The document discusses current inspection trends and data metrics from the Therapeutic Goods Administration (TGA) in Australia. It provides compliance ratings for domestic and overseas inspections from 2010-2016, showing most inspections receive an A1 or A2 rating. For 2016, the most common deficiencies related to poor investigations, automated systems, validation, procedures, and quality control. Specific issues for sterile and API manufacturers are also summarized.

1. Data Metrics and Current Inspection Trends
Jenny Hantzinikolas
Director, Inspections, Manufacturing Quality Branch
Medical Devices and Product Quality Division, TGA
International Regulatory Convergence for MTP GMP

2. Overview
• Close out process
• Performance metrics and outcome
• Inspection compliance outcomes
• Managing the risk
• Monitoring compliance
• Common deficiencies
Data Metrics and Current Inspection Trends 2

3. Current inspection trends
New close out process
• Issue post-inspection letter.
• Responses received on a close out template with
a CAPA plan.
• Up to 3 responses then escalate to an internal
review process.
Data Metrics and Current Inspection Trends 3

4. Current inspection trends
New close out process
• Objective evidence requested only under certain
situations e.g. initial, recurring issues
• Final inspection report sent once the inspection
responses are completed
• Addition of time at the next inspection for A2 and
A3 manufacturers to review the evidence from the
CAPA PLAN.
Data Metrics and Current Inspection Trends 4

5. Performance metrics
16/17 Financial Year
95.43% 95.12%
78%
80%
82%
84%
86%
88%
90%
92%
94%
96%
98%
GMP Clearances using Overseas Approvals Inspections Closed Out within Target Timeframes
Source: data extracted 1 November 2016 5

6. Domestic inspection outcomes
FY 10/11 FY 11/12 FY 12/13 FY 13/14 FY 14/15 FY 15/16
A1 35.33% 30.84% 28.42% 32.22% 51.49% 33.00%
A2 41.28% 47.76% 55.33% 52.35% 35.50% 38.92%
A3 21.10% 16.92% 13.20% 14.09% 7.69% 15.27%
U 1.83% 4.48% 2.03% 0.00% 0.59% 0.99%
In Progress 0.46% 0.00% 1.02% 1.34% 4.73% 11.82%
0%
10%
20%
30%
40%
50%
60%
6

7. Overseas inspection outcomes
FY 10/11 FY 11/12 FY 12/13 FY 13/14 FY 14/15 FY 15/16
A1 30.92% 26.77% 42.71% 46.00% 42.86% 53.73%
A2 46.71% 61.42% 44.79% 46.00% 47.62% 25.37%
A3 18.42% 9.45% 11.46% 6.00% 8.57% 2.99%
U 3.95% 2.36% 1.04% 0.00% 0.95% 1.49%
In Progress 0.00% 0.00% 0.00% 2.00% 0.00% 16.42%
0%
10%
20%
30%
40%
50%
60%
70%
7

8. Managing manufacturing quality risks
“Where the risk of non-compliance is
high or the consequence of non-
compliance signficant, there is a higher
degree of monitoring.”
Data Metrics and Current Inspection Trends

9. Managing the risks – registered medicines
and blood, tissues and cellular therapies
Risk
rating
Third and subsequent
consecutive A1
Second consecutive A1 First A1 A2 A3
H 36 + reduced scope
inspection
36 24 18 12
M 36 + reduced scope
inspection
36 30 20 15
L 36 + reduced scope
inspection
36 + reduced scope
inspection
36 24 18
Data Metrics and Current Inspection Trends 9

10. Managing the risks – listed medicines
Risk
rating
Third and subsequent
consecutive A1
Second consecutive A1 First A1 A2 A3
L 48 + reduced scope
inspection
48 42 30 18
Other • Reinspection only if risk information or complaint
• Biennial compliance review (desk top)
Data Metrics and Current Inspection Trends 10

11. Monitoring and ensuring compliance
“A full suite of regulatory tools is appropriately
utilised to ensure compliance.”
Data Metrics and Current Inspection Trends

12. Monitoring and compliance tools
• Collaboration with international regulators
• Manufacturing quality signal detection
• Unannounced inspections
• Bring planned inspections forward
• Condition, cancel, suspend GMP licence
• Cancel GMP clearances
Data Metrics and Current Inspection Trends 12

13. Current inspection trends
Most common types of deficiencies in 2016 related to
• Poor investigations
• Automated systems
• Validation
• Procedures
• Quality control
Data Metrics and Current Inspection Trends 13

14. Common deficiencies for sterile manufacturers
2016 – Domestic manufacturers
Poor procedures Quality Risk management
Microbial contamination Environmental monitoring
Automated systems Potential for cross contamination
Poor records Training
Validation Cleaning
Data Metrics and Current Inspection Trends
14

15. Common deficiencies for sterile manufacturers
2016 – Overseas manufacturers
Poor procedures Quality risk management
Inadequate Investigations Environmental monitoring
Automated systems Change control
Poor records Microbial contamination
Validation Training
Data Metrics and Current Inspection Trends 15

16. Common deficiencies for API manufacturers
2016 – Both domestic and overseas manufacturers
Poor procedures Records
Inadequate Investigations Process Validation
Training Automated Systems
Cleaning validation Potential for cross contamination
Annual product review Batch records
Data Metrics and Current Inspection Trends 16

17. Summary
• More than 85% inspections are closed out on time
• The inspection compliance rating trends for 2016 for both
overseas and domestic manufacturers were provided
• The types of deficiencies observed have been provided for
2016 for all types of manufacturers, sterile manufacturers
and API manufacturers.
Data Metrics and Current Inspection Trends 17

18. Questions
Data Metrics and Current Inspection Trends 18