Inspection RelianceGMP Clearance

Stephen FarrellDirector - GMP ClearanceChair – PIC/S Inspection Reliance Working GroupManufacturing Quality BranchMedical Devices and Product Quality DivisionTherapeutic Goods Administration

12/05/2021

Overview

1

Inspection Reliance: The benefits and challenges

GMP Clearance: Our take on inspection reliance

The impact of COVID-19

Looking ahead

2

Inspection Reliance: The benefits and

challenges “With the complexity of global supply chains, the demand for inspecting pharmaceutical manufacturing facilities far exceeds what any one National Competent Authority (NCA) can accomplish”

• Mutual Recognition/full reliance? or;• Collaboration, information

sharing/partial reliance?

3

What is Inspection Reliance?

“Where informed decisions on the GMP compliance of a manufacturing facility can be made, in certain circumstances, based on the outcome of work by another regulatory authority or authorities”

• Reduces regulatory burden on manufacturing facilities

• May reduce the risk of delays to Marketing Authorisation Applications (MAA)

• Avoids duplication of work between Regulatory Authorities

• Allows more efficient deployment of inspection resources 4

What are the benefits?

5

Scenario

Potentially 6 overseas GMP inspections reduced down to 1 or 2

• Significant differences in regulatory frameworks and legislation

• Differences in adoption of the PIC/S guide to GMP

• Different risk-appetite leading to different risk-based re-inspection models

• Different types and scopes of GMP inspections 6

What are the challenges?

7

Scenario

Up to 4 different regulatory frameworks and approaches and scopes to interpret

• PI 048-1 ‘GMP Inspection Reliance’ was adopted by the PIC/S committee in April 2018 and entered into force in June 2018

• From January to December 2019 PIC/S Participating Authorities provided statistics on the use of Inspection Reliance – Total Inspections waived: 7300– 75% relied on PIC/S evidence

8

How is it used?

9

GMP Clearance: Our take on

Inspection Reliance

• Non-Statutory • Predicated on the agreements and

arrangements with other regulators• Risk-based • Funnelled through the Australian

Marketing Authorisation Holder• Addresses Australian specific

requirements or gaps10

The GMP Clearance framework

11

7%

93%

Inspection Reliance vs TGA inspection

On site inspection

GMP Clearance

31%

69%

MRA vs CV

CVMRA

55%45%

API vs Product

ProductAPI

11

12

3.05%

92.84%

3.15%

0.95%

0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00% 90.00% 100.00%

Canada

EEA

New Zealand

Singapore

MRA Pathway – Full Inspection Reliance

13

GMP Clearance Metrics

44.02% 28.78% 9.24%

4.67%

1.85%

CV Pathway – Partial Inspection Reliance

India US China Japan

Israel Taiwan Korea - Republic of Mexico

Argentina Slovenia Romania Bulgaria

Malaysia Croatia Macau - SAR of China Turkey

Brazil South Africa Oman United Arab Emirates

United Kingdom Serbia - Republic of Thailand Ukraine

Chile Colombia Estonia Germany

Indonesia Italy Jordan Bangladesh

13

14

Processing times

15

Impact of COVID-19

15

• Domestic and overseas on-site inspections postponed / cancelled

• Introduction of remote/virtual inspections or distant assessments

• Existing MRA’s tested• Blanket extensions from other regulators• Increased uncertainty for industry and

regulators16

Impact on Inspection Reliance

17

GMP Clearance response

MRA Pathway• Increased our collaboration with

MRA partner regulators• Began accepting ‘distant

assessment’ certificates • Aligned expiry dates to the end

of 2021 in line with EMA guidance

17

18

GMP Clearance responseCV pathway• Introduced GMP Clearance

questionnaire to bridge the gap between the last on-site inspection and the current GMP assessment

• Requested additional documents as required

• Allowed additional time for MAH and manufacturers to address questions raised during assessment 18

19

GMP Clearance – Applications on hand

20

3145

34833286

3867 3785

2396

3589 3540 3538 3519 3586

2461

0

500

1000

1500

2000

2500

3000

3500

4000

4500

Jul - Dec 2018 Jan - Jun 2019 Jul - Dec 2019 Jan - Jun 2020 Jul - Dec 2020 Jan - Jun 2021

GMP Clearances received vs completed

Applications received

Applications completed

21

1024943

905

1226 1234

753

11931266

11421210

1084

601

926

1273 1238

14241465

1040

0

200

400

600

800

1000

1200

1400

1600

Jul - Dec 2018 Jan - Jun 2019 Jul - Dec 2019 Jan - Jun 2020 Jul - Dec 2020 Jan - Jun 2021

GMP Clearances received by type

Extend

New

Variation

22

212 (33%)

80 (13%)76 (12%)

65 (10%)

62 (10%)

41 (6%)

38 (6%)

29 (5%)

17 (3%) 16 (3%)

CV Applications (636) – Status Breakdown

Yet to be assessed - ready

Yet to be assessed - incomplete

Assessment in Progress - Total

Awaiting Payment

WOE - Assessment

Yet to be receipted

Signal

Letters of Access to be processed

WOE - Receipt

Receipt in Progress

22

Approvals:• Remdesivir provisional approval• Pfizer BioNtech provisional approval and supply chain variations• AstraZeneca/Oxford provisional approval and supply chain

variationsSubmissions:• Janssen vaccine• Novavax vaccine • Sotrovimab monoclonal antibody treatment submission 23

COVID-19 Vaccines & Treatments

24

Looking ahead

25

Prioritise, assess and provide GMP approvals for COVID-19 vaccines and treatments manufactured overseas

25

26

Continue to offer risk-based and flexible GMP options for industry to ensure continued supply of medicines to Australia

26

27

Continued collaboration with other international regulators as we navigate our way out of the pandemic

28

Continue our journey of Digital Transformation aiming to deliver better GMP systems and processes

29

If your question is unable to be addressed please email it to GMPClearance@health.gov.au