GMP Clearance Stephen Farrell Director (A/g), GMP Clearance Section Darika Sowana Assistant Director, GMP Clearance Section
Overview • Where we are now, future direction and focus • GMP agreements and the PIC/S guide • Answers to Industry’s most frequently asked questions • GMP Clearance for listed, over-the-counter and prescription medicines 1
Where we are now, future direction and focus 2
Background - January 2016 • GMP Clearance team of 7 within the licensing and certification section: – 4 in application receipt – 3 in assessment • Mutual Recognition Agreement (MRA) backlog • Compliance Verification (CV) backlog 3
Background - January 2016 • Sterile CV’s performed by Inspectors • GMP Clearance mailbox backlog • Extensions backlog • Transfers and name changes backlog • Outdated guidance • Poor system processing and data capture • Poor quality applications 4
Progress – 2016 to 2017 Initially Improved Re-wrote the Targeted internal Re-designed GMP Streamlined MRA, monitoring the Clearance receipt and extension and application e- guidance and assessment Measure and email reporting form introduced processes backlogs capabilities CAAT Training Recruitment 5
Progress – 2018 to 2019 Introduced Reduction of Several Published TGA vs the CV back- guidance new target industry log updates timeframes Measure time Training Recruitment 6
November 2019 • We are now a GMP Clearance Section of 20 staff ‒ 5 in application receipt ‒ 15 in assessment • No backlogs across the section • Accurately capturing TGA vs Industry time • Improved data analytics to ensure no return to backlog 7
November 2019 • Published processing times ‒ MRA – 30 working days ‒ Non Sterile API – 60 working days ‒ Sterile API – 75 working days ‒ Non Sterile finished product – 90 working days ‒ Sterile finished product – 120 working days 8
Our impact MRA vs CV 32% Overseas Manufacturers MRA 68% CV 7% On-site Inspections GMP Clearance API vs Product 93% API 44% 56% Product 9
MRA or equivalent breakdown MRA Pathway 0.96% SINGAPORE 3.71% NEW ZEALAND 92.03% EUROPE 3.30% CANADA 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00% 90.00% 100.00% 10
Compliance verification breakdown CV pathway 1.76% 44.79% 27.41% 9.94% 1 4.36% 1.89% India US China Japan Israel Taiwan Korea - Republic of Mexico Slovenia Argentina Romania Turkey Croatia Bulgaria Macau - SAR of China Thailand Brazil United Arab Emirates United Kingdom Malaysia Oman South Africa Serbia - Republic of Bangladesh Chile Hong Kong - SAR of China Indonesia Italy Jordan Canada 11
GMP clearance metrics CVs total MRAs total 700 600 500 400 649 606 584 572 548 559 530 561 525 494 504 494 512 520 518 487 482 492 452 432 300 221 182 156 159 196 209 170 168 176 139 146 189 161 152 106 200 136 172 169 166 100 85 0 12
CV applications by type 13
CV incoming vs outgoing 14
CV applications (474) - status breakdown 1 Nov 2019 15
MRAs not issued 16
CVs not issued 17
Future direction and focus • Expect a period of stability • Continue to select complete over incomplete applications • Further education and engagement with industry • Focus will be on internal processes and improvements • Continue to evolve our data analytic capabilities • Only action true priority requests i.e. for reported medicine shortages • Increased involvement in the Indo-Pacific Regulatory Strengthening Program 18
Future direction and focus • Increased focus on 2 key areas of assessment: – Release For Supply – GMP agreements • These areas are the biggest source of deficiencies for finished product GMP Clearances 19
Future direction and focus Why focus on Release for Supply and GMP agreements? – Australia has no Qualified Person (QP) system – We do not license our sponsors or regulate Good Distribution Practice (GDP) – Proposed update to Annex 16 (Certification by the Authorised Person and Batch Release) 20
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GMP agreements and the PIC/S guide 22
Manufacturer outsourced activities • Cleaning • Regulatory affairs consultants • Training • Outsourced vendor auditing • Waste management • Expert consultation • Outsourced engineering for • Certification facilities and equipment • Calibration • Contract hire services • Testing and analysis • Suppliers of materials and • Contract manufacture components 23
Finished Finished Product Product MNF MNF Release for Testing Supply (AP) Laboratory MAH MAH Alternative Testing Outsourced Testing Outsourced Laboratory OR Laboratory Activities Alternative Activities API/Drug Finished Substance Product MNF MNF Alternative Secondary Finished packaging Steriliser Product MNF MNF 24
PIC/S Chapter 7 Clause (updated text in red) Requirements for GMP Clearance 7.1 There should be a written contract covering the All outsourced activities outsourced activities, the products or operations to need to be covered by a which they are related, and any technical arrangements contract made in connection with it. 7.3 Where the Marketing Authorisation holder and the Generally, contracts manufacturer are not the same, appropriate must be in place arrangements should be in place, taking into account between the sponsor the principles described in this chapter. and manufacturer 25
PIC/S Chapter 7 Clause (updated text in red) Requirements for GMP Clearance The Contract Giver 7.4 The Pharmaceutical Quality System of the Contract Giver should How is the Contract include the control and review of any outsourced activities. The Acceptor Contract Giver is ultimately responsible to ensure processes are in reviewed/controlled? place to assure the control of outsourced activities. These processes should incorporate quality risk management principles…. MAH should 7.4.1 Prior to outsourcing activities, the Contract Giver is responsible demonstrate the for assessing the legality, suitability and the competence of the Contract Acceptor to carry out successfully the outsourced activities. suitability/legality of the The Contract Giver is also responsible for ensuring by means of the contract acceptor. contract that the principles and guidelines of GMP as interpreted in this Guide are followed. 26
PIC/S Chapter 7 Clause (updated text in red) Requirements for GMP Clearance 7.4.3 The Contract Giver should monitor and review the Need processes for performance of the Contract Acceptor and the monitoring of identification and implementation of any needed outsourced activity improvement. 27
PIC/S Chapter 7 Clause (updated text in red) Requirements for GMP Clearance 7.7 The Contract Acceptor should ensure that all products, materials Evidence of appropriate and knowledge delivered are suitable for their intended purpose. knowledge transfer 7.8 The Contract Acceptor should not subcontract to a third party any Evidence of appropriate of the work entrusted under the contract without the Contract Giver’s knowledge transfer prior evaluation and approval of the arrangements. Arrangements made between the Contract Acceptor and any third party should MAH must be made ensure that information and knowledge, including those from aware of subcontracting assessments of the suitability of the third party, are made available in as well as issues with the same way as between the original Contract Giver and Contract subcontractors Acceptor. 28
PIC/S Chapter 7 Clause (updated text in red) Requirements for GMP Clearance 7.11 A contract should be drawn up between the Contract Giver and Modification to existing the Contract Acceptor which specifies their respective responsibilities agreements may be and communication processes relating to the outsourced activities. required Technical aspects of the contract should be drawn up by competent persons suitably knowledgeable in related outsourced activities and Review and assess the Good Manufacturing Practice. All arrangements for outsourced suitability of your existing activities must be in accordance with regulations in force and the agreements Marketing Authorisation for the product concerned and agreed by both parties. Emphasis may need to be on the communication processes to ensure these are clear and unambiguous 29
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