Provides an overview of the improvements made to the GMP clearance process including the revised guidance, the introduction of an application assistance tool, the redesigned application e-forms and the compliance verification process.

1. TGA – GMP clearance information session
GMP Clearance process Improvements
Hongxia Jin & Stephen Farrell
5th – 7th September 2017

2. Welcome & Introduction
Hongxia Jin – Director, Licensing & Certification section,
Manufacturing Quality Branch
Stephen Farrell – Assistant Director, Licensing & Certification section,
Manufacturing Quality Branch
1

3. 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

4. GMP Clearance Overview
• Approval and assessment of overseas manufacturers
• History and background
• Improvements made
• Achievements to date
• Current status
3

5. 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

6. 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

7. 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

8. GMP Clearance – Applications received annually
FY
16/17
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
NumberOfApplications
FY
10/11
FY
11/12
FY
12/13
FY
13/14
FY
14/15
FY
15/16
Data taken on 03 July 2017 7

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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 be
processed
Yet to be assessed -
Total
Assessment In
Progress - Total
14

16. 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

17. Questions?
16

18. GMP Clearance guidance revision
17th edition (May 2011) Version 18 (Sep 2017) 17

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. Commonly misunderstood information
We aim to clarify misunderstandings around
the importance of knowing the details your
supply chain
26

28. 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

29. Evidence requirements
17th edition (May 2011) Version 18 (Sep 2017) 28

30. 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

31. 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

32. 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

33. 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

34. 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

35. 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

36. 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

37. 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

38. 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

39. Questions?
38

40. Clearance Application Assistance Tool (CAAT)
39

41. 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

42. 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

43. 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

44. 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

45. 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

46. 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

47. 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

48. Clearance Application Assistance Tool (CAAT)
Draft tool demonstration
GMP Clearance Application Assistance Tool
Clearance Application Assistance Tool
47

49. Questions?
48

50. GMP Clearance Interim Solution
49

51. 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

52. 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

53. 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

54. Manual
entry of
details
Manual
entry of
details
Improved
guidance
Selection of
registered
TGA details
– no free
text entry
No
duplication
of details
53

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

56. 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

57. 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

58. 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

59. 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

60. Variation
types
Additional
options
Updated format – standardized
with new application form
Limited options – no details
about type of variation
Old format form

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

62. 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

63. 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

64. 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

65. 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

66. 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

67. Questions?
66

68. Sponsor responsibilities and CV strategy
67

69. 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

70. 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

71. 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

72. 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

73. 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

74. 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

75. Questions?
74