Unmasking the Blind of Over-Encapsulation 6/10/09
By Richard Shannon, Head of Business Development (Eur), Almac Clinical Services
This article is taken from the Pharmaceutical Manufacturing and Packing Sourcer, Spring 2007 issue, pages 62, 64 and 65. © 2009 Samedan Ltd.
Almac Clinical Services
For more information, please contact
Richard Shannon at:
Email: Richard.shannon@almacgroup.com
Tel: +44 (0)28 3836 2436
Web:www.almacgroup.com
Richard Shannon at Almac Clinical Services, assesses the impact of over-encapsulation in the clinical supplies industry.
Richard Shannon joined Almac Clinical Services (formerly Clinical Trial Services) in 1999 and has served in various business development functions during this time. He began his Almac career in Europe, before relocating to Almac, US, in 2001, where he gained valuable insight into the US clinical trial supply market and was integral in establishing a new business development team. Richard returned to Almac Europe in October 2005, and was appointed Head of Business Development (Europe). Prior to joining Almac, Richard was employed by MDS Harris (now MDS Pharmaservices) where he performed various clinical trial conduct roles. Richard holds a BSc (Hons) from Queen's University, Belfast.
A study conducted by the Tufts Center for the Study of Drug Development estimated that the cost of bringing a novel compound to market is in excess of $800 million, so the need to prove superior efficacy and safety when compared to an already marketed product is of critical importance. When developing protocol designs, blinding or masking of clinical supplies is an integral part of many studies. This can help remove both investigator and patient bias due to the visibility of the marketed product, and can limit any potential placebo effect. One ofthe extensively used mechanisms available to sponsor companies to promote blinding is the over-encapsulation of tablets or capsules.
Over-encapsulation is now a widely accepted mechanism used throughout the clinical supplies industry, and while the process itself may appear relatively straightforward, packaging for clinical supplies is a complex process that is strictly controlled by good manufacturing practice (GMP). The principle of over-encapsulation is simply the addition of a product or products to a hard gelatin capsule, which may or may not be backfilled with an inactive bulk agent or excipient. This process can be used for comparator products, investigational medicinal products (IMP) and/or placebos, providing an output of visually identical capsules for each product or strength, thus maintaining the blind and removing any potential bias.
This article will review the mechanisms and techniques currently available to promote successful over-encapsulation. However, there are a number of key GMP challenges that
need to be addressed in order to ensure product and study result integrity. Annex 13 defines the data that should be available (for example stability, comparative dissolution and bioavailability) to show that there has been no significant quality change within the product, and also clarifies how expiry dates should be justified and assigned (1). In addition, there is a need to tightly control and scrutinise the manufacturing process, not only to ensure that the product is blinded appropriately, but also to allow rapid identification of the product in the case of any possible emergency (1). Allied with this is the visible branding of commercial products either via the placement of product/sponsor logos directly onto products, or patented shapes/designs, meaning that encapsulation is not as easy as it may initially appear.
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