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Single-Use Technologies in Fill-Finish Operations by Amy Ritter


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Single-Use Technologies in Fill-Finish Operations by Amy Ritter

  1. 1. Special Report: Disposables At the End of the Line: Single-Use Technologies in Fill-Finish Operations Amy Ritter T he surge in the number of biologics natural transition from bench-top to large-The incorporation in the drug-development pipeline, scale cell culture, and have evolved in sizeof single-use over 900 according to the latest report from the Pharmaceutical Manu- and complexity to fit the special needs of manufacturing-scale operations. Dispos-components in facturers Association, introduces pressure able downstream-processing tools have on manufacturers to handle increasing also been adapted to meet the demands ofthe fill-finish line numbers of small-volume products (1). In large-scale bioprocessing. At the very endprovides increased fill-finish operations, this means manu- facturers must have the ability to quickly of the biomanufacturing line is the fill-fin- ish operation, where single-use technolo-flexibility to and efficiently switch their fill line from gies are just beginning to make inroads. product to product without compromising Fill-finish is the last step in the man-multi-product product quality or sterility. Manufactur- ufacturing operation, after which themanufacturers. ers are beginning to take advantage of the benefits afforded by single-use technolo- product is passed to the patient. As such, product quality and the possibility Image: Influx productIons, photodIsk, getty Images gies to address these needs. of contamination are of special concern Single-use technologies are now when a manufacturer is considering widely-accepted tools in drug manufac- whether to implement single-use tech- turing, particularly manufacturing of bio- nologies. The fill occurs downstream of logics. A recent biomanufacturing survey the last filtration step, so there is a height- in Pharmaceutical Technology indicated ened sensitivity to sterility risks and the that 66% of respondents use at least some introduction of particulates. As with all disposable components in their manufac- disposable applications, product/mate- turing operations, and an additional 9% rial interactions and extractables and of respondents indicated that they use all leachables are also a concern. disposables (2). Disposable upstream- In some cases, manufacturers may be processing tools, such as bioreactors and reluctant to switch to a disposable line media storage containers have made a from a well-validated stainless-steel fill2 Pharmaceutical Technology  OctOber 2011  P h a r mTe c h . c o m
  2. 2. Special Report: Disposablesline, where process engineers have exten- tant factor in the decision to implement its simplest, a filling line can consist ofsive experience in cleaning and validat- a single-use fill line. “Market pressure a product container bag, a pump and aing the system and are confident in their and good business sense dictate that we filling needle, all connected by plasticquality control operation. Kent Payne, need to use our filling assets for manu- tubing. Disposable filling lines, suitablevice-president and general manager, facturing product, not for getting ready for smaller-scale fills are available asDevelopment Services, Catalent Pharma to manufacture product. The need to get “plug-and-play” systems, where the lineSolutions indicated that in general, a big the most product out of the process is in- comes fully assembled and presterilized,obstacle to adopting single-use technolo- creasingly critical to the business. That ready to be used, and needing only to begies in other parts of the manufacturing said, the paradigm of a few blockbuster attached to a peristaltic pump. Such sys-process has been a reluctance to change. vaccines allowing for long campaign tems are adequate for small-scale fills, but“The biggest challenge we faced in ap- operation and few product-to-product do not operate at high speed and may notplying single use systems elsewhere was changeovers is under pressure as prod- be suitable for high-viscosity products.changing mindset to be open to new ap- ucts portfolios become more focused on Pump technology has improved to theproaches from what we were used to,” he multiple (lower annual volume) biolog- point where disposable filling lines aresays. For single-use systems, validation of ics. This means that a production facility feasible, but further improvements aresterility and integrity is done by the sup- is faced with the challenge of more fre- possible. Peristaltic pumps have only re-plier of the components, rather than the quently changing the facility and equip- cently achieved the accuracy required formanufacturer. Handing these important ment over to process different products. fill applications. They are still limited byquality checks over to another party re- The reduction of changeover time has speed, and the tubing that runs throughquires a leap of faith that some may not therefore become one of the primary the pump is subject to degradation and de-be comfortable making. influences in our decision to implement formation over time. Plastic, disposable, On the other hand, single-use tech- single-use technology for current fill- rolling-diaphragm pumps are currentlynologies, offer advantages over stainless ing facilities.” Indeed, Beyeler reported available and offer an alternative. How-systems in control of contamination. a reduction in changeover time from 16 ever, more rigorous applications, whereIn the PharmTech survey, a majority of hours to two hours when switching to a high-volume, high-speed, or high-pressurerespondents, listed reduced risk of con- single-use line. In addition, a recent re- are required, may be places where stainlesstamination as an advantage to single use port produced by authors from Millipore steel continues to be the better (2). A single-use filling line can demonstrated a similar reduction in total There is plenty of room for new tech-be configured to have fewer connection processing time, from 19 hours to 1.5 nology to adapt to these challenges. Beye-points than a fixed-pipe line, thus reduc- hours, when switching from a stainless ler says “At the moment, I think what hasing the risk of microbial contamination. system to a single-use system (3). been offered is that which is the easiestMoreover, since the line is only used for On average, biotech companies out- and least risky to develop from the equip-a single product, there is no risk of carry- source 81% of their fill-and-finish require- ment vendors, a single-use version of whatover contamination. Althea Technologies ments. Biotechnology and pharmaceuti- is already on the market. Some equipmentuses disposable technologies in all of its cal companies with in-house capabilities suppliers for upstream processing have in-fill operations. According to Chris Duffy, outsource 40% of their requirements (4). novated beyond the “also in single-use”vice-president of operations, “Preventing This means that CMOs are handling a type of approach and have developedcross-contamination is an issue that Al- large variety of filling operations, and specifically new technologies. As vendorsthea takes very seriously. To ensure that can benefit from the flexibility afforded increasingly see the potential competitivethere is no carryover from project to proj- by single-use systems to handle multiple advantages for single-use technologies Iect, Althea has stringent changeover pro- products. Althea’s Duffy notes, “Stainless am looking for them to specifically investcedures and operates its fill facility with equipment requirements vary from client R&D in developing innovative fillingdisposable technology in virtually 100% to client. When not in use, these must be technologies.“ The requirements for speedof our fill operations, from small-scale stored and when they are placed back into and cost-effectiveness in multiproductphase I clinical supplies to commercial service must be cleaned again.” The ability manufacturing will drive the develop-manufacturing.” to quickly reconfigure the line to accom- ment of new disposable technologies for modate different size runs, different bio- fill-finish operations.Time savings and flexibility safety requirements, or different productPerhaps the biggest benefit to be gained containers (e.g., vials versus syringes) adds Referencesby implementing a single-use filling line greater flexibility to the filling operation. 1. Biotechnology Medicines in the savings in time gained by eliminat- PhRMA (September, 2011). 2. M. Hoffman, Pharm. Tech. 35(5), s6 (2011).ing the cleaning and validation steps. Na- Evolving equipment requirements 3. E. Jenness and V. Gupta, BioProcess Int.than Beyeler, process engineer at Merck It is often the case that equipment evolves 9(s2), 22–25 (2011).Sharp and Dohme, cited the decrease to fill an unmet need, and this is the 4. J. Hartingan and W. Downey, GEN 31(10),in changeover time as being an impor- case with disposables for fill-finish. At (2011). PT4 Pharmaceutical Technology  OctOber 2011  P h a r mTe c h . c o m