Recently, Anhui Provincial Food and Drug Administration issued two suspension of production notice, the two pharmaceutical companies involved were suspended because of unqualified flight inspection.
GMP flight inspection is one of the forms of effective supervision of pharmaceutical enterprises. Its purpose is to further strengthen the supervision of drug manufacturers, strengthen the prevention and control of safety risks, consolidate the achievements of drug GMP re-certification, further improve the quality management level of drug production, eliminate hidden dangers of drug quality and safety, and ensure drug quality and safety.
As an important link and core content of the six systems of GMP inspection, quality management module is very important for a robust pharmaceutical quality system.
Then, how to establish and implement an effective quality management system to reduce the compliance risk during flight inspection and drug quality risk? Commonly used grippers include change, deviation, CAPA and annual quality review.

1. Change management
In the process of drug production and quality management, the change plays an important role in product quality, so it is one of the key contents to be audited. However, change management is just the weak link in quality management of pharmaceutical enterprises, and change is increasingly paid attention to by enterprises.

1. Definition of change
Alteration refers to the change of sources, methods and control conditions in the production, quality control and use conditions of drugs that are about to be put on the market or have been approved for the market.
2. Change your purpose
Any drug manufacturer should establish and implement a change control system related to the drug manufacturing process to ensure that changes in all aspects of the product production are executed, approved, reviewed and documented in a timely manner.
3. Change process
(1) Departments involved
It may involve all departments within the drug manufacturing enterprise, including the production department, logistics department, quality department, research and development department, sales department, Marketing Department, etc.
(2) Change application
After the change is confirmed, the applicant shall fill in the "Change Application Approval Form" with a detailed change implementation plan, and submit it to the quality department after the approval of the head of the department.
(3) Evaluation and review of change applications
The quality department shall conduct a preliminary review of the proposed changes, and if necessary, call relevant departments to evaluate the risks of the changes and give review opinions. If the change is not approved, feedback is required to the application department. If the change is approved, prepare for the change and make the implementation plan according to the requirements of relevant regulations and corresponding technical guidelines.
(4) Preparatory work before the implementation of the change
After the change is approved, relevant departments shall make preparations according to the implementation plan. It includes comparison of properties and indicators before and after product changes, research on process validation, research on product stability, formulation of new management system, modification of existing management system, training of relevant personnel, etc. For major changes, do a good job in filing or approval of drug regulatory authorities.
(5) Change tracking, evaluation and implementation
The quality department shall confirm and evaluate the implementation results of the changes, including the implementation of the changes, changes in documents related to the changes, changes training and other change tracking.
(6) Feedback and evaluation of changes
After the tracking work is completed, the quality department shall timely feed back the change application, change approval and change implementation to relevant departments and personnel.
(7) Change document filing
All approved or rejected change documents, as well as relevant information must be established and kept by special personnel.
Two, deviation management
Deviation management is the focus of GMP inspection, and it is also the key point to find defects easily in GMP inspection. Deviation management is a window into whether a company's quality system is capable of meeting its legal obligations.
1. Definition of deviation
Deviation is an unexpected event that may affect the safety, quality and effectiveness of a product. According to the ICH definition, a deviation is any deviation from an approved directive or prescribed standard. Any inconsistency with approved quality standards, inspection methods, operating procedures, management documents, process procedures, environment and various relevant influencing factors in the whole process of production shall be deemed as deviation.
2. Reasons for strengthening deviation management
To prevent risks caused by deviations to drug safety; Prevent recurrence of problems; Increase understanding of the process and drive continuous innovation and improvement of technology, quality and process
3. Processing process of deviation
(1) Timely report, investigation, analysis and impact assessment when deviation occurs
(2) Develop effective corrective and preventive measures to avoid the recurrence of deviation
(3) Complete corrective actions and deviation reports, and file deviation records
(4) Trend analysis of deviation system and continuous improvement to ensure product quality in line with GMP requirements
4. Responsibilities of each department in the deviation
Deviation detection department and quality department
• Immediately record the detailed process of problem occurrence and report to quality department
• The Quality Department classifies deviations
• Suggest corrective actions that need to be implemented immediately
Deviation Investigation Department
• Investigate the root cause of the deviation promptly
• Develop corrective and preventive measures
Related Departments
• Actively assist relevant departments to investigate the cause of deviation
• Handle the deviation strictly according to the deviation handling suggestions
• Evaluate product quality
• Complete corrective and preventive actions on time to avoid the recurrence of similar deviations
Quality Department
• Root cause of approval bias
• Approve corrective and preventive actions
• Approve product quality impact assessments
• Track the completion of corrective actions
• Evaluate the corrective effects of deviations
Iii. CAPA (Corrective and Preventive Action)
CAPA system is a core part of the quality management module. The establishment of an effective CAPA system can effectively help pharmaceutical enterprises to improve the quality system management and achieve continuous improvement of product quality.
1. Definition of CAPA
As defined by the FDA, the purpose of the CAPA program is to collect information, analyze information, identify and investigate product and quality problems, and take appropriate and effective corrective and preventive actions to prevent their recurrence.
Corrective action: Prevent recurrence of identified problems.
Preventative action: Prevent the recurrence of similar potential problems.
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2. Purpose of CAPA
Establish a CAPA system to find the root cause of defects, take preventive measures to prevent the recurrence of similar defects, and conduct a series of management activities such as statistics, analysis and evaluation, proactive preventive measures and tracking management for single defects found in various ways, so as to prevent the recurrence of similar defects in other aspects and different product lines.

3. Processing flow of CAPA
(1) Defect discovery, cause analysis and risk assessment
When product defects are found, they should be reported to the quality department in time. The quality department should investigate and analyze the causes, and then conduct risk assessment to confirm the severity of the problem and whether corrective measures should be taken.
(2) Formulation of CAPA
When problems or hidden dangers are found, corrective and preventive measures should be proposed to the quality department. The quality department will summarize the measures and distribute them to relevant departments for implementation upon approval.
(3) Implementation and tracking of CAPA
All relevant departments shall strictly carry out the rectification according to the approved CAPA and complete the rectification according to the planned time. The quality department shall track the completion of the rectification of all relevant departments according to the specific completion time plan, and file the tracking results and report them to the management regularly. If necessary, report to the drug regulatory department.
(4) Effectiveness evaluation of CAPA
When all rectification projects are completed, the quality department shall evaluate the effectiveness of CAPA. If it is found unreasonable, relevant departments shall be organized to discuss. If the evaluation is valid, shut down CAPA.
In addition, the quality department shall review the current year's CAPA in the annual quality review every year, including the effectiveness of CAPA and the effect after implementation.

Iv. Annual quality review
Product quality review is an important link in drug production quality management, and it is a mandatory item for GMP certification.
1. Product quality review definition
Product quality review refers to that drug manufacturers periodically review and analyze a series of product-related production and quality data, evaluate the consistency of product production process, analyze the applicability of relevant materials and product standards, identify their trends, and control the adverse trends, so as to ensure that the product process is stable and reliable, in line with the quality standards. Quality activities that provide basis for continuous improvement of product quality.
2. Purpose of product quality review
The core of product quality review is to evaluate and confirm the consistency of current production process, the suitability of material and finished product standards, timely identify product quality trends and improvement points, constantly improve quality, and ensure continuous quality improvement.
3. Workflow of product quality review
(1) Make annual product quality review plan
The quality department shall formulate the annual product quality review plan, assign it to all functional departments, and stipulate the completion time limit.
(2) Data collection and trend analysis
All functional departments shall collect product related information and data as required and submit to quality department on time. The quality department will summarize and sort out the data, conduct trend analysis, and then organize meetings for discussion and analysis, and carry out risk assessment on major issues.
(3) Analyze and review the results, and formulate corrective and preventive measures
The quality department shall analyze and summarize the meeting discussion results, form a report, and formulate corresponding corrective and preventive measures.
(4) Report preparation and distribution
After the report is prepared and approved, it will be distributed to the relevant functional departments.
(5) CAPA (Quality Correction and Prevention) tracking and confirmation
All functional departments shall implement improvement measures within a limited time according to relevant requirements, and summarize the implementation status in the next annual review report.

Product quality review flow chart

Drug quality is related to the health and safety of people's livelihood. In the process of drug production, no small detail can be ignored.
conclusion
As an important link and core content of the six system modules of GMP inspection, quality management module is the cornerstone to support a robust pharmaceutical quality system. To establish a sound and effective quality management system is an important guarantee for the development of pharmaceutical enterprises and product quality. As a member of the pharmaceutical industry, everyone should adhere to the responsibility and mission of pharmaceutical workers, and escort the quality and safety of drugs.