This guideline describes scientific and regulatory considerations for the development, implementation, operation, and lifecycle management of continuous manufacturing (CM) of drug substances and drug products. It involves the continuous feeding of input materials into, the transformation of in-process materials within, and the concomitant removal of output materials from a manufacturing process.
Different Modes of Continuous Manufacturing (CM)
- A manufacturing approach in which some unit operations operate in a batch mode while others are integrated and operate in a continuous mode.
- A manufacturing approach in which all unit operations of a drug substance or drug product manufacturing process are integrated and operate in a continuous mode.
- A manufacturing approach in which drug substance and drug product unit operations are integrated across the boundary between drug substance and drug product to form a single CM process (i.e., the drug substance is continuously formed and processed into the drug product through integrated unit operations).
As per ICH Q7, A batch is defined as a specific quantity of material produced in a process or series of processes so that it is expected to be homogeneous within specified limits. Base on this definition, the size of a batch produced by CM can be defined in terms of one of the following:
- Quantity of output material
- Quantity of input material
- Run time at a defined mass flow rate
Other approaches to define batch size are possible, if scientifically justified based on the characteristics of the CM process and Good Manufacturing Practice. A batch size can also be defined as a range. For example, a batch size range can be established by defining a minimum and maximum run time.
Scientific Considerations
This guideline discuss on different scientific approach of continuous manufacturing, where include –
- Control strategy
- Changes in Production Output
- Continuous Process Verification
The development of a control strategy for CM is enabled by a holistic approach, considering aspects specific to CM, principles outlined in ICH Q7, Q8, Q10 and Q11, and quality risk management described in ICH Q9.
Regulatory Considerations
The dossier for a CM process should be in accordance with ICH M4Q. Some CM-specific considerations are provided below –
- Description of Manufacturing Process and Process Controls
- Control Strategy (Input material attributes, Process monitoring and control, System operation etc.)
- Batch Description and Batch Size
- Process Models
- Drug Substance and Drug Product Stability
- Conversion of a Batch Process to CM
- Process Validation
- Pharmaceutical Quality System
- Lifecycle Management
The dossier should include information as outlined in ICH M4Q. Additional elements relevant to CM should also be provided in the dossier when applicable.
