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 marketed

• verseas

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

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 (10 months) 20

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