Capital Versus Disposable Costs – Asset Protection
Engineering discussions around containment for large or small enclosures, piecing operations, maintenance tasks, and laboratory purposes, goes into great detail about normal operations. Yet the greatest value of any containment is at times when abnormal operating conditions prevail, such as process leaks, spills, in-process adjustments, sampling, etc., i.e. whenever open materials handling or emissions are involved. Keeping the processed materials within the equipment confines is an entirely different proposition from preventing migration during known equipment materials releases.
When comparing virtues and costs of any approach, emphasis should also be placed on such conditions. This is especially important for batch operations where frequent clean up is a quality requirement. This is the very nature of contract manufacturing providers. In practice, repeat operations for a single active are few in number, being mostly limited to drug materials still manufactured under patent.
It makes sense to consider predominantly rigid containment solutions, with the flexible containment relegated to areas involving spatial and ergonomic limitations where the goal is long-term operation. The construction of clean room suites for both parenteral and tableted formulations is the standardized approach that is most readily accepted by regulatory agencies. Such operations are heavily invested in cleanable wall, floor, and ceiling surfaces. Once validation is accomplished, the challenge remains to ensure that proper operator training and procedures are documented, and followed. Flexible containment introduced into such operations must follow the same cGMP requirements. However, a prototype flexible containment solution can often assist in selecting the appropriate long-term solution as several of our clients have discovered. The ability to receive and test a simulated prototype flexible containment within mere weeks of ordering, and at a fraction of the cost of a rigid solution, can save thousands of dollars to the final project. The ability to install, stress test, and gain operator acceptance, for several iterations of a flexible mock-up, both economically and in a short time frame, has helped clients to specify a functional design for a rigid containment. Foreknowledge that the planned rigid solution will work with a minimum of on-site modification has saved much effort, reduced cost, and shortened time to operational performance. Making structural changes to validated equipment after the fact can be avoided by such pre-planning.
For contract manufacturers and small scale development providers to quickly ready themselves for such containment performance, rigid containment creates four major roadblocks: speed of delivery, cost, infrastructure for automation and cleaning for multiple products manufacture, while ensuring operational performance. Alternatively, many of our existing and performance tested flexible containment solutions have been adopted for design, delivery, and installation ready for use within less than 6 weeks and at low cost. Sizes ranging from complete containment suites with gowning and decontamination capability to small-scale equipment enclosures are routine rapid response services that FabOhio Inc. provides. All our flexible products are fabricated at our Uhrichsville, Ohio site. Examples of many client solutions may be seen in the image galleries at our web site fabohio.com.
Dispensing suites are of critical concern. They are frequently part of a multi-purpose building including warehouse storage. This means that multiple products pass through the shared hallways. Agencies have requested proof of performance for all containment strategies used for materials handling in non-dedicated buildings.
There are no published protocols for proof of migration control. However, one client has used clean room sampling strategies, coupled with a statistical design adopted from the extensive archives of the nuclear industry. They documented non-detectable levels (<0.04 ng/cu.m) of an oncolytic API in a worst case study using our dispensing glove bag within a negative pressure cascade dispensing suite. This result was recorded both within the dispensing suite and also the outer shared hallway. These results were accepted by the regulatory agency, which had previously cited the use of a non-dedicated facility.
Similar testing was performed in a shared dispensing suite for clinical trials. The dispensing suite had a laminar flow exhaust. Using an early prototype dispensing glove bag for low volume dispensing resulted in no measurable emissions during either dispensing or cleanup. Interestingly, sample control measurements taken in an outer storage room containing mixed drums of the API's showed high airborne levels. The presence of multiple product drums in the storage room immediately triggered a massive cleanup and procedural improvements to contain drummed materials all the way back to their sources.
These combined observations provided further confirmation that once an API is synthesized as a bulk material, containment measures should be followed throughout their entire production, handling, and distribution pathways. This also includes the many waste handling operations since it is rare to find degradable API's in current production.
It is wise to extend a bulk buildings design and operational aspects beyond the battery limit of the project.
All waste handling - solid, liquid, and vent emissions, should undergo a risk assessment (Process Hazard Review - PHR requirements) recognizing that operations such as waste piping and sampling systems, sludge handling, and waste drum on-site storage and shipping for incineration (regulated under EPA’s RCRA regulations) all have potential for spillage of potent and sensitizing drugs and by-products. The Love Canal incident and similar industrial HazMat sites show the potential risk for the generator or handler with the deepest pockets.
An unprotected API drum or package can undergo unintentional, and often unrecognized, damage leaving a trail of contamination along its pathway. Once a leakage is identified, a major investigation usually ensues often followed by intensive clean-up efforts, which places unanticipated burdens on company support and operational staff. It may also lead to widespread use of Personal Protective Equipment, i.e. extension of the respirator program and cost of full body protection, decontamination, and disposal. Extreme situations may require the use of licensed cleanup and disposal services.
Rigid containment solutions are only instituted in dedicated handling areas within manufacturing and laboratories. Flexible containment solutions are amenable to these as well as transportation and handling issues that arise with current manufacturing processes, especially those areas covered by regulations such as FDA/EMA and other advisory and regulatory agencies, such as those impacting worker protection and the environment.
Working alongside our clients, FabOhio Inc. has a long track record for developing low cost flexible containment solutions to satisfy a wide range of potential fugitive emission controls as the need has arisen. Once a client identifies a need and approaches us we typically deliver a prototype solution within a short time. We have a large inventory of existing solutions that have already been implemented and tested in the real world. When visiting our web site at fabohio.com you can view several of these. We serve not only the major drug companies but also many of the smaller specialty and contract providers worldwide. Many solutions shown are from international sources.
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