Confirmation] How to do a good workmanship validation

Equipment validation (or validation) and system validation, cleaning validation, analysis method validation, etc. that need to be completed prior to implementation of the process validation are not covered by this sharing (excluding, for example, inconsistencies between registered and actual processes). 

How to do a good job of process verification? A person or a department can do a good job of verification? In the forum often see a verification manager to complete the company's full verification documents (programs and reports), such a verification can be done to be discussed! 

Validation is an inter-departmental work that is related to multiple departments and requires close cooperation of relevant departments. Therefore, we must have a team for the verification of the concept of verification, which is a necessary precondition for verification (Note: For the whole company to verify a single person or a department to complete, while trying to do their own, and your Leading communication to allow more relevant personnel involved). It is important to verify this. 

Here I elaborate on my understanding of process validation in several ways:

1. First of all, verify the plan, the plan is to do from the bottom up, that is to say each workshop to be the unit to do the process Verification Plan your own plan according to the production plan and the specific conditions of the workshop, submit the uniform balance to the quality manager in charge, and draw up the company's total process verification plan. Pay attention to the time node and possible changes here, and list as far as practicable annual total Planned, submitted to the production and quality of the responsible person approved issued to the relevant departments, the quality of the department responsible for the verification of tracking the total list of projects to be completed each month, in time to track the completion of the situation, do all aspects of communication and coordination (Note , The Quality Assurance Manager is not the person who drafted the program and the report, is the audit and coordination);

2. With regard to the assignment of responsibility, although there are provisions in the verification management or verification master plan, those who are not generally involved in the verification of verification for the specific verification implementation should take note of the specific work involved in drafting the verification plan and audit To be implemented to specific people, but also training in place, so that each involved a verification program to identify their own responsibilities, in advance to prepare for validation in the smooth progress. Develop habits that form a process that can validate validation as planned. 

3. Process validation required to be completed before the implementation of the project: This in your company documents will be clearly defined. 
(1) The key quality attributes and the key process parameters have been determined; the documents related to the verification are to confirm whether the current version (including process rules, SOPs of all processes, all records (batch production records, batch inspection records, cleaning records, equipment operation records, etc.) standards, testing procedures); 
verify or confirm ⑵ plant facilities, systems and equipment (including calibration or verification of measuring instruments, analytical method validation and product testing equipment validation or confirmation) has been completed; 
⑶ involved in the implementation process validation of all personnel Of the training has been completed (aseptic preparations to complete the dressing to confirm the replacement of sterile staff), the person in charge is responsible for the organization of process validation training, the drafters are responsible for training programs; 
⑷ process validation materials and packaging materials tested and qualified (Such as: operating room and equipment and site environment to meet the technical requirements; public system to meet the technical requirements (process water, air, nitrogen and purification system test results pass) 

4. process validation program (report) drafting 
process validation Drafters To have sufficient knowledge of product technology, research Metastasis to the process of production verification by the R & D process development personnel and production units craft jointly drafted (involving changes have jointly drafted); Process daily production and product verification drafted by the manufacturer, the production unit processes the person in charge; 

5. verification Implementation of 
process validation by the approval of the validation program one by one implementation of the production workshop responsible person to do a good job plan staff distribution, craft and QA do a good job of verifying the process of data collection records consolidation analysis, tracking control of intermediates, to verify the process Change and deviation processing.

6. Verification Report Drafting: 
Most enterprises are QA to carry out the verification report drafting, I suggest that the workshop technicians and QA co-drafting, statistical analysis of key process parameters by the craftsmen to do, intermediate and finished product indicators from the QC statistical analysis, QA summarizes all verification records and concludes. 
The quality manager and production manager will review and approve the verification report. 

7. Process validation status of the maintenance of 
7.1 End of the verification batch of commercial production, pay attention to daily routine key process parameters and quality indicators of statistical analysis (production units for statistical analysis of process parameters; QC quality indicators for statistical analysis; QA regular collection Data such as monthly or quarterly assessment, defect detection, timely correction); 
7.2 verification to complete the following conditions to assess whether to re-verify: 
7.2.1 production process has changed; 
7.2.2 raw materials, packaging materials have changed (Including manufacturer's changes) may affect the quality of the product; 
7.2.3 Equipment and facilities have major changes; 

8. Process validation program included 
Case 1 Sterile preparation 
cover: Verification program name, number, version Approval; Drafting, Reviewing (Heads of Related Authorities), Approval 
1. Purpose 
2. Scope 
3. Responsibilities 
      Available in List Form 
Name Title Duties 

4. Referenced legislation and guidance 
typically include: Good Manufacturing Practices 2010 Edition ";" Guidelines for the Implementation of Quality Control of Pharmaceutical Production "(2011 edition); "Guide to the Validation of Pharmaceutical Production" (2003 Edition); " Chinese Pharmacopoeia " (2010 Edition) and the Company's Verification Master Plan and Validation Management Rules.

5. Product Overview (Product Overview (Product Category, Clinical Use, Registration, Registered Process Change Information and Production History) and Process Description (Formulation, Process Flow Chart) 

6. Pre-Validation Verification 
6.1 Validation of         Production Environment and Facilities Humidity, pressure differential confirmation, cleanliness test results meet the requirements of the appropriate level of clean area; confirm the public facilities (air purification system, purified water and water system for injection, air compression system) has been verified to meet the requirements) 
6.2 production equipment to confirm (whether the main equipment Verify and comply with the regulations, you can list the description) 
6.3 Preparation of documents (documents related to process validation check, list confirmation, pay attention to if the new plant process and cleaning procedures may be approved draft) 
6.4 Verification of equipment and instrument calibration Instruments, meters, measuring instruments have been confirmed or verified and within the validity period) 
6.5 Participate in the verification of the verification personnel (personnel training: list all participants to attend this certification list, check the training files to confirm whether the staff involved in the verification Training? Training is qualified? : Authentication scheme; GMP(2010) basic knowledge, basic knowledge of microbiology, where the jobs and equipment operation, maintenance, cleaning SOP; staff out of the general production area clean areas and standard operating procedures; enter the sterile area, dressing confirm Meet the requirements, access to the confirmation report and health records; Acceptance criteria: confirm whether the post operator certificate holder;) 
6.6 verification of the confirmation of the materials used (raw materials and packaging materials, list description: material name, material code, quality standards, test results ) 
7. Sampling plan and evaluation criteria 
can be centralized list description can also be described separately in each process 
8. Process Verification Implementation of the 
process specification Brief 
process flow to confirm the key process parameters 
8.1 Bottle sterilization (brief purposes; Operational requirements and record requirements; list itemized verification items, standards; evaluation requirements)
8.2 rubber stopper cleaning, sterilization (for the purpose of brief; operation requirements and record requirements; list itemized verification items, standards; evaluation requirements) 
8.3 Weighing, preparation of filtering (brief purposes; operational requirements and recording requirements; Item to write out the verification items, standards, evaluation requirements) 
8.4 Filling (Brief description purpose; Operation requirements and record requirements; List itemized verification items, standards; Evaluation requirements. Operation and process monitoring; filling and cleaning tools after sterilization transfer) 
8.5 freeze-dried (brief purposes; operational requirements and record requirements; list itemized verification items, standards; evaluation requirements. 
8.6 cover (brief purposes; operation requirements and record requirements; list itemized verification items, standards; evaluation requirements. Including the production environment, sterilization parameters, disinfection procedures, equipment operation and process monitoring; and metastasis) 
8.7 light inspection (Objective: confirmation light detecting remove substandard quality product performance, process light inspection good product is not formed and nonconforming Confusion; the implementation of "lamp inspection post SOP." And light inspection machine SOP, the operation of the process recorded in a timely manner light inspection records; Project and standards: aluminum cover and bottle: Capping tight, No cracks, no foreign body outside the bottle wall; bottle: colorless point, no glass crumbs or other foreign matter, powder no discoloration, no crystal bottom shape, pinch waist phenomenon; can remove empty bottles, liquid glue wall, Plug, there are significant differences in the amount of product or have other problems. Record the results of the verification, the evaluation gives the conclusion, if deviations, according to the deviation processing program execution). 
8.8 packaging (summary purpose; operational requirements and record requirements; list item by item to write out the verification project, standards; evaluation requirements) 
8.9 total material balance (brief purpose; material balance range; evaluation requirements)
9. Finished Product Quality Inspection and Stability Test (Purpose: To confirm whether the products manufactured according to the manufacturing process of the product meet the statutory standards and internal control standards.) Operation and Record Requirements: To examine the inspection records and inspection reports of the products, Standard and internal control standards are checked item by item, the test results are within acceptable limits, recorded in the verification records and compared with the last verified batch, the product quality is evaluated, and the stability test is added if necessary. 
10. Deviation Report (Determine the processing requirements in case of deviations in the verification process) 
11. Evaluation and its conclusion (The verification team makes the final evaluation based on the verification results and make corresponding assessment and conclusion according to the verification conditions.) 
12. Verification Status Maintenance (Revalidation ) 

attachments: process flow diagrams; sampling plan; risk assessment report. Process verification process records, deviation records and other 

product process verification report 
Cover: verify the report name, number, version number; approval: drafting, review (relevant department heads), to approve the 
process verification program to provide records of all test items Have been completed and are attached to the Summary Report to certify that all changes and deviations have been documented and approved and are attached to the report and submitted for approval. The report includes: 
Verification Implementation Description: 
1. Validation of Program Implementation Start and End Time , validation lot information (lot number, production) 
2. verify embodiment is briefly 
3. verify process embodiments: by recording and evaluating programs (recorded programs completion table) for each of the results, trend analysis, if necessary; 
4. Finally, the entire verification is summarized and evaluated. The evaluation results are attached to the report. 
5. Revalidation