Pharmaceutical excipients series 2-comparison of domestic and foreign pharmaceutical excipients regulatory regulations

Effective supervision and control of the quality of pharmaceutical excipients is inseparable from a unified and complete national standard system for pharmaceutical excipients

"Announcement of the General Administration on Matters Concerning the Related Review and Approval of Pharmaceutical Packaging Materials and Excipients and Drugs" (2016 No.

Figure 1 Classification of high-risk pharmaceutical excipients

Compared with other types of excipients, pharmaceutical excipients of animal origin have certain particularities, such as the perishability of raw materials, the proneness of endogenous residues or exogenous pollutants (such as proteins, microorganisms, viruses, pesticides, veterinary drugs, etc.

Figure 2 Classification of pharmaceutical excipients of animal origin

PART 0 2.

Comparison and characteristics of domestic and foreign pharmaceutical excipient regulations

(1) Supervision of pharmaceutical excipients in the United States

The United States adopts the DMF (Drug Master File) management system for pharmaceutical excipients, which is a system for original and auxiliary packaging companies to submit their confidential information to regulatory agencies to support applications submitted by third-party drug applicants

Figure 3 U.

In addition to the use of DMF to manage excipients, the United States has also established a drug production registration system and inactive ingredients database (IID) and other supporting measures.

(2) European supervision of pharmaceutical excipients

The European Medicines Quality Administration (EDQM) has also carried out corresponding supervision on pharmaceutical excipients, including two methods for the registration of pharmaceutical excipients (CEP) and the European Drug Administration File (EDMF)
.
The CEP certificate can only handle the substances collected by the European Pharmacopoeia, including raw materials and pharmaceutical excipients, which can control the quality of drugs used in medicines.
China's pharmaceutical excipients can also apply for CEP certificates; while EDMF is applicable to the left and right sides except for biological materials.
For APIs, if the excipient has obtained a CEP certificate, the relevant information in the excipient part of the marketing authorization application can be replaced by the CEP certificate; second, for the excipients not included in the European Pharmacopoeia, they will be reviewed together with the preparation
.

(3) Japan's supervision of pharmaceutical excipients

In order to protect the technical secrets of producers and make the marketing authorization management procedures more reasonable, Japan has introduced the MF registration system (Master File System) in the management of pharmaceutical excipients
.
When the MF registration information is replaced with the official registration number (similar to the registration number), the scientific review of the drug marketing application will start
.

(4) Domestic supervision of pharmaceutical excipients

China’s drug regulatory authorities are paying more and more attention to the management and quality of pharmaceutical excipients, and gradually established a quality control system from on-site verification, process control to product inspection, and complete standards.
The scientific regulatory model of joint review and approval has been adopted.
The excipient industry has developed to a greater extent, with an average annual growth rate of more than 10%, which guarantees the accessibility of excipients for drug research and development and the improvement of overall quality
.
In terms of pharmaceutical excipients, based on the classification method of large molecules and small molecules, the quality of domestic small molecule pharmaceutical excipients is in good condition, while the quality of large molecule pharmaceutical excipients needs to be improved, especially in terms of functional indicators and inter-batch stability.
Strengthen the comparison and consistency research with foreign pharmaceutical excipients in order to improve the quality of medicines in China
.

In the effectiveness of preparations, research on the key quality attributes of pharmaceutical excipients should be strengthened, and a database of functional indicators of excipients should be constructed through the establishment, measurement and evaluation of functional indicators of pharmaceutical excipients and the establishment, verification and evaluation of functional methods.
, To find out the difference in functional indicators between domestic excipients and original research excipients, and guide domestic pharmaceutical excipient companies and preparation companies to achieve a leap from randomization of excipient selection and empirical formulation design to scientific selection of excipients and quantitative and qualitative formulation design.
Guide domestic pharmaceutical excipient companies to effectively improve the quality of domestic excipients to achieve the same quality as the original research
.

Table 1 Comparison of excipient management systems in different countries

Good preparations depend on good excipients.
If there are no good excipients, there will be no good preparations.
Without good preparations, there will be no safe and effective drugs.
Pharmaceutical excipients are closely related to the quality and safety of drugs.
Safety, stability and suitability for different medical requirements are inseparable from the scientific excipient standard system
.