美国FDA验证高级培训

FDA

美国FDA验证高级培训 美国 验证高级培训Denis Kluba 博士 吴培栋 博士

FDA

目录Table Of Contents1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 验证定义 CGMP对验证的要求 对验证的要求 验证历史与期望 验证综述 验证主方案与规划 实施验证的方法 验证的技术内容要求 执行验证方案 工作流程 改变控制 再验证 总结2

FDA

Part One: What is Validation?第一部分：验证定义

FDA

What is Validation?验证的含义？

For this Seminar it refers to two things: 1. The USA FDA requirements that must be met in order to successfully and continually sell drug products in the USA 2. Activities that will contribute to the success of the company in the manufacture of drug products4

FDA

Validation业内对验证的理解“Anything which you cannot understand is indistinguishable from magic.” Arthur C. Clark

“Validation may not be magic!” C. Edwards5

FDA

Validation Is.....FDA对验证的定义 “Documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.”

FDA

Why Do We Validate?验证的作用/目的Product Compliance Confirm Design Test within Specification Establish Operating Boundaries Establish Baselines7

To Consistently Produce A Desired Known Product

FDA

How Do We Validate?验证流程图Identify Equipment Systems

Details Will Follow But This is the General ModelAmend Test

Develop Tests

Conduct Tests

Write Protocols

Amend Protocol

Collect Data Evaluate DataReport Results

Results OK? yes

No

Validated System System Modified?8

FDA

First three steps to CGMP compliance 符合CGMP要求的头三步

document

document

document9

FDA

Boundaries of Validation验证的界限/范围

DOCUMENTEDCOMMISSIONING STANDARD OPERATING HIGH DEGREE OF START-UP PROCEDURES ASSURANCE MFG BATCH RECORDS TROUBLE SHOOTING CONSISTENTLY PERSONNEL TRAINING MEETS TRIAL RUNS CALIBRATION PREDETERMINED CYCLE DEVELOPMENT PREVENTATIVE MTCE SPECIFICATIONS PROCESS DEVELOPMENT CHANGE CONTROL COMPLIANCE ENGINEERING STUDIES VENDOR AUDITS VENDOR SERVICE REPORTS ANNUAL REVIEWS FACTORY ACCEPTANCE TEST COMPLAINTS SAFETY “AS-BUILT” DRAWINGS10

PROGRAM

FDA

Validation Life Cycle ApproachNew / Revised Process / ProductProspective / ConcurrentDefine Specifications Equipment Process Requirements Procedures Define ProcessDevelop Procedure Spec.

验证生命周期: 新的/修改过的工艺/产品

Design/Specify Equipment Install Equipment Data Qualify Equipment

Verify Procedure Specifications

One Lot Concurrent

Validation Report

Develop Validation Protocol Obtain Data on Process Obtain Data on Process Change Control AcceptanceThree Lots Prospective

Ongoing Evaluation

FDA

Validation Life Cycle ApproachExisting Process / ProductRetrospectiveDefine System Specifications Equipment Procedures Qualify Equipment Review Process Capability,

Specifications, Procedures, Operating Instructions Develop Validation Protocol Data

验证生命周期: 现有工艺/产品

Validation Report

Acceptance Conduct Testing (If Needed) Ongoing Evaluation

Change Control

FDA

Benefits of Validation 验证带来的好处 Increased Throughput Reduction In Rejections and Reworks Reduction In Utility Costs Avoidance Of Capital Expenditures Fewer Complaints About Process Related Failures Reduced Testing – In-process and Finished Goods More Rapid / Accurate Investigations Into Process Upsets More Rapid and Reliable Startup Of New Equipment Easier Scale-up From Development Work Easier Maintenance Of The Equipment Improved Employee Awareness Of Processes More Rapid Automation

FDA

Elements Of Contemporary Validation In The US当今美国验证包含的内容

Equipment Calibration - Process and Validation Equipment Equipment Qualification - Installation and Operational Process Development Process Documentation Performance Qualification - "Validation" Maintenance of Validation - Process and Equipment Change Control14

FDA

cGMP and ISO-9000 - SimilaritiesCGMP和 ISO 9000的相似之处

Aimed at Quality Require Documentation Require Specific Quality Program QA and QC Included15

FDA

cGMP and ISO-9000 - DifferencesCGMP和 ISO 9000的不同之处 cGMP Aimed at Product ISO-9000 Includes Design and Service, as well cGMP Covers Activities Directly Related to Manufacturing ISO-9000 Covers Broader Range of Activities (e.g.. Purchasing) cGMP Requires Formal Validation ISO-9000 Requires Applicable Statistical Methods16

FDA

Benefits of the Systems Approach to Validation系统验证方法的好处 More Rigorous Control Over Operations Centralized Planning for all Validation Related Aspects Ties Existing Sub-elements into Cohesive System Establishes Validation as a Program, not a Project Provides for Continuity of Approach Affirms Validation as a Discipline Much like Others Allows For Personnel Growth within the Validation Expertise Usually Results in Centralization of Validation Expertise More Compatible with the Accomplishment of a Corporate Objective for Validation 17

FDA

The Validation Program验证项目/规划 Establish Goals and Objectives as to What Must be Validated Qualify or Re-qualify the Equipment Establish Validation Protocols for each, and obtain Approval of the Protocols Establish Personnel Requirements and Training Records Procedure Design and Conduct Experiments. Collect Data Evaluate the Data Prepare Summary Reports Outlining the Results of the Experiments. Obtain the Necessary Approvals Establish and Maintain Validation Files Including Raw Data Institute a Change Control Procedure to Insure the Ongoing Acceptability of the Work18

FDA

Part Two: GMP Requirements第二部分：GMP对验证的要求

FDA

GMP requirement

sGMP要求

Part 211: Current good manufacturing practice for finished pharmaceuticals §211.68 - Automatic, mechanical, and electronic equipment. §211.84 - Testing and approval or rejection of components, drug product containers, and closures. §211.110 - Sampling and testing of in-process materials and drug products. §211.113 - Control of microbiological contamination. §211.165 - Testing and release for distribution. §211.166 - Stability testing.20

FDA

cGMP in the Pharmaceutical Industry制药行业的cGMP

GMP is the abbreviation of “Good Manufacturing Practice” which is adopted by the medical and health related industries including the pharmaceutical industry in an effort to maintain the highest standards of quality in the development, manufacture and control of medicinal products. Since the industry standards are subject to continuous improvement, the letter ‘c’ in the abbreviation “cGMP” refers more specifically to the current or the latest version of the GMP requirements.21

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