Best Practice
Regulatory
Processes for OTCs
A Joint Industry/Regulator
Collaboration
Deon Schoombie
Background
• In July 2009 TGA National Manager called a meeting of
company CEOs to discuss options for improving the
regulatory system & business processes for OTCs
• There was a need for fundamental changes to ensure
regulatory activities are more efficient & cost-effective
• CEO Forum established - TGA Executive & CEOs of
companies to identify key issues & provide strategic
direction
• A TGA/Industry Working Group to development options
for reform
Terms of Reference of the CEO Forum
• Advise TGA following consultation with the sector on:
– Industry priorities
– Communication & implementation considerations for proposed
new processes
• Provide strategies & direction for communicating
progress in the development & implementation of new
processes to industry & the Working Group
• Provide strategies & direction for engaging the industry
in the implementation of changes
• Identify opportunities for communication with
stakeholders
• Monitor activities & progress of the Working Group
Terms of Reference of the Working Group
• Advise TGA following consultation with industry on
issues relating to:
–
–
–
–
current market authorisation processes
proposed changes to current processes
potential risks & benefits of any changes
implementation considerations
• Communicate progress on development &
implementation of new processes
• Assist in developing documentation describing the new
processes
• Engage industry in the implementation of changes
• Provide advice to TGA on matters related to the project
Key issues identified by Industry
•
•
•
•
•
A prescription medicines mindset applied to OTCs
A culture of risk-aversion
Poor understanding of commercial imperatives
Lack of clarity in relation to regulatory requirements
Unpredictable & unacceptably long timeframes resulting
in inability to plan ahead with certainty
• Inconsistency in regulatory decisions
• Poor communications with applicants during evaluation
process
• Lack of meaningful metrics to measure performance
Status before reforms
FEATURE
IMPACT
Application categories very broad (new
products, variations, clones, notifications).
One process target time for all new
product applications
One process target time for all variations.
Meaningless metrics - averaging
timeframes of simple and complex
applications – providing no predictability
of timeframes.
All applications landed into one pile – 1st
in 1st served
No streaming by application type.
‘The Queue’ - no resource planning for
evaluation of complex applications.
No workload planning.
No screening to ensure applications
were complete and effective.
The quality of submissions was variable.
TGA were flexible on dossier formats –
difficult to locate the necessary data.
Poor quality submissions diverting TGA
effort from effective high quality
submissions,
Further compounding queue time.
(Queue time was typically 5 - 6mths until
assigned for evaluation).
Status before reforms
FEATURE
IMPACT
No limits on:
the number of RFIs or
the timeframe for the sponsor to respond to
RFIs.
Business priorities may have changed by the
time the RFI was received. Leading to variable
response times -2 weeks or in 2 years.
Due to ineffective applications some needed to
generate data to address questions.
Increased unresolved applications creating
increasing backlog
Delays required repeat evaluation, further
exacerbating the queue time.
New data able to be added at any time.
New data would often generate the need for
new RFIs.
“Work Arounds” - Applicants submit prior to
having complete data packages to get a place in
the queue, e.g. submitting insufficient stability
data:
By the time the application was assigned to the
evaluator, the sponsor could provide the
minimum data set.
By first Request for Information (RFI) the
applicant would have sufficient data to support
a commercial shelf life.
Summary of negative impact
• All applications processed in the same way – no
differentiation in terms of complexity or risk
• First in/first served resulted in long queue
• Timeframes dependent on the number of applications in
the queue
• A backlog of unresolved and incomplete applications
clogged the system
• Quality of submissions extremely variable in terms of
appropriate data & level of completeness
• Poor quality submissions taking up TGA resources to the
detriment of high quality submissions
Industry expectations
• Regulatory processes that are efficient, cost-effective &
proportionate to the inherent risks of products.
• Clarity & consistency of the regulatory requirements that
will ensure comprehensive applications that will meet the
regulator’s expectations.
• Predictable evaluation timeframes to assist forward
planning
• Transparent processes & visibility to track the progress
of product evaluations.
• Processes for measuring performance - quality of
applications & the efficiency of business processes.
9
Regulator expectations
• Pretty much the same as industry
• But with a few additional requirements to ensure
expectations can be met:
– A Common Technical Document (CTD) format to ensure quality
submissions that contain all the necessary data for an effective
evaluation.
– Prompt responses to “Requests for Information” (RFI) – while still
fresh in people’s minds – not 18 months later – to avoid reevaluation.
– No new data permitted in response to RFI – removing the need
for whole new evaluation and new RFIs.
– Limitation on the number of opportunities to address the RFI.
The reform process
• TGA and Medsafe (NZ) evaluators formed the drafting
team
• Industry Working Group of senior regulatory affairs staff
provided a sounding board.
• In September 2012 a comprehensive public consultation
commenced through workshops with all stakeholders
• In April 2013 a staged implementation of the new
processes commenced
Main features of new processes
•
•
•
•
•
Alignment of process between Australia & NZ
Categorisation or streaming of applications based on risk.
CTD format mandated
Electronic submissions via an online application portal
Applications screened to determine completeness – incomplete
applications not accepted resulting in loss of application fee
• No new data can be submitted after acceptance of application.
• Maximum of 2 rounds of RFI for complex applications & single round
of RFI for other applications
• A limited number of opportunities to address the RFI & a limited
period to respond. If unresolved loss of application & evaluation fees
Note – data requirements unchanged but specified by application type.
Risk Categories for New Products
Risk rating
Application level
Low
New Generic Medicines
Negligible
N1
A 'Clone‘ or flavour/fragrance/colour (FFC) variant of a fully evaluated parent where the total content of
the FFC agent(s) affected is ≤ 2% w/w or w/v.
•the product name does not include an umbrella segment categorised as requiring a higher level of
assessment.
N2
An OTC Medicine Monograph.
•the product name does not include an umbrella segment categorised as requiring a higher level of
assessment.
N3
Generic Extensions
/NCEs
N4
Moderate
Categorisation of application level
N5
New application for a 'generic' medicine (as defined in ARGOM Appendix 1) other than those 'generic'
applications in levels N1, N2 or N4
•the product name does not include an umbrella segment categorised as requiring a higher level of
assessment.
An application for a ‘generic’ medicine where the medicine:
1. is included in Appendix X (but which is not a level N1 application) and/or
2. includes an umbrella branded product name where the umbrella segment
Appendix X includes: products like:
is categorised as requiring a higher level of assessment and/or
• Modified release products.
3. requires supporting safety and/or efficacy (clinical/ toxicological) data or
• Generics needing BE data.
a justification for not providing such data.
• Formulation dependent topicals.
An application for a new product that is an extension to a ‘Generic category’ product
including:
· new therapeutic indications
· new strengths
· new dosage forms
· new directions
· new combination products
· different patient population
An application for a product containing a new chemical entity as an active ingredient.
Risk categories for Variations
Risk rating
Application level
Categorisation of application level
Quality and non-quality changes
Negligible
C1
· Includes minor non-quality and quality related changes.
Previously categorised as an ‘N’ (notification)
Quality changes
· Changes to quality aspects of a product excluding those in levels C1 or C4
C2
Non-quality changes - no safety & efficacy data required
· Changes to the non-quality aspects of the product excluding changes described in C1, C3 or C4
and those requiring the provision of S&E data (or a justification for not providing such data).
Low
Umbrella branding: higher level of assessment
· Changes to the product name where the new name includes an umbrella segment categorised as
requiring a higher level of assessment
C3
Non-quality changes - safety & efficacy data may be required
· Changes requiring evaluation of safety and/or efficacy data (or a justification for not providing
such data) to support changes to labelling (incl. PI or Data sheet / CMI) except those changes
described in C4.
Moderate
C4
Non-quality changes – data are required
· Where safety and efficacy data (clinical and/or toxicological) are required to support the
proposed changes or where a justification for not providing such data would be required.
65
N1
85
N2
Target Total evaluation time 55 wd
N5
Target screening time 25 wd
Target total evaluation time 210 wd
- TGA time
- Sponsor time
254
Target total evaluation time 170 wd
working
days
Target screening time 20 wd
299
Target total evaluation time 150 wd
N4
Target screening time 20 wd
working
days
N3
234
Target Screening time 15 wd
working
days
Target Total evaluation time 45 wd
working
days
Target Screening time 15 wd
working
days
Timelines for New Medicines
30
Target Screening time 20 wd
Target Total evaluation time 64 wd
- TGA time
- Sponsor time
204
Target total evaluation time 170 wd
working
days
Target screening time 25 wd
259
Target total evaluation time 120 wd
C4
Target screening time 20 wd
working
days
C3
C2
99
Target Total evaluation time 20 wd
working
days
C1
Target Screening time 5 wd
working
days
Timelines for Variations
Results - efficiency, timeliness, visibility
• Eradication of backlog over 18 month period, of
approximately 500 applications that was present at the
beginning of the OTC reforms
• Average processing times for:
– new medicine applications reduced from ~131 working days to
~76 working days
– variation applications reduced from ~64 working days to ~33
working days
• Online application system eradicates need for paper
applications:
– Cost saving
– Online tracking of each application
Other benefits
• Disincentives resulted in improved quality of applications
• Reduction in number of non-acceptance of applications
• Reduced timeframes for evaluation of all categories of
applications
• Continuous improvement in terms of predictability &
clarity of requirements
• Raised the standard of the entire industry
• It set a new benchmark for all other business process
reforms within TGA
Industry feedback
• Efficient, cost-effective processes proportionate to risk
• Clarity & consistency of regulatory requirements ensure
high quality applications
• Predictability of evaluation timeframes facilitates
business planning.
• Meaningful process metrics for feedback on application
quality & process efficiency tracking
19
Metrics - Before
Non-prescription medicines – OTC medicines average processing times ( working days)
2011
Jul-Dec
All N1 – N5
application
timeframes averaged
All C2 – C4 application
timeframes averaged
2012
Jan-Jun
Jul-Dec
2013
Jan-Jun
Jul-Dec
New applications and variations referred to Advisory Committee on Non-prescription Medicines
(ACNM)
Receipt and payment to Delegate’s
decision – target 71 working days
55
83
102
96
48
Company response time
135
354
204
109
120
Percentage completed within target
73
55
51
56
80
Receipt and payment to Delegate’s
decision – target 32-45 working days
69
85
66
55
48
Company response time
43
88
92
42
20
Percentage completed within target
50
38
43
69
66
Receipt and payment to completion –
target 20 working days
23
9
9
10
9
Percentage completed within target
92
99
91
93
93
Variations not referred to ACNM
Notifications
Note average
sponsor
response
times
Metrics - Now
Table 10 Processing times against target time by application category Jul –Dec 2014
Elapsed working days1
Application
category
Number
Range
Mean
Median
Target time2
%within
target
N1
106
1-52
30
31
45
94
N2
8
26-44
29
26
75
100
N3
19
6-101
51
43
150
100
N4
46
19-169
125
133
170
100
N5
12
89-137
123
137
210
100
C1
257
0-52
8
6
20
96
C2
129
0-107
16
10
64
99
C3
3
24-176
84
51
120
673
C4
0
N/A
N/A
N/A
170
N/A
Total
580
The Opportunity has
already been seized to
reduce some of these
target timeframes.
This table reports on performance undertakings made during the design of the new OTC premarket business processes. These are subject to ongoing review. As at 31
the average processing times were well below the target.
N/A=Not applicable.
1Between
2The
3 C3
acceptance of application to a formal notification of decision
target is 80% completed within the agreed timeframe.
applications were low in number and one of the three applications exceeded the target time due to atypical complexities.
Has it been successful?
• Industry: feedback from companies & reduction in
number of complaints from companies and/or requests
for intervention on their behalf
AND
• Regulator: reduction in number of complaints from
industry & more efficient & cost-effective allocation of
regulatory resources
Yes!!