Date:
After the baptism of July 22nd and the promotion of consistency evaluation of generic drugs, the pharmaceutical industry has been reborn. With the continuous improvement of policies and regulations, increasingly sophisticated instruments and equipment, and accumulated talent reserves, the domestic pharmaceutical industry has gradually reached a new level in just 7 years. On the other hand, oral sustained-release formulations and conventional injections are facing a cluster of applications from enterprises due to their relatively low technical difficulty. The subsequent centralized procurement of national drugs resulted in a significant decrease in the prices of generic drugs. This has led more pharmaceutical companies to re-examine product project initiation and focus on complex formulations with technical barriers and relatively low competition, while others have begun to focus on the larger international market.
The 4th CMC China Forum, where hundreds of industry colleagues gathered for complex drug formulations. More than ten senior experts and practical backbone in the industry have shared the development strategy of IVIVC based sustained and controlled release formulations, transdermal drug delivery formulations, suspensions, ophthalmic drug formulations, hot melt extrusion technology, standards and impurity related issues and outcome plans, complex formulation dissolution technology, and discussed project initiation strategies with a focus on the future.
Academic sharing meeting, thought collision meeting, and practical exchange meeting, all at the 4th CMC China!
1. Development strategy for sustained and controlled release formulations based on IVIVC
Zhang Lianlang
The head of IVIVC platform at Ze zheng Pharmaceutical
Mr. Zhang shared the development strategy of sustained-release formulations based on IVIVC technology, first introducing the classification and release mechanism of sustained-release formulations. Taking pregabalin sustained-release tablets, diclofenac sodium sustained-release tablets and theophylline sustained-release tablets as examples, IVIVC analysis was carried out from the formulation design to the absorption process, and then the formulation process was optimized based on the dissolution and pre-test results. IVIVC is a comprehensive technology that integrates formulation technology, analytical technology, clinical statistics, and mathematical modeling. It provides in vitro evaluation endpoints for formulation development by searching for single or multiple point correlations that exist in vitro and in vivo. For the development of slow-release and controlled release products, especially those with high difficulty, modification mechanisms, and PIV, it is particularly important for IVIVC to provide a clear in vitro evaluation endpoint when only the in vitro dissolution curve is consistent and cannot achieve equivalence, or even in many cases cannot achieve consistency with the RLD dissolution curve.
2. Application of flow-through cell dissolution instrument in formulation research and development
Duan Yunjian
Technical Director of Shenzhen Wahyong
Mr. Duan shared the application of the flow pool dissolution instrument in the development and dissolution of formulations. The flow pool method is included in both the Chinese, American, European, and Japanese pharmacopoeia. The flow cell method utilizes the flow of the dissolution medium to dissolve drugs. In the experiment, the type of dissolution medium can be automatically changed, and the dissolved samples are promptly taken out of the flow cell system, which can better reflect the dissolution behavior of drugs in vivo (biological related dissolution method), greatly increasing the reliability of in vivo prediction of behavior using external methods. It is used to guide prescription selection, process optimization, and in vitro and in vivo correlation research. Finally, Teacher Duan provided a detailed case study on the application of the flow cell dissolution instrument in insoluble drugs, sustained-release formulations, controlled release formulations, microspheres, etc. Professional instruments and knowledge bring a feast of audio-visual technology to everyone.
3. Research and development of high-end transdermal drug delivery formulations
Wu Chuanbin,
Founder of Xinji Pharmaceutical Co., Ltd.
Mr. Wu introduced the huge market prospects of transdermal drug delivery products. High end transdermal drug preparations include microneedle transdermal drug delivery preparations, hydrophilic gel plaster preparations and in situ gel spray preparations. Teacher Wu elaborated on the technical advantages, challenges, and industrialization of different types of formulations. New transdermal drug delivery formulations have a short development cycle, low risk, and high return rate, making them one of the mainstream directions for drug companies in the new situation. Guangzhou Xinji Pharmaceutical focuses on the development of high-end pharmaceutical formulations, has established multiple high-end formulation research and development platforms, and has accumulated numerous projects for extensive cooperation with the industry.
4. Concerns and solutions for impurities in improved drugs
WangBo
Bai Lun Testing, General Manager
Mr. Wang first introduced the definition and advantages of improved new drugs. Then, starting from the ICH guidelines and pharmacopoeia requirements, he elaborated on the impurity limit requirements of improved new drugs. Finally, he analyzed the impurity spectrum of improved new drugs with a case study, from process impurities to impurities generated by the interaction between raw and auxiliary materials, to impurities generated by the compatibility of packaging materials and the interaction between compound APIs. Finally, a impurity research strategy tree was formed.
5. Research and development of ophthalmic drug formulations
Li Mingli
Shandong Nuomingkang, Dean of the Research Institute
The number of patients with ophthalmic diseases is large and the incidence rate is high. The increase in demand and the development of drug technology have greatly promoted the establishment and research and development of ophthalmic drugs. The common barrier, anterior segment barrier and posterior segment barrier lead to the difficulty of ophthalmic absorption. Delivery technologies such as gel, emulsion, micelles, polymer nanoparticles, liposomes and prodrugs have different advantages and disadvantages when applied to ophthalmic drugs. There are many ways of ocular administration, including local (intra conjunctival sac) administration, systemic administration, subconjunctival injection, anterior chamber injection, and vitreous injection, which are suitable for different indications. Mr. Li conducted a detailed analysis of different ophthalmic drug formulations. The design of a new eye drug delivery system mainly focuses on extending eye surface retention time, increasing drug permeability in eye tissues, and improving drug bioavailability in target tissues.
6. Common problems during the use of pharmaceutical standards/reference materials
Yang Yanli
LGC Pharmaceutical Product Manager at the UK Government Chemist Laboratory
In addition to meeting technical requirements, pharmaceutical standard/reference materials also need to meet compliance requirements during use. Teacher Yang shared in detail the basic information, use and management, as well as common problems of standard/reference materials. LGC's high-quality products and services have won the trust of numerous pharmaceutical companies.
7. Key Technologies of Hot Melt Extrusion
Yang Gaopin
General Manager of Suzhou Pupeishan
With the increasing complexity of drug structures, many small molecule drugs are insoluble drugs, and the solubilization technology of insoluble drugs is in front of every pharmaceutical company. Hot melt extrusion (HME) utilizes a co rotating parallel twin screw extrusion system to uniformly disperse API into polymer based carriers, thereby achieving solubilization. Hot melt extrusion has the advantages of continuous process, fewer process steps, high repeatability, solvent-free, online monitoring, low fixed investment, and small footprint, making it increasingly widely used. Suzhou Pupeishan focuses on hot melt extrusion devices, with professional design and high-quality software and hardware support to assist in the research and production of insoluble drugs.
8. Process development of complex powder requirements API and its application in suspension formulation products
Li Hao
General Manager of Bono Kangyuan
The particle size, particle size distribution and particle shape of drug powder affect the specific surface area, chemical reaction rate, adsorption performance, dispersion, rheology, sedimentation rate, dissolution performance of the powder, and then affect the bioavailability of drugs. Inhalation formulations have higher requirements for particle size such as API. Particles with different particle sizes and surface properties can be obtained through processes such as crystallization and crushing, and their properties can be characterized through various XRD, DSC, SEM, AFM, angle of repose, etc. Teacher Li also introduced various engineering platforms and production bases of Bozeglin. The company has a complex powder API product line, an international level of research and development production system, quality that meets the requirements of national pharmacopoeia and customers, and strong global registration capabilities.
9. Trends and Forecast of Registration and Application for Complex Preparations in China from 2016 to 2022
Li Lang
Director of Lilang Pharmaceutical Society
Mr. Li introduced the types of complex preparations and analyzed the clinical, marketing, and consistency evaluation applications of oral films, enteric preparations, inhalants, microspheres, controlled release preparations, sustained-release preparations, etc. that have been undertaken by CDE since 2016. With the increasing competition for commonly released formulations, complex formulations have attracted much attention.
10. Research and development of anti infective drugs and sharing of application cases between China, the United States, and Europe
Feng Shengxi
Founder and General Manager of Aiqixi Pharmaceutical
Mr. Feng, first of all, introduced the development status of some new antibacterial drugs and Aiqixi Pharmaceuticals' anti infective drugs that have been launched or are currently undergoing phase II/III clinical trials both domestically and internationally in recent years. Then elaborated on the issues of API and formulation supplement, and shared the experience of registration and application between China, the United States, and Europe through case studies. Over the years since its establishment, Aiqixi Pharmaceutical has maintained close business relations with many large pharmaceutical companies at home and abroad by virtue of professional services in the fields of new drug and generic drug R&D, innovative drug CDMO services, impurity reference customization, unknown impurity structure confirmation, genotoxicity impurity research, etc.
