Milling and Micronizing Pharmaceutical Powders in High Containment
ILC Dover’s recent webinar discussed the ins and outs of milling and micronizing pharmaceutical powders in high containment. The manufacturing of products within the micronized powders space is growing, especially for inhalation and injectable products. With particle sizes generally ranging from 2-20 microns, manufacturers face a huge challenge in terms of containing such small particles.
Micronization is a common process in the pharma industry throughout the drug development cycle, from chemical synthesis to oral solid dosage plans for patients. This process is also known to require a lot of energy, and very often creates an over-pressure inside the processing equipment. With the market showing an increased rate of production of highly potent milled and micronized powders, this also creates a larger risk of exposure to employees and the environment. The pharma and biopharma industries are now facing new challenges with powder handling on a scale never seen before. In recent years, production facilities across the globe must handle an ever-increasing amount of powder, creating bottlenecks and inefficiencies throughout the entire product pipeline.
The Containment Challenge for Each Type of Mill
When assessing the containment design needed for a particular mill, there are some challenges depending on the type of equipment, airflow needs, and particle sizes involved in the process. Each type of mill, whether a low energy oscillator mill or a high energy micronizer, produces a certain volume of air exchange during the process. Teams must figure out how to handle the processed gas and then release that processed gas without contaminating the area or releasing particulates. Another consideration is the type of material being processed; is it a granular powder with a larger particle size, or a fine particle cut, very airborne and potentially contaminating? These are the types of challenges one must think about during containment design for a size reduction system.
Containment solutions for size reduction applications are often complicated. These solutions usually lead to a sole reliance on PPE or facility ventilation types of controls, instead of designing a system that would contain at the source to keep the powder in the system to protect the operators and the environment. Fitting traditional isolation systems onto advanced machinery is thought by many in the industry to be too expensive and time consuming. For example, installing heavy mills through doorways in most facilities is difficult, leading to systems being permanently installed in the isolator. Another example is retrofitting existing mills, which, unless exceedingly small, can be costly if choosing traditional hard-wall isolators. Not to mention the extreme limitations to operator’s access, and challenging cleaning and maintenance procedures where hard-wall isolators are already in place.
Containment considerations for Risk Assessment of new or existing size-reduction applications:
- What is the containment performance target and not just OEL?
- Sampling protocol and frequency?
- Does the powder have a low MIE and require inerting?
- What are the processes before and after milling?
- Product contact materials for regulatory compliance and non-product contact materials for compatibility, i.e., solvents?
- Ergonomics – what are the easiest solutions for your specific process?
Critical Issues that Impact Containment Performance
Let’s start with how much powder we are processing as our first important issue to tackle. Laboratory scale and pilot plants are going to have different sizes of powder handling equipment than larger production facilities producing commercial-scale quantities. Each facility needs to determine its proposed volume of powder capacity and how that will possibly impact containment performance. Another critical issue to look at is the flow characteristics of the powder and how that affects containment performance. All powders seem to flow differently and have slightly different moisture content. Believe it or not, these powder properties can dramatically change the containment performance and design, and a common need for that is negative pressure control.
One of the biggest issues is the size of the equipment that needs isolation. The mill type makes all the difference in the complexity of the containment design, with more on that below. Transfers in containment is another critical issue, as the transfer process can be quite detailed depending on the scale of the plant production. All connections that directly transfer through the isolation area are most at risk, which will need to be addressed early on in the process.
Flexible Containment Minimizes the Complexities
With flexible containment, the options for pre-existing equipment are endless. The containment can be retrofitted to the equipment with minimal or no hardware changes. When needed, ILC Dover can install a floor pan or flange design, and a 5-sided isolator for introducing larger components if required. In most scenarios, the final milled powder is contained with an external flexible containment system, so the “containment package” has no contamination or cleaning requirements.
Jet Mill equipment can be installed in a flexible isolator with a cyclone receiver to separate the air and the micronized powder for optimum containment performance. ILC Dover’s flexible solution can contain all transfers in and out of the area, including the product container, feeding the hopper, and safely taking samples of micronized powder. Any scale micronizer can be added to a flexible isolator system with a baghouse receiver to separate the air and the micronized powder. A passive flexible isolator can easily be installed to contain the mill. The connections for powder charging and collections can be integrated with any ILC Dover flexible product for seamless operation throughout the containment zone.
Advantages of Flexible Containment
Flexible containment systems used by multi-product facilities have many benefits over traditional containment. Some of the advantages of flexible containment:
- Low capital expenditure for retrofit or new installation
- Single-use consumables are purchased only when needed
- Proven high containment
- Reduced cleaning and faster turnaround times
- Reduced risk of cross contamination
Stainless steel bins require an SBV for containment, a precision lift to position, and a complete washing system. These additions can increase costs by nearly $500,000 and require even more fixed floor space for traditional isolation systems. By contrast, single-use DoverPac has a patented high-containment connection, requires only a simple hoist system to position, and requires virtually $0 for cleaning. It’s easy to see the value in ILC Dover’s products.
Interested in Learning More?
ILC Dover is a world-leader in developing effective solutions to routine powder handling and containment activities, producing single-use bags and systems for powder media and buffer processing along with high-containment solutions. Does your team have a need for any of these technologies in your facility? To see all these products in action, be sure to watch the full webinar for more information.