FDA Inspectional Approach. Gina Brackett Benjamin Dastoli Laureen Geniusz Phillip Pontikos

Transcription

1 FDA Inspectional Approach Gina Brackett Benjamin Dastoli Laureen Geniusz Phillip Pontikos

2 Types of FDA inspections Level I Level II Level III For Cause Risk Based Workplan Pre-Approval Note: All inspections cover corrective actions related to previous FDA-483 observations.

3 QUALITY SYSTEM INSPECTION TECHNIQUE (QSIT) 7 Subsystems *CAPA *Design Controls *Production and Process Controls *Management Controls Records/Document/Change Control Material Controls Facility and Equipment Controls *Major systems

4 Level I Inspections Routine inspections CAPA plus either Production and Process Controls or Design Controls Selection of P & PC or design based on various triggers such as: new design/changes, CAPA issues, new processes, field actions

5 Level II Inspections Baseline inspection. Coverage of the four major systems (Design, CAPA, Management, P & PC) These can also be routine Typically first time inspections Foreign inspections Random work plan selection

6 Level III Inspections Comprehensive follow-up inspections Previously violative FDA inspections, i.e. Warning Letter Focus on previous FDA-483 observations, as well as, coverage of the 4 major systems

7 Other Types of Inspections For Cause- Complaints/MDR, Recalls, Consumer/Trade Complaints, Center Directed Assignments Pre-Approval Inspection (PMA)- Includes pre and post market inspections.

8 Typical issues we find during inspections:

9 CY 2011 Top Seven FDA-483 cites by Regulation CY Design Control Complaints CAPA P&PC Purchasing Controls Acceptance Activities Process Validation

10 CY 2012 Top 7 FDA-483 cites by Regulation (1/1/12-4/25/12) CY Design Control Complaints CAPA Acceptance Activities P& PC Purchasing Controls Process Validation

11 CY 2011 Top 20 FDA-483 Turbo Citations Number of Citations Ref No Short Description CFR (a) CAPA - Lack of or inadequate procedures CFR (a) Lack of or inadequate complaint procedures CFR (b) CAPA - Documentation CFR (a) Lack of or inadequate process validation CFR DMR - not or inadequately maintained CFR Purchasing controls, Lack of or inadequate procedures CFR (a) Nonconforming product, Lack of or inadequate procedures CFR (i) Design changes - Lack of or Inadequate Procedures CFR Quality audits - Lack of or inadequate procedures CFR (c) Investigation of device failures CFR (b) Training - Lack of or inadequate procedures CFR (a) Process control procedures, Lack of or inadequate procedures CFR Lack of or inadequate DHR procedures CFR (d) Lack of or inadequate final acceptance procedures CFR DHR - not or inadequately maintained CFR (c) Management review - Lack of or inadequate procedures CFR DHR content CFR (a) Calibration, Inspection, etc. Procedures Lack of or Inadequ CFR Quality Audit/Reaudit - conducted CFR (a) Design control - no procedures

12 CY 2012 Top 20 FDA-483 Turbo Citations (1/1/12-4/25/12) Number of Citations Ref No Short Description CFR (a) CAPA - Lack of or inadequate procedures CFR (a) Lack of or inadequate complaint procedures CFR (b) CAPA- Documentation CFR Purchasing controls, Lack of or inadequate procedures CFR DMR - not or inadequately maintained CFR (a) Documentation- Process validation CFR (a) Complaints CFR Procedures not adequately established or maintained Document Control CFR DHR - not or inadequately maintained CFR (c) Investigation of device failures CFR (a) Nonconforming product, Lack of or inadequate procedures CFR (a) Lack of or inadequate process validation CFR Quality Audit/Reaudit - conducted CFR Quality audits - Lack of or inadequate procedures CFR Lack of or inadequate DHR procedures CFR (d) Lack of or inadequate final acceptance procedures CFR (b) Training - Lack of or inadequate procedures CFR (a) Process control procedures, Lack of or inadequate procedures CFR (i) Design changes - Lack of or Inadequate Procedures CFR (b) Training records

13 Corrective and Preventive Actions Not identifying AND analyzing quality data sources based on risk and appropriate statistical methodology.

14 CAPA Quality Data Sources Examples: Complaints Non-conforming products Internal audits External audits Rework Scrap Acceptance activities (in-process and finished product) Service Returns Lawsuits

15 CAPA Verification / Validation of corrective actions (c/a): Is it effective and did the c/a not adversely affect the device Lack of documentation of whether verification or validation is needed Corrections/Corrective actions must be considered for all CAPA s. How often are data sources analyzed? Appropriate statistical methodology to analyze your data sources: i.e: action/alert limits defined risk based! What criteria triggers a CAPA??? Risk based. Complaints: (b) Not documented when no investigation needed and who made the decision.

16 Design Controls Vague or not measurable design inputs. i.e. device will meet user needs, lightweight, durable. Verification testing not confirming that the design inputs were met. Traceability matrix- not a requirement but helpful. Easy way to confirm outputs = inputs.

17 Production and Process Controls Process validation : All processes requiring validation not identified Not challenging the process, worst case scenario testing for example: material types, dimensions, complexity, batch size, etc. Considerations of failures Not monitoring critical variables Confusing process validation with design validation. These are different!

18 Production and Process Controls Engineering Changes Procedures and documented assessment unclear when validation or verification necessary Note: Risk needs to be considered when making the evaluation Lack of documentation supporting changes made

19 Production and Process Controls Purchasing Controls Increased emphasis- covered during all inspections Supplier oversight not defined/vague Supplier quality data not captured and analyzed Not approving or reviewing validated processes for your contract manufacturer Responsibility not defined

20 Other Issues Servicing vs. Complaint Define routine service vs. unexpected failures which may constitute complaints Corrective actions as a result of Management Review Corrections and Removals reporting requirements- 10 day rule. Documenting rationale for not reporting field actions

21 Inspection Classification NAI No Action Indicated VAI Voluntary Action Indicated OAI Official Action Indicated

22 Official Action Indicated Forwarded to District Compliance Branch for review. Determine if Situation 1 has been met

23 Situation 1 The district has documented evidence indicating that one or more major deficiencies with the Quality System regulation.

24 Situation 1 Cont Total failure to define, document or implement a quality system or one of the subsystems. A deficiency in one or more element(s) of the subsystem

25 Situation 1 Cont The existence of products which clearly do not comply with the manufacturer s specifications and/or the Quality System regulation and which were not adequately addressed under CAPA. Non-correction or inadequate of major deficiencies from previous inspection(s). Repeat deficiencies of same or similar deficiencies.

26 FDA-483 Response If you respond within 15 working days, response will be included in the Warning Letter

27 FDA-483 and Warning Letter Responses Should be Comprehensive Address the system not just the Specifically listed on the FDA- 483 and/or Warning Letter.

28 Questions