RadiolabellingMeeting your isotopic labelling needs throughout drug development

API Services &Chemical Developmentwww.almacgroup.com

> Supply of API & IMP

> Comprehensive product analysis

> Storage and repurification

> Stability testing

> 14C peptide synthesis

> MHRA 14C manufacturing licence and cGMP compliance certificate

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Meeting your isotopic labelling needs throughout drug development.

Almac has the knowledge, expertise and commitment to meet your isotopic labelling needs. Combining our established track record in 14C labelling with our strong quality culture, we offer an industry leading service in the preparation of 14C labelled drug substance and drug product which will meet your quality, cost and delivery time expectations.

Almac offers an industry leading service in the preparation of 14C labelled APIs (Drug Substance) and IMPs (Drug Product) for human ADME studies.

Almac holds a 14C IMP (Investigational Medicinal Product) licence and a cGMP compliance certificate issued by the MHRA. We employ highly trained radiochemists and analysts utilising state of the art facilities and equipment. We can offer our customers savings in both time and cost through effective integration with our other service areas (e.g. API manufacture; formulation and analytical services).

Radiolabelling cGMP Radiolabelling for Human ADME Studies

Chemistry and Biocatalysis> Route design and implementation, including identification of suitable labelling position.> Complementary stable isotope labelling.> Biocatalysis reaction options.

Analytical > Analytical method transfer.> Analytical method development and validation.

Physical Sciences > Physical form selection and characterisation> Control of particle size by milling> Preformulation and formulation development services

Quality and HSE> MHRA 14C manufacturing licence and cGMP compliance certificate> Active environmental stewardship.> Full compliance with all relevant legislation.

Supporting Capabilities

Chemistry and Biocatalysis

> GMP compliant synthesis and release of 14C API and drug product > Manufacture of 14C oral dosage and injectable drug products. > Expertise in development of conditions to control morphic form, and ability to control particle size by milling where required.> QP release. > Stability storage and testing. > Storage and repurification. > Active environment stewardship and full compliance with all relevant Health and Safety legislation

> Comprehensive analysis of 14C materials to support release of 14C APIs and IMPs, including: • Characterisation of product and determination of purity levels of product- related and non-product-related substances (including solvent determination, metals analysis). • Solid form of the API using particle size and XRPD analysis. • Disintegration/dissolution analysis for capsules. • Analytical method transfer / development.

Supporting Capabilities

> Route was redesigned and implemented from available starting materials (14C barium carbonate).

> 29.5mCi of in-spec. material was supplied to the client. (Kitson et al, J. Lab. Compd. Radiopharm., 2010, 53(3), 140-146.)

> Successful project delivery by an integrated peptide chemistry / radiochemistry team.> Stability study performed.> 2mg of in-spec product was delivered to our client.

Case Study 1 Our client required synthesis of 25mCi

of non cGMP material for ADME studies.

The synthesis of unlabelled API was not

suitable for a 14C synthesis.

Case Study 2Our client required synthesis of a 14C

labelled biotinylated 84mer peptide.

The project required expertise in peptide

chemistry and analysis, radiochemistry

and purification.

www.almacgroup.com

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For European Enquiries:AlmacSciencesAlmac House20 Seagoe Industrial Estate, Craigavon, BT63 5QD, United Kingdom.T: +44 (0) 28 3833 2200E: sciences@almacgroup.comwww.almacgroup.com

For American Enquiries:Almac Group Incorporated25 Fretz RoadSouderton, PA 18964United States of AmericaT +1 (215) 660 8500 E: sciences@almacgroup.com

www.almacgroup.com

> Chemistry and analytical methods successfully transferred in-house.> cGMP synthesis of API.> API stability study.> Powder-in-Capsule IMP manufacture.> XRPD analysis to confirm morphic form.> Almac QP release of IMP.

> Chemistry and analytical methods successfully transferred in-house.> cGMP synthesis of API.> API stability study.> Seamless project management of sterile filtered ethanolic solution IMP manufacture.> Customer QP release of IMP.

Case Study 1Our client required synthesis of this

target molecule, presented as

Powder-in-Capsule IMP.

Case Study 2Our client required synthesis of this target

molecule, presented as a sterile filtered

ethanolic solution.

Case Studies