• Agios’ approach for pediatric formulation design 
• Pediatric formulation platform selection 
• Palatability and excipient selection
• Manufacturing and packaging consideration
  

• An overview of common developability assessment tools utilized to differentiate molecules based on oral absorption potential during drug discovery. 
• Novel computational approaches to augment in silico developability assessment including quick crystal structure predictions and crystalline solubility predictions.
• Use of automated platforms for robust in vitro physicochemical profiling data to facilitate developability assessment on limited material.

Developability assessment related to determining the oral absorption potential of small molecules is not a new concept. The Dose Number (Do) concept was published by Amidon and coauthors in the 1990’s and the Developability Classification System (DCS) by Butler and Dressman followed in the 2000’s. It is established how to use these concepts that rely on human dose and simple in vitro parameters like solubility and permeability to assess oral absorption risk and provide guidance on formulation strategy. What has evolved is usage of such concepts earlier in the drug discovery process to differentiate molecules, influence chemical series prioritization, and guide chemical design. However, gathering high-quality data on the volume of molecules present this early in the discovery process remains a barrier to leveraging Do and DCS to influence chemical design. Here, we discuss emerging computational approaches that can predict properties relevant to oral absorption and automated platforms that enable teams to get robust data at the right time enabling earlier developability assessment.

The following topics will be discussed related to oral bioavailability of large molecules 

• Barriers to oral absorption of large molecules
• Oral biopharmaceutic mechanisms applied in formulation approaches
• Review of the oral formulation approaches will be discussed
• Recent formulation advancements
  

The expansion of biopharmaceuticals into so called “novel modalities” have encountered new challenges and opportunities during CMC development and clinical administration/drug delivery. This presentation will cover some of the pain points for novel modalities and highly potent (low dose) biotherapeutics, considerations for Drug Product design, formulation, manufacturing, and compatibility in-use studies, and case studies for early clinical studies.

• Overview of subcutaneous delivery in the current market
• Considerations when developing a target product profile for subcutaneous delivery
• Identifying early challenges and opportunities in formulation and device development
• Technology down selection and moving forward towards the target image
  

Amorphous formulation becomes an attractive strategy to deliver poorly water soluble drugs owing to its higher solubility. This presentation will cover three major topics for amorphous drug product development to support clinical studies – (1) theoretical solubility calculation for amorphous drugs; (2) effect of ASD composition on the disintegration and drug release of ASD tablets; (3) a case study of developing an ASD formulation to improve bioavailability and mitigate mechanical instability risk of crystalline form for early phase clinical studies. The first topic will discuss different methods of calculating amorphous drug solubility and the experimental evaluation of these equations. Based on the evaluation, one calculation equation was recommended based on the overall accuracy and complexity. The validated amorphous solubility calculation provides a guidance for ASD composition screening and developing ASD formulation. To successfully apply ASD formulation in clinics, final dosage form (e.g. ASD tablets) is usually needed. Owing to great amount of polymers in the ASD composition, the disintegration and drug release usually become an issue for ASD tablets especially when ASD loading increases. The second topic will discuss how polymer type, ASD loading in tablet and polymer-drug ratio affect the disintegration and drug release of ASD tablets. At last, the third topic will present a case study of developing an ASD tablet, guided by amorphous solubility calculation, to improve the drug bioavailability and mitigate mechanical instability risk of the selected crystalline form. To summarize, the overall goal of this presentation is to provide an industrial perspective for the design and formulation of amorphous drug products based on fundamental understanding of amorphous materials.

Nitrosamines, in the absence of toxicological data, are regarded as potential mutagens, and ICH M7 considers N-nitrosamines as part of the highly mutagenic cohort of concern. Recently, several drug withdrawals have been resulted from the contamination of drugs with nitrosamines. To ensure patient safety and access to life saving drugs, it is important to understand the phenomenon of the formation of nitrosamines in drug products and how to inhibit the formation of nitrosamines in drug products. We will present data, primarily, on the formation and inhibition of formation of nitrosamines in solid oral dosage form.