This year’s highlights and what’s ahead for 2017

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


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


Risk Based Inspection We have made changes to:

• product / process risk matrix • reinspection frequencies

for medicines and blood, tissue and cellular therapies


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


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


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


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.”


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)


Monitoring and ensuring compliance

“A full suite of regulatory tools is appropriately utilized to ensure compliance.”


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


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


Common deficiencies 2015 – Overseas manufacturers Poor Investigations

Testing

Inadequate procedures Labelling Storage

Document control

Validation

Potential for cross contamination

Automated systems

Training


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


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


Questions

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Documents

This year’s highlights and what’s ahead for 2017