Yu Qiangqiang

Recently, Dr. Qiang Yuqiang, Acting Director of the FDA's Office of Pharmaceutical Science, published the report on Pharmaceutical Quality Supervision in the New Era at the 2014 IPEM 2014 graduation ceremony. Yu Qiangqiang used to be Deputy Director of the FDA's Office of Generic Drugs. He is a designer and implementer of Quality Based Design (QbD). His speech brought us information on the latest changes in the global regulatory authority for pharmaceuticals, highlighting the FDA's strong external communication.

In the report, we learned that the FDA has set up a new quality office to deliver a unified voice of quality control through integrated CMC (chemical, production and control) review, cGMP compliance review and cGMP on-site inspection. Quality standards are linked to patients from beginning to end, and are no longer based on simple medical data. Through this report, we not only comprehend the technical changes, but also the sympathetic arts between FDA departments and even the art of governance in the entire industry.

With the strong support of IPEM of Peking University, the full text of this report is published for readers. We are also very honored to have invited IPEM student Wu Xiaoming to write an article entitled “Listen to the Yu Qiang report”.

Thanks to the passing of the "Generic Drug Producer Payment Act" (GDUFA) last year, we feel particularly "rich", and the budget of nearly 300 million U.S. dollars per year has expanded very quickly. The FDA still has a backlog of more than 3,900 generic drugs. We need a lot of people.

An anti-cancer drug can significantly prolong the patient's life and is superior to existing drugs. At this time, the FDA will not consider the problems found during the inspection so severe that the drug may be approved. This is not to say that cGMP is not important, but the approval of a drug is based on science and patient-oriented.

I "love and hate" the dissolution rate. "Love it" is because it can effectively measure the speed at which a drug leaves the formulation. It may be the only way. "Hate it" because it often goes wrong, and it is not related to the body.

Good morning, teachers and classmates!

The topic I am talking about today is "New Drug Quality Supervision in the New Era" and introduce the newly established Office of Pharmaceutical Quality of the FDA/CDER (Pharmaceutical Review and Research Center). This is a new FDA department and we are in a great transformation.

In January last year, I left the FDA's Office of Generic Drugs and focused on the entire quality control of generic drugs, generic drugs, biological products, and botanicals.

Why did FDA establish a new pharmaceutical quality office? What is the relationship between this office and the existing Office of Pharmaceutical Science and the Office of Generics?

Speaking of the office, we have only 4 to 5 impressions of Chinese people. Actually, there is a department under the FDA office setup and a team in the department.

Thanks to the passing of the "Generic Drug Producer Payment Act" (GDUFA) last year, we felt particularly "rich". The budget of nearly 300 million U.S. dollars per year has expanded very quickly. So far, we have recruited nearly 700 people. The quality and review system is very large. It is planned to reach more than 4,500 people in the future. At present, there are more than 3,900 people. In particular, the generic reviewer recruits 10 to 20 people every two weeks. In one month, 31 people were recruited at one time. Because the FDA still has more than 3,900 generic medicines, we need a lot of manpower.

Strengthening inspection and review team cooperation

Looking at the FDA's quality department setting, there are three lines in brief: The first one is particularly large, it is the preparation office, there are more than 800 people. The task of this department is to review and approve drugs, including production, quality standards, APIs and finished product standards, and review the production process.

The second line is the cGMP inspection office. The on-site inspection and review of the two lines is very clear, then the third line is CDER's compliance office.

There is sometimes inconsistency and conflict between these three lines. For example, the inspector found that there was a 483 warning letter, but when it came to CDER, we focused on how much risk and benefit the drug had for the patient. If it is an anti-cancer drug, it can significantly prolong the patient's life and is better than the existing drugs. At this time, we will not regard the problems found in the inspection as serious. The drug may be approved but it will inform the company, although the FDA After you have been given drugs, the problem still exists. Since I was promoted to act as acting director in January last year, I have encountered two such examples. This of course does not mean that cGMP is not important, but that the approval of a drug must be science-based and patient-oriented.

There is currently a gap between these three lines, which is why CDER set up a pharmaceutical quality office. The Pharmaceutical Quality Office merged the preparation office with a large block of cGMP inspections. All quality-related content, including pre-approval reviews, quality standards, cGMP inspections, and cGMP reports, were all placed in this office.

Inspectors need to be part of the central review team. This is because the inspectors spent five days inspecting and writing reports for several months. When they arrived at CDER, they were not adopted, leaving the inspectors very frustrated. In the future, we hope that all questions found during the investigation and writing of the report will be directly linked with CDER's team. Our goal is: First to be professional and second to be teamwork.

In addition to strengthening internal cooperation, the establishment of the Pharmaceutical Quality Office is also related to the shortage of pharmaceuticals in the United States. It is difficult for FDA to know in advance whether the company will produce the drug after approval. It is necessary to rely on market data to find out the problem.

The international benchmark for pharmaceutical quality supervision

The Mission and Mission of the Pharmaceutical Quality Office are described below. Our mission is: The Pharmaceutical Quality Office ensures the supply of high-quality pharmaceuticals to the American public; our vision is: The pharmaceutical quality office will become the international benchmark for pharmaceutical quality supervision.

Everyone may think that these things are jargon, but careful study, each word, every sentence in the future of our new drug approval has a great influence.

The Value Statements of the Pharmaceutical Quality Office are the strategic and operational guidelines of the Quality Office. I personally spent a lot of time drafting the value declaration. In terms of the richness of language, there is no one verb that is repetitive. It takes four weeks for each word to be repeated and discussed.

Patient-oriented directional change

The quality assurance of pharmaceuticals at the Pharmaceutical Quality Office will lead to a change in direction - Put Patients First. If you carefully study the history of the FDA quality review, you will find that when the data is good, the quality standards become very high, that is to say, the FDA sets the quality standards often linked with the data, not with the patient. Data refers to Quality data, not patient data. This is a big difference.

The second change is to achieve a sound quality supervision. We just talked about three lines. CDER told the company that the products are very good, but the inspectors may think that there are a lot of problems and they are not coordinated. Companies often say that CDER has changed, but inspectors have to change. In turn, the inspection was done well and CDER's assessment had to be changed. If you do not understand each other, it may not be scientific and appropriate. After the establishment of the Pharmaceutical Quality Office, the company received only one letter from the FDA. The raw material medicine, product, and production are included in one step.

The third is to ensure clinical effects by establishing scientific and reasonable quality standards. Quality standards should be linked to the clinic rather than looking at the data completely. Dissolution may be a good example. Dissolution is also essentially a patient-related issue. I “love and hate” it, and “love it” is because it can effectively measure the speed at which a drug leaves a formulation. It may be the only one. Method; "hate it" because it often goes wrong, and there is no correlation with the body. What is the purpose of this test? Do we experiment for experimentation? The test must be linked to the patient and it does not have anything to do with the patient. Why test it? This issue hopes to get the attention of peers, and academics, industry, and regulators should work together to solve this problem.

The fourth is the application of a risk-based approach that maximizes the efficiency of review. Before the review, the team first think about it: Where is the risk of this drug? Our review system is to focus on solving problems. We must control high-risk points from high-risk to low-risk. This is the purpose of our supervision. Low-risk review opinions do not need to spend so much time writing so much. page.

Finally, let's emphasize innovation. Technological advances are changing with each passing day, but the regulatory authorities are often not motivated but have become resistance.

The FDA has many laws and regulations. It is not appropriate for new things to come up and often try to plug in old regulations. We cannot measure new things with old ideas. We must develop new laws and new ideas for new things. Patient-oriented, emphasizing science, and emphasizing quality standards are linked to patients, not data; at the same time, I also emphasize that regulators must become promoters and sponsors of new technologies and new sciences rather than resistance!