Small Scale Bio-Manufacturing for Clinical Trails; an Introduction to the Clinical Biotechnology Centre

Transcription

1 Small Scale Bio-Manufacturing for Clinical Trails; an Introduction to the Clinical Biotechnology Centre Keith Williams Business Development Manager - Clinical Biotechnology Centre

2 CBC - Aims and Objectives To provide facilities for the small to medium scale GMP production of recombinant proteins and plasmid DNA for use in clinical trials Manufacturing Authorisation for DNA plasmids and recombinant proteins as Investigational Medicinal Products, to comply with EU Clinical Trials Directive. To support research workers within the NHS and elsewhere as their research progresses from pre-clinical to phase I and II clinical trials Advise on regulatory issues Help with clinical trial applications To develop processes and expertise in the manufacture and QC of a range of sterile biological products.

3 CBC - Historical Milestones Concept mid 1990 s Facility opened April 1999 First Recombinant Protein released for Clinical Trial February 2001 First plasmid DNA released for Clinical Trial May 2001 Voluntary MHRA Inspections Successful Cancer Research UK audit May 2003 Manufacturing Authorisation for DNA plasmids and recombinant proteins as Investigational Medicinal Products, to comply with EU Clinical Trials Directive, granted by the MHRA May 2004 Variation to MHRA licence to Import IMP s 2008 Strategic alignment with UCL Gene Therapy Consortium and adoption of their GMP Facility onto licence in January 2011

4 The Regulatory Framework Human Tissues Authority (HTA) Cellular therapies 83 NHS/Academic sites licensed in UK ( HTA list of licensed sites November 2009) Medicines and Healthcare Regulatory Agency (MHRA) Medicinal products 4 NHS/Academic sites licensed in UK to produce biological active starting materials (MHRA register of holders of MA (IMP) October 2009)

5 The Regulatory Framework Advanced Therapeutic Medicinal Products (ATMP) EU directive 1394/2007 published 2007; came into force in Dec 2008; transitional period to Dec 2011 for full implementation gene therapy somatic cell therapies containing cells that have been manipulated to change their biological characteristics tissue engineered products that have been modified to replace, regenerate of repair damaged tissues

6 CBC services Contract Manufacture of Biological IMPs for clinical trials EU Clinical Trials Directive (2001), since 2004 IMP manufactured at an MHRA licensed GMP site 4 sites licensed in UK academic/nhs centres* 5 commercial sites licensed in UK * Importation license granted to CBC in 2008 * MHRA register of holders of MA (IMP) October 2009

7 CBC services Contract Manufacture of Biological IMPs for clinical trials Pre-clinical regulatory expert advice Process development to meet GMP requirements Master Cell Banking Pilot batch manufacture Clinical trials batch manufacture, QC and stability trials Qualified Person batch release Assistance in preparation of clinical trials application to MHRA

8 CBC services Importation of Biological Investigational Medicinal Products from outside the EU GMP audit of manufacturing site Importation and storage under GMP at an MHRA approved site Qualified Person batch record review and release for clinical trial Validated shipment to clinical trials sites.

9 CBC Services Regulatory advice and QA support for other NHS/Academic Centres NHSBT uniquely placed to provide assistance on: GMP Quality management systems QA internal audit MHRA submissions Clinical trials applications Qualified Person batch record review and release for clinical trial CBC/UCL Collaboration

10 CBC/UCL Collaboration CBC services UCL have funded the design and build of clean rooms to manufacture viral vectors as IMP for gene therapy They have no expertise in GMP, QA, provision of QP, quality system management CBC provide this expertise partly funded by the provision of plasmid precursors for viral vector production UCL gene therapy viral vector production facility now a named site on NHSBT IMP manufacturer s authorisation

11 CBC services Provision of QC assay services All internal assays are European Pharmacopeia compliant, where applicable. All internal assays are validated following local SOPs and and are approved by named QP The MHRA have approved CBC as a provider of QC assays to cgmp.

12 Gene Therapies The developing role of CBC UK has world renown for research in the field of gene therapy Translational research skills not as prevalent in UK academia or the NHS GMP, QA, provision of QP, quality system management. BSGT/DH Gene Therapy Working Party Report 2004 Sourcing materials overseas costly and inflexible Facilities stuck in design phase A UK Gene Therapy Consortium was proposed

13 The developing role of CBC Commercialisation of services. Governmental arms length body review. NHSBT are looking to further commercialise services CBC are looking to explore the development of further commercial collaborations

14 Why work with CBC? 11 years proven track record of small scale GMP production of DNA plasmids and recombinant proteins 3 years experience of GMP importation of materials manufactured outside the EU Accredited internal QC assays Regulatory expertise in the field of production of biological molecules as IMPs. QA/QP support provided by NHSBT quality experts.