Use of Disposables in Final Filling Operations Converting to disposable filling components can result in significant benefits - no matter what product you are processing
By Jeff Jackson
Director of Product Management
North American Pharmaceutical Operations
Bosch Packaging Technology
Single use technology continues to gain popularity in pharmaceutical and biopharmaceutical operations. One area where single use technology would be very beneficial is in product final filling. The following paper highlights the various benefits of disposables for product filling operations.
Product Path Considerations
Typical filling equipment has a product path constructed primarily of stainless steel. Operation of hard systems requires cleaning and sterilization operations. The product path needs to be disassembled for offline cleaning and autoclaving of product contact parts. This is a highly labor intensive operation that reduces the life of parts due to wear and breakage. System disassembly also increases the chance of leakage and subsequent product contamination when piping is misaligned or connections loosened. Online, automated CIP and SIP operations can be used to supplement or replace manual cleaning. However, CIP and SIP are a drain to utilities and are expensive to operate.
Neither of these processes is necessary with an appropriately designed pre-sterilized, single use system. The product path assembly is attached to the filling system and connects to the product stream via sterile plug-and-use connections. No preparatory steps like cleaning, assembly and disassembly, autoclaving, CIP or SIP are required. Once the fill process is completed, the product path assembly is removed. The pre-sterilized assembly can be replaced as needed before or during the filling process, thus reducing the impact of leaks or other failures.
Another trend in product filling operations is the need for a non-reactive product path. Certain products react adversely with metallic surfaces. The product potency, efficacy and safety can be negatively affected during the filling operations. A non-metallic product path is required for successful filling operations of certain drugs.
Decreased capital costs for hard equipment, as well as elimination of high-cost process steps like CIP and SIP, are primary drivers for conversion to disposables. The typical product path for filling operations includes a bulk product tank, supply piping, a product surge tank, filter housings, a product manifold, dosing system parts, supply tubing and filling needles. Several sets of product path components are needed to support a filling line. Multi-product filling operations often require dedication of equipment, which adds to the number of sets of equipment on hand. Hard equipment also has a limited useful lifetime due to normal wear, particularly the dosing system parts. The operation of piston pumps, for example, can change over time as they wear or when they are scratched, dropped, or otherwise damaged.
Converting to a single-use product path eliminates most if not all of the product path hard equipment. Product supplied via a bag is piped using peristaltic tubing to a tubing manifold where it is dosed using a disposable dosing system parts to single use filling needles. Disposable filter cartridges are strategically placed in the product stream. The only non-disposable parts associated with the product path may include such items as tubing and filter cartridge supports, bag holders, dosing system hardware and filling needle holders.
Another cost consideration associated with filling method development is the expense of scaling up processes from lab to manufacturing. The process development laboratory environment already relies heavily on disposables for scale-down of processes. A properly designed disposable dosing system will change very little from R&D to commercial scale. Scale down of the product path would be a matter of reducing the number of filling stations from the typical eight or more for commercial filling to one or two for lab use.
Potent Products and Containment
Single use components are also strongly desired for products that are very difficult to clean. Highly potent biologic products often require dedicated stainless steel process equipment. Successful cleaning verification and validation are often impossible to execute due to the high pharmacological activity of biological compounds like monoclonal antibodies. Highly active compounds also require containment to protect operators and the environment from the product. It is difficult to fully contain residual product after filling with a hard product path unless CIP processes are used, and then the liquid waste from this process must be contained prior to treatment. Treatment of waste material can be lengthy and significantly costly due to high chemical use and specialized treatment processes.
Use of a disposable product path means eliminates the need for post-use CIP and processing of the resulting waste. Full containment of residual product in the tubing after use is also possible. Tubing can be welded and/or mechanically sealed and then cut into manageable pieces using commercially available systems, all without spilling product. The product path can then be placed in sealed bags for incineration, thus eliminating operator contact with the residual liquid material.
Using disposables reduces the risks associated with filling operations. Some of the risks, including product leakage from hard connections, product reactivity with stainless steel surfaces, and exposure of operators to potent compounds have already been discussed. Ability to replace the product path at will during processing greatly reduces if not eliminates failure of an overall filling operation.
Another risk is associated with fluctuations in cleaning and sterilization efficacy. Although CIP and SIP can be validated processes, in reality they are prone to failure. Many CIP and SIP cycles have to be terminated and repeated due to utility failures, valve failures, pump failures and in the case of CIP, simply running out of cleaning chemicals. Single use components are assembled in a cleanroom environment and used without previous exposure to product. Sterilization of these systems is accomplished using Gamma exposure which is a highly effective, consistent and validated method.
Using disposable components greatly reduces the risk of product cross-contamination and eliminates the need to dedicate product-contact parts. This is particularly the case when filling potent, hard to clean products. Filling needles are often dedicated to specific products due to cross-contamination concerns. Elimination of product-specific cleaning validation for the product path is alone worth the transition to disposables.
There are significant benefits to converting product filling operations to single-use, pre-sterilized systems. A reduction in operating steps, increased flexibility, reduced capital and operating expenses, full product containment, as well as reduced product risk are all realized using a disposable product path and components.
About the Author: Jeff Jackson
Director of Product Management
North American Pharmaceutical Operations
Bosch Packaging Technology Web: www.boschpackaging.com.
Phone: (763) 493-6133. E-mail: Jeff.Jackson@boschpackaging.com
Jeff Jackson holds a BSME degree from University of Minnesota. He has worked for Bosch Packaging Technology since 1996, beginning his career as a Technical Sales Engineer on complex liquid filling lines. Upon completion of a European work assignment in 1999, he became the first Product Manager at the US pharmaceutical location. In 2003, he was promoted to Director of Product Management where he has responsibility for all pharmaceutical products sold in the US as well as marketing and product development in North America. Along with being a member of ISPE, Jeff has been involved in a number of large customer projects and industry events.