Literature based submission the options and lessons Regulatory - PowerPoint PPT Presentation

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

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 LBS… the options and lessons

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 Type of application marketed Conventional Mixed Literature overseas based < 5 years Yes No No 5-10 years Yes Yes No 10+ years Yes Yes Yes LBS… the options and lessons

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

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

• 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

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

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

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

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

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

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