Economic Advantages of Original Container Closure Systems in Combination Product Development: Scenarios with Expert Validation and Industry-Quantified Cost-Time Savings.

Abstract

Many on-body delivery systems (OBDSs) for subcutaneous (SC) delivery require a change in primary container closure system (CCS). This necessitates compatibility and stability testing with original packaging materials and distribution and assembly, which are often laborious and time-consuming. Exploring new primary CCSs rather than using an original CCS can introduce risks, prolong timelines, and increase costs. In this study, 21 US-based combination product experts completed a double-blinded online survey between 6 October and 20 November 2023. The survey included 15 screening questions and 23 survey questions, including questions about compatibility issues between new CCSs and drugs and stability testing for new CCSs. The largest proportion of participants (28.6%) reported that 5-10% of products they had worked directly on had experienced compatibility issues between a new CCS and a drug, with a weighted average of 11.9%. The most common compatibility issues were particulate challenges in 55.6%, sterility in 27.8%, and leachables in 16.7%. Most respondents (76.2%) rated the timeline showing that using an OCC can save 12-24 months as somewhat (38.1%) or very (38.1%) representative. Most participants (57.1%) estimated that the range of direct costs, including development costs, drug product, engineering runs, line changes, and other costs, when using an OBDS with a new CCS is $1015 million, 38.1% estimated <$10 million, and 4.8% estimated $2125 million. Most participants (80.9%) reported that challenges in the primary CCS qualification/validation process delay entry of combination products into clinical trials or delay their commercial launch. The weighted average of the delay was 9.7 months. Using an original CCS during combination product development would therefore be of significant economic benefit to the development of combination products in terms of time, cost, and risk.