An update on post-market regulatory requirements Elspeth Kay Director, Risk Management Plan Evaluation Section Pharmacovigilance and Special Access Branch ARCS Conference 23 August 2018
Overview • TGA’s regulatory compliance framework • Pharmacovigilance Inspection Program • RMP Compliance Monitoring Program An update on post-market regulatory requirements 1
TGA’s approach to monitoring 2 An update on post-market regulatory requirements
TGA’s approach to compliance Low compliance risk High compliance risk TGA’s approach to compliance Help and support Inform and advise Correct behaviour • Make ongoing • Help to become and stay Enforce • Deter by detection compliance easy compliant Regulated entity – attitude to compliance Opportunistic non-compliance Voluntary compliance Accidental non-compliance Intentional non-compliance • Resistance to compliance • Effective compliance • Ineffective and/or developing • Deliberate non- • Limited or poor compliance systems compliance systems compliance systems • Management is • Management compliance • No compliance systems • Management not compliance compliance oriented oriented but lacks capability • Criminal intent oriented "Committed to doing the "Trying to do the right thing but "Don't want to comply but will "Decision to be non- right thing" don't always succeed" if made to" compliant" 3
Pharmacovigilance Inspection Program • PV requirements and inspections • When will I be inspected? • The inspection process: how to make an inspection a smooth process • Summary of common findings • How can we help? An update on post-market regulatory requirements 4
What are your pharmacovigilance requirements? www.tga.gov.au/publication/pharmacovigilance-responsibilities-medicine-sponsors An update on post-market regulatory requirements 5
Pharmacovigilance Inspection Program (PVIP) • The PVIP began on 1 September 2017 , with inspections starting in January 2018. • The PVIP applies to all sponsors of medicines on the ARTG including: – Listed or registered – prescription medicines – over the counter medicines – complementary medicines. An update on post-market regulatory requirements 6
Pharmacovigilance Inspection Program Guidelines www.tga.gov.au/publication/pharmacovigilance-inspection-program-guidance-medicine-sponsors 7 An update on post-market regulatory requirements
Aims of the PVIP • safeguard patient safety by ensuring the ongoing positive risk-benefit balance of a medicine in the Australian context • verify sponsor compliance with their pharmacovigilance reporting requirements (serious ADRs, significant safety issues) and other related legislative requirements • educate sponsors to assist them to meet their requirements • promote continuous improvement in pharmacovigilance ‒ PVIP is part of an enhanced vigilance framework for the TGA An update on post-market regulatory requirements 8
Scheduling of inspections • Risk-based scheduling – Routine inspections prioritised based on the risk we have assigned to a sponsor or their pharmacovigilance system. • How we assess risk: – Risk assessment survey: open 31 January-31 March 2018: obtained data on inherent product, sponsor, system and inspection-related risk factors. Now using the data obtained from this survey to assist in risk based scheduling of inspections. – Internal intelligence: may include whistleblower information, information from regulatory compliance, previous PV inspection history, overseas agency data – Non-compliance with other TGA requirements : PSUR submission, RMP commitments, GMP findings, PV reporting requirements, updating PIs • In addition to routine inspections, sponsors may be selected for random or “for cause” inspections An updat e on post-market regulatory requirements 9
Current risk areas that are being prioritised for inspection • Uncertainty about a medicine’s risk profile (including new classes of medicines and provisionally registered medicines) • Whether the medicine’s registration requires specific safety conditions • Products with known or emerging important safety concerns • Evidence that a sponsor has failed to comply with TGA regulatory requirements such as legislative pharmacovigilance requirements, good manufacturing process, RMP activities or the submission of PSURs • Compliance history, including previous pharmacovigilance or other inspection findings • Information on non-compliance with pharmacovigilance requirements from whistleblowers An updat e on post-market regulatory requirements 10
The Inspection Process • Notification, planning and preparation Pre-inspection • Agenda, logistics and initial document requests • Opening meeting Inspection • Interview sessions and document reviews • Closing meeting • Issuance of inspection report Post-inspection • CAPA response • Close-out of the inspection An update on post-market regulatory requirements 11
What we inspect Management of AE Reports Signal Collection of Detection AE Reports Report Contracts and significant Agreements safety issues Reference QPPVA safety oversight information PSUR and QMS RMP Commitments An update on post-market regulatory requirements 12
How to prepare for an inspection (a few pointers) • Ensure you have nominated an Australian contact person for PV through eBS • Ensure an appropriate quality management system is in place as a basis for an effective PV system, including up to date SOPs, training and auditing • Ensure all potential sources are being monitored for ADRs, including but not limited to marketing programs, medicines information, product quality complaints, literature, company sponsored internet sites and social media, post market clinical trials etc. • Ensure you have a robust and secure system to collect, process and analyse safety data • Ensure all serious Australian ADRs are being reported to the TGA within required timeframes • Ensure ongoing monitoring for safety signals is occurring on a regular basis and includes ALL safety data An update on post-market regulatory requirements 13
How to prepare for an inspection (a few pointers) • Ensure there are procedures in place to receive notification of significant safety issues from global counterparts and report to the TGA within required timeframes, where required • Ensure you have safety agreements in place with required partners and contractors • Ensure PSURs are complete and submitted on time • Ensure any RMP commitments are being met • Ensure the Australian person responsible for PV has appropriate oversight of the system • Ensure CAPA from any previous PV inspection has been completed • Ensure all safety data is being held indefinitely for the life of the product and for 10 years after its removal from the ARTG An update on post-market regulatory requirements 14
How to ensure the inspection runs smoothly • Have a designated point of contact for the inspectors and sponsor staff to liaise through (prior to and during the inspection) • Make sure you know who to go to in the company for requested information – who does what (i.e. market research program management, contract management, training of sales representatives etc.) • Have a database expert available to run requested reports (if applicable) • Ensure IT systems and any teleconference/video conference facilities are working • Provide documents in an accessible way to the inspectors i.e. via USB or hardcopy • Label each document with the specified number given so it can be easily tracked • If you don’t understand a request - ASK! • If you cannot provide what we are asking for - TELL US! An update on post-market regulatory requirements 15
Inspections update • 10 inspections scheduled for 2018; 5 completed Critical Major Minor Nil 25 12 • failure to report significant • deficiencies in safety data safety issues exchange agreements and • deficiencies in case collection, company SOPs follow up and seriousness • deficiencies in assessment pharmacovigilance training • late reporting of serious cases • quality management system • delay in updating reference procedures safety information (PI and CMI) An update on post-market regulatory requirements 16
Some common deficiencies identified Communication of significant safety issues • Deficiencies in communicating significant safety issues – Sponsors must report all significant safety issues to the TGA within 72 hours (Pharmacovigilance Guidelines) – Significant safety issues may include: actions taken by comparable international regulatory agencies for safety reasons identification of new safety issue or risk factors that may impact on the safety or benefit-risk assessment of the product An update on post-market regulatory requirements 17
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