John Skerritt, National Manager
Pharmaceutical Law Conference
May 2014
An update from the Medicines Regulator:
Managing an...
Regulators don’t always get good press….
We need to be forward looking
Macquarie Dictionary
definition doesn’t help
reg·u·...
The nature of medicines has changed…
and their regulation has had to evolve too
Medicines use patterns have changed
…and so must regulation
• Shift from short-term use of therapies (e.g. for infections)...
Traditional clinical trials (drug vs placebo)
assessed efficacy (whether the treatment works) and
safety but not effective...
Clinical trial evidence requirements
for medicines registration are evolving
• What endpoints to use ?
– Surrogate endpoin...
The call for more “nimble” regulation
started with the HIV/AIDS crisis in the 1980s
Are regulators keeping up ?
• Emergence of biosimilars
• “Off-label” medicines prescribing
• Fast-track registration revie...
Off label medicines prescribing
• When a medicine is prescribed for an ‘indication’ or a patient
group that is not include...
Biosimilars
• A follow-on version of a biological medicine already registered
– e.g. filgrastim (for neutopenia) and epoet...
Fast track registration
• Full phase III trials usually but not always
been completed
• USFDA works closely with the spons...
Adaptive licensing – now being trialled in Europe
• Licensing of medicines prior to full
phase III trials subject to monit...
Are regulators too conservative in
the eyes of patients?
– Especially when prognosis is poor
or few effective treatments e...
Understanding patient perspectives
hopefully we have come a long way from this ?
TGA market research and initiatives in response
• Extensive consumer surveys and focus groups conducted in 2013
• Establis...
Encouraging greater consumer reporting
of adverse medicines events at TGA
• Sponsor reporting of adverse events
compulsory...
System for Australian Recall Actions
• Provides public access to information about
recall actions occurring since July 201...
Early warning system
Current and historical information on safety concerns
for medicines and devices that TGA has identifi...
Medicines shortage information initiative
Collaboration between TGA, Medicines Australia and Generic Medicines
Industry As...
Why seek international regulatory
convergence?
• Medicines and device industries and supply
chains are global
• Avoid dupl...
Multilateral medicines initiatives
• ICH (Intl Conference on Harmonisation of Technical
Requirements for Registration of P...
Constraints to work sharing /convergence
Systemic issues
• Different risk appetites between regulators
• Inconsistent deci...
Countries can have very different risk appetites
US and Europe can make different decisions
using the same data
Some examples from 2013
Approved by US FDA but banned or re...
Constraints to work sharing /convergence
Human issues
• Initial increase in cost and work with cooperation initiatives bef...
The delicate issue of trust - use of reviews
by other regulators....
International Coalition of Medicines
Regulatory Agencies – formed Dec 2013
• First regulatory coalition at agency head lev...
TGA approach to disclosure of
commercially confidential information (CCI)
Following public consultation, the new
document ...
Circumstances where release of official
information is permitted
TGA may release official information (including informati...
Sensitive information and privacy
The TGA remains bound by the Privacy Act 1988 in relation to
the collection, use and dis...
Conclusions
• Regulation approaches will continue to be reviewed and be cognisant
of the importance of public health and s...
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John Skerritt, Theraputic Goods Administration - An update from the Medicines Regulator: Managing and Communicating Risk and Strengthening International Regulatory Convergence

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John Skerritt delivered the presentation at 2014 Pharmaceutical Law Conference.

The Pharmaceutical Law Conference is the foremost meeting place and networking hub of the pharmaceutical law industry, and the only pharmaceutical law event in the Asia-Pacific region. The 2014 event highlights included pharma law reform, IP, competitive strategies, industry transparency, sustainable drug pricing and patenting life sciences and more.

For more information about the event, please visit: http://www.informa.com.au/pharmalawevent14

Published in: Business, Health & Medicine
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John Skerritt, Theraputic Goods Administration - An update from the Medicines Regulator: Managing and Communicating Risk and Strengthening International Regulatory Convergence

  1. 1. John Skerritt, National Manager Pharmaceutical Law Conference May 2014 An update from the Medicines Regulator: Managing and Communicating Risk and Strengthening International Regulatory Convergence
  2. 2. Regulators don’t always get good press…. We need to be forward looking Macquarie Dictionary definition doesn’t help reg·u·la·tor (rgy-ltr)n “One, such as the member of a governmental regulatory agency, that ensures compliance with laws, regulations, and established rules”
  3. 3. The nature of medicines has changed… and their regulation has had to evolve too
  4. 4. Medicines use patterns have changed …and so must regulation • Shift from short-term use of therapies (e.g. for infections) to management of chronic disease with medicines • Molecular targeting of cancers instead of using cytotoxic agents • Orphan drugs are becoming mainstream business • Generics – focus on bioequivalence and manufacturing quality • Biosimilars and biologicals – neither NCEs nor generics • Reimbursement rather than registration often now seen as the “real point of market access” • Complexity from globalisation of medicines supply chains 3
  5. 5. Traditional clinical trials (drug vs placebo) assessed efficacy (whether the treatment works) and safety but not effectiveness i.e. “just” require new therapies to get over the bar
  6. 6. Clinical trial evidence requirements for medicines registration are evolving • What endpoints to use ? – Surrogate endpoints vs clinical outcomes (mortality/ disease incidence) – Better use of patient-defined endpoints – Ensuring populations in clinical trials are representative • Benefit/ risk tolerance differs for different populations and individuals • Personalised medicine – small patient groups • Comparative effectiveness trials – more closely reflect decisions on treatment in routine clinical practice – compared with efficacy trials in narrow populations with few co-morbidities • Adaptive trial designs using data gathered during the trial • Can trial designs meet needs of both registration and reimbursement ?
  7. 7. The call for more “nimble” regulation started with the HIV/AIDS crisis in the 1980s
  8. 8. Are regulators keeping up ? • Emergence of biosimilars • “Off-label” medicines prescribing • Fast-track registration review and Adaptive licensing • Getting decisions right – Recall of medicines is hard solely on basis of poor efficacy (as opposed to safety grounds) ‒ Medicines withdrawn/ highly restricted for safety reasons after being licensed where suitable alternatives existed (Type 1 error) – Failure to allow a beneficial medicine onto the market (Type 2 error) • Recent international developments 7
  9. 9. Off label medicines prescribing • When a medicine is prescribed for an ‘indication’ or a patient group that is not included in the approved product information – may be because the patient group was too small to seek registration and/or clinical trials did not include this patient group • Not illegal, but puts responsibility on to the doctor to ensure that prescribing is appropriate – medicines are not eligible for PBS reimbursement and – adverse event reporting may be incomplete • A dilemma, since – TGA cannot initiate registration of off-label indications and may be little economic incentive for sponsor to do so, especially for generic drugs – EMA program encourages registration, especially for paediatric indications
  10. 10. Biosimilars • A follow-on version of a biological medicine already registered – e.g. filgrastim (for neutopenia) and epoetin lambda (anaemia) • TGA guidelines published late 2013 – www.tga.gov.au/industry/pm-argpm-biosimilars-00.htm – treated as NCEs not generics for purposes of evaluation – reference products, comparability studies and pharmacovigilance are key – encourage prescription by name and close monitoring of patients starting a product or switching • Nomenclature – TGA follows WHO recommendations – e.g. if a company registers a biosimilar for infliximab for autoimmune diseases, the product uses the ABN infliximab sim-abcd
  11. 11. Fast track registration • Full phase III trials usually but not always been completed • USFDA works closely with the sponsor in advising on trial design requirements • Some priority schemes in Europe and Japan exist but they are less regularly used • Both fast track and provisional schemes MAY provide earlier access to cancer medicines but they will less thoroughly tested in patients • Also creates dilemmas for setting suitable reimbursement levels
  12. 12. Adaptive licensing – now being trialled in Europe • Licensing of medicines prior to full phase III trials subject to monitoring of ‘real-life’ effectiveness and safety • A development plan is agreed to provide information on risk versus benefit to enable subsequent authorization • Will it lead to lowered evidence standards ? • Who will be accountable if there is a failure associated with a product ? • Difficulties in withdrawing a medicine once a patient cohort has been established • Implications for reimbursement
  13. 13. Are regulators too conservative in the eyes of patients? – Especially when prognosis is poor or few effective treatments exist – Patients are often prepared to take greater risks than regulators  Natalizumab for Crohns disease/MS – risk of progressive multifocal leukoencephalopathy  Herceptin for metastatic breast cancer – risk of cardiomyopathy  Thalidomide for inhibiting angiogenesis in multiple myeloma – risk of teratogenicity
  14. 14. Understanding patient perspectives hopefully we have come a long way from this ?
  15. 15. TGA market research and initiatives in response • Extensive consumer surveys and focus groups conducted in 2013 • Established a Public Contact Team (call centre) – Received 31,790 enquiries (11,229 from the general public) in 2013 • Website content/ social media on issues raised by focus groups, e.g. ‒ the role of the TGA ‒ the risk versus benefit approach we take to regulating higher (e.g. prescription) - and lower-risk (e.g. herbal) medicines ‒ evaluation of generic medicines ‒ travelling with medicines • ‘Translate’ service in TGA search engine for non-English speakers • Developed teaching materials for universities on regulation • Exhibition booths at non-mainstream conferences
  16. 16. Encouraging greater consumer reporting of adverse medicines events at TGA • Sponsor reporting of adverse events compulsory but patient/ doctor reporting optional • Why encourage reporting ? Real life / long term drug use, co-morbidities • Research project to explore consumers’ opinions about experiencing, managing and reporting adverse events will inform development of awareness activities • Web-based consumer reporting form and guide released after usability testing with consumers • Pharmacist dispensing software and training for adverse event reporting
  17. 17. System for Australian Recall Actions • Provides public access to information about recall actions occurring since July 2012 • Searchable for recalls for product correction and hazard alerts • Recall actions are included on SARA two working days after the decision to commence recall action to allow time for the sponsor/supplier/importer to distribute the recall communication • Consumer level recalls and recalls involving implantable medical devices are also published on the alerts page
  18. 18. Early warning system Current and historical information on safety concerns for medicines and devices that TGA has identified Monitoring communications • early communications intended to highlight potential safety concerns • TGA aims to encourage further research and reporting to provide more information as these concerns have not been fully investigated Alert communications • issued once a safety concern has been investigated • provide advice on actions that may need to be taken by health professionals and consumers
  19. 19. Medicines shortage information initiative Collaboration between TGA, Medicines Australia and Generic Medicines Industry Association in consultation with states and territories, health care professional groups and the Consumers Health Forum Comprises: • Agreed Protocol (and guidance document) for classifying shortages according to potential impact and advises on reporting processes • A website to deliver information to health professionals and consumers – temporary or permanent disruption to supply of prescription medicines – on anticipated, current and resolved shortages/discontinuations through email and RSS feeds • A communication and education strategy • Operates in addition to the current responsibilities of TGA and industry
  20. 20. Why seek international regulatory convergence? • Medicines and device industries and supply chains are global • Avoid duplication of others’ efforts • Access to pharmacovigilance data from larger populations or different racial mixes • Exchange of public and confidential safety alerts and data • Share best regulatory practices and emerging policy thinking • Development of new regulatory science
  21. 21. Multilateral medicines initiatives • ICH (Intl Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals) • PIC/S (Pharmaceutical Inspection Cooperation Scheme) • International Generic Drug Regulators Pilot • Heads of Agencies Consortium (Australia, Singapore, Switzerland and Canada) and Australia-Canada Regulatory Cooperation initiative – Manufacturing compliance and enforcement – Generic medicines – New chemical entities / orphan drugs – Good review practices – Risk communication methodology – Secure portal for information exchange – OTC medicines (Australia-Canada)
  22. 22. Constraints to work sharing /convergence Systemic issues • Different risk appetites between regulators • Inconsistent decisions reached yet based on identical evidence • Codified processes in regulations limit flexibility of some regulators • Differing financial models - cost-recovery vs government funding • Differences in timing in receiving applications from industry • Delays in receiving reports can outweigh benefits for industry • Legal / confidentiality issues between regulators and with sponsors • Confidence building , e.g. trusting reports from emerging regulators • Incompatibility of IT and other systems between regulators • Different languages and terminology in reports
  23. 23. Countries can have very different risk appetites
  24. 24. US and Europe can make different decisions using the same data Some examples from 2013 Approved by US FDA but banned or rejected in Europe • Lorcaserin, Phentermine/topiramate for weight loss • Mipomersen injectable cholesterol-lowering agent Approved in Europe but not approved for these indications in the US • Fluticasone/vilanterol inhaler for asthma • Rivaroxaban for prevention of atherothrombotic events in acute coronary syndrome So who would Australia follow here ?
  25. 25. Constraints to work sharing /convergence Human issues • Initial increase in cost and work with cooperation initiatives before they are integrated into business as usual • Limited benefits for big regulators – In-house systems and attitudes long-established – Workload implications for them in providing and explaining reports – “FDA is not here to be the World’s regulator” FDA Commissioner • Incompatibility of IT and other systems between regulators • Staff may see their jobs as being under threat • Differing priorities between regulators – e.g. some don’t regulate generic medicines
  26. 26. The delicate issue of trust - use of reviews by other regulators....
  27. 27. International Coalition of Medicines Regulatory Agencies – formed Dec 2013 • First regulatory coalition at agency head level – 23 countries plus EMA, EU and WHO • Leverage/ strategic oversight of existing initiatives • Initial priorities: – Establish better Information sharing mechanisms between regulators (e.g. IT systems, commercial in confidence, united industry engagement) – GMP Inspection worksharing – Generic medicines convergence and worksharing – Capacity building of emerging regulators
  28. 28. TGA approach to disclosure of commercially confidential information (CCI) Following public consultation, the new document covers: • information that was classified as 'COMMERCIAL- IN-CONFIDENCE' is now classified as 'For Official Use Only‘ • criteria applied by the TGA in determining whether information provided is commercially confidential • the approach that TGA takes to the release of CCI to the public, and underlying principles Not a fundamental change in approach
  29. 29. Circumstances where release of official information is permitted TGA may release official information (including information provided by a third party) in certain circumstances, such as: – to the extent required by law or by lawful requirement of a government or governmental body, authority or agency including in a review, audit or inquiry – if required in connection with legal proceedings – for purposes of public accountability, including disclosure on request to other Government Agencies, and a request for information by Parliament or the Minister – to allow the TGA to fulfil its statutory functions including release of information necessary to ensure safe use of therapeutic goods (s61 of TG Act 1989) – for exercise of Auditor-General, Ombudsman or Privacy Commissioner functions • Whether the owner of information provided to the TGA regard particular information as CCI is relevant but not determinative of its status • Other than in the circumstances described above, TGA does not release CCI except where we can justify it in the public interest and it is lawful
  30. 30. Sensitive information and privacy The TGA remains bound by the Privacy Act 1988 in relation to the collection, use and disclosure of personal information • Any such information cannot be released by the TGA under the Freedom of Information Act 1982 unless the person to whom it relates has been consulted and has had the opportunity to make submissions as to why it should not be released • Other than in circumstances described above for release of official information, TGA does not release to the public the identity of individuals or companies that provide information to us More information is at www.tga.gov.au
  31. 31. Conclusions • Regulation approaches will continue to be reviewed and be cognisant of the importance of public health and safety • Greater international collaboration between regulators is critical • Registration requirements and clinical trial designs are evolving • Regulators are increasing their engagement with patient groups • But high cost of many new medicines mean that reimbursement rather than regulatory approval is trigger for access • Options for faster regulatory approval for medicines being explored internationally • Importance of public communication and education on regulation • Recent public consultation aimed to clarify, agree and document TGA approach to disclosure of commercially confidential information

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