EMMA WRIGHT
NITTO DENKO Avecia Inc.,125 Fortune Boulevard, Milford MA, USA

Abstract

As more oligonucleotide based products move into late phase clinical trials and submission of filings, sponsors and manufacturers of these products need to ensure they are prepared for regulatory inspections. This article outlines what a manufacturer may expect during an inspection, actions which can be taken to prepare for such inspections, and provides guidance on managing regulatory inspections in order to maximize inspection and product success.

INTRODUCTION

There are now a significant number of oligonucleotide based products in Phase III clinical development, with two oligonucleotide containing or oligonucleotide products being the subject of recent regulatory filings. KYNAMRO™ (mipomersen sodium, Genzyme/Isis) received approval from the FDA on January 29, 2013 as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol, apolipoprotein B, total cholesterol, and non-high density lipoprotein-cholesterol in patients with homozygous familial hypercholesterolemia (1). HEPLISAV™ (Dynavax) contains an immunostimulatory oligonucleotide sequence as an adjuvant and is the subject of current Biologics Licensing and Marketing Authorizing Applications (2, 3). In addition, other products such as PRO051/GSK2402968 (Prosensa/GlaxoSmithKline) and Custirsen OGX-011/TV-1011 (OncoGenex/Teva) are in Phase III clinical trials (4, 5). Therefore, drug sponsors and contract manufacturing organizations (CMOs) need to consider whether they are ready for regulatory inspections.
Prior to the approval of KYNAMRO™, the most recent approval of an oligonucleotide containing ...