Q13 Continuous Manufacturing of Drug Substances and Drug Products is the new guidance that describes scientific and regulatory considerations for the development, implementation, operation, and lifecycle management of continuous manufacturing. This guidance provides clarification on CM concepts and describes scientific approaches and regulatory considerations specific to CM of drug substances and drug products.
In this guideline, fundamentals for being able to meet the main aspects of the Food and Drug Administration (FDA) and other regulation expectations, good manufacturing practices and key aspects for successful CM are provided with the premise that the output materials from the batch and continuous processes should have comparable quality.
Manufacturers who want to convert the approved batch process to a continuous manufacturing process look must always first obtain regulatory approval.
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Regulatory Considerations |
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Focus Area |
Key aspects for submission of the Common Technical Document (CTD) |
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Description of manufacturing process and process controls |
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Control strategy |
Must ensure that output materials made over time are of the desired quality. Must consider:
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Batch description and batch size |
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Process models |
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Drug substance and drug product stability |
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Conversion of a batch process to CM |
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Process validation |
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Pharmaceutical Quality System (PQS) |
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For batch-sized manufacturing processes, the segregation of non–conforming products can be clearly defined. Procedures are normally in place to describe how to define the frontiers between a good product and a bad product. CM expectations are not different from this, however, now the diversion concepts become relevant. Diversion is the procedure in which materials are isolated and separated from the product stream in the manufacturing process, therefore, based on the control strategy and the sampling procedures, diverse products can be approached in different ways.
Essentially, two aspects are relevant to this new ICH Q13 Guideline. The first is that it has a wider scope than others, covering not only pharmaceuticals and APIs that can commonly be put under the same umbrella but also takes into account biotechnological/biological processes with the non-clear boundaries of what those types of processes include.
The second aspect is that Continuous Manufacturing basically has the same requirements that batched size manufacturing processes. What makes total sense and includes enforcing consistent good manufacturing practices, making robust quality assurance for pre- and post-production tasks, ensuring robust control strategies and warranty of stability of products, are the key points in CM.
A really interesting point is how to explain all of the previous aspects as clearly as possible in the CTD, following a risk-based approach and making it clear for those that need to approve it is the real first challenge. Then, how to sustain a lifecycle of these types of products and processes will be the next endeavor. We now have been given the directions.
