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Against the clock: continuous manufacturing reinvented

Fette Compacting describes how direct compression acts as an innovative and target-orientated system for continuous tablet production.

Key highlights:

In recent years, machine manufacturers have been working at making continuous pharmaceutical and nutrition production ready for the market. At Fette Compacting, too, the focus of development has been on continuous manufacturing. Now the company has achieved a breakthrough, with direct compression proving to be a target-oriented process. This is mainly due to a lean plant design that can be combined with highly efficient process analysis. The result is an innovative modular system for continuous tablet production.

It is a well-known fact that continuous manufacturing offers numerous advantages for the production of medicines and food supplements: integrated processes increase both efficiency and process reliability. Compared to batch processes, process time is also reduced, while the specific production output increases. Another advantage is the higher speed of market launches and more flexible production, overall. In addition, continuous production is a quality-driven technology. Thus, it fulfils all regulatory requirements. According to the Food and Drug Administration (FDA), continuous manufacturing is even capable of making a significant contribution to modernising the pharmaceutical industry. This is due mainly to the high product quality and patient safety that go hand in hand with increased process control.

Lean design, easy operation

In recent years, there has been a growing acceptance of continuous direct compression in tableting. It appears attractive in terms of process technology and can be realised with a leaner plant design as compared to batch-to-batch production. Nevertheless, many manufacturers continue to rely on the latter. The reasons for this lay primarily in enduring reservations about continuous systems.

One central concern stems from the often large footprint and room height necessitated by existing continuous systems, as this is often accompanied by modifications to existing buildings or even the need for new builds. In addition, many companies fear long lead times for design and production, while at the same time tending to invest heavily in customised facility designs. Since scientific staff are required for such installations, and specially trained users for the operation, manufacturers also shy away from anticipated complexity. This is further compounded by the assumption of lengthy cleaning and refitting times, which could threaten smooth operation due to extended downtime. As a result, many companies anticipate disproportionate investment and operating costs.

Low capital expenditure thanks to lean design

Fette Compacting has developed a continuous tableting system from scratch that serves to eliminate the reservations outlined above. The system comprises a closed dosing-mixing unit with powder transport system (FE CPS) as well as a rotary tablet press and an operating terminal. Full integration of the system into existing production areas is on one level only and largely dispenses with the requirement for structural investments and modification.

The range of formulations covers throughputs from about 5 to 200 kilograms per hour. This allows flexible use both with both smaller batches and large-volume production. The FE 55 tablet press used enables longer pressure holding times at a lower pressure via three compression stations rather than two.

Design principle for safety and easy operation

The process area of the FE CPS was designed to be dust-tight, and its closed construction – including sealed glass panes and negative pressure in the process area – provides additional protection for operators.

Cleaning and changeover, which were previously considered time-critical steps in continuous systems, are also carried out with less effort in Fette Compacting’s new design. This is due mostly to the dosing-mixing unit being designed with significantly fewer parts and interfaces, and having separate, easily accessible process and technical areas. The process parts of the refilling stations, the dosing stations, and the specially developed mixer are located in the process area. The drives, the electronics, the cabling, and other components are housed in the dust-tight, and separate, technical area. All components are thus easily removed from the process area for cleaning.

Additionally, the design principle of the direct compression line makes operation, changeover and maintenance particularly easy. Central to the design is a Human Machine Interface (HMI) that provides, on a single terminal, an overview of all parameters for dosing, mixing, tableting, and process analysis – including recipes, logs, events and diagnostics. Continuous operation of the HMI is very user-friendly and thus quickly learned.

Process analysis, not only for specialists

The quality and efficiency of continuous production depend above all on the appropriate process analytical technology (PAT). PAT is not yet widely used in tablet production because the complex integration of software from third-party systems often means safe and efficient handling can only be achieved through the employment of experienced specialists.

Here, too, the continuous direct compression line takes a completely new approach: an innovative technology for inline process analysis (embedded PAT, or ePAT for short) is used to monitor the most critical quality attributes. Sophisticated sensors are integrated into the process units and can be positioned at four points for continuous monitoring of production parameters: at the outlet of the mixer, at the inlet of the tablet press, at the Fill-O-Matic, and in the process area of the tablet press. Corresponding inline measurements, which take place directly in the production flow, allow swift reactions to quality deviations and direct adjustment of the production process.

The system also enables data acquisition and analysis in real time and thus significantly higher measurement and reaction speeds. The particularly efficient measuring method used is near-infrared spectroscopy (NIRS), which is particularly good at detecting many active substances in this spectral range. The infrared rays penetrate deep into the tablet without causing any damage. NIRS ensures ultra-fast quality checks on larger sample quantities and is thus ideal for tablet presses such as the FE 55 and the upstream mixer. The result is a systematic unity of plant and process analysis – and thus continuous manufacturing, which is – finally - economically viable.

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