GMP Clearance updates – Mutual Recognition Agreements (MRA) and Compliance Verification (CV) processes

1. GMP Clearance
Stephen Farrell Acting Director,
Clearance Section, Manufacturing Quality Branch
Medical Devices and Product Quality Division, TGA
GMP Forum, 26 June 2018

2. Introduction – GMP Clearance Section
Stephen Farrell – A/g Director, GMP Clearance section,
Manufacturing Quality Branch
Darika Sowana - Assistant Director, GMP Clearance section,
Manufacturing Quality Branch
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3. Today’s agenda
• History and overview
• International comparison
• Improvements made
• Where we are now
• Ongoing challenges
• The future of GMP clearance
• Afternoon sessions (Q&A)
2

4. History and overview
• All medicine manufacturers must receive an approval from the TGA
before manufacture and supply of products to Australia, 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)
3

5. History and overview
• GMP Clearance process is a non-statutory mechanism used to verify that
overseas manufacturing sites comply with the principles of GMP for the
products being supplied to Australia
• Clearances are required for the purpose of ARTG registration or listing and
for continued supply once products have been registered or listed
• Clearances are granted to Australian sponsors for a specific time period
only
• Two pathways to obtain a GMP clearance:
– Desk top based assessment
– TGA on-site inspection
4

6. History and overview
• The GMP Clearance process was introduced as a way to reduce the
regulatory burden on industry while maintaining assurance that the
suitability of manufacturing processes and quality control procedures are
appropriate
• Prior to the introduction of the GMP Clearance process, the default
requirement was to have an on-site inspection of the overseas
manufacturing facility
• As at 30 June 2017, there were 207 manufacturing sites that were subject
to TGA inspection and approximately 2,700 overseas manufacturing sites
that relied on evidence from recognised regulators
5

7. History and overview
• The clearance process has continually evolved in order to keep pace with
changes in the global regulatory environment and industry trends
• The TGA has continued to work with other international regulatory
authorities to promote harmonisation and have entered into several Mutual
Recognition Agreements (MRA) and co-operative arrangements
6

8. History and overview
• The evidence requirements for GMP Clearance are carefully considered
based on risk and can vary depending on:
‒ The location of the manufacturer
‒ The inspecting authority and the agreement in place
‒ The risk/complexity of the product/process
• The evidence requirements have evolved through each iteration of the
GMP clearance guidance
• Historically these requirements have been reduced as confidence in
overseas regulatory authorities has increased
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9. Applications received annually
FY
10/11
FY
11/12
FY
12/13
FY
13/14
FY
14/15
FY
15/16
FY
16/17
FY
17/18
Clearance
Applications
2418 3900 3941 4222 4048 5657 5471 5327
0
1000
2000
3000
4000
5000
6000
NumberOf
Applications
8

10. International comparison
• We are one of the few regulators that have adopted a Desk Top
Assessment (DTA) process in lieu of an onsite inspection
• Health Canada also use a desktop process for overseas manufacturers
however they inspect and license their importers and distributors
(sponsors)
• PIC/S recently adopted a new guidance on GMP inspection reliance
based on the draft by the International Coalition of Medicines Regulatory
Authorities (ICMRA) of which Australia is the vice-chair
• The level of adoption by PIC/S participating authorities remains voluntary
but reflects the increasing international trend on utilising DTA processes
where appropriate.
9

11. Improvements made in 2017
• Complete revision of the GMP clearance guidance document and the
first update in over 6 years
• Re-design of the GMP clearance application e-forms to allow for
improved data capture during submission
• Creation of Clearance Application Assistance Tool (CAAT) to assist
applicants prior to submitting actual applications
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12. Improvements made in 2017
• Streamlined receipt and assessment process for CV applications
consisting of:
– Progression of applications from receipt to assessment once all
fees have been paid
– Reduction in several rounds of correspondence to applicants during
assessment
• Improved communication by providing regular updates to industry via
the TGA website, TIWGG, TGA Business Services (tBS) portal and
email signature blocks
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13. Benefits realised to date
• 30% reduction in the number of invoices TGA staff have to raise internally
• Improved quality of applications submitted, since Sept 2017, we estimate
that approximately 70% of applications are submitted with the required
evidence
• Reduction of approximately 250 emails per month received to the GMP
clearance mailbox
• Reduction in time and effort by TGA staff to produce internal reports, by
approximately 40%. This allows improved management of applications
by TGA
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14. Benefits yet to be realised
• Data analytical reporting potential cannot be fully realised until all
applications in the system migrate to the new e-form
• The impact of the streamlined receipt and assessment has not yet been
felt by industry due to the current backlog of applications
• Continued education will be required to:
– Increase the number of applications that don’t require fees to be raised
by TGA staff
– Decrease the number of applications submitted with insufficient
evidence
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15. Where we are now
1215117211981141113411021087101910561001 978 933 873 846 830 829 805
164 149 164 200 174 226 217 182 185 168 166 182 196 155 155 153 138
0
200
400
600
800
1000
1200
1400
GMP Clearances - Total
# CV's
total
# MRAs
total
Process
Improvement
2017
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16. Where we are now
545 538
513 497 492 477
440 437 421 398 389 368 347 337 314 311 314
90 91 90 89 90 87 105 90 114 108 98 98 84 80 93 91 81
206 210 217 211 208 207 219 205 225 202 202 195 187 176 181 185 182
340 333 330 343 344 325 323
297 292 293 289 272 255 253 242 242 228
0
100
200
300
400
500
600
700
16-Aug-17
23-Aug-17
30-Aug-17
6-Sep-17
13-Sep-17
20-Sep-17
27-Sep-17
4-Oct-17
11-Oct-17
18-Oct-17
25-Oct-17
1-Nov-17
8-Nov-17
15-Nov-17
22-Nov-17
29-Nov-17
6-Dec-17
13-Dec-17
20-Dec-17
27-Dec-17
3-Jan-18
10-Jan-18
17-Jan-18
24-Jan-18
31-Jan-18
7-Feb-18
14-Feb-18
21-Feb-18
28-Feb-18
7-Mar-18
14-Mar-18
21-Mar-18
28-Mar-18
4-Apr-18
11-Apr-18
18-Apr-18
25-Apr-18
Applications by type - Trend over time
Non Sterile API
Sterile/Biotech API
Sterile/Biotech FP
Non Sterile FP
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17. 5%
1%
11%
30%
24%
21%
8%
CV Status Breakdown 18 Sep 2017 (%)
Yet to be receipted
Receipt In Progress
Awaiting Payment - receipt
WOE
Yet to be assessed - Total
Assessment In Progress - Total
LOA to be processed
16

18. 7%
5%
3%
15% 43%
23%
4%
CV Status Breakdown 1 May 2018 (%)
Yet to be receipted
Receipt In Progress
Awaiting Payment - receipt
WOE
Yet to be assessed - Total
Assessment In Progress -
Total
LOA to be processed
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19. Ongoing Challenges
• The number of GMP clearance applications remains a high level
year on year
• Incomplete CV applications and poor quality applications
• Increase of competing priorities for applications (i.e. priority and
provisional pathways)
• Historical backlog of CV’s resulting in extended processing timelines
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20. The future of GMP clearance - TGA perspective
• The GMP Clearance process will remain an integral part of our
regulatory framework
• We aim to monitor changes to the international regulatory environment
(such as the PIC/S adoption of GMP inspection reliance) and assess
any impact
• We will continue to work with industry to improve the efficiency and
clarity of the process through the appropriate forums (TIWGG and
associated working groups)
• We aim to continue to communicate updates, issues and trends for GMP
Clearance through the TGA website, the TBS portal and through email
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21. Afternoon Sessions
• Understanding your supply chain (GMP agreements for GMP
clearance)
• Common mistakes made with applications
• GMP Clearance Question time
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