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Radiolabelling
References
Table 1: Large Pharma with internal isotope groups radiolabelled API to GMP in compliance with FDA
ABPI: Guidelines for Phase 1 Phase I guidance and has opened a second GMP
Clinical Trials 2007.
Abbott facility to meet demand. Unlike the other suppliers
http://www.abpi.org.uk.
covered here, PerkinElmer also offers C-14 cata-
EMEA: Guideline on the
Astra Zeneca
requirements to the chemical
logue items under its NEN-Radiochemicals brand.
and pharmaceutical quality
These companies and a number of other suppli-
Bayer Schering Pharma
documentation concerning ers are active participants of the International
investigational medicinal
Boehringer Ingleheim
Isotope Society which promotes radiolabelling and
products in clinical trials
use of isotopically labelled compounds.
CHMP/QWP/185401/2004
Bristol-Meyers Squibb
final.
EMEA: Guideline for the
Clinical labs using C-14
Eli Lilly
Environmental Risk The nature of this work lends itself to specialist
Assessment of Medicinal
companies which are expert in their field and
Products for Human Use. (1
GlaxoSmithKline
licensed to work with C-14. The radiolabelled API
June 2006).
FDA: Guidance for Industry
Johnson & Johnson can be sent to the most appropriate specialist to
CGMP for Phase 1
perform the Phase I clinical trial.
Investigational Drugs (July
Merck & Co Inc
An example of a Phase I unit licensed to use
2008).
C-14 is LCG Bioscience, other Phase I units
FDA: Guidance for Industry
Merck Serono
licensed to perform the GMP manufacture and for-
Safety Testing of Drug
Metabolites (February 2008)
Novartis
mulation of the radiolabelled IMP include:
http://www.fda.gov.
Hammersmith Medicines Research (HMR),
Pfizer
housed in a new 100 bed clinic; PRA International
based in Netherlands; SGS in Belgium and
Roche
Covance and HLS in the UK.
Sanofi-aventis
Analysis of C-14 clinical samples can be per-
formed, for example, by Charles River in Edinburgh.
Internal radiolabelling groups
Another radiolabelling group to be acquired by a Many of the large pharmaceutical companies have
CRO is the former Eagle Picher group (ex Chem one or more internal radiolabelling groups (Table
Syn) which is now part of Aptuit. Following the 1). They can benefit from outsourced overflow
acquisition it has moved to new laboratories in buffer capacity, which can be available immediate-
Kansas City, Missouri. ly to meet urgent requests and ensure projects are
not delayed by a lack of resources. When large
Almac has more than 2,500 employees and added pharma acquire a project from a biotech, their first
a radiolabelling group, based in Craigavon UK, to request may be for GMP radiolabelled API and
its CMC supply chain activity in 2005. Like with no internal experience of the project, as
Quotient it favours the integrated model and has would normally be the case for an internal project,
recently announced a broader early stage drug an outsourcing company provides a very cost-
development package by partnering with a CRO, effective solution. It is no longer unusual for inter-
Covance. In 2009 Almac announced it was nal groups to consider outsourcing GMP concepts
expanding its radiolabelling team with three new radiolabelled API synthesis.
laboratories and publicised that it has an MHRA Many mid-size pharmaceutical companies regu-
GMP licence for radiolabelled IMP (Drug Product) larly outsource their custom radiolabelling, some-
manufacture and formulation including QP release times using FTE arrangements to ensure resources
to the clinical trials facility. are immediately available to work on their proj-
ects. One advantage of carrying out route develop-
PerkinElmer acquired the former NEN (New ment in advance is that radiolabelling can be
England Nuclear) radiolabelling group based in removed from the critical development path.
Boston, Massachusetts (once part of DuPont) in The number of internal isotope groups has been
1996. In 2008 PerkinElmer announced it was in steady decline for decades. A consequence of
expanding its radiochemical manufacturing facility industry consolidation has lead to closure of iso-
and relaunched custom radiolabelling under the tope groups while formation of new groups has
‘Under One Roof’ label. It has been very active been hampered due to entry barriers such as the
publicising its ‘elite’ custom synthesis service for requirement for licences, decommissioning liability
58 Drug Discovery World Winter 2009/10
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