Table 1.
Lessons for developers.
| Number | Lesson |
|---|---|
| 1 | Talk to the regulators in your jurisdiction about proposed changes as early as possible |
| 2 | Be clinically specific and have a well-defined product and process understanding |
| 3 | Understand variation; understand allowable operating limits; control variation |
| 4 | Developers should focus on the key steps of: (1) process transfer; (2) product and process comparability |
| 5 | Measure the right process parameters and intermediates as well as the final product to establish a baseline: product and process knowledge will require measurements over and above product release criteria |
| 6 | Use a risk-assessment approach to define the experimental program necessary for comparability and start as early as you can; use the analysis as a mechanism to direct resource |
| 7 | Key stage gates and value inflection points are pivotal preclinical work, and pivotal clinical trials – key studies need to be done before these |
| 8 | Recall that in the EU Phase III clinical trials are intended to verify putative modes of action |
| 9 | Use historical analytical and process data to help set limits |
| 10 | Be careful with the definitions of active substance, strength and product and process impurities |
| 11 | Characterize as much as you can as early as you can, characterization will be product specific. Do not confuse identity with potency; question the value of your biomarkers |
| 12 | Understand your assay and equipment; use appropriate and sustainable equipment and technology to future proof in case you need to reproduce the technique beyond the lifetime of more bespoke instruments |
| 13 | All assays used should be validated for the intended use. For licensed products this means conformance to International Council for Harmonisation Q2(R1) [19]. Different assays would normally be used for identity, purity and potency testing. |
| 14 | Use assays that are able to detect the change you aim to execute |
| 15 | You may have to run processes ‘side by side’ (rather than comparing the changed process to retained samples) |
| 16 | Academic developers require regulatory support in manufacturing scale-up |