One of approaches to take would be to look “easy” fixes first (e.g. improve packaging configuration first, then propose modifications to the device, then propose modifications to the combination product) so we can try to identify the root cause, followed by quick lab tests that can provide objective evidence about the root cause identification and mitigation. These tasks would be part of the project management and would be prioritized by support from management. For example, one item at a time would be evaluated as follows:
Proposed Packaging Configuration: syringe packaged in Tyvek sealed blister to control humidity.
Perform Accelerated stability study in support of DSD shelf-life requirement. This study will give an idea if the packaging configuration helps protect the product against humidity.
Accelerated aging testing to be conducted in accordance to ASTM F1980, and ANSI/AAMI/ISO 11607-1 under the following test parameters/ conditions:
Proposed redesign of syringe to include dual chamber: this device allows users to reconstitute the protein suspended in carboxylmethyl cellulose (CMC) with calcium sulfate dihydrate just prior to the injection. Both syringe chambers are sealed from each other to prevent premature reconstitution. The syringe with dual chambers is packaged in Tyvek sealed blister to control humidity.
Quick functional test will be performed with 5 syringes that will be reconstituted and injected (into a beaker) using Instron to measure injection force. The syringes will be injected after reconstitution at the following times: 1) time zero (immediately following reconstitution), 2) 5 minutes, 3) 10 minutes, 4) 30 minutes, and 5) 1 hour. All samples will be assessed to evaluate whether the content was expelled.
Proposed change in carrier from calcium sulfate dihydrate to Chitosan. This combination of Chitosan and CMC with growth factor will be tested as combination product following approach #1 and #2 aforementioned.