Reasons for purchasing or upgrading existing equipment for containments are for enhanced production capability, to protect the workers, mitigate cross contamination, and protect the facility. The focus is on the manufacturing effort and not areas outside the major manufacturing equipment and process. Even risk assessments focus on the manufacturing and ancillary equipment rather than an entire facility.
Catastrophic situations can occur when you fail to look beyond manufacturing. Processing equipment is routinely inspected for signs of leakage. Yet throughout a facility there are many potential release points that can create significant materials migration and cleanup challenges – long before they are identified. Even inside the processing suite there are many potential sources:
- Piping flanges with gaskets
- Valve stems and actuating devices
- Sampling systems
- Pump seals
- Piping using overloaded tri-clover fittings
- Process line filter canister housings
- In-process sensors requiring in-process calibration or replacement, e.g. pH and level sensors
Process validation including opening large pieces of equipment, e.g. a granulator for a statistical measure of homogeneity and random sampling of product within a filter/dryer across the filter surface to assess product dryness
In fact there are many more potential fugitive release points than those commonly identified around contained equipment. This applies to both new and retrofitted equipment and processes.
Even diaphragm pumps are subject to releases. While the pump doesn’t have a release point within the body of the design, rupture of the diaphragm is an ever-present problem. This situation is most common with Teflon diaphragms, which are variable from lot to lot.
One of the unusual discoveries regarding piping occurred in a Pilot Plant operation. A six-inch diameter vertical steel pipe was attached to an elbow using a tri-clover fitting. The elbow was connected to the flange of the discharge valve of a filter/dryer. The packaging method was being monitored to evaluate containment performance. When the sampling data was available it became evident that there was a leak of measurable proportions. Investigation showed that the tri-clover fitting was flexing, allowing the six-inch fitting to oscillate under load. This in turn stressed the gasket allowing material release. Applying a flexible containment around the tri-clover connection allowed the release to be eliminated until the final lots were packaged. The site adopted a guideline of no ≤4 inch diameter pipe for a vertical loading and ≤6 inch diameter pipe on a supported horizontal run when used for potent compound applications. In all cases the fitting was to be contained.
Teflon lined process piping also deserves special attention. Teflon is a semi-permeable membrane, allowing solvent to pass through it at a finite rate. For this reason either the enclosing pipe has a breather hole, or corrugated washers are used between the flare of the Teflon and the connecting flange to allow for solvent release, i.e. to breathe. Unfortunately Teflon linings are subject to pinhole leaks allowing process fluids to enter the outer shell and then released at the openings.
Fortunately, many of the pipe flange, valve, pipe vents, valve stems and actuators have a simple solution, which can be installed during turnaround or even processing. Unfortunately there is no picture in our archive. It consists of a simple sleeve long enough for tie off and bag-over capability and having an appropriate filter – HEPA for water based processes and sorbent style for solvent emissions. By placing a sorbent pad inside the sleeve, process releases can be observed due to a build-up of salt deposits on the pad. Addition of glovesleeves allows for maintenance access in-situ.
Potent compound manufacturing facilities have needed to address such issues. Collaboration efforts between manufacturers, along with design and fabrication assistance from vendors such as ourselves has resulted in a battery of simple solutions. A common problem is lack of space for installing a rigid containment solution, along with the need to enclose moving parts. This is an area in which flexible containment and supporting expertise excels.
Examples can be found on this website. By selecting from the different categories of interest you can find a brief description, and images, of installed systems. They may not appear elegant, since client budgets do not allow for cosmetic solutions, but they are all functional solutions delivered at minimal cost.
Another area that is often overlooked is turnaround and change-out. Piping needs to be refitted for a new process, piping skillets need to be fitted, valves need to be removed and either cleaned in-situ or taken to a shop for cleaning, inspection, and reassembly, new sensors need to be installed, etc.
A short visit with craftspeople in maintenance shops and site services will reveal their issues with the many tasks involved in servicing and refitting a process area:
Warehousing (receiving, storage, dispensing, shipping)
Environmental control (piping, pumps, dedicated pumping and storage systems, effluent sampling, incineration, biological treatment, shipping manifests, deployment)
Environmental air-filter canisters and bag-house dust removal (laboratory hood and open face enclosures, downflow booths, house vacuum systems, processing room exhausts such dryers and filter/dryers at all scales of production)
Site transportation (pallet and drum handling, spill control)
Any materials recycle services such as solvent recovery, intermediates recovery, etc.
Maintenance shops (equipment tear-down and refurbishment such as valves, dryers, vessels, etc.)
In-situ maintenance tasks include process filter change-out during processing and always during a turnaround. These include liquid canister filters and dryer exhaust filters housed in heavy enclosures.
In all cases there is potential for worker exposure, environmental releases, and cross contamination potential.
Efforts to minimize these release risks can save a manufacturer from costs of lost processing time due to cleanup, protect a site from spills on roadways, minimize both worker and environmental exposures, and in the extreme prevent a site from becoming a superfund cleanup site.
These issues become of greater significance when contractors are present in a building for maintenance and refurbishment. The best in-situ cleaning of a process is unable to remove solid deposits collected at the gasket joints of piping. Unless contained flanges and fitting are adopted, breaking piping for modification will cause a spontaneous release of material that can shower onto a worker or become airborne. The liability aspect of such an event is rarely addressed. As a consequence, management will enter a crisis mode when such an event occurs. This can be prevented economically with a little pre-planning.
Manufacturers and flexible enclosure providers have again collaborated to develop effective, low cost, containment approaches to address the many site wide issues. Most of these are unique applications for which there are no of-the-shelf solutions. Working closely with an experienced provider is key to achieving a successful outcome.
Along with containment measures for all of the above, a continuing assessment program needs to be in place. One client used a continuous monthly collection scheme for samples placed statistically random throughout a four level manufacturing facility having 17 discrete containment zones. Samples were analyzed immediately upon collection. Ancillary services such as warehouse storage and dispensing were also monitored with the same frequency. The results were then assessed to identify any areas showing measurable releases with immediate follow-up and remediation. In this manner they were able to identify breaches due to equipment weaknesses, procedural issues, planned maintenance operations, etc. to determine whether to anticipate routine preventive measures or single incident cleanup.
This high potency compound manufacturing facility and ancillary services were tracked for over 6 years while maintaining a shirtsleeve working environment for all but planned events. When the facility changed to an Industrial Hygiene scheduled assessment program, equipment and process breaches were not identified until several months after events occurred. Despite extensive cleanup throughout the manufacturing building, most areas continue to require fully protected workers.
The lesson learned at a few Pharmaceutical facilities is:
ONCE THE CAT IS OUT OF THE BAG YOU’LL NEVER CONTAIN IT AGAIN
Many of the solutions are simple, low cost, quick delivery, and readily introduced with minimal effort on the part of workers. Most are small and require minimum storage and inventory control. With proper selection of materials of construction they have a shelf and storage life in excess of 3 years. One enclosure has been used in an outdoor environment since 1997 with no loss of integrity.
Efforts taken to evaluate and control the risk from releases across a manufacturing, dispensing, warehousing, Quality and research laboratories, and site services will save extensive efforts and costs for cleanup while ensuring maximum availability for product manufacture.