Pharmaceutical isolation today focuses more on isolating equipment and processes to ensure safety, and less on protecting operators with Personal Protective Equipment (PPE). Engineering firm CH2M Hill Lockwood Greene has a wealth of experience in isolation projects at its LG Scott office in Puerto Rico, and two of its experts process manager Monica Colberg and project manager Javier Rivera share insights about whats current in containment for solid-dosage processes.Pharmaceutical Manufacturing: A current trend in isolation is to contain the process to protect operators, not just to prevent contamination from entering the process. What are you seeing in this regard?MC/JR: An industry trend is toward the manufacture of potent drugs that have very stringent operator exposure limits (ranging from10 microgram per m3 to less than 1 nanogram per m3). Ideally the process should be an enclosed one, with Clean-in-Place or Wash-in-Place capabilities to prevent operator exposure during cleaning or maintenance. However, this is not always possible with current unit operations because existing equipment may not offer containment or processes were not established with containment in mind.We are seeing more use of equipment designed for containment, such as compression machines, coaters, fluid bed dryers (with stainless steel filters instead of removable filters), roller compactors, and high-containment valves such as split butterfly valves and cone valves.The most challenging applications include the retrofit of existing equipment to meet stricter process containment requirements. This includes the integration of isolation equipment such as glove boxes and containment valves into the unit operation, and also the addition of isolators to pilot-scale equipment such as V-blenders, oscillators and compactors.P.M.: What other isolation trends are you seeing? What new challenges are you facing for high-containment projects?MC/JR: Manufacturers are building equipment that contains the product. The equipment also includes CIP and WIP systems to remove active ingredient before breaking the integrity of the contained system to perform product changeover or equipment maintenance.Since Puerto Rico is developing as a hub for biotechnology and pilot plants, we are seeing more pilot equipment requiring containment. Pilot plants require flexibility in process steps, parts change-out and material/product changes, so equipment is typically designed for this i.e., its usually benchtop, nonproduction equipment thats easy to disassemble and not for containment. Modular isolation systems may work in these cases, as long as they are retrofitted to make them flexible and easy to use.P.M.: Whats the secret to containment without sacrificing equipment functionality?MC/JR: Always remember that an isolator is a physical barrier between the equipment and the person. This barrier, if not designed with the process in mind, may become a barrier in the use of the equipment itself. It can also impact product yield. The design should make it easy for maintenance personnel and operators to access the equipment without breaking system integrity. An example would be to retrofit benchtop equipment so that controls and motors are on the outside of the isolator while the product contact areas are inside.For every project, its important to develop a mock isolator and go through all the production and maintenance steps with the mock unit. This step ensures that operators will be happy with the design outcome.P.M.: In the planning and design stages, what steps do you take to determine what kind of containment will suit a given unit operation or manufacturing line?MC/JR: Product containment, especially isolators, greatly impacts operator movement and accessibility. Every step of the process must be analyzed. This requires a team that includes people from operations, maintenance, safety and quality/validation, and from the equipment and isolator manufacturers.Key factors to analyze include:
- Batch processing requirements
a. Unit operations
b. Temperature and humidity requirements
c. Product weight range and volume
d. Product yield
- Production sequence and product movement through the unit operations (i.e., weigh, blend, add product, blend, oscillate, blend)
- Safety requirements
a. Product explosiveness
b. Ergonomic factors (reach, weights, lateral movement through an isolator)
- Quality requirements
b. NDA requirements
c. Equipment interchangeability as specified by the FDA Guidance for Industry SUPAC-IR/MR Manufacturing Equipment Addendum.
- Equipment restrictions
b. Human Machine Interface (HMI)
c. Other manual controls
d. Equipment settings and parts
- Isolation restrictions
a. How is product going to enter and exit the isolator?
b. How is waste going to exit the isolator?
c. How will equipment parts and tools enter and exit the isolator?
d. How will the isolator react when system integrity is broken?
e. How will the isolator be cleaned?
- Rapid Transfer Ports (RTPs)
- Containment valves
- Inflatable seals for docking of drums
- Bag In/Bag Out rings
- Having dust collection points in strategic locations;
- Proper grounding of the isolator;
- Using explosion-proof equipment;
- Removing sources of ignition such as motors and controls to the outside of the isolator;
- Inerting the isolator.