The R&D investment is 70 billion, and the acceptance number has increased by 71%. Where is the way out for the development of innovative drug preparations?

Reporter: What are the main points to consider when choosing a dosage form for innovative drug preparations? What is the difference between the first, second and third phases?

Zhou Xiaotang: The choice of dosage form needs to consider many aspects, including the physical and chemical properties of the material (such as solubility, permeability, stability, etc.
); it also depends on its bioavailability in the body, absorption, etc.
; third, it also needs to be considered the clinical needs, such as the anticipated route of administration, dosage, and administration frequency range
.

At the same time, the choice of innovative medicaments needs to be combined with the strategies of pharmaceutical companies.
For example, does the company want to be faster or do more research
?

In different clinical research stages, the choice of dosage forms is quite different
.

The first-phase preparation study mainly considers the safety of the preparation, and does not make clear requirements for the dosage form
.
Customers are very urgent for the first-phase clinical time requirements, and the time schedule is relatively high.
Usually the dosage form is simple, and more screening and research are not required
.

The start of the second phase of the formulation research is related to the effectiveness.
It is a transitional period to the third phase.
Future dose adjustments and whether there are problems with human absorption will be considered, and the formulation can be optimized and improved
.
The dosage form of the second phase is not limited, but the final dosage form of the third phase and after the market should be considered
.
For Phase III preparation studies, a large number of cases will be included in the trial, and it is not recommended to change the dosage form in Phase III.
It is necessary to determine the ideal formulation after the market is launched before Phase III is launched
.

Reporter: From the perspective of new drug delivery systems, such as compound preparations, sustained and controlled release preparations, and new nano-drug drug delivery systems, how to innovate drug formulation development ideas?

Zhou Xiaotang: In the early stage of the development of innovative drugs, it is not recommended to directly consider the new drug delivery system, because the new drug delivery system has unsatisfactory technology maturity, difficult development, long development time, and high cost.
Big problem
.
Unless some drugs cannot achieve research purposes through conventional preparations
.

Regarding the types of compound preparations and sustained-release preparations, I suggest that consideration should be given to single-prescription and regular-release preparations after a certain basis is established in order to save research costs and reduce development risks
.

After the conventional innovative drugs are on the market, or when they enter the second and third phases of the clinical phase, they have a clear grasp of the nature of the drug.
You can see whether it is necessary to develop a new drug delivery system from the perspective of clinical needs.
The upgrade of the product extends the life of the product
.

Reporter: In your opinion, what are the key strategies for the research phase (clinical research, phase I clinical research)?

Zhou Xiaotang: Research on innovative drugs is gradual and uncertain
.

The focus of the first phase of clinical trials is safety
.
For example, in terms of impurities in pharmaceutical research, it includes comprehensive analysis of impurity profiles with existing knowledge, analysis and control of potential genotoxic impurities
.

In addition to impurities, attention should also be paid to ensuring that the stability of new drugs meets requirements during clinical trials
.
Third, for sterile preparations, such as injections, eye drops or other sterile preparations, aseptic protection is also very important, which directly has a greater impact on the safety of the preparations
.
For new biological drugs, we must also pay attention to its immunogenicity and immunotoxicity
.

Reporter: What are the key strategies for the comprehensive development phase (Phase II and Phase III clinical studies)?

Zhou Xiaotang: The second and third phases began to pay attention to the effectiveness of the drugs simultaneously
.
In this dimension, there have been many research results, and we should focus on some key batches that have been developed
.

Comparative example do critical mass batches, including research, study the stability batches, each batch of clinical drug safety evaluation and other batch, focus impurities, polymorphs, and the like in vitro dissolution
.
If the clinical samples of the Phase III study undergo major changes from the Phase I and Phase II studies, the impact on safety and effectiveness needs to be reassessed
.
In the research process of a new drug, it is difficult to encounter a situation where the prescription process of a compound is unchanged from phase one to phase three.
Change management is more important and inevitable
.

Reporter: What are the differences between the formulation research of innovative drugs and generic drugs?

Zhou Xiaotang: Innovative drugs focus on " newness " and generic drugs focus on " identity "
.

The research process of innovative drugs is unknown, and the research is gradual and uncertain, and continuous research is required; while the reference preparations of generic drugs have been evaluated for safety and effectiveness when they are on the market, so generic drugs are developed It is only necessary to note that all aspects are the same as the reference preparation
.

Reporter: As the person in charge of the preparation department of CRO companies, how do you think domestic CRO companies can maximize value in the era of the rise of innovative drugs?

Zhou Xiaotang: At present, the research and development of domestic innovative drugs is relatively hot, the clinical demand is relatively strong, and the performance of anti-tumor drugs is more prominent
.

I personally support the phenomenon of hot research and development of innovative drugs.
Only by continuous investment in research and development can we gradually meet clinical needs and promote the development of the industry
.

However, the research and development of innovative drugs has the characteristics of long R&D cycle, large capital investment, and high R&D risk.
Therefore, it is hoped that researchers can be more cautious in the initial stage of compound screening to increase the probability of successful product launches
.

The CRO model of new drug research and development can help companies accelerate the pace of clinical and marketing of innovative drugs, reduce research and development risks, and save costs.
This is a good model
.

As a pre-clinical one-stop R&D service platform, Medicilon has 17 years of experience in R&D outsourcing services, and has always supported companies in the development of innovative drugs, including drug discovery, pharmaceutical research, preclinical research, and registration
.

As the person in charge of the preparation department, I also hope to help companies to a greater extent and break through the preparation problems in the development of innovative drugs
.

Reporter: After Medicilon's development in CDMO, how will it interact and interact with the current business and better complete the research and development of innovative drug preparations.
Can you share your experience?

Zhou Xiaotang: After 2020, Medicilon has established GMP workshops for phase I and phase II clinical samples of preparations, which can carry out a full set of clinically relevant phase I and phase II pharmaceutical research, including laboratory research and development, clinical drug production, and Including APIs and preparations, Medicilon officially entered from CRO to CDMO
.

With the expansion of CDMO business, on the one hand, it reduces the technical risk of transferring laboratory research and development results to factories other than Medicilon, and will also reduce expenses.
On the other hand, it will also help customers better manage their projects, such as The research and development timeline is more compact, and it can efficiently coordinate with various departments to improve the research and development level and provide a one-stop research and development service
.

With the continuous development of the company, the production capacity will be gradually expanded in the future to meet the production needs of Phase III and Phase IV clinical samples
.

This summit invited 100+ academicians, experts, and 1,000+ pharmaceutical enterprise elites to gather in Chongqing, China, focusing on pharmaceutical policy and innovation development, drug R&D innovation and AI, innovative drug R&D trends and strategies, key technologies, and improved new drug R&D trends and Conduct academic reports and share discussions on hot topics such as strategies and key technologies
.

From August 20th to 21st, we look forward to your trip to Chongqing with us to see the Smart Expo, discuss the innovation and development of pharmaceuticals, and witness the grand release of the "2021 China Pharmaceutical R&D Strength Rankings"~

Editor in charge: Houttuynia cordata

Yaozhi interview

Expert introduction in this issue

Zhou Xiaotang, Master of Pharmacy from Shenyang Pharmaceutical University, Peking University International Pharmaceutical Engineering Management, China Europe Business School Mini-MBA
.
With more than 15 years of experience in formulation research and development, focusing on the research and development of high-end formulations, rich experience in solid slow and controlled release, compound formulations, inhalation formulations, suspensions and sterile formulations, and has worked in Hengrui Pharmaceuticals in new drugs, generic drugs and new dosage forms Formulation research
.
He has experience in R&D and application of multiple innovative drugs Phase I/II preclinical, first generic drugs, consistency evaluation varieties, complex formulations and international projects.
At the same time, he has rich experience in preparation pilot scale-up, workshop construction and GMP
.

annotation:

[1]: The data comes from China Commercial Industry Research Institute, link: https://