Points for discussion

Transcription

1 Points for discussion International trends in biopharmaceutical products & Gary Walsh Industrial Biochemistry Programme University of Limerick 1 Biopharm. global status Monoclonal antibodies (Mabs) Technical trends product engineering Biosimilars Gene therapy What's in the pipeline? Processing cells, titers& yield Facilities of the future? 2 Biopharmaceuticals: Global Status 33 years since Humulin 255 approved for human use All except 4 are proteins Global market value: $141 billion More than 2,000 in development Approval numbers (EU/US) 3 4 Overall approvals profile (by product class) Biopharmaceuticals Blockbusters (2014) 5 6 1

2 Some notable recent approvals First Glycoengineered mab approved Monoclonal antibodies (Mabs) First biosimilar antibody approved First plant-produced product approved A new inhaled insulin product approved First gene therapy product approved 7 8 Mab approvals (EU/US) Mabs market value 9 Anti-TNF Mabs: Anti-cancer Mabs: $ 34.4 bn $ 25.5 bn 10 Biopharm. Product Evolution Trend engineered biopharmaceuticals Simple replacement Engineered Protein Initial PTM Eng. Fundamental PTM Eng

3 Some Mab engineered formats BiTE technology (Bispecific antibody fragment) Targetsurface antigen (antigen A) CD3 (antigen B) Antigen A Antigen B Cancer cell T cell BiTE Blincyto approved 2014 (USA) (Acute Lymphoblastic Leukaemia) Bispecific formats Targets CD 19 surface antigen on B lymphocyte surface Glycoengineered Mabs Biosimilars Roche: Glycomab technology Biowa: Potelligent cells Biopharmaceuticals & patent protection Biosimilars approved thus far in EU Many early products loosing protection Generic versions? API complexity & biological synthesis renders manufacture of an identical product impossible

4 Inflectra/Remsima(infliximab) Biosimilar monoclonal antibodies (Mabs) Approved Sept. 2013, launched Feb Reference = Remicade (anti -TNF) Remicade v Inflectra/Remsima Upstream SP2/0 C168J continuous perfusion SP2/0-Ag14, fixed batch duration Harvest/clarification Harvest & Filtration Harvest & Filtration Gene therapy Purification Affinity, Anion exchange, Protein A affinity, Anion exchange (?) Final formulation Gene therapy 1992 gene therapy trials to date Glybera (alipogene tiparvovec) 2012 (EU) Lipoprotein lipase deficiency Future (products) Replication deficient adeno-associated viral vector EMA rejected in 2009 &

5 What is in the pipeline? Biotech pipeline dominated by proteins: Approx 360 in clinical trials Mabs (240) Other proteins (120) Major indications: Cancer/ infectious disease/heart disease Biosimilars Growing acceptance of validity in developed markets Next wave: blockbuster targets ~ 73 biosimilar mabs in development All eyes on the US Gene therapy Glybera a watershed, but weakness in approval data Only a few in late stage active trials mabs Biopharmaceutical manufacture Biosimilar mabs Originator products: Fc & glycoengineered ADCs Antigen-binging fragments Recombinant polyclonal mabs Genetically engineered (producer) cell Upstream Downstream 27 Product 28 Mammalian v non-mammalian producer cells (upstream) Cells used

6 How much product needed? Estimated values (2013): Product titers(upstream) Industry average: 2.5 g/l (>3.0 g/l for new) Up to 7.0 g/l reported Key manufacturing efficiency benchmarks: Product titer(g/l) Yield (%) BioProcessingJournal (2014), 13, Product yield (downstream) Average yield estimate: 69% Global production capacity Upstream no longer (generally) problematic Increased titer Increased stainless steel capacity Advent of single use technology However, some ownership & geographical mismatch Downstream potentially tighter BioProcessingJournal (2014), 13, Facilities of the future? Smaller scale production (100 kg pure API 25 2,000 L) Singe use technologies (up-& downstream) International trends in biopharmaceutical products & Standardized, modular facility design, allowing rapid & flexible deployment globally Gary Walsh Industrial Biochemistry Programme University of Limerick, Ireland