Continuous manufacturing (CM) has been a goal for the pharmaceutical industry for several years. While small molecule drug substances and drug products have achieved this in many cases, biologics are behind the global implementation of CM because of their more complex manufacturing processes.
However, the regulatory agency members of the International Committee for Harmonization (ICH) now have enough experience in the registration, review, and approval of CM processes to issue a new guideline for industry.
The ICH’s Continuous manufacturing of drug substances and drug products Q13 Draft version describes the scientific and regulatory considerations for the development, implementation, operation, and lifecycle management of CM.
Building on existing ICH quality guidelines, it aims to clarify concepts, describe scientific approaches, and present regulatory considerations specific to CM. The ICH has asked for comments from industry as part of the document’s public consultation.
With its dedication to the manufacture of biologics, BioPhorum’s perspective on the guideline is unique. Working with a group of subject matter experts from its Regulatory Team and BioPhorum Technology Roadmapping , BioPhorum has published Industry feedback on ICH harmonized guideline: Continuous manufacturing of drug substances and drug products Q13 Draft version.
Overall, BioPhorum thinks the draft reads well and the concepts and ideas are aligned with its thinking on CM for biologic drug substances and drug products.
Charles Heise, Senior Staff Scientist at FUJIFILM Diosynth Biotechnologies, said, “Collaborating on BioPhorum’s feedback built up our company’s confidence that our interpretations and the discussions around the points of clarification will reduce the risk when implementing appropriate controls and operational strategies for CM in the near future.”
However, the draft describes end-to-end continuous processes, whereas the reality is more complex. This is especially the case in biologics, where current processes are, at best, a mix of batch and continuous steps. Therefore, regulatory guidance on how to move from intermediate to true CM should be added to the ICH draft. Also, while the concepts and principles of the guideline are directly relevant to new chemical entities, some would be different from biologics, which is not covered in the draft.
Furthermore, the biologics example in the appendixes could be much stronger as it only contains aspirational statements. The team recognizes the challenges involved in this area (e.g., not many companies have filed a full/partly continuous process for the manufacture of biologics) and would be happy to explore the most mature examples available with the ICH, e.g., continuous perfusion at a scale of 500L. This would help change the aspirational statements into a true case study and allow for an easier extrapolation to other process steps.
BioPhorum’s in-depth feedback includes more than 40 line-by-line, detailed comments on the ICH document. These include the need for improved definitions of terms, their alignment with those already developed by industry (e.g., in the ASTM standards for continuous processing) and the need to consider ‘process fatigue’.
Other comments include clarifying the wording on batch sizes, clearer guidance on regulatory expectations on what constitutes a pilot batch for CM, and the need to align statements with ‘quality by design’ principles.
BioPhorum and the ICH share the objective of patient safety and product quality. The feedback from BioPhorum is a clear example of how it provides ‘one voice’ of the biomanufacturing industry to communicate expert feedback on consultations.