The presentation provides an overview of the differences in Literature Based Submissions, the TGA’s experience and new guidance.

1. Literature based submission… the options and lessons
Regulatory requirements
Dr Michael Coory
Director, Prescription Medicines Clinical Unit 5
Medicines Authorisation Branch
Market Authorisation Division, TGA
ARCS Scientific Congress 2015
6 May 2015

2. What is a literature based submission (LBS)?
• Relies on published (non-sponsor) studies to satisfactorily establish
efficacy and safety
• As opposed to conventional submissions, which rely on company-
sponsored studies to satisfactorily establish efficacy and safety
LBS… the options and lessons

3. Types of submissions
• Conventional
– Full study reports of company-sponsored studies
• Literature based
– Published studies
• Mixed
– Combination of above
LBS… the options and lessons

4. When is it acceptable to submit a literature based
submission?
Case-by-case, depending on the regulatory history in Australia and overseas
*This table is a guide only
Years medicine
marketed
overseas
Type of application
Conventional Mixed Literature
based
< 5 years Yes No No
5-10 years Yes Yes No
10+ years Yes Yes Yes
LBS… the options and lessons

5. Acceptable overseas countries
• United States
• United Kingdom
• Netherlands
• Sweden
• Canada
• New Zealand
LBS… the options and lessons

6. Most common types of literature based
submissions
• New product
– but active ingredient (moiety) already registered via a different product
LBS… the options and lessons

7. • Major variation
– change in posology/dosing instructions
– change in route of administration
– change in strength
• Extension of indications
• New chemical entity (uncommon, but possible)
LBS… the options and lessons

8. Number of literature-based submissions
Financial year Number
2010–2011 16
2011–2012 16
2012–2013 20
2013–2014 11
2014–Apr 2015
(10 months)
20
LBS… the options and lessons

9. When is it not acceptable to submit a literature
based submission?
• Module 3
– need a conventional Module 3 for all applications with a quality
component
• Changes to the clinical trials section of the PI
LBS… the options and lessons

10. Pre-submission
• Contact case manager about intention to submit LBS
• Discussion could be either by email or teleconference or face-to-face
• Need to get confirmation that
– LBS is acceptable
– search strategy is acceptable
LBS… the options and lessons

11. Why do we need a systematic search of the
literature?
• Cherry pick particular studies
• Narrative versus systematic review
LBS… the options and lessons

12. Even with a systematic search of literature,
still the potential problem of publication bias
• The research that is published in medical journals is not representative of
all studies that have been done.
• ‘File-drawer’ problem
LBS… the options and lessons

13. Occasional problems with literature-based
submissions
• Too many studies
– especially for ‘old’ active ingredients
– review of systematic reviews and clinical practice guidelines
– d/w delegate
• No reasoning about efficacy and safety
– dump of studies
• Not enough emphasis on post-marketing experience overseas
LBS… the options and lessons