Critical considerations in the formulation development of parenteral biologic drugs.

Biopharmaceuticals, unlike chemically synthesized small-molecule drugs, are marginally stable, with most of them requiring 3D structures to retain their activity and/or potency. This implies challenges to formulate these molecules for a shelf life >2 yrs and also to minimize the cost of goods for manufacturing. Patient compliance has become a key consideration in the design and development of suitable dosage forms in the modernized world.

Feasibility of Freeze-Drying Oil-in-Water Emulsion Adjuvants and Subunit Proteins to Enable Single-Vial Vaccine Drug Products.

To generate potent vaccine responses, subunit protein antigens typically require coformulation with an adjuvant. Oil-in-water emulsions are among the most widely investigated adjuvants, based on their demonstrated ability to elicit robust antibody and cellular immune responses in the clinic. However, most emulsions cannot be readily frozen or lyophilized, on account of the risk of phase separation, and may have a deleterious effect on protein antigen stability when stored long term as a liquid coformulation.

Critical considerations for developing nucleic acid macromolecule based drug products.

Protein expression therapy using nucleic acid macromolecules (NAMs) as a new paradigm in medicine has recently gained immense therapeutic potential. With the advancement of nonviral delivery it has been possible to target NAMs against cancer, immunodeficiency and infectious diseases. Owing to the complex and fragile structure of NAMs, however, development of a suitable, stable formulation for a reasonable product shelf-life and efficacious delivery is indeed challenging to achieve.

Comparative evaluation of disodium edetate and diethylenetriaminepentaacetic acid as iron chelators to prevent metal-catalyzed destabilization of a therapeutic monoclonal antibody.

Understanding the effect of metal chelators with respect to their ability to inhibit metal-catalyzed degradation in biologic products is a critical component for solution formulation development. Two metal chelators, disodium edetate (Na(2)EDTA) and diethylenetriaminepentaacetic acid (DTPA), were evaluated for their ability to stabilize IgG2 mAb in solution formulations spiked with various levels of iron. Real-time stability attributes such as oxidation, soluble aggregate formation, deamidation, and fragmentation demonstrated that DTPA was equivalent to Na(2)EDTA with respect to inhibiting iron-induced degradation over the range of iron concentrations studied.

Rapid and refined separation of human IgG2 disulfide isomers using superficially porous particles.

A rapid reversed-phase HPLC separation of recombinant human immunoglobulin gamma 2 (IgG2) disulfide isomers using columns packed with superficially porous particles is reported. Under optimal conditions, a separation of monoclonal IgG2 disulfide isomers was achieved in 10 min using a Poroshell™ 300SB-C8 column via a combination of high column temperature (85°C), mobile phases with high eluotropic strength (e.g.

Quantitation of plasmid DNA deposited on gold particles for particle-mediated epidermal delivery using ICP-MS.

DNA-plasmid-based vaccines are a promising class of next generation therapeutics. Particle-mediated epidermal delivery is an attractive method for the administration of DNA plasmid vaccines. This technology utilizes minute quantities of DNA plasmid which have been deposited onto the surface of 2-3-microm gold particles, and so the development of this technology requires the use of analytical methods that can accurately quantitate the amount of the DNA on the particle.