Technological advances
PharmTech: What are some recent technological advances in facility and equipment design for high-potency manufacturing?
Cascone (Metrics): Many equipment vendors are pre-engineering their equipment to be contained whereas in the past this was considered an optional
upgrade. New equipment is more modular in nature. Product-contact modules can be cleanly removed from drive units and disassembled
and cleaned in remote washing areas. This reduces downtime and exposure risks.
Bormett (SAFC): There has been an increasing interest idisposable containment options for potent-compound handling, especially for larger-scale
operations. Disposable systems reduce the time for cleaning and can eliminate the potential for cross-contamination. They
also may be used as secondary isolation around fixed equipment to improve overall containment of the process to meet lower
OELs. Improvements in local exhaust systems, with proper filtration for potent-compound capture, also have been implemented
to further reduce potential exposure to employees or the facility. The integration of two types of equipment, in some instances
by two different equipment vendors, also is an area that has seen improvement. This could include engineering glovebox isolation
equipment onto Nutsche filter/dryers or lyophilizers to allow for containment during discharge of potent compounds.
Iliopoulos (Euticals): There is a growing trend in powder processing. Closed systems for powder handling and special valves are being developed
along with engineering advances in the equipment used to contain the highly potent APIs or hazardous compounds. The term containment
itself directs engineers in developing methodologies and structures to isolate the highly potent compounds. Charging materials
to reactors, discharging a centrifuge, charging of a mill and packaging in closed systems are becoming popular practices in
dealing with highly hazardous substances produced in multipurpose facilities. Traditional technologies are not easy to clean,
and the risk of material remaining on the surfaces is too high. Disposables used in the closed system solve these problems,
but have limitations with some solvents. Some examples of currently used isolation technologies using disposables are drum-sampling,
dispensing, transfer sleeves, filter-change containment, decontamination, and cleaning containment. The benefit is that with
low investment, one can achieve the desired containment level. I am sure that the future development will be focused in the
development of isolation technologies at the level of dust generation.
Nettleton (Cambrex): With improved awareness and hazard recognition related to high-potency API development and manufacturing, there is a greater
appreciation of proper risk management associated with HPAPI handling in general. Industry leaders are working to move away
from administrative containment strategies to more robust engineering conrols. Specifically in regards to micronization of
HPAPIs, Cambrex maintains GMP micronization suites equipped with high-level containment engineering controls. These containment
systems units have demonstrated performance to 1 ng/m3.
Doherty (Ferro): What I am seeing is a lot of small improvements to potent-handling equipment, such as better means of cleaning split butterfly
valves that provide continuous improvement in containment. These small improvements should not be underestimated in their
beneficial impact.
References
1. ISPE, ISPE Good Practice Guide: Assessing the Particulate Containment Performance of Pharmaceutical Equipment (2nd Edition, Tampa, FL, May 2012).
2. ISPE, Baseline Guide: Risk-Based Manufacture of Pharmaceutical Products (Risk-MaPP) (Tampa, FL, Sept. 2010).
3. ICH Q9, Quality Risk Management (Nov. 2005).
4. EMA, Concept Paper on the Development of Toxicological Guidance for Use in Risk Identification in the Manufacture of Different
Medicinal Products in Shared Facilities (London, Oct. 2011).
5. M.S. Maier, Toxicol.Mech.Methods
21 (2), 76–85 (2011).
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