Presentation #5 Enforcement Activities

FDA-483, WL, Recalls Recent Events

Establishment Inspections vs. FDA-483 Issued (SJN-DO)

FY
2008 2009 2010 EI 483 Issued Conducted 18 11 14 11 6 10

%
61% 55% 71%

Top 3 Observations (SJN-DO) Medical Devices

CITATION 820.100 (b) CAPA 820.75 (a)
Process Validations

FY 2008

FY 2009

FY 2010

TOTAL

11

10

820.198 (a)
Complaint Files

Top 10 Medical Device Observations for FY 2010 Nationwide

Reference 21CFR820.198(a) 21CFR820.100(a) 21CFR803.17 21CFR820.100b 21CFR820.75 21CFR820.22 21CFR820.22 21CFR820.20 21 CFR820.30(a) 21CFR820.30 (i) Short Description
Complaint Handling Procedures not established CAPA Procedures Incomplete/Not Implemented/Not followed MDR Procedures have not been developed/maintained/implemented CAPA activities and/or results have not been [adequately] documented Process whose results cannot be fully verified has not been [adequately] validated Quality Audits/Re-Audits have not been performed Procedures for Quality Audits have not been [adequately] established Effective Quality System Not Implemented Design Control Procedures not established Design Change Procedures not established

Count 1083 1050 929 836 779 725 633 615 603 536

Top 5 Observations for FY 2010 SJN-DO Medical Devices

Observation
820.100 (b) 820.70 (a)

Description
Lack of documentation of CAPA activities Process Controls Procedures Lack of process validation activities and/or documentation CAPA procedures not [adequately] established Complaint files not adequately maintained

Count
6 4

820.75 (a)

820.100 (a) 820.198 (a)

4 3

Top deficiencies cited in SJN-DO Warning Letters from 2007-2010

Observation
820.90 (a) 820.80(d) 820.100(a)(3) & (a)(5) 820.198(c) 820.6 820.22

Description
Control of nonconforming product

Receiving, in-process, and finished device acceptance.

CAPA Complaint files Distribution Quality Audits

Recalls 2009
Medical Devices Jan Feb Mar Apr May 3 3 1 2 2 Drugs 3 3 2 3 2

Jun
Jul Aug Sep Oct Nov Dec Total

3
6 2 4 5 3 3 37

0
3 1 1 1 2 4 25

At least one of them report sterility/particulate issues

Corrective and Preventive Action

One of the three(3) top observation for 483s issued in 2010 by the FDA. Cited in 6 out of 11 inspections conducted in FY 2010 Main Observations
CAPA Procedures incomplete/not implemented/ not followed CAPA activities and/or results have not been (adequately) documented Lack of documentation of CAPA activity CAPA procedures not (adequately) established

Recent Developments
How they might impact future FDA Inspections
Tolerance of Regulatory Agencies
Warning Letters Corrections without delay Inspections directed towards previous corrections

Thorough review of Quality Systems Recalls and their extension should be few and far apart. Supplier purchase agreements, quality agreements qualification and audits might be closely scrutinized.

Corrective and Preventive Action

Tools used to identify real root cause are:
Cause-Effect/Fishbone diagram 5Whys DMAIC Is/Is Not Diagram Trend analysis- history records Contradiction Matrix Flow Charts Time line Mistake Proofing

FMEA
A failure modes and effects analysis (FMEA)
is a procedure for analysis of potential failure modes within a system for classification by the severity and likelihood of the failures helps identify potential failure modes based on past experience with similar products or processes widely used in manufacturing industries in various phases of the product life cycle is designed to improve the quality and reliability of designs is a living document

FMEA
Failure modes Any errors or defects in a process, design, or item, especially those that affect the customer, and can be potential or actual.
Effects analysis Refers to studying the consequences of those failures.

FMEA
Step 1: Severity Step 2: Occurrence (or probability) Step 3: Detection (failure to detect) Usual range used is 1 to 10 Risk priority numbers (RPN ) = (Severity) x (Occurrence) x (Detection)

Discussion of recent FDA-483 and Warning Letter citations and Recalls

Concerns Clarifications

Question and Answer Session