FDA 官员 David Doleski（Acting Deputy Director, OPF，FDA/CDER/OPQ）在行会上介绍过题为 “Pre-approval inspection program update”的报告，分享了药品质量办公室（OPQ）下的药品批准前检查（PAI），原报告出自“2015 GPhA CMC Workshop”，可从GPhA网站上下载，参见 [pdf][原文链接]，
*产品生命周期办公室（Office of Lifecycle Products，OLDP）
*新药产品办公室（注意，不同于大家熟知的 OND，此处为 Office of New Drug Products，ONDP）
*监管事务办公室（Office of Regulatory Affairs, ORA）
IQA团队
集中审评和检查的好处
Fully informed risk-based decision making related to quality
Unified voice within FDA regarding quality
Benefit to review, as reviewer better understands the implementation of the process and controls
Benefit to inspection, as reviewer contributes their knowledge and expertise of review process
Unified voice from inspection and review functions
Enhanced risk-based decision making related to quality
PAI检查的好处
Verification of veracity of data submitted in the application
Determination of significant issues in manufacturing not reported in the application
Actual verification of condition of manufacturing facilities, equipment, and processes as described in the application
Assurance that controls are in place prior to approval and distribution
Readiness to manufacture, veracity of data, adherence to application commitments drives firms to be ready for PAI and to pass inspection
Resolution of issues prior to approval
Prevent poor quality products from reaching market
是否进行PAI？
旧有模型
优先PAI：基于风险的方法
Facility reviewer performs a site compliance evaluation to determine if a PAI should be performed using:
PAI triggers
Profile evaluation
Related profile to those previously inspected
Compliance status
Time since last inspection
Input from review team and ORA
First time in an application?
First application filed by an applicant?
First generic application?
New Molecular Entity?
Narrow therapeutic index or titrated dosing?
History is unacceptable or not recently updated?
Substantially different process than previously covered at facility?
Product/process is high risk (API derived from animal tissue) or intended use has changed (API for non-sterile drug product (DP) to sterile DP)?
Certain site/process/product changes that are expected to pose significant challenge to the state of control? Numerous submissions?
Decision to Initiate Inspection:
Facility Risk: What are the risks associated with the inspectional history for this facility, the capabilities of the facility, and current operations that impact the state of control for this facility?
Process Risk: What are the manufacturing risks associated with the proposed unit operations for this product?
Product Risk: What product risks are associated with this formulation or dosage form? What is the connection between manufacturing and clinical efficacy and patient safety?
PAI与监督检查的检查重点比较
PAI
监督（Surveillance）检查
Product development documentation
Bio/clinical batch manufacturing
Proposed manufacturing process, operational procedures, and batch records
Analytical method development
Data integrity (supporting application)
Products in distribution
Quality systems
Actual conditions and practices
Analytical methods
Ongoing state of control over processes and operations
Data integrity (information maintained on the site)
