During the past five to ten years, pharmaceutical industries have been producing an increasing amount of potent drugs where the active pharmaceutical ingredient(s) (API) is part of the incipient composition. Potent drugs have the capability of achieving a pharmacological effect with very small amounts of active ingredients. Airborne particles can present risks to the operator if released into the room environment. Potent drugs can enter the bloodstream through the respiratory airways and skin, among others.
Potent drugs are classified in different containment bands defined by operational exposure limits (OEL) and peak exposure limits (PEL) also called short term exposure level (STEL). While an OEL is based on an average amount over an eight- or twelve-hour period, the PEL considers a maximum amount of exposure at any given time (typically 15 minutes). Often, it is simpler to meet the OEL than it is the PEL requirements. In general, these limits are product dependent and are determined by the manufacturer’s Industrial Hygenist / Toxicologist based on potent ingredient testing.
Contained Tablet Press Considerations
Dust Collection: Tablet presses require dust collection. An independent dust collection unit per tablet press is recommended versus a centralized unit. Potential ductwork contamination and difficulties with balancing of the tablet presses air handling in high containment presses might occur. Bag-in/bag-out HEPA filters are recommended. These units should come with a spray nozzle for wetting the unit and removing airborne contaminants prior to opening them for maintenance. The dust collection unit must be designed to allow for connection and disconnection of powder drums in a contained manner (i.e. continuous liners, glove boxes, and/or containment valves among others). If the dust collection system to be used is a central unit, cleaning of the ductwork must be designed into the system via sprayballs and low point collection drains. Further, balancing of the press isolator, press dust collection and other facility pick up points is difficult to achieve and will result in a high risk of product release within the facility should a power failure or other event occur that impacts system balance. Ductwork design must consider dust explosion potential and should not be seamed or spiral ducting in order to ensure conductivity throughout the line. Some containment facilities use smaller portable dust collectors with HEPA filtration, containment and electrical classification instead of the centralized units. These smaller units can be dedicated to the tablet press, allow for system balancing and meet containment requirements without the need for installing, operating and cleaning ductwork throughout the facility.
Air Handling Units: Most tablet presses with containment operate under negative pressure in order to prevent any potential leaks from becoming sources of contamination. As the levels of containment approach Band 5 and frequently Band 4 as described in the table above, the tablet presses are supplied with air handling systems that control the pressurization of the tablet press isolator while in operation, dust extraction for machine cleaning and containment breach. The air handling system must meet the following requirements:
* Pressure level inside the equipment needs to be at least 0.5 KPa (2 in H2O) below the surrounding environmental pressure. * Negative pressure needs to be maintained until wash fluid has moistened all dust or flushed the majority of the product cake from surfaces before opening. * System must ensure negative pressure in emergency cases.