Literature based submissions (LBS)... the options and lessons

Literature based submission… the options and lessonsRegulatory requirements

Dr Michael Coory

Director, Prescription Medicines Clinical Unit 5

Medicines Authorisation Branch

Market Authorisation Division, TGA

ARCS Scientific Congress 2015

6 May 2015

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

Types of submissions

• Conventional

– Full study reports of company-sponsored studies

• Literature based

– Published studies

• Mixed

– Combination of above


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


Acceptable overseas countries

• United States

• United Kingdom

• Netherlands

• Sweden

• Canada

• New Zealand


Most common types of literature based

submissions

• New product

– but active ingredient (moiety) already registered via a different product


• Major variation

– change in posology/dosing instructions

– change in route of administration

– change in strength

• Extension of indications

• New chemical entity (uncommon, but possible)


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


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


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


Why do we need a systematic search of the

literature?

• Cherry pick particular studies

• Narrative versus systematic review


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


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


Health & Medicine

Literature based submissions (LBS)... the options and lessons