The trending preferential parenteral route of administration of monoclonal antibodies is via subcutaneous autoinjectors with increased patient autonomy, compliance and reduction in healthcare trips and costs. A notable source of device failure is from highly viscous protein solutions, requiring increased force for full injection. A multitude of studies have focused on alterations in formulation composition and there are increased emerging trends in device engineering solutions. However, an earlier and alternative cost and time-effective strategy is introducing single point mutations in the variable domains of mAbs. This project focuses on the latter, with unique aims to holistically characterize biophysical profiles of candidate mutants as well as their viscosity.

Advanced AI/ML models can be applied to protein science, specifically in high-concentration antibody formulation. In silico methods improve the selection process and design steps in protein development. This presentation summarizes strategies being developed and implemented for structural assessment of biotherapeutic proteins in combination with designing high-throughput formulation using modeling and simulation.

Subcutaneous biopharmaceutical drug products are often supplied in a siliconized syringe with stopper. Levels of component siliconization vary from lot to lot leading to different levels of drug product-silicone interactions during storage. This presentation includes an assessment of product quality for three drug products using two syringe systems, an unsiliconized glass syringe with polytetrafluoroethylene coated stopper, and a siliconized syringe and stopper. The study demonstrates that an unsiliconized presentation is a suitable alternative to traditional siliconized presentation.

Development of a high concentration monoclonal antibody formulation poses multiple challenges. Often, accelerated timelines and clinical targets to achieve a high dose require a fine balance between speed-to-market and development of a product for patients that meet the required viscosity and product quality specifications. This presentation will focus on high throughput formulation development strategies enabling faster product development with reduced material usage. Additional aspects, including device-related viscosity constraints, associated rheological characterization, and product quality assessments relevant to high concentration formulations will be covered.

• Overconcentrating mAbs generates a web of problems. Most of the challenges arise because of increased viscosity or decreased stability.While viscosity does not directly present itself as an 
• upper bound for DP concentration, the variability in viscosity and other formulation characteristics brought on by high concentrations does represent an effective limit to concentration.
• The maximum concentration for a DP is a compromise between acceptable DP variability due to manufacturing ranges and a shrinking stable formulation space.

The present research provides a comparative evaluation of scalable manufacturing strategies to develop low viscosity (150mg/mL) formulation for lyophilized biosimilar IgG1; suitable for single, subcutaneous injection ~600mg/3.0mL, per dose.IgG1 was concentrated to ~200mg/mL and provides a comparative evaluation of manufacturing strategies and their impact on the chemical and structural stability of IgG1. Techniques used for the concentration of IgG1 are tangential flow filtration (TFF), spray drying (SPD), and spray freeze drying (SFD).

Drug products undergo handling by patients and healthcare professionals, including reconstitution of lyophilized products, transfer to syringes, and dilution into IV bags for administration. In-use compatibility studies are performed to show that stability and concentration are maintained, ensuring patient safety and accurate dosing. However, regulatory expectations are not well-defined, leading to uncertainty in study parameters. Recent cross-product data and a multi-company collaboration offer guidance for streamlined experimental design.

Despite the benefits that Prefilled Syringes (PFS) can provide to patients, the silicone oil pre-coated on the glass barrel may migrate into the drug product and impact drug product quality. Due to current supply chain shortages and procurement preference for commercial product, the PFS source may have to change in the middle of development and a need of establishing source duality is also required by health authorities. The presentation focuses on risk assessment of silicone oil migration to enable a thorough and optimal selection of primary container closure and de-risk the impact of silicone oil on drug product quality.

As healthcare systems increasingly rely on medical care administered at home, the focus on ease of administration, safety, compliance and sustainability is driving the development of combination products for home use. This presentation will discuss approaches to addressing three key challenges: i) drug-device compatibility, ii) reliability and robustness of performance and iii) usability issues in the context of high concentration mAb formulations.

• Polypeptide composition and glycosylation profiles
• Lyophilization,gelatin, simple sugars and amino acids as excipients and Ionic and zwitterionic buffers and pH to support solubility and reconstitution
• Silanized glass vials and drug/product silicone interactions​

In 2022, FAERS showed over 39,657 adverse event reports related to the COVID vaccine, an incredible ~440% increase compared to 2020. There are at least ~350,000 individuals in the USA with known PEG allergy. These numbers highlight why a PEG-free vaccine option is needed, and why all COVID vaccines carry an FDA contraindication warning to patients with known allergies to PEG. For the realization of the full potential of this technology, a safe and functional replacement for PEG is urgently needed that exhibits several desirable features of PEG while maintaining equivalent capabilities for mRNA delivery, comparable to current products.

Recombinant adeno-associated virus (AAV) has emerged as a promising gene delivery vector for the treatment of various diseases. There are marked differences in buffer selection for formulation development with AAVs and protein therapeutics, which must be considered in the context of product manufacturing, long-term storage, in-use administration, and shipping/handling. This entails screening for buffer pH, ionic strength, and the impact of added surfactants on stability/degradation trends of drug product.

Liposome and LNP formulations have evolved as highly potent drug delivery systems. Recent literature gives valuable insights in developing and manufacturing these formulations, with focus mainly set on delivering different liposome and LNP compositions/sizes. This presentation will give some insight into thermodynamic equilibrium considerations, such as long-term (size) stability of liposomes and LNPs at various temperature, as well as equilibrium radius considerations in manufacturing liposomes and LNPs.

Lipid nanoparticle (LNP) technology, as currently one of the most promising and emerging technologies, shows the ability to deliver nucleic acid therapeutics for non-viral gene therapy (NVGT). Compared to intramuscular vaccine delivery, intravenous (i.v.) delivery of a LNP formulation for gene therapy shows unique challenges. An LNP formulation for gene therapy via i.v. may require different lipid and formulation design. Here, we will discuss the considerations and challenges in early LNP development and impact on tissue targeting for NVGT.

In the development of LNP-based drug product, the choice of manufacturing technology is one of the key factors for success. The choice of technology can have a significant impact on the biophysical properties, structural characteristics, colloidal stability, and efficacy of the LNP. This study describes the impact of different manufacturing parameters and the scale-up consideration to enable successful LNP drug product manufacturing.

In this talk, we discuss de-risking mRNA adduct formation in lipid nanoparticle formulation intended for glycogen storage disease type-1a using analytical tools.