High-concentration protein therapeutics have become more popular as they favor subcutaneous (SC) administration. Successful development of high dose biologics requires adopting certain formulation approaches to overcome technical challenges such as viscosity, solubility, stability, process issues, and delivery limitations. There is no one approach that fits all. This talk will outline some key aspects while designing high concentration protein therapeutics from the formulation and process standpoint.

In recent years, there has been an increasing trend towards high-dose subcutaneous protein products. However, various challenges such as drug product physical properties, stability concerns, manufacturing limitation, and drug product-device compatibility impose constraints on the concentration of biotherapeutics. This presentation will summarize a comprehensive review of state-of-the-art formulation technologies tailored for the development of high-dose subcutaneous formulation.

The accelerated timelines in the evaluation of novel drug products and getting 1st to the market, demand a fast formulation development. Here we present one step global formulation development approach that is able to select a formulation based on malty factor interaction in less than 4 months.

Biologics drug development has experienced rapid growth in recent years. To meet the need biologics formulation development has quickly acquired a set of automation tools and analytical techniques to provide robust drug products for patients. This has motivated the adaptation of our tools to meet the increases in process complexity for the benefit of patients globally.

Adeno-associated viruses (AAVs) have been widely used as the delivery vehicles for CNS gene therapies. Intra-cisterna magna (ICM) administration was one of the local delivery administrations, which has benefit of widespread transgene delivery in both brain and spinal cord. This presentation summarized the work of an AAV drug product ICM administration device selection and studies for both animal tox study and clinical trial study.

The clinical use of small interfering RNA (siRNA) and antisense oligonucleotides has required, in some cases, the implementation of invasive routes of administration such as intrathecal or intraocular injection. Chemical modification of siRNA increased stability to extend therapeutic durability to minimize the trauma of repeat dosing. However, this improved durability is mitigated by clearance of siRNA. We present a microcapsule-based method to extend the activity of cholesterol-conjugated siRNA locally. We show that the microcapsules protect the siRNAs from being cleared and enable them to be released over 3 months compared to unencapsulated siRNAs.

Formulation development activities are often challenged by the availability of representative material and the clinical timeline, which often requires development scientists to leverage “platform” compositions.  Often these formulations are sufficient for early clinical phases, but how do we enable a large change in the desired target product profile such as the need for an ultrahigh protein concentration in a prefilled syringe?  Thermodynamic assessment of formulations can provide key information on self-association behavior in crowded protein solutions that can predict long-term stability trends with respect to colloidal stability of candidate formulations.

Molecular properties that impact developability attributes and outcomes comprises of conformational, chemical, colloidal, and other interactions. These attributes are measured using relevant analytical methods to assess the developability/ manufacturability of the molecule in different formulation. Developability assessment of monoclonal antibodies has been long studied and applying this assessment using the right tools to new modalities such AAV will help streamline capsid selection and candidate selection from discovery to development for new modalities

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, and shipping/handling. This entails screening for buffer pH, ionic strength, and the impact of added surfactants on stability/degradation trends.

• Process considerations for manufacturing autologous and allogeneic cell therapy products
• Drug product considerations for hematological malignancies and solid tumor indications
• Clinical vs commercial supply chain needs: Integrated drug product design​

Prime editing is a next-generation genome editing technology that could theoretically correct up to 90% of known genetic variants associated with human diseases. We have developed a universal lipid nanoparticle (LNP) for the delivery of Prime Editors (PE) to the liver. This presentation will highlight process development and CMC considerations for the development of PE-LNPs and provide selected case studies for PE RNA components and LNP-formulated PE process unit optimization.

Maintaining the stability of viral vectors through formulation assessment is essential for cell and gene therapy products. In this presentation, I will describe a study conducted to evaluate the stability of particle characteristics and functional titer for lentiviral vectors under varying buffer, pH, and excipients conditions. Through our screening experiments and comprehensive analytics, I will discuss how stability for these complex modalities is multifaceted and requires careful investigation.