Presentation on the background of medicine shortages, definitions, reporting requirements, assessment and management, Section 19A and the compliance framework

1. Reporting of Medicine Shortages
Anna Nhan
Medicine Shortages team, Risk Management Section
Pharmacovigilance and Special Access Branch, TGA
ARCS – August 2019

2. Overview
• Background
• Definitions
• Reporting requirements
• Assessment & management
• Section 19A
• Compliance framework
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3. Background
• Worldwide issue
• Lack of a universally accepted definition of a “medicine shortage”
• Varying degrees of patient impact
• Medicine shortages are unavoidable and cannot be prevented in most cases
• Need for timely communication of medicine shortages
2

4. Causes of shortages
• Unavailability of raw materials
• Manufacturing/Quality related issues
• Changes in product manufacturer
• Commercial decision by sponsors
• Unexpected fluctuations in demand
3

5. Shortage reasons reported
3%
9%
46%
26%
16%
2017
2%
14%
50%
16%
1%
17%2018
22%
46%
17%
1%
14%
2019
Commercial changes
Discontinuation
Manufacturing
Other
Product recall
Unexpected increase
in demand
4

6. How shortages have been managed until now
• Previously no consistent and co-ordinated approach to the communication and management of medicine
shortages in Australia
• Healthcare professionals and consumers left uninformed
• Based on voluntary notifications from sponsors
• Medicine Shortages Information Initiative (MSII) webpage was launched on 26 May 2014.
5

7. Limitations
• Voluntary scheme vs FDA and Health Canada where reporting of shortages is mandatory
• Not all shortages notified
• Health care professionals and patients aware of shortages before they were reported
• Lack of accuracy of information
• Information out of date
6

8. Changes to how shortages are communicated and
managed in Australia
• End of 2017 - Health Minister requested change to current system
• Issues considered:
o definition of a medicine shortage
o reporting obligations and timeframes for sponsors
o introduction of the “Medicines Watch List” (MWL)
o penalties for non-compliance
7

9. Changes to how shortages are communicated and
managed in Australia
• Goals:
o Improve management and communication of medicine shortages
o Increase transparency
o Early identification of alternative medicines where necessary
• Therapeutic Goods Act 1989 amended
o mandatory reporting for all “reportable medicine” shortages to the TGA to commence from
1 January 2019
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10. Overview
• Mandatory reporting of all “Reportable medicines” (include all S4, S8 and some S3 medicines)
• Mandatory publication on the MSII if Critical Impact
• Critical Impact medicine shortages
• Medicines Watch List
• Reporting of critical impact shortages vs low/medium impact
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12. Definition – Medicine shortage
A medicine shortage is defined in the Act as:
a shortage of a medicine in Australia at a particular time if, at any
time in the 6 months after that particular time, the supply of that
medicine in Australia will not, or will not be likely to, meet the
demand for the medicine for all of the patients in Australia who take,
or who may need to take, the medicine.
11

13. Discontinuation - Legislated timeframes
The discontinuation of the supply of a medicine (a permanent shortage) must also be notified to the
TGA as outlined in the legislation:
(a) if the discontinuation is likely to be of critical impact:
(i) at least 12 months before the discontinuation is proposed to occur; or
(ii) if the person is unable to comply with subparagraph (i)—as soon as practicable after the decision is
made; or
(b) in any other case:
(i) at least 6 months before the discontinuation is proposed to occur; or
(ii) if the person is unable to comply with subparagraph (i)—as soon as practicable after the decision is
made.
12

14. Reportable medicines
Reportable medicines are defined in the legislation as:
(1) For the purposes of this Act, registered goods are a reportable medicine if:
(a) the goods are medicine; and
(b) either:
(i) the medicine contains one or more substances included in Schedule 4 or 8 to the current Poisons
Standard; or
(ii) the medicine is determined in an instrument under subsection (2).
(2) The Minister may, by legislative instrument, determine medicine for the purposes of subparagraph
(1)(b)(ii).
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15. Reportable medicines
Non-prescription medicines:
• critical to the ongoing health of the patient (e.g. salbutamol inhalers)
• inclusion of the medicines is critical for public health (eg naloxone injections)
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17. Critical impact vs Low/Medium
• A risk assessment framework
• Nature and size of the population affected
• Availability of alternative products
• Assists in determining patient impact – critical, medium or low
16

18. Impact assessment framework
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19. Medicines Watch List (MWL)
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20. Reporting a shortage – Timeframes
Critical impact
• If on the Medicines Watch List, or assessed as having critical patient impact – must report to the TGA within
2 working days.
• Either complete all fields and submit to the TGA within 2 working days
OR
• Submit initial report within 2 working days containing certain information that is required. Submit remaining
information within 3 working days
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21. Reporting a shortage – Timeframes
Critical impact
• minimum information required:
o impact of the shortage
o nature of the shortage
o sponsor details
o ARTG number – which will provide the ARTG name
o primary contact for TGA to liaise with
o date the shortage was known to the sponsor
o estimated dates for the start and end of the shortage
o availability
o proposed date of publication on the TGA website
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22. Reporting a shortage – Timeframes
Low/Medium impact
• sponsor has 10 working days to notify TGA
• completion of all fields in the notification form is mandatory
21

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24. Manage
Investigation of alternative products
• Identify products that may be available for substitution
• Same pharmaceutical substance, dose form and strength but sourced from another supplier
• Different substance but in the same therapeutic class
• Suitable products may be sourced from overseas
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25. Communicate
Critical impact
• Mandatorily published on the Medicines Shortage Information Initiative website.
• Sponsor to undertake the following communications as appropriate:
o hospital medicines
o community/retail pharmacy medicines
o PBS medicines
o National Immunisation Program vaccines
o National Blood Authority plasma components (registered medicines)
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26. Communicate
Low/Medium impact
• Highly encourage to be published on the Medicines Shortage Information Initiative website.
• Sponsor to notify other stakeholders as required, eg supply chain
• Minimise lack of publicly available information creating difficulties in the community
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27. Role of TGA
• Manages the medicines shortage information initiative website
• Review the sponsor’s initial risk assessment of the shortage and communicate the shortage as needed
• Approve temporary supply of a substitute medicine during a shortage
• May undertake additional communication activity where necessary
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28. Role of sponsors
• Maintain continuity of supply for a medicine through various business processes
• Assess supply and demand gaps and develop a response
• Implement management activities to secure supply
• Implement communication activities to the supply chain
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31. ARTG name:
AUST R:
Active ingredients:
Sponsor:
Phone:
active ingredient - medicine shortage information
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34. Number of new notifications
0
20
40
60
80
100
120
140
160
180
200
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
2018
33

35. Number of new notifications
0
50
100
150
200
250
300
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
2018 2019
34

36. Number of total notifications
0
50
100
150
200
250
300
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
2018 35

37. Number of total notifications
0
100
200
300
400
500
600
700
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
2018 2019 36

38. Section 19A
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39. Section 19A
• Allows a sponsor to import and supply a medicine not on the ARTG because:
o The Australian registered medicine is in shortage or unavailable
o The medicine is needed in the interest of public health
 availability of other treatments
 consequences of discontinued treatment or changing treatment
 projected demand for the product
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40. Section 19A
• Included in Schedule 10 to the Therapeutic Goods Regulations 1990
• Approvals are granted for a specified period of time
• Subject to any relevant conditions
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41. Suitable substitutes – what to consider
• Identify and assess suitability of all potential substitutes included in the ARTG
• Availability of substitutes included in the ARTG
• Suitability of s19A product:
o how close it is to ARTG product in shortage/unavailable
o how appropriate it is to use the substitute in the intended patient population
o how appropriate is the dosage form
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42. Specified foreign countries
• S19A(1): Medicine must be registered and marketed in at least 1 of 9 specified countries
• S19A(1A): Medicine is registered and marketed in a country other than the above
Canada Sweden
France Switzerland
Germany United Kingdom
Netherlands United States of America
New Zealand
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43. Conditions of approval
• Current GMP
• Labelling in English (at least easily identifiable)
• Product information in English
• Dear Health Care Professional Letter
• Over-label with Australian sponsor’s name and address
• Adverse event reporting
• Reporting on supply
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44. Multiple applications
• Usually only grant one approval
• Consider granting approval to subsequent application(s) if supply cannot be met and where appropriate
• An effective application is one that:
o has been completed in full
o provides all relevant attachments
AND
o meets the criteria for approval.
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46. Compliance framework
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47. Reporting requirements - recap
• A medicine is in ‘shortage’ if its supply in Australia will not, or will not likely, meet the demand for it at any
time in the next 6 months, for all the patients in Australia who take it or who may need to take it
• ‘Critical impact’ shortage – no later than 2 working days
• Any other shortage – within 10 working days
• Discontinuation of ‘critical impact’ – at least 12 months
• Any other discontinuation – at least 6 months
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48. Information gathering powers
• Power to require a person to provide information or documents in relation to:
o whether or not there is a shortage of the medicine in Australia;
o if there is a shortage of the medicine in Australia – the shortage, or
o any decision of the person to permanently discontinue the supply of the medicine in Australia
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49. Medicine shortage reporting non-compliance
• Compliance obligations and penalties commenced on 1 July 2019
• In accordance with the TGA’s Regulatory Compliance Framework.
• Graduated, risk-management approach to compliance
• TGA’s response to non-compliance guided by:
o whether there is a potential for detriment to the health of consumers, and
o sponsor's behaviour prior to and in relation to the non-compliance with their reporting obligations.
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50. Regulatory compliance and enforcement tools
• Legal obligations letter
o informs a sponsor that their reporting may not be compliant
o provides educational and guidance material
o does not seek a response
• Formal warning letter
o sponsor is aware of reporting obligations but have not met them
o requires the sponsor to respond to the TGA
o TGA will publish the names of sponsors who do not comply
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51. Regulatory compliance and enforcement tools
• Infringement notice
– may be given where a sponsor has, within 12 months, contravened a civil penalty provision of the Act for
non-compliance with their reporting obligations relating to medicine shortages or discontinuations.
• Enforceable undertaking
– a promise able to be enforced by a court
• Civil penalty litigation in the Federal Court
– can result in large fines being imposed on the alleged sponsor
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52. Compliance risk
Low Medium High Extreme
Help and support
• Make ongoing
compliance easy through
clear education and
guidance material
Inform and advise
• Direct education and
guidance in a legal
obligations letter to help
the sponsor become and
stay compliant
Correct non-compliant
behaviour
• Send a formal warning
letter and giving notice of
available compliance and
enforcement options
available to the TGA
• Publish names of non-
compliant sponsors
Enforce penalties
• Civil penalties
• Infringement Notices
• Enforceable
Undertakings
Voluntary compliance
• Effective compliance
systems in place
• Management is
compliance oriented
Accidental or
opportunistic non-
compliance
• Ineffective compliance
and/or developing
compliance systems
• Management is
compliance oriented but
lacks capability
Regular non-compliance
• Resistant to compliance
• Management is not
compliance oriented
Intentional non-
compliance
• Deliberate non-
compliance
• No or ineffective
compliance systems
• Reckless attitude
towards reporting
obligations
“Committed to doing the right
thing”
“Try to comply but don’t always
succeed”
“Don’t want to comply but will if
made to”
“Conscious decision to be non-
compliant” 51

53. Publication of outcomes
• Details about the sponsor and action undertaken by the TGA may be published on the TGA website:
− formal warning letter
− infringement notices
− enforceable undertaking
− civil penalties
• Transparency of the TGA’s compliance handling processes
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