Manufacturing capacity, safety and increasing costs are among the main concerns for drug manufacturers and CMOs. These crucial elements are also driving development within the pharmaceutical milling industry, a key component of drug manufacturing. But these aren’t the only factors in play. In this article, we explore the top six trends in pharmaceutical milling today, how they are impacting the industry, and propose some solutions.
1. Increasing manufacturing capacity
With the growing demand for pharmaceutical products, manufacturers are focusing on increasing their manufacturing capacity. This involves investing in advanced milling equipment and optimising production processes.
Frewitt, a leading powder size-reduction technology company, understands this and has developed its products to be modular by design. In one example, a leading drug producer contacted Frewitt because of a worldwide surge in demand for blood sugar-lowering drugs, requiring the company to evaluate a new processing line for increasing capacity.
Frewitt re-engineered its DelumpWitt crusher and grinding line so this could be incorporated as the core of the process. Thanks to the DelumpWitt‘s compact construction and 2-in-1 process, only one, rather than two lines, were required for the crushing and grinding process, increasing capacity while saving space, time, and cost, thus providing a total RoI in less than 3 months.
2. Safety
Today, manufacturers are investing heavily in advanced technologies and equipment to ensure the safety of workers and quality of products. Keeping operators safe also includes implementing measures to prevent contamination, such as ensuring proper handling of raw materials, maintaining a clean and controlled environment, using the correct PPE, and conducting regular inspections.
For instance, high-impact milling involves handling and processing highly toxic materials, which can pose unique safety challenges. These materials can not only pose risks to human health but also cause cross-contamination with other drugs.
Proper containment of these substances is crucial. Dust explosion risk can be minimised by using isolators or purging equipment with inert gases, and fire hazards can be mitigated by proper ventilation, and fire-detection and suppression systems.
For Frewitt, safety is always its greatest priority. For example, processing with the Frewitt Power Mill PM-320 (patent-protected) takes place in a negative atmosphere. The mill operates in a partial vacuum, controlled by pressure sensors, and features a temperature measurement sensor. The negative atmosphere lowers the air density, but the percentage of oxygen remains the same (21% O2). The mill housing is designed and certified to resist to maximum explosion pressure, so that in the event of combustion, operator safety is guaranteed.
3. Automation and digitalization
Automation and digitalization are transforming the pharmaceutical industry. Manufacturers are adopting advanced technologies such as robotics, artificial intelligence, and data analytics to improve efficiency, accuracy, and productivity. This includes automated milling processes, real-time monitoring, and predictive maintenance.
Autonomous processing also ensures the safety of operators. For instance, the Nano Mill Skid SIP/CIP/WIP from Frewitt is an autonomous equipment platform for developing and validating nano-scaled particles in a sterile, pharmaceutical suspension. The modular design is based on Frewitt’s proprietary Nano Mill Lab. The system is equipped with actuators, enabling the system to run automatically without human intervention, ensuring the safety of workers. The equipment is controlled by touchscreen and can run entirely autonomously.
4. Quality control
Quality control is vital in pharmaceutical milling to ensure that products meet the required standards. Quality control activities include the inspection and testing of raw materials, in-process testing, and final testing of finished products. These tests are conducted according to pre-specified criteria to ensure that the products meet the required quality standards. This is especially important when manufacturing high value APIs.
Frewitt has been developing and manufacturing premium-quality mills in Switzerland since 1946, using renown Swiss quality standards. For successful completion of chemical conversion processes, the steps of potential impurities detection, the monitoring of temperature, pressure, flow rate, rotation speed, oxygen levels, and in-line particle size distribution monitoring can all be required. These factors can impact the API and must be analysed separately according to ICH Q7A guidance. Reliable and quality process analytical technology (PAT) is crucial for the manufacturing process.
5. Sustainability and ESG
Sustainability is becoming a significant focus in the industry. Manufacturers are adopting eco-friendly practices and technologies to minimise their environmental impact. This includes reducing energy consumption and waste, as well as increasing the use of sustainable packaging materials.
Frewitt is reducing its ESG impact with equipment such as the PMV-320 high-impact pin mill, which offers increased reliability and efficiency. The patented system combines containment and micronization processes via a controlled vacuum, reducing the risks of explosion and out of specification heating of the API product. The mill uses minimal electricity consumption and no liquid nitrogen supply, reducing costs and greenhouse gas emissions.
Conscious of its own environmental footprint, Frewitt is implementing sustainable technologies such as heat pumps and solar panels in its buildings, aiming to increase its own energetic self-sufficiency and reduce carbon emissions by over 40%.
6. Innovation and research (R&D)
Innovation and research are the driving forces behind advancements. Manufacturers are investing in R&D to discover new milling techniques, improve product formulations, and enhance drug delivery systems to improve product quality, efficacy, and patient outcomes. This includes collaborations with academic institutions, and partnerships with technology providers.
In one example of this cooperation, Frewitt took part in a ground-breaking set of experiments with a leading university in Switzerland, designed to explore nanomilling techniques for reducing micron-sized particles to nanometric size, and how to measure/characterise highly concentrated API suspensions using Modulated 3D Dynamic Light Scattering.
Frewitt introduced the University to its FlexMill-Lab NanoWitt, a modular milling solution for R&D and analytical laboratories, featuring a patented dynamic separator that doesn’t depend on a standard filter to ensure no milling media or impurities pass in the final product.
The researchers successfully milled Naproxen and Fenofibrate to 79nm and 173nm and demonstrated the accuracy of measuring ground active ingredient size using modulated 3D Dynamic Light Scattering, highlighting the potential of advanced particle size analysis for quality and process control in nano milling processes.
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