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
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
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
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
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
Drivers for change
6 This year's highlights and what's ahead for 2017
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
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.”
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Understanding manufacturer compliance risk
9 This year's highlights and what's ahead for 2017
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
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Domestic inspection outcomes
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FY 10/11 FY 11/12 FY 12/13 FY 13/14 FY 14/15 FY 15/16A1 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%
Overseas inspection outcomes
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FY 10/11 FY 11/12 FY 12/13 FY 13/14 FY 14/15 FY 15/16A1 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%
Understanding intrinsic product/process risks
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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
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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.”
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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
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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)
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Monitoring and ensuring compliance
“A full suite of regulatory tools is appropriately utilized to ensure compliance.”
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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
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
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
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
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
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
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
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Questions
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