TGA – GMP clearance information session GMP Clearance process Improvements

Hongxia Jin & Stephen Farrell 5th – 7th September 2017

Welcome & Introduction

Hongxia Jin – Director, Licensing & Certification section, Manufacturing Quality Branch Stephen Farrell – Assistant Director, Licensing & Certification section, Manufacturing Quality Branch

1

Agenda • GMP Clearance Overview - 30 minutes • GMP Clearance guidance - 45 minutes • Break - 15 minutes • Clearance Application Assistance Tool (CAAT) – 20 minutes • Redesigned e-form – 40 minutes • Sponsor responsibilities and CV Strategy – 15 minutes• Q&A Session – 15 minutes

2

GMP Clearance Overview • Approval and assessment of overseas manufacturers • History and background • Improvements made • Achievements to date • Current status

3

Approval of Medicine Manufacturers • All medicine manufacturers must receive an

approval from the TGA before manufacture and supply, subject to exemption provisions and other requirements

• Approvals – demonstrate compliance to the principles of Good Manufacturing practice

– Australian manufacturers - GMP licence

– Overseas manufacturers - GMP clearance to product sponsors

• An application must be lodged via the TGA business portal (licence, GMP clearance or GMP certification)

4

Assessment of O/S Medicine Manufacturers GMP clearance • GMP Clearance process is a non-statutory

mechanism used to verify that overseas manufacturing sites comply with the principles of good manufacturing practice

• GMP clearances are required for the purpose of ARTG registration and listing, and continued supply once products are registered or listed

• GMP clearances are granted to Australian sponsors for a specific time period

• Two pathways to obtain a GMP clearance: – Desk top based assessment – TGA on-site inspection

5

GMP Clearance – Desk top assessment pathway

• If current evidence is available from a recognised regulator using an equivalent standard and it covers the required scope, a GMP Clearance may be issued to the Australian sponsor via desk top assessment pathway

• Evidence required will vary depending on the international agreements, location of the manufacturer, the competent authority and complexity of the manufacturing process

– MRA assessment

– Compliance verification (CV) assessment The TGA reserves the right to undertake an inspection of an overseas manufacturing site, irrespective of any other evidence supplied

GMP Clearance – Applications received annually

FY16/17

Clearance Applications 2,418 3,900 3,941 4,222 4,048 5,657 6,506

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

Num

ber O

f App

licat

ions

FY10/11

FY11/12

FY12/13

FY13/14

FY14/15

FY15/16

Data taken on 03 July 2017 7

GMP Clearance - History Situation in late 2014 / early 2015: • Annual volume of GMP clearance applications

received had increased • Backlog of all GMP clearance applications types

(MRA & CV) • Backlog of emails (GMP clearance mailbox),

requests to extend or transfer GMP clearances • MQB’s IT system (MIS) did not effectively capture

application management information • Incomplete applications - evidence submitted with

an application was not always complete/correct • Unable to raise online invoices for CV

assessment fee 8

GMP Clearance – Improvements What we have improved to date:

• Improved work management system (implemented in June 2015) allowing for improved data analysis

• Updated internal guidance, work instructions and procedures

• Engaged additional staff with appropriate skill set

• Improved training processes

9

GMP Clearance – Improvements What we have improved to date:

• Developed a forecasting tool for MRA applications to assist in managing processing times

• Implemented a streamlined process for MRA applications (Implemented in March 2016)

• Improved communication and transparency by providing regular updates to industry via the TGA website, email signature blocks and the TGA Business Services (tBS) portal

10

GMP Clearance - Achievements

What we have accomplished to date: • Reduced response time for emails

received via GMP Clearance mailbox: from >3 weeks to ≤ 5 days

• Eliminated the MRA backlog of applications from 800 to on average ~130-200

• Reduced MRA processing timelines: from 18 weeks to ≤ 6 weeks

11

GMP Clearance - Achievements

What we have accomplished to date: • Eliminated the backlog of GMP

Clearance extension and transfer requests

• Eliminated the backlog of applications awaiting to be receipted: from >500 in September 2016 to on average ~50

• Reduced the total number of GMP clearances in the system

12

GMP Clearance - Challenges

• Incomplete CV applications or inadequate evidence

• Inefficiency in processes:

• Unable to raise online invoices for CV assessment fee

• Multiple rounds of correspondence at receipt and assessment phase

• Backlog of CV applications and long processing timelines

13

GMP Clearance – CV status

6% 1% 10%

29%

7%

23%

18%

6%

Yet to be receipted

Receipt In Progress

Awaiting Payment

WOE

Letters of Access to beprocessed

Yet to be assessed -Total

Assessment InProgress - Total

14

GMP Clearance Process Improvements Current Initiatives

GMP Clearance Guidance

• clearly document requirements for GMP Clearance applications

GMP Clearance Application Assistance Tool (CAAT)

• web based assistance tool to assist applicants preparing GMP Clearance applications

GMP Clearance Interim Solution

• redesign of online GMP Clearance application forms

Streamline receipt and assessment processes for CV applications

15

Questions?

16

GMP Clearance guidance revision

17th edition (May 2011) Version 18 (Sep 2017) 17

GMP Clearance guidance revision Guidance revision topics • Aim of the revision • Industry consultation • Structure and readability • Step by step instruction • Commonly misunderstood information • Evidence requirements • Examples of specific evidence • Other evidence types

18

Aim of the revision

• To improve the structure, readability and user experience • To clarify the most commonly misunderstood information • Address the most frequently asked questions • To provide clarification around the evidence requirements for different

application types • To provide step by step instructions for preparing and submitting GMP

clearance applications • To reflect our current practice

19

Industry consultation

• Industry consultation was performed via the TGA Industry Working Group on GMP (TIWGG) and was conducted between March – May 2017

• The TIWGG is a consultative forum established in 2014 to facilitate consultation between TGA and industry

20

Industry consultation

• The TIWGG comprises the following peak industry associations: – Accord – Australia New Zealand Industrial Gas Association (ANZIGA) – Active Pharmaceutical Ingredient Manufacturer’s Association of

Australia (APIMAA) – Australian Self Medication Industry (ASMI) – Complementary Medicines Australia (CMA) – Generic and Biosimilar Medicines Association (GBMA) – Medicines Australia (MA).

21

Structure and readability

• Removed duplicated information available elsewhere on the TGA website

• Identified information that could be extracted into stand alone webpages. For example: – Responsibilities of Sponsors webpage – International agreements and

arrangements for GMP clearance webpage

• Structured the guidance into 3 distinct sections…….

22

Structure and readability

Prior to submitting your

application • Understanding your

supply chain and establishing agreements

• Identifying the appropriate GMP clearance pathway

• Identifying what documentation is required

Submitting your application

• Creating your application

• Selecting your scope • Providing your

evidence • Submitting your

complete application and paying fees

After submitting your application

• Application receipt • Application screening • Application

assessment • Making a

determination and assigning expiry dates

• Maintaining your active GMP clearance

23

Step by step instruction The guidance will contain a step by step instructions for: • Creating your applications • Selecting your scope • Providing your evidence • Validating and submitting complete

applications • Paying the required fees • Maintaining your active GMP clearances

– Variations, renewals, extensions etc. • Transferring your GMP clearance

applications

24

Commonly misunderstood information We aim to clarify commonly misunderstood information by providing: • Links to the relevant regulatory guidelines (i.e. ARGOM,

ARGPM) for ease of reference • Contact information of the product regulatory areas to have a

mechanism to check whether GMP clearance is required for the purpose of ARTG listing or registration.

• Clarification around liaising including: – what evidence we can liaise for – what regulatory authorities we can liaise with – under what circumstances the liaising fee will be applied

25

Commonly misunderstood information We aim to clarify misunderstandings around the importance of knowing the details your supply chain

26

Evidence requirements

We aim to clarify the evidence requirements by:

• Reducing the number of evidence tables

• Renaming evidence lists from A, B, C & D to manufacturer types (i.e. Sterile finished product manufacturer)

• Hyperlinking within the table to further information on the evidence requirements

27

Evidence requirements

17th edition (May 2011) Version 18 (Sep 2017) 28

Evidence requirements

For each piece of evidence, we will add the following explanatory sections to assist sponsors with the requirements: • why we require it • what you should provide • take particular care • alternative evidence (where applicable)

29

Examples of specific evidence GMP, quality or technical agreements Why we require it GMP, quality or technical agreements are required because they provide: • information about the roles and responsibilities

of each party in relation to the critical aspects of GMP

• any specific technical aspects related to the product’s manufacture

• further information as to the roles and responsibilities of the Australian Marketing Authorisation (MA) holder in relation to post market surveillance obligations.

30

Examples of specific evidence GMP, quality or technical agreements What you should provide Provide the signed GMP, quality or technical agreement relevant to the scope of your application. Ensure that it: • meets the full requirements of

chapter 7 of the PIC/S guide to good manufacturing practice for medicinal products – Part I.

31

Examples of specific evidence GMP, quality or technical agreements Take particular care Ensure that the GMP, quality or technical agreement: • clearly identifies the products and

steps of manufacture (activities) relevant to the scope of your GMP clearance application

• clearly describes the role of each party subject to the agreement

• has been signed by all parties to the agreement.

32

Examples of specific evidence GMP, quality or technical agreements Alternative evidence Depending your scope and/or relationship with the manufacturer, you may provide the:

• signed GMP, quality or technical agreement between the principal manufacturer and its subcontractor

– E.g. contract laboratories, sterilisers etc.

• equivalent signed documentation that clearly outlines the roles and responsibilities of the Australian MA holder (Sponsor) and the other entities in the supply chain.

– E.g. for subsidiaries of the same parent company 33

Examples of specific evidence Release procedures Why we require it The release procedure is required because it provides: • information about how the

authorised person at the site performs the release for supply or release for further processing (if applicable) step of manufacture.

34

Examples of specific evidence Release procedures What you should provide Provide the release for supply procedure(s). Ensure that: • the procedure is applicable to the product

types and dosage forms in your application • sufficient information about how the authorised

person ensures each batch has been manufactured and checked for compliance with the relevant Marketing Authorisation (MA)

• all relevant appendices to the procedure are provided—for example, batch release checklists.

35

Examples of specific evidence Release procedures Take particular care Ensure the procedure describes in detail how the release for supply process operates, for example, the process for reviewing critical records and verifying compliance with GMP and the MA. For more information please see Guidance on release for supply.

36

Other evidence types

• We will clarify the correct use of Letters of Access (LoA) including: – how these should be presented – what information they should contain – what additional sponsor specific information should be

submitted to support the application.

• We will clarify the correct use of TGA certificates including: – Under what circumstances they can be accepted – what additional information should be submitted to support the

application

37

Questions?

38

Clearance Application Assistance Tool (CAAT)

39

Clearance Application Assistance Tool (CAAT) Background – Original CAAT

• The Clearance Application Assistance Tool (CAAT) was created as a way to assist sponsors preparing better quality GMP clearance applications

• It was previously distributed to industry as an excel document

• Feedback from users found that it was helpful in determining the requirements based on their specific selections

40

Clearance Application Assistance Tool (CAAT) Updated version

• The updated GMP CAAT is an interactive online tool designed to assist sponsors or applicants in determining the general evidence requirements for their GMP clearance applications.

• It is intended to complement the updated GMP Clearance Guidance and the redesigned e-forms

• Sponsors can access the tool directly from the TGA website or via hyperlinks in the GMP clearance guidance and the redesigned e-forms

41

Clearance Application Assistance Tool (CAAT) How it works

• You will be presented with information at the beginning of each page to assist you in making the relevant selection or to provide you with information about the previous selection made

42

Clearance Application Assistance Tool (CAAT) How it works

• Beneath the information section there will be a question followed by a list of available options

• You will need to select the option that is most relevant to the GMP clearance application you wish to submit

• If the wrong selection is made you can go back or restart the process

43

Clearance Application Assistance Tool (CAAT)

• When all of your selections are made you will be presented with information based on those selections

• You will also be provided with specific references and links to the GMP clearance guidance and e-form

44

Clearance Application Assistance Tool (CAAT) How it should be used:

• We strongly encourage applicants to use this tool to:

– Verify their understanding of the evidence requirements prior to submitting their application

– Improve their understanding of the requirements outlined in the guidance

– Improve the quality of applications submitted for assessment

45

Clearance Application Assistance Tool (CAAT) What we would like to see

• After publishing the assistance tool we would like to see:

– A Reduction in the number of queries via the 1800 line and the GMP clearance mailbox

– An improvement in the quality of applications submitted for assessment

46

Clearance Application Assistance Tool (CAAT) Draft tool demonstration

GMP Clearance Application Assistance Tool

Clearance Application Assistance Tool

47

Questions?

48

GMP Clearance Interim Solution

49

GMP Clearance Interim Solution Interim solution topics

• Key items to be addressed • Comparison between current and new e-forms • Implementation • What you need to do

– Prior to launch – Other application types

• Launch

50

GMP Clearance Interim Solution Key items to be addressed • Improved user experience for submissions:

– Reduced duplication in data entry for applicants – Pre-population of information using client details registered with

TGA and the use of information from the ingredients database – Improved help functions on the form to assist applicants

• Improved invoicing: – All fees can be selected & paid at the time of submission

• Allowing extension requests to be submitted via tBs: – Currently these requests are submitted via email, there will be an

extension request application form.

51

GMP Clearance Interim Solution Key items to be addressed

• Improved application ‘smarts’: – A customisable list of evidence will be displayed on the e-form

based on the application types – Evidence naming convention, this aims to assist TGA staff in

receipting applications • Improved data capture

– Allowing improved management of applications by TGA

52

Manual entry of details

Manual entry of details

Improved guidance

Selection of registered TGA details – no free text entry No duplication of details

53

Duplication

Free text entry New request form to register a manufacturing site – no free text entry

No indication of application type No assistance for what evidence to provide

Selectable Application Type

Customizable list of evidence based on application pathway (MRA or CV)

55

Additional information to assist TGA assessors Eg: priority applications

• Additional Delivery methods for evidence

• Visual indicators for applicants

• Customizable list of evidence for CV applications

Free text entry

No validation with code tables

No validation with code tables

Search of Ingredients database – no free text

Validation with code tables

57

Not all fees can be applied at time of lodging application

No breakdown of fees to be charged (only total sum)

Desktop fee can be charged upfront

Breakdown of fees shown

58

Variation types

Additional options

Updated format – standardized with new application form

Limited options – no details about type of variation

Old format form

Ability to request an extension to a current GMP Clearance via tBS No more email requests for extensions

Implementation

• There will be a planned outage of the GMP Clearance application forms for 1 week between: – Tuesday 19th September at 09:00 (AEST) – Tuesday 26 September at 09:00 (AEST)

• You will not be able to submit GMP Clearance, Licence or Certification applications via tBS, during this time

• If the application forms are available earlier, we will update you via our website.

61

Prior to launch

What you need to do

• Submit any 'draft' GMP Clearance applications using the current form, before the planned outage

• Any draft GMP clearance applications not submitted will be lost

• Applications submitted up to and including 18th September at 17:00 (AEST) will not be affected 62

Other application types Plan ahead

• If you need to submit a GMP Licence or Certification application, please ensure that it is lodged before 17:00 (AEST) on 18th September

• Alternatively, please plan to lodge your GMP Clearance, Licence or Certification application after 09:00 (AEST) on 26 September onwards

• There are no changes to the GMP Licence or Certification application forms

63

Launch What to do on 26th September

• Prior to submitting new or variation GMP Clearance applications we strongly encourage all sponsors and applicants to: – Familiarise yourself with the updated

GMP clearance guidance – Utilise the GMP CAAT tool – Follow the step by step instructions

for submitting new or variation applications

64

Launch What to do on 26th September

• If you encounter any issues when using the e-form, please contact GMPclearance@tga.gov.au and provide a screenshot of the issue.

• We welcome all feedback that helps processes be improved and would encourage you to provide any feedback you have on the updated GMP clearance guidance, CAAT and redesigned e-form.

65

Questions?

66

Sponsor responsibilities and CV strategy

67

GMP Clearance – Challenges • The number of GMP clearance

applications continues to increase annually

• Incomplete CV applications and insufficient evidence requires multiple rounds of correspondence at both receipt and assessment

• Backlog of CV’s resulting in long processing timelines

• Sponsors who provide complete and sufficient supporting evidence are disadvantaged

68

GMP Clearance – Sponsor responsibilities Prior to submission, ensure that:

• The scope of your application is relevant to the activities carried out by the manufacturer and is reflected in the supporting evidence provided

• All required evidence is attached when submitting your application or provided directly by the manufacturer

– any evidence intended to be sent directly to the TGA will be provided no later than one month from the submission of the GMP clearance application.

• All information to be provided is accurate, current and not contradictory

• The signed and effective GMP, quality or technical agreements are in place and provided (where applicable)

69

GMP Clearance – Sponsor responsibilities

During processing, ensure that:

• Any additional information or clarification requested by the TGA during the assessment of GMP clearance applications is provided within the specified timeframe

70

GMP Clearance – Sponsor responsibilities

Post-approval, ensure that you:

• Monitor regulatory actions by other authorities for manufacturing sites for which you hold an active GMP clearance

• Notify us of these regulatory actions and of any significant changes to the manufacturing site

• Maintain GMP, quality or technical agreements with your manufacturers

• Submit renewal applications at least 6 months prior to the expiry of your current clearance, or alternatively, if evidence for a renewal is not available, request TGA certification

71

GMP Clearance – CV Strategy Improve Process efficiencies

We intend to be more efficient by: • Reducing the amount of

correspondence • Applying due dates to requests for

information or clarification and making determination after the due dates

• Issuing clearance for the scope that is supported by the evidence

• Not issuing clearance for incomplete applications that meet specific criteria

72

Summary of timelines Key dates

• Monday 18th September – Submit all draft GMP clearance applications by 17:00 (AEST)

• Tuesday 19th September – GMP clearance planned outage at 09:00 (AEST) – Publication of updated GMP clearance guidance and Clearance

Application Assistance Tool (CAAT) • Tuesday 26th September

– GMP clearance redesigned e-form operational at 09:00 (AEST) – Implementation of CV strategy

73

Questions?

74