1. Structural Framework
A framework of basic requirements plus appendices is adopted.
This revision carefully studied the overall structure design of GMP and decided to adopt the model of basic drug GMP requirements plus appendices. This is the same as the overall structure of EU GMP and my country's current GMP, and is also in line with the compliance of the Chinese public. Habit. The advantage of this model is that the basic requirements are relatively fixed and universal. The appendices provide special requirements for specific drug types and technical management and can be added step by step to meet regulatory priorities or at any time based on development and regulatory needs. Supplement or add new appendices. This revised GMP involves basic requirements and five appendices for sterile drugs, traditional Chinese medicine preparations, raw materials, biological products and blood products.
II. Main content
The new version of GMP currently includes basic requirements and 5 appendices (sterile drugs, blood products, biological products, traditional Chinese medicine preparations, raw materials) medicine). The appendix requirements for non-sterile drugs in the original 98 edition of GMP were merged into the basic requirements.
Appendices such as traditional Chinese medicine pieces, radioactive drugs, and medical gases in the 98 version of GMP will continue to be used and will not be revised for the time being. Those that are not suitable for the new version of GMP must comply with the new version. In this way, the pharmaceutical GMP for enterprises to implement will have one basic requirement, 5 new appendices and 3 old appendices.
The basic requirements of GMP and the appendix for sterile drugs are the top priorities of this revision, and the blood products appendix is ??a newly added appendix in this revision.
1. Basic Requirements for Drug GMP
The new version of GMP Basic Requirements*** has 15 chapters, 335 articles, and more than 35,000 words. It describes in detail the basic requirements for drug production quality management, and the content involved in the articles is basically retained. It contains most chapters and main contents of the 98 edition of GMP, covers the basic requirements of EU GMP and the main principles of WHO GMP, and is applicable to the production of all pharmaceuticals.
The new version of GMP revision embodies the characteristics of emphasizing personnel and quality system construction.
2. Sterile Drug Appendix
In order to ensure the safety of sterile drugs, it has been modified in accordance with EU and WHO standards.
The Sterile Drug Appendix adopts the EU and the latest WHO A, B, C, and D classification standards, and puts forward very specific requirements for the cleanliness level of sterile drug production.
Especially for the static and dynamic monitoring of suspended particles, monitoring of planktonic bacteria, sedimentation bacteria and surface microorganisms, detailed regulations are set and clear instructions are given on the monitoring conditions. The requirements for culture medium simulated filling, sterilization verification and management are refined, specific requirements for aseptic operations are added, and sterility assurance measures are strengthened, in order to provide regulations and measures to effectively ensure the safety and quality of sterile drugs. Scientific basis.
3. Biological Products Appendix
The Biological Products Appendix, based on the characteristics of biological products production, emphasizes a series of requirements for strict control of production processes and intermediate processes and the prevention of contamination and cross-contamination, and strengthens production management, especially Management requirements for seed batches and cell bank systems and specific requirements for production operations and raw and auxiliary materials.
4． The blood products appendix
The blood products appendix is ??a brand-new appendix formulated with reference to the EU's relevant GMP appendix, my country's relevant regulations, pharmacopoeia standards, and the requirements of the 2007 Blood Products Production Rectification Implementation Plan.
The key content is to ensure the safety of raw plasma, intermediate products and finished blood products, re-inspection of raw plasma, setting of quarantine period, traceability of plasma donor information and product information, and safety of intermediate products and finished products Specific requirements are put forward to ensure the safety of raw plasma, intermediate products and finished products in various aspects such as testing of sexual indicators, management of in vitro diagnostic reagents for testing, input and production, virus inactivation, and processing of unqualified plasma.
5. Appendix for Traditional Chinese Medicine Preparations
The Appendix for Traditional Chinese Medicine Preparations strengthens the management requirements for quality control, extraction process control, and extract storage of Chinese herbal medicines and herbal pieces.
Comprehensive requirements are put forward for the quality control projects of Chinese herbal medicines and Chinese medicine preparations, as well as requirements for the control of recycled solvents during extraction.
6. API Appendix
The revision of the API Appendix is ??mainly based on ICH’s Q7. At the same time, the content in Q7 that overlaps with the basic requirements is deleted, and the special requirements for APIs are retained.
The API Appendix strengthens software requirements, adds control requirements for classic fermentation processes, and clarifies specific requirements for API recovery, rework, and reprocessing.
3. Main features
Focus on refining software requirements
The focus of this revision is on refining software requirements to make my country's GMP more systematic and It is scientific and comprehensive, and refines some principle requirements in the 98 version of GMP to make it more operable and avoid ambiguity as much as possible.
Strengthened document management
The new version of GMP refers to the basic requirements of EU GMP and the relevant requirements of US GMP, and controls the main documents (such as quality standards, production process procedures, batch production and batch packaging records). etc.) has put forward specific requirements for writing by category; it has put forward specific requirements for the copying and issuance of batch production and batch packaging records, which greatly increases the difficulty of operating illegal records and non-standard records.
Absorbing advanced international GMP standards
The new version of GMP basic requirements and five appendices all refer to international GMP standards during the revision process, adding such things as quality risk management and supplier audits and approval, change control, deviation handling and other chapters, in order to strengthen the control and management of relevant links by domestic enterprises.
Some concepts have been introduced or clarified
Some of these concepts have been implemented in pharmaceutical manufacturers, and some are being trialled in some provinces in my country.
(1) Qualified Person
The new version of GMP clearly stipulates the qualifications, responsibilities and independence of the person responsible for product release, which greatly strengthens the requirements for product release. It strengthens the legal status of quality management personnel and provides legal guarantee for quality management personnel to independently perform their duties.
(2) Quality risk management
The new version of GMP puts forward the basic requirements for quality risk management, making it clear that enterprises must monitor the entire life cycle of drugs based on scientific knowledge. and experience to assess risks to quality and ultimately relate them to the goal of protecting patients. In the quality risk management process, the extent, form and documentation of the enterprise's efforts should be commensurate with the level of risk.
(3) Design confirmation
It has been clarified and strengthened in the new version. During the GMP implementation process in the previous period, pharmaceutical manufacturers lacked sufficient justification for the new construction or renovation of factories and the selection of equipment, resulting in large or small investment losses. On the basis of summarizing past lessons, more specific and clear provisions are made on "design confirmation", requiring enterprises to clarify their own needs and confirm whether the design of the plant or equipment meets the needs and GMP requirements to avoid blindness. , increase the scientific nature.
(4) Change control
There are no requirements for change control. Change the prescription and production process, change the quality standards and sources of raw materials and excipients and packaging materials in direct contact with the drug, and change the production plant. , facilities and equipment without traceability is common among enterprises.
The new version of GMP specifically adds a section on change control in the "Quality Management" chapter, which puts forward requirements for classified management of changes. The increase in these management requirements provides management methods to stop the random behavior of enterprises. In conjunction with the change control requirements recently proposed in drug registration management, it helps to form a regulatory synergy between drug production supervision and drug registration management.
(5) Deviation handling
The new version of GMP has added a section on deviation handling in the chapter on quality control and quality assurance, referring to the relevant requirements of ICH Q7 and the US FDA's GMP. It clarifies the definition of deviations and stipulates the requirements for classified management of deviations, providing an effective management method to prevent enterprises from random behaviors that do not strictly formulate document provisions.
(6) Corrective and preventive actions (CAPA)
The new version of CMP adds the requirements of CAPA in the chapter on quality control and quality assurance, requiring enterprises to establish a corrective and preventive action system. Investigate and take corrective and preventive actions on complaints, product defects, recalls, deviations, self-inspection or external inspection results, process performance and product quality monitoring trends, etc. The depth and form of the investigation should be appropriate to the level of risk.
(7) Investigation of out-of-standard results (OOS)
The new version of GMP adds requirements for OOS investigation in the chapter on quality control and quality assurance, requiring enterprise quality control laboratories to establish out-of-standard results Written procedures for investigation. Any out-of-standard results must be fully investigated in accordance with the written procedures, and corresponding records must be kept, further standardizing the laboratory's operational behavior.
(8) Supplier audit and approval
The new version of GMP basic requirements sets up separate relevant chapters to clarify the specific requirements for supplier audit and approval, further standardizing the company's supply Business assessment system.
(9) Product quality review analysis
The new version of GMP basic requirements introduces the concept of "product quality review audit", which requires enterprises to conduct regular inspections of each product produced in the previous year. Conduct quality review and analysis for each type or category of products, detailing the quality of all production batches, batches of unqualified products and their investigations, changes and deviations, stability inspections, and confirmation of production plants, facilities or equipment etc., the introduction of this new method can strongly encourage enterprises to pay attention to product quality in the long term and at all times. They must pay attention to the quality and changes of each product, especially those that are inconsistent with the content or requirements of registration approval, and regularly correct them. Summary and evaluation, which is consistent with the purpose of implementing GMP, which is to "ensure the continuous and stable production of drugs that are suitable for the intended use and meet registration approval requirements and quality standards."
(10) Continuous stability inspection plan
The new version of CMP basic requirements introduces a continuous stability inspection plan, aiming to promote pharmaceutical manufacturers to pay attention to the quality monitoring of post-marketing drugs. To ensure the quality of medicines within the validity period. The new requirements clearly stipulate under what circumstances the stability inspection of finished products or intermediate products is usually required, what the stability inspection plan needs to include, how to analyze and evaluate the product quality change trend based on the stability inspection results, and how to take measures for products that have been put on the market. corresponding measures. This is one of the methods to strengthen post-marketing supervision of drugs.
Through the above new additions or clearer requirements, the concept that enterprises are the first responsible person has been brought to an operable and inspectable level, prompting pharmaceutical manufacturers to proactively prevent drug-related incidents caused by drug production quality. .