Talking about: Application of QbD in Drug Development (Part 2)

Text | Johnson

In the previous article: Application of QbD in drug development (Part 1), a brief introduction was made to "The origin of QbD", "The origin of the US FDA and QbD", and "The deepening of QbD by ICH".

Global research status on Qbd

As of press time, the author has searched the "sciencedirect" website and entered the keyword "FDA QbD" and found that before 2008 (including 2008), there was very little literature, and since 2009, the amount of literature began to increase, of which, after 2011, the amount of literature increased significantly.

FDA's CMC pilot program for QbD

First of all, the FDA believes that although the QbD principle has not been proposed for a long time, actual drug R&D companies have carried out many QbD practices in the process of drug quality control, but they have not risen to the height of theory.

In this process, "Universal Pharmaceutical Factory" Pfizer performed outstandingly.

Based on many years of practical experience, most companies believe that the implementation of QbD makes the process of the drug life cycle more standardized, can quickly and effectively reduce the overall cost of the drug life cycle, and accelerate the process of drug listing.

The response attitude of pharmaceutical companies to QbD

First of all, the objective problem is that "usually, the patent protection period of a new drug is more than 10 years.

In this process, innovators in the original research drug industry continue to debate the advantages of ICH Q8, Q9 and Q10 regulations; on the contrary, many generic drug companies rarely discuss the advantages of ICH Q8 and Q9, but Silently understand the principles of QbD and apply them to existing business models; major generic drug manufacturers such as Teva and Mylan strive to achieve the first ANDA to declare generic drugs through a deep understanding of QbD, PAT, etc.

Although, Januvia of Merck Pharmaceuticals in the United States became the first drug to pass the review using the QbD concept (2006).

Pfizer presented examples of QbD declarations and other products in multiple public seminars, shared experiences and lessons in the ICH region, and discussed with regulatory agencies in emerging market countries (including China).

The benefits of QbD for consistency evaluation

In the past two years, the hottest keyword in the domestic pharmaceutical industry has not been "consistency".

The application of QbD in consistency evaluation is mainly divided into the following steps: 1) Determine the quality profile and quality parameters of the target product according to the reference preparation; 2) Determine the key quality attributes and key process parameters of the product; 3) Design the R&D production process Space; 4) Implement comprehensive quality control and continue to produce high-quality products.

☆Conducive to research and development

The lack of a correct process is one of the important factors restricting the consistency evaluation of generic drugs.

☆Conducive to production

Produce in a standardized operating space, strictly control the key attributes and key process parameters of raw materials and intermediates, and control the quality of the final product from the source; focus on the formation process of product quality attributes, not just the laboratory test results, and Ensure the sustainability of product quality.

☆Conducive to supervision

At present, the main purpose of drug inspection in my country is not to reflect the quality of the drug, but to show that the drug meets the registration standards.

☆Conducive to review

A detailed and systematic study of the relevance of original research drugs and generic drugs CQAs, raw materials, and process parameters to determine the normal operating space is conducive to improving the quality of generic drugs and the standardization of application materials, and increasing the possibility of passing the review.

Quality design thinking

I want to talk about it first.

In product development, the core of design is the process of reasoning, that is, starting from the value of the product, the process of deductive reasoning from the needs, functions and attributes to the final form and use conditions of the product.
Design integrates science from various aspects such as concepts, thinking methods, knowledge and evaluation systems, and clarifies the essence of things.
Therefore, design plays a decisive role in product quality.
QbD emphasizes "start with the end", which is the implementation of design thinking.
Starting from the end, that is, taking the clinical patient as the goal and fundamental, first analyze and understand the needs of the patient, and then decompose the problem into the functional requirements of the drug (ie QTPP), and assign the drug treatment function to the appropriate physical, chemical and biological characteristics, and then Find a reasonable drug development and manufacturing plan, and finally combine all levels of control strategies to form a global solution to achieve specific drug functions and meet expected needs.
This mentality is also!

Little touch

Okay, let's conclude this first, let's briefly talk about your feelings! Not long ago, I saw a sentence, "A good SOP is the best master".
.
.
Indeed, a good SOP allows a scientific researcher to enter his job role faster and more standardized.
But as the saying goes, "the master leads the door, and the practice depends on the individual.
" If you want more in-depth research and learning, it still requires constant hard work and hard work.
At this time, how do you work hard? How to fight? Where is the direction? Is very important.
Although QbD thinking is not omnipotent, it is still necessary for R&D workers who practice in a certain period of time to slowly polish their understanding in the project.
Sometimes, when you don’t know "Who are you? Where are you? What are you doing?" It is very useful to prevent "wasting" too much time at one point!

reference:

ICH official website information

CNKI information