Clinical trial material & ATMPs By Dirk Francken December 16, 2016

Index Introduction to ATMPs & Regenerative Medicine Clinical trial material (supply chain) Future perspectives Challenges

ATMPs Advanced Therapy Medicinal Products Gene therapy medicines Somatic-cell therapy medicines Tissue-engineered medicines Combined ATMPs ”  these contain cells or tissues that have been modified so they can be used to repair, regenerate or replace human tissue” Source” http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000294.jsp&mid=WC0b01ac05800241e0 EMA website on ATMPs Source: EMA on regulation of ATMPs

Regenerative Medicine “[The] process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function” Regenerative Medicine, 2008, 3(1), 1–5 [47] Different methods: Gene editing (Stem) cells Small molecules / biologicals Scaffolds Bioprinting

RM vs. Conventional medicine Focus on the source of disease/damage instead of symptoms Repair & reverse damage instead of alleviating damage Vs.

Gene editing Different methods: Virus-based: Transduction Lipid-based: Transfection CRISPR/Cas system Source: Biontex

Gene editing Source: Reuters, Nature, MIT

Stem cells Different sources: Embryonic Adult Induced pluripotent Regenerate tissue trough stem cell differentiation and proliferation

Small molecules / biologicals Expose damaged tissue to compounds which enhance the body’s capabilities to heal tissue Growth factors Immunosuppressive compounds

Scaffolds (Tissue engineering) To create structures to ‘fill up’ damaged tissue or as a loading vessel for: Compounds: Controlled release of a drug/factor (Stem)cells: Support and protect cells while they regenerate tissue

3D Bioprinting Create custom tailored 3D models of organs, skin, bone, etc. Source: Knowlton et al. 2015, Bioprinting for cancer research

Total market value of regenerative medicine 2012 2019 2012 http://www.transparencymarketresearch.com/regenerative-medicines-market.html Source: Transparency Market Research, Regenerative Medicine Market Report

Future perspectives API Production CS Team CRO CT sites CTM management CTM mfg SC management  Constant information exchange Reconciliation

Future perspectives ATMP Production CS Team CRO CT sites Will require novel facilities CS Team Will advanced facilities and experience CRO CT sites CTM management Will require advanced facilities and experience CTM mfg Will require new facilities & training/personnel SC management of strict cold chain  Constant information exchange on product viablity & dataloggers Reconciliation Clinical trial sites require advanced facilities Will require new training & experience Will require new facilities

Challenges All have to comply to new GMP, GCP & GTP guidelines Personnel at all locations will require training on ATMPs CROs require sufficient knowledge Short shelve lives ATMP Production Personnel CTM mfg Storage CT sites