USP article on pharmaceutical continuous manufacturing

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17-19 September 2024

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GMP Compliance and Technology for the Manufacture of Oral Solid Dosage Forms

In the latest edition of the Pharmacopoeial Forum 44(6), the US pharmacopoeia USP has published a so-called Stimuli Article on pharmaceutical continuous manufacturing. A continuous process means the continuous feed of input materials, their processing and the continuous removal of output materials. This definition is universally valid; however, the paper focusses on the manufacture of oral solid dosage forms (OSD).

Apart from important definitions, the document contains further information that is important for continuous manufacturing. The document includes the following interesting sections:

• Definitions
• Material properties and characterisation
• Risk management, PAT and statistical tools
• Regulatory considerations

The part "Definitions" discusses terminology such as the batch, flow rate, residence time & residence time distribution, state-of-control und steady-state and control strategy.

When processes are carried out continuously, material properties in terms of processability are of much greater importance than in discontinuous batch production. Therefore, a whole section has been dedicated to this topic which still only covers materials for manufacturing oral solid dosage forms and an example for direct pressing of tablets. Also using the tablet as an example, it shows possible errors in individual process steps and their possible root cause in the form of material properties.

The section "Risk Management/PAT" contains little specific information on risk management; it does, however, contain two concrete examples on the use of PAT (Process Analytical Technology). One example is the non-spectroscopic determination of active substance concentration during the feeding. The second example is a spectroscopic measurement of content uniformity during the process.

The section on regulatory considerations is not very specific; it does show, however, which key aspects pharmaceutical companies and (regulatory) authorities should cover in order to secure the quality of continuously manufactured medicinal products. These aspects (e.g. material properties, process dynamics, process monitoring, deviation handling, material traceability, batch definition, quality control and sampling strategy, etc.) should be paid close attention to during the development of a continuous process as well as in the regulatory review.

The article is part of the most recent Pharmacopoeial Forum:
44(6) Stimuli to the revision process: USP (Pharmacopoeial) Perspective for Pharmaceutical Continuous Manufacturing

Access to the document is free of charge, only a free registration is necessary.