-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
There is no doubt that China's GMP (2010 Revision), which came into effect on March 1, 2011, has played a key role in standardizing the business practices of Chinese pharmaceutical companies, promoting the improvement of quality systems, and ensuring product quality
.
However, with the advancement and deepening of the reform of China's pharmaceutical administration system launched in 2015, this normative document, which has been implemented more than 10 years ago, has become increasingly uncoordinated, and the industry has called for its revision
.
In 2021, China's NMPA launched the process of
joining the PIC/S organization.
The core requirement of this work is that countries or regions that intend to join the PIC/S organization should revise their own GMP regulations or guidelines, or revise specific inspection standards to achieve global consistency
in compliance inspections of pharmaceutical companies.
According to such a comprehensive international and domestic situation, the revision of China's GMP (2010 revised version) is particularly necessary
.
This article will analyze the deficiencies and errors in China's GMP (2010 Revision), and discuss the content of the proposed revision, hoping to provide reference and reference
for Chinese pharmaceutical colleagues.
Q1 - Some clauses and appendices of the General Principles of GMP in China are not coordinated
For example, Article 244 of the 2010 General Principles of China GMP states: When changing raw and auxiliary materials, packaging materials in direct contact with drugs, production processes, main production equipment and other major factors affecting drug quality, the quality of at least three batches of drugs shall also be evaluated
after the implementation of the change.
If the change may affect the expiration date of the drug, the quality assessment should also include a stability study
of the drug produced after the change is implemented.
Analysis: The above clauses do not distinguish between specific situations, and it is inappropriate
to require the evaluation of three batches after the change.
Because according to the Measures for the Administration of Post-Market Changes of Drugs (Trial Implementation) and the supporting technical guidelines for pharmaceutical changes in listed chemical/traditional Chinese medicines/biological products, changes in drug registration matters are divided into minor changes, medium changes and major changes
.
Not all changes require a three-batch evaluation after the change
.
Question 2 - Chinese GMP documents should be incremented with document history and numbering
Although the NMPA requires pharmaceutical companies to establish a sound documentation system when inspecting them, we reluctantly see that the imperfection of the regulatory documentation system of the NMPA itself is obvious
.
When the 2010 version of the GMP was released on March 1, 2011, the numbering of Appendices 1-5 was still clear, and the relevant appendix numbers were difficult to clarify, which was not conducive to the study and popularization
of regulations.
It is recommended to refer to the EMA and ICH document systems, establish document drafting and revision history for each chapter of the China GMP General Rules, and also establish numbering and document history introduction information
for all appendices of China GMP.
At the same time, considering that the CFDI under the NMPA has issued many technical guidelines, the format and numbering of these technical guidelines should also be unified
.
Question 3 - Part of the appendix has incorrect technical content and should be revised
For example, parts of the GMP Appendix "Computerized Systems", which came into effect on 1 December 2015, are incorrect
.
Article 1 This Appendix applies to computerized systems
applied in the process of drug production quality management.
A computerized system consists of a series of hardware and software to meet specific functions
.
Analysis: The second half of the above paragraph is wrong
.
Because a computer system only includes hardware (including firmware) and software, a computerized system includes not only hardware and software, but also the environment, various procedures and personnel
that support the operation of the system.
For details, see the figure below:
Based on the above analysis, some provisions in the Requirements for Drug Recording and Data Management (Trial) issued by the National Administration on July 1, 2020 are also inappropriate and need to be revised
.
Question 4 - Some of the provisions of the Appendix need to be harmonized with other legislative amendments
For example, in the 2020 revision of the GMP Appendix "Biological Products", the definition of biological products is described as follows:
Article 52: When using more than two types of pathogens for production, the resulting dirt and suspected contaminated articles shall be disinfected in situ and completely inactivated before they can be removed from the work area
.
Analysis: The concept of more than two types of pathogens mentioned in the above article is consistent with the old classification of pathogenic microorganisms in China.
However, the old List of Pathogenic Microorganisms Transmitted by Humans is obviously inconsistent with the WHO classification and has been proposed for revision
.
In the revised opinions of the "Catalogue of Pathogenic Microorganisms Transmitted by Human Transmission", it is mentioned that in the 2006 edition of the "List of Pathogenic Microorganisms Transmitted by Human Transmission", the pathogenic microorganisms transmitted between humans are divided into four categories according to the degree of harm: the first category, the second category, the third category and the fourth category; On December 31, 2021, the National Health Commission issued the Catalogue of Pathogenic Microorganisms Transmitted by Human Transmission (Draft for Comments), which intends to classify pathogenic microorganisms in line with the Laboratory Biosafety Manual (Third Edition) issued by the World Health Organization, and divide them into Category IV, Category III, Category II and Category
I according to the degree of harm from high to low.
Question 5 - Some clauses in Appendix 1 of China's GMP for sterile drugs are described as mechanical, which restricts the reasonable choice of enterprises
For example, Article 13 of Appendix 1 Sterile Drugs of China's GMP (2010 Revision) mentions that the recommended levels of products produced by the final sterilization process are as follows:
Analysis: According to the chart above, if a sterile pharmaceutical company adopts the final sterilization process to produce a product, and the drug is assessed as a high contamination risk product, the core area cleanliness level can only be selected: local grade A in the context of grade C
.
The reality is that if the company adopts C-RABS technology or uses isolator technology, the company can choose A-level in the context of D level to organize production
.
Comparatively speaking, the provisions of Annex 1 (2022 version) of the EU GMP are reasonable (see the table below):
Similarly, when it comes to sterile drugs produced by aseptic processes, China's current version of GMP Appendix 1 regulations are also unreasonable
.
See the chart below:
The following table is the EU GMP Annex 1 (2020 version) requirements:
Analysis: Similar
to the above.
For enterprises that use aseptic processes to produce sterile drugs, the chart in Appendix 1 of China's GMP is unreasonable and restricts excessive death
.
Annex 1 (2022 edition) of the EU GMP only describes in the chart which areas are used as level A; As for the background zone level used in these A-level areas, they are described in detail in the relevant articles, and the thinking and power
of enterprises to adopt QR rm assessment are repeatedly emphasized.
In this way, enterprises can better choose the appropriate background level
according to their actual situation.
Q6 - China's GMP system should be consistent with the MAH management system that has been implemented
With the entry into force and implementation of the Drug Administration Law amended in 2019, the MAH system has become a key system in China's pharmaceutical administration system, and its influence is expanding
.
The China GMP (2010 Revision), which is currently being implemented, was drafted based on China's regulatory system tied to registration approvals and production addresses, which is no longer appropriate
.
For example, Article 217 stipulates that the personnel, facilities and equipment of a quality control laboratory shall be commensurate
with the nature of the product and the scale of production.
Enterprises are generally not allowed to conduct commissioned inspections, and if they really need to entrust inspections, they shall entrust external laboratories to conduct inspections in accordance with the provisions of the entrusted inspection part of Chapter 11, but this shall be explained
in the inspection report.
Analysis: With the implementation and extensive implementation of the MAH system, the work of complex drug production links can be entrusted to entrusted enterprises, and the "enterprises are usually not allowed to carry out entrusted inspection" mentioned in the above article is very inappropriate
.
summary
Through the above analysis and sorting, I believe that most readers should understand that the current China GMP (2010 revised version) has obvious deficiencies in the overall thinking, key clause setting, internal content coordination, and external coordination of relevant laws and regulations, and needs to be revised
as soon as possible.
However, the more significant the revision work, the more challenging the capacity of the team responsible for the revision work at the national Office became
.
From the current point of view, if the national office wants to initiate a comprehensive revision of both the General Principles and Appendices of China's GMP, it is estimated that it will not be enough
.
The following recommendations are therefore made:
First.
In view of the obvious errors in the General Principles and the obvious inconsistency with the current system, a strategy
of partial revision is adopted.
In this way, the work can be focused on a specific field, the revision can be completed quickly, and the results can be achieved quickly, without affecting the development of Chinese pharmaceutical enterprises and the implementation of
regulations.
Second.
Adopt a strategy
for overall revision of certain key appendices.
In this way, in the absence of significant changes in the GMP General Rules, the revision team of a GMP appendix can concentrate on dealing with this specific appendix without repeatedly spending a lot of energy considering the relationship between
the part and the whole.
I think even with this arrangement, the revision of such a key document as Appendix 1 sterile drugs would take a long time
.
After all, the EU GMP mobilized so many resources to revise Annex 1 of the EU GMP, and it took more than 5 years to complete
.
Third.
The key staff in the revision team must have an open mind and working attitude, and the main person in charge or consultant must have a sufficiently high international perspective
.
Countless works in the past have shown a similar truth
.
Fourth.
China's GMP revision work should not only consider the GMP business area, but should consider the impact
of the front registration and the second stage of drug marketing and circulation in the technical team formation and revision process.
Of course, the assessment of the interaction between GVP and GMP also needs to be included in this revision work
.
Fifth.
Finally, it is hoped that the NMPA will really adhere to the idea of social co-governance and actively involve the participation
of social and technical forces at every stage of the revision work.
Note: This article does not constitute any value judgment or investment advice
.
About author:zhulikou431, senior engineer, PDA member, ISPE member, ECA member, PQRI member, senior aseptic GMP expert, has deep knowledge in aseptic process development and verification, drug research and development and registration, CTD document writing and review, regulatory audit, international certification, international registration, quality system construction and maintenance, as well as sterility inspection, environmental monitoring and other fields
.
In recent years, he has begun to focus on the trend analysis of the macro field of pharmaceuticals and the risk management of M&A projects of
pharmaceutical enterprises.
All rights reserved, may not be reproduced
without permission.
