD principles, product knowledge and process understanding The QbD implementation plan is run by the new drug application; CDER’s generic drug office OGD implements the QbD generic drug review model; CDER’s compliance office OC evaluates the feasibility of commercial links and confirms process control by optimizing the pre-approved inspection links Whether it meets the requirements of the ICH Q10 quality system life cycle to further promote the implementation of QbD and the application of QbD in bio-licensing applications.

Although QbD can better design and predict product quality, it is also important to verify the actual performance of processes and raw materials in pilot trials and commercial production practices.

Figure 2 FDA "Quality by Design" model

ICH~QbD~Q8&Q9&Q10&Q11

As mentioned above, after the FDA proposed QbD, ICH quickly incorporated it into its quality system.

In 2005, ICH issued relevant guidelines ~ Q8 on drug development and Q9 on quality risk management.

♪♪♪~ ICH Q8

It includes two parts: drug research and development (Part 1) and its supplementary content (Part 2).

♪♪♪~ ICH Q9

ICHQ9 quality risk management is one of the core strategies of the QbD system.

♪♪♪~ ICH Q10

Pharmaceutical quality system (pharmaceutical quality system) ICH Q10 explains in detail how to adopt the QbD concept, apply scientific management and quality risk management two core tools to establish an effective pharmaceutical quality system.

The goal of the pharmaceutical quality system: to obtain products that meet the quality attributes of the target product, establish and maintain the controlled state of the product, and promote continuous improvement of product quality.

♪♪♪~ ICH Q11

ICHQ11 focuses on the development and manufacturing of APIs.

summary

Due to space reasons, the remaining content such as "Global Research Status of QbD", "FDA's CMC Pilot Program for QbD", "Enterprises' Response to QbD", "Consistency Evaluation", etc.
, will be continued in the "Part 2" Introduction.

reference:

ICH official website information

CNKI information