Sadettin S. Ozturk, Ph.D.Cell Culture Process for Recombinant Protein ProductionLecture 1: Cell Culture TechnologybySadettin S. Ozturk, Ph.D11Sadettin S. Ozturk, Ph.D.Outline•Biopharmaceuticals: Medicines from recombinant DNA technology•Host cell options and microbial systems•Cell culture technology•Complexities and challenges in cell culture systems•Alternatives to cell culture systems•Cell culture: current state-of-the-art•New directions in cell culture22
Sadettin S. Ozturk, Ph.D.Insert DNAinto host cell lineThe Industry of Biopharmaceuticals Started with Recombinant DNA Technology in 1980sGrow cells in BioreactorsSeparate cells out, collect productPurify ProductHost CellIdentify the gene and DNA to treat the diseaseFormulate and Fill 33Sadettin S. Ozturk, Ph.D.Since 1980s Many Biopharmaceuticals Got Approval as Medicines44
Sadettin S. Ozturk, Ph.D.Biopharmaceuticals are now a Major Player in Pharmaceutical Industry5Small moleculesBiopharmaceuticals5Sadettin S. Ozturk, Ph.D.Small Molecules vs. Biopharmaceuticals Sales: US Market66
Sadettin S. Ozturk, Ph.D.Global Biopharmaceuticals Sales were $380 Bln in 2019CAGR: Compound Annual Growth Rate77Sadettin S. Ozturk, Ph.D.Worldwide Revenues: 7 of the top 10 Drugs are Biopharmaceuticals8CEN News, Volume 93 Issue 48, p. 19, Issue Date: December 7, 20158
Sadettin S. Ozturk, Ph.D.Biopharmaceutical Market is Concentrated in the Western World, because People can Afford Expensive Medicines99Sadettin S. Ozturk, Ph.D.Medical Treatment using Biopharmaceuticals is Very Expensive1010
Sadettin S. Ozturk, Ph.D.Why are Biopharmaceuticals Very Expensive: They are More Complicated than Chemical Drugs, More Difficult to MakeAspirin180 daltonsmAb150,000 daltonsFactor VIII~250,000 daltonInsulin5,700 daltons1111Sadettin S. Ozturk, Ph.D.Why are Biopharmaceuticals Very Expensive: The Drug Development Process is Very Long, Expensive, and Risky 12Review ApprovalReg. FilingPhase III Clinical TrialsSubmit BLA Early Clinical DevelopmentPhase II Clinical TrialsManufacturing ActivitiesLate Clinical DevelopmentClinical and Product Development ActivitiesPh I BatchProcess ValidationLaunch PreparationYear-2Year1Year2Year3Year4Year5Preclinical StudiesTargetResearchPhase I Clinical TrialsSubmit INDBLA PrepToxMatPh II BatchPh III BatchProcess Development ActivitiesProcess CharacterizationLate Phase Process Dev Early Phase Process DevelopmentTech Transfer BLA Prep SupportYear0Year6IND: Investigational new drug application (first in human) (Clinical Trial Application, CTA in EU)BLA: Biologics license application (Marketing Authorization Application, MAA in EU)12
Sadettin S. Ozturk, Ph.D.Genetic Engineered Organisms to Produce Biopharmaceuticals: Host Options1313Sadettin S. Ozturk, Ph.D.