FDA Compliance Update:
A Regulator’s Focus on
the Future
U.S. Food and Drug Administration
Erin McCaffery
Compliance Officer
New Jersey District
September 12, 2013
1
OVERVIEW
• Compliance Trends
• FDA Responses…What Counts?
• Further Global Initiatives
– PIC/s
– GDUFA
• Hot Topics
• Conclusions
• Questions
2
District Level Responsibilities
• Workplan
– Domestic and Foreign
– Assignments from Centers
• Pre-Approvals
• For Cause
• Consumer Complaints
• Trade Complaints
• Recalls
• Referrals from State, OCI, DEA
• Case Monitoring
Trending by Fiscal Year
2008
2009
2010
2011
2012
Warning
Letters
445
474
673
1,720
4,882
Seizures
8
6
10
15
8
Injunctions
5
11
17
16
17
Total actions
458
491
700
1,751
4,907
4
Seizures
Fiscals Years 1993 – 2012
140
120
100
117
98
80
73
60
20
25
35
27
13
20
03
20
01
19
99
19
97
19
95
19
93
0
25
10
20 17
6
8
8
10
15
8
20
11
35
20
09
46
20
07
36
20
05
40
5
Injunctions
Fiscals Years 1993 – 2012
25
23
20
21
16
15
15
11 10 11
10
17
12
12
12
8
15
17 16 17
15
17
9
5
5
2012
2011
2010
2009
2008
2007
2006
2005
2004
2003
2002
2001
2000
1999
1998
1997
1996
1995
1994
1993
0
6
Warning Letters
Fiscal Years 1996 – 2012
6000
5000
4882
4000
3000
2000
1000
582 725 535 538 471 445 473 673
19
96
19
97
19
98
19
99
20
00
20
01
20
02
20
03
20
04
20
05
20
06
20
07
20
08
20
09
20
10
20
11
20
12
0
10381140905 900 11541032
755
1720
7
FY12 WARNING LETTER
BY FDA CENTER
Center
• CTP
• CDER
• CDRH
• CBER
• CFSAN
• CVM
Warning Letter
4,146
95
210
20
335
76
8
LEGAL ACTIONS
FY2004 to FY2012
Fiscal Year
2004
2005
2006
2007
2008
2009
2010
2011
2012
Drug
9
2
4
4
1
1
5
2
4
Total
19
13
13
14
7
6
18
23
20
9
New Jersey Compliance Data
FY’13 to date
(all program areas)
• 12 Warning Letters • 2 Injunctions
• 0 Seizures
Turbo Citations
21 CFR 211 Drug Citations (Top 10 as of 9/3/2013)
211.22(d)
211.110(a)
211.100(b)
211.165(a)
211.192
211.25(a)
211.160(b)
211.67(b)
211.100(a)
211.188
11
Turbo Citations
21 CFR 211 Drug Citations (Top 10 as of 9/3/2013)
211.22(d)
211.100(b)
211.192
• The responsibilities and procedures applicable to the quality control unit shall be in writing; such written procedures shall be followed. • Written production and process control procedures shall be followed in the execution of the various production and process control functions and shall be documented at the time of performance…
• …Any unexplained discrepancy…or the failure of a batch or any of its components to meet any of its specifications shall be thoroughly investigated whether or not the batch has already been distributed…
12
Turbo Citations
21 CFR 211 Drug Citations (Top 10 as of 9/3/2013)
211.160(b)
211.100(a)
• Laboratory controls shall include the establishment of scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in‐
process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality and purity…
• There shall be written procedures for production and process controls designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess…
13
Turbo Citations
21 CFR 211 Drug Citations (Top 10 as of 9/3/2013)
211.110(a)
211.165(a)
211.25(a)
• …Such control procedures shall be established to monitor the output and validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in‐
process material and the drug product…
• For each batch of drug product, there shall be appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release.
• …Training shall be in the particular operations that the employee performs and in current good manufacturing practice regulations…as they relate to the employee’s functions…
14
Turbo Citations
21 CFR 211 Drug Citations (Top 10 as of 9/3/2013)
211.67(b)
211.188
• Written procedures shall be established and followed for the cleaning and maintenance of equipment, including utensils, used in the manufacture, processing, packing or holding of a drug product…
• Batch production and control records shall be prepared for each batch of drug product produced and shall include complete information relating to the production and control of each batch…
15
What Situations Warrant
Follow Up
•
•
•
•
•
Seriousness of Problem
Willingness of Firm to Correct
System(s) Out of Control
Adulterated/ Misbranded Products
Pattern of Failure
16
RESPONSE TO FDA-483
What Counts?
• Executive summary including time frames
for corrective actions
• Original FDA-483 observation with your
response and attachments
• List of corrections already made by date
• Sent within 15 days
• Captain Joseph McGinnis, Director of Compliance,
New Jersey District
17
Warning Letters
(What triggers them?)

Re-occurring violations, significant
violations that show adulteration or
misbranding

No response to FDA-483 or inadequate
response

Unwilling or Unable to comply
18
Issues that frequently result in
regulatory action…
• Failure of the Quality System • Process data unsupported by validation activities
• Potential cross contamination
• Unjustified deviations from manufacturing process
• Changes that are not supported by data
• Poor investigations that were not expanded to other products or batches of the same product
• Deficiencies in analytical method validation
• Outdated methodology
19
Proactive Preparation
• Be ready for Inspection (Have a Plan)
• Daily Wrap Up / Discussion
• Final Discussion
• Handling of FDA 483
• Preparing a Response
20
PIC/s Ukraine
GDUFA Progress
Hot Topics
•
Pharmacy Compounding
•
Virtual Companies
•
Contractor responsibilities
•
Quality Agreements
•
Changes without submissions
•
Virtual Companies
•
Consultants vs. In-house Expertise
Conclusions
• Be proactive, not reactive
• Be transparent with regulators to build trust
• Poor quality has high cost
• Strive for greater process knowledge to
reduce risk and cost
• Compliance is a marathon, not a sprint
Questions?
CONTACT
erin.mccaffery@fda.hhs.gov
973-331-4993
26