title: Manufacturing of High-Concentration Monoclonal Antibody Formulations via Spray Drying-the Road to Manufacturing Scale.
abstract: Spray-dried monoclonal antibody (mAb) powders may offer applications more versatile than the freeze-dried cake, including preparing high-concentration formulations for subcutaneous administration. Published studies on this topic, however, are generally scarce. This study evaluates a pilot-scale spray dryer against a laboratory-scale dryer to spray-dry multiple mAbs in consideration of scale-up, impact on mAb stability, and feasibility of a high-concentration preparation. Under similar conditions, both dryers produced powders of similar properties-for example, water content, particle size and morphology, and mAb stability profile-despite a 4-fold faster output by the pilot-scale unit. All formulations containing arginine salt or a combination of arginine salt and trehalose were able to be spray-dried with high powder collection efficiency (>95%), but yield was adversely affected in formulations with high trehalose content due to powder sticking to the drying chamber. Spray-drying production output was dictated by the size of the dryer operated at an optimal liquid feed rate. Spray-dried powders could be reconstituted to high-viscosity liquids, >300 cP, substantially beyond what an ultrafiltration process can achieve. The molar ratio of trehalose to mAb needed to be reduced to 50:1 in consideration of isotonicity of the formulation with mAb concentration at 250 mg/mL. Even with this low level of sugar protection, long-term stability of spray-dried formulations remained superior to their liquid counterparts based on size variant and potency data. This study offers a commercially viable spray-drying process for biological bulk storage and an option for high-concentration mAb manufacturing.
  
  
  
  This study evaluates a pilot-scale spray dryer against a laboratory-scale dryer to spray-dry multiple monoclonal antibodies (mAbs) from the perspective of scale-up, impact on mAb stability, and feasibility of a high-concentration preparation. The data demonstrated that there is no process limitation in solution viscosity when high-concentration mAb formulations are prepared from spray-dried powder reconstitution compared with concentration via the conventional ultrafiltration process. This study offers a commercially viable spray-drying process for biological bulk storage and a high-concentration mAb manufacturing option for subcutaneous administration. The outcomes of this study will benefit scientists and engineers who develop high-concentration mAb products by providing a viable manufacturing alternative.
authors.affiliation: Pharmaceutical Processing and Technology Development;
authors.forename: Benson
authors.initials: B
authors.lastname: Gikanga
authors.affiliation: SPX Flow Technology Systems, Inc., Elkridge, MD.
authors.forename: Robert
authors.initials: R
authors.lastname: Turok
authors.affiliation: Late-Stage Pharmaceutical Development, Genentech, Inc., a member of the Roche Group, South San Francisco, CA; and.
authors.forename: Ada
authors.initials: A
authors.lastname: Hui
authors.affiliation: Pharmaceutical Processing and Technology Development;
authors.forename: Mayumi
authors.initials: M
authors.lastname: Bowen
authors.affiliation: Pharmaceutical Processing and Technology Development;
authors.forename: Oliver B
authors.initials: OB
authors.lastname: Stauch
authors.affiliation: Pharmaceutical Processing and Technology Development; maay@gene.com.
authors.forename: Yuh-Fun
authors.initials: YF
authors.lastname: Maa
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry; D001120:Arginine / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D004355:Drug Stability; D005240:Feasibility Studies; D005612:Freeze Drying; D010316:Particle Size; D010865:Pilot Projects; D011208:Powders; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D014199:Trehalose / Q000737:chemistry; D014783:Viscosity
chemical_list: D000911:Antibodies, Monoclonal; D011208:Powders; D001120:Arginine; D014199:Trehalose
keywords: Monoclonal antibody (mAb); Powder collection yield; Powder reconstitution; Scale-up; Spray drying; Water content