This presentation provides an update on the new close out process for inspections, the new risk matrix and reinspection frequencies, as well as plans for the Inspections Section for 2017.

1. This year’s highlights and what’s ahead for 2017
Jenny Hantzinikolas
Director, Inspections, Manufacturing Quality Branch
Medical Devices and Product Quality Division, TGA
Parenteral Drug Association end of year event
29 November 2016

2. Overview
• Close out process
• Product/process risk matrix changes
• Reinspection frequencies changes
• Common deficiencies from sterile manufacture inspections for 2015
and 2016 (to date)
• What’s ahead
This year's highlights and what's ahead for 2017 2

3. Close out process
There is a new close out process
• Issue post inspection letter
• Responses received on a close out template
• Objective evidence requested only under certain
situations, e.g. initial, recurring issues
This year's highlights and what's ahead for 2017 3

4. Close out process
• Final inspection report written once the inspection
is closed out
• Addition of time at the next inspection for A2 and
A3 manufacturers to review the evidence from
the CAPA Plan
This year's highlights and what's ahead for 2017 4

5. Risk Based Inspection
We have made changes to:
• product / process risk matrix
• reinspection frequencies
for medicines and blood, tissue and cellular therapies
This year's highlights and what's ahead for 2017 5

6. Drivers for change
6This year's highlights and what's ahead for 2017

7. TGA’s purpose
To safeguard and enhance the health of the Australian
community through the effective and timely regulation of
therapeutic goods.
Health
Safety
Regulation
7
This year's highlights and what's ahead for 2017

8. Regulator performance
framework
KPI 3 - Actions undertaken by
regulators are proportionate
to the regulatory risk being
managed
“Efficient regulatory risk assessment takes
account of the regulated activity,
the nature of the regulated cohort,
including its compliance history, and
other external factors affecting risk.”
8

9. Understanding manufacturer
compliance risk
9This year's highlights and what's ahead for 2017

10. Understanding compliance attitudes
Voluntary
compliance
Accidental non-
compliance
Opportunistic non-
compliance
Intentional non-
compliance
• Effective
compliance
systems
• Management is
compliance
oriented
• Ineffective and/or
developing compliance
systems
• Management is
compliance oriented but
lacks capability
•Resistance to
compliance
•Limited or poor
compliance systems
•Management not
compliance oriented
•Deliberate non-
compliance
•No compliance
systems
•Criminal intent
Committed to
doing the right
thing
Trying to do the right
thing but don't always
succeed
Don't want to comply
but will if made to
Decision to not
comply
10

11. Domestic inspection outcomes
11
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%

12. Overseas inspection outcomes
12
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%

13. Understanding intrinsic
product/process risks
13This year's highlights and what's ahead for 2017

14. Revised product/process risk matrix
Product
/process Risk
Medical Product Description BTCT Product Description
High
Sterile medicines, single step sterilisers, sterile APIs to be used in
aseptic conditions, biotechnology APIs
Primary collection, processing and storage sites
for blood, including human haematopoietic stem
cells (HPCs), tissue banks and complex
processing, cellular therapies
Medium
Other sterile APIs used with terminal sterilisation step, registered
non-sterile medicines (including registered herbal medicines)
Secondary blood collection and separation sites
(including apheresis), tissues banks with low
manipulation
Low
Non-sterile APIs for registered medicines ,all listed medicines
(including listed herbal medicines), sunscreens, medicinal gases,
single step – labelling/packaging; release for supply, storage
Other (not primary or secondary) blood
collection sites, including mobile units
Other
All remaining non-sterile APIs,
homoeopathic products N/A
14

15. Managing manufacturing quality risks
“Where the risk of non-compliance is high
or the consequence of non-compliance
significant, there is a higher degree of
monitoring.”
15This year's highlights and what's ahead for 2017

16. Managing the risks – registered medicines,
API’s 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
16

17. 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)
17
This year's highlights and what's ahead for 2017

18. Monitoring and ensuring compliance
“A full suite of regulatory tools is
appropriately utilized to ensure
compliance.”
18This year's highlights and what's ahead for 2017

19. 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
This year's highlights and what's ahead for 2017 19

20. Portfolio Budget Statement
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 20

21. Common deficiencies
2015 – Domestic manufacturers
Poor Investigations Quality risk management
Inadequate procedures Environmental monitoring
Automated systems GMP contracts
Poor records Microbial contamination
Validation Training
This year's highlights and what's ahead for 2017 21

22. Common deficiencies
2015 – Overseas manufacturers
Poor Investigations Testing
Inadequate procedures Labelling
Storage Document control
Validation Potential for cross contamination
Automated systems Training
This year's highlights and what's ahead for 2017 22

23. Common deficiencies
2016 – Domestic manufacturers (trends up to August 2016)
Poor procedures Quality Risk management
Microbial contamination Environmental monitoring
Automated systems Potential for cross contamination
Poor records Training
Validation Cleaning
This year's highlights and what's ahead for 2017 23

24. Common deficiencies
2016– Overseas manufacturers (trends up to August 2016)
Poor procedures Quality risk management
Inadequate Investigations Environmental monitoring
Automated systems Change control
Poor records Microbial contamination
Validation Training
This year's highlights and what's ahead for 2017 24

25. What’s ahead
• The adoption of the latest PIC/S revision
• Continued work with PIC/S
• Greater awareness of Data Integrity areas (not new)
• Revision of the GMP guidelines for overseas
manufacturers
• Embedding the new risk based inspection processes
This year's highlights and what's ahead for 2017 25

26. Questions
26