Many of the foods we eat and beverages we drink have used membranes during their processing. Orange juice can be concentrated by membranes to make a concentrate which retains more of the flavour than does evaporation. Milk can be concentrated slightly by means of a membrane before making a cheese in a process which produces no whey. Gases rising from the ground in a waste tip can be piped away and the carbon dioxide separated from the methane by a membrane process allowing the methane then to be used as a fuel, simultaneously saving energy and reducing the greenhouse effect since methane is more effective as a greenhouse gas than carbon dioxide.
As processes mature, and the cost of membranes continues to dramatically reduce, so their applications and use are set to expand. Process engineers need access to the latest information in this area to assist with their daily work and to help to develop and apply new and ever more efficient liquid processing solutions. This book covers the latest technologies and applications, with contributions from leading figures in the field.
Throughout, the emphasis is on delivering solutions to practitioners. Real world case studies and data from leading organizations -- including Cargill, Lilly, Microbach, ITT -- mean this book delivers the latest solutions as well as a critical working reference to filtration and separation professionals.
Covers the latest technologies and applications in this fast moving bioprocessing sector Presents a wide range of case studies that ensure readers benefit from the hard-won experience of others, saving time, money and effort World class author team headed up by the Chair of Chemical Engineering at Oxford University, UK and the VP of Plant Operations and Process Technology at Cargill Corp, the food services company and largest privately owned company in the US.
It has significant advantages over competing separation technologies. Protein bioseparation is an important component of this application segment. Ultrafiltration is used for protein concentration, desalting, clarification and fractionation i. Concentration, desalting and clarification are technologically less demanding and have been in used in the bioprocess industry for some time.
Protein fractionation, on the other hand, is a challenging proposition and is definitely a more recent development. This book focuses primarily on protein fractionation. Marine Bioprocess Engineering Author : J. The symposium focused on the bioprocessing of marine natural products. Bioprocess engineering has been the key to success in the commercialization of biotechnology, especially with respect to biopharmaceuticals. In marine biotechnology, both new and existing biotechnological techniques are developed an applied to organisms from marine sources.
For marine biotechnology, bioprocess engineering represents the link between discovery and commercialization. The diversity of marine life points to a myriad of new bioproducts waiting to be discovered and developed commercially. The volume begins to bridge the gap between the isolation of products from marine organisms in the laboratory and industrial applications by focusing on the bioprocess-engineering aspects.
Reviews and recent developments in product discovery, bio-energy production, cultivation of marine organisms, scale up and product recovery are presented. This publication should ensure that the engineering aspects of marine biotechnology will receive further attention in the future. Exploration of new bioproducts from the ocean should be followed up by a sustainable exploitation of these valuable resources.
While there are obviously other books published in and around this subject area, they seem to be either older c. The that going forward the relationships established production and development teams worked very with WHO and other regulators will continue to closely together, and there was also extensive col- lead to improved interactions.
Janssen has proven that tion team, which headed up the project. Establishing an experienced team to manage supply chain and Lessons learned logistics issues that can also work closely with pro- The heightened level of effort observed at Jans- duction is also important and requires effective sen and other vaccine manufacturers in response collaboration and communication. Combining new approaches with newer processing The better we know the product and what confers technologies can also accelerate vaccine develop- immunogenicity and effectiveness, the easier it is ment.
In addi- understanding of vaccine manufacturing technol- tion, disposable technologies offer the potential ogy—preferably platform technologies, whether to eliminate equipment cleaning, process clean- for adeno viral vectors or bacterial vectors, is cru- ing validation, and cross-contamination, plus fa- cial for achieving rapid scale-up and getting the cilitate changeovers between processes, according vaccines to those who need them.
Combined with the application of platform Continuous processing is also attracting atten- technologies for related pathogens, they will also tion as a means for reducing the cost, scale, and further enhance the acceleration of vaccine devel- speed of vaccine manufacturing. Jornitz and Sidney Backstrom I Flexibility now guides n the lifecycle of pharmaceutical and biopharmaceutical com- cleanroom design and mercial manufacturing, the one constant has been change.
Dur- plant construction. More recently, improved expres- sion levels in mammalian cell-culture processes and growing im- plementation of single-use process technologies have allowed the biopharmaceutical industry to evaluate smaller cleanroom infra- structures in facility design projects.
Smaller facilities may provide enhanced containment required for processing highly potent compounds, or the special aseptic fill- ing and processing needed for cell therapy production. Smaller vol- ume filling has also created opportunities for new aseptic processing technologies e.
As modular facilities replace traditional methodologies, ar- chitecture and engineering firms are embracing this new tech- Maik W.
Moreover, modular companies are collaborating, which Sidney Backstrom is director could signal mergers and acquisitions in this space, similar to of Business Development, both at G-CON Manufacturing, Inc.
The question of when process equipment design has moved in the other di- to invest in such product-dedicated facilities re- rection, from multi-use to single-use 1. A facility can- quired years of planning and seven- to eight-figure not be considered flexible just because it uses single-use capital budgets.
The first generation of modular process equipment. If the layout of the facility does not container-based facilities was designed to be more allow easy access or movement, the potential benefits flexible than traditional large-scale plants, but in of flexible process equipment will be lost 2, 3, 4.
These systems proved and the required ductwork is interconnected into to be more flexible than the container-based de- the cleanroom from the larger facility, a change as signs and could be erected in a shorter period of small as the addition of a second fermenter or tank time. If expansion is required, wall panels could be could result in having to rebuild the entire room. If, however, the cleanroom were built with its own In most instances though, this means that the air handler and the process required the addition of existing cleanroom areas and processes are inter- another fermenter and tank, a second cleanroom rupted, and the entire cleanroom space will need could be easily added without interrupting the exist- to be rebalanced and perhaps additional HVAC ing process.
In the first example, the arrangement added or modified after the renovation. In addi- is static—dedicated to the product produced at only tion, the cleanrooms must be built on site, inter- one scale. Once more product is needed, or the pro- rupting manufacturing and requiring resources cess is changed, the layout no longer works. Even In the second example, the facility was built with so, the modular panel structures offered multiple flexibility in mind, so a change in the process required advantages over traditional brick-and-mortar fa- only a small addition, rather than a design change.
Such an approach represents the next generation of The latest generation of modular infrastructures, cleanroom systems, which are not interconnected, but prefabricated cleanrooms, are available in differ- are designed to be autonomous units 3, 5.
In one example of a cleanroom project, use of such facilities reduced labor requirements by hours. It also improved worker safety, because the work was performed at ground level within an en- vironment with plenty of space and supervision. Offsite-built modular cleanrooms do not require laydown or dedicated work areas as is common for onsite built rooms.
For some of the stick-built cleanrooms, laydown areas for materials can often be as much as the size of the ultimate cleanroom.
Should the product lifecycle bled to an entire facility, which makes these more of the product to be manufactured end, the whole flexible, relocatable, and repurposable. One of the first expiration. And additional unit operations such as manufacturing facilities to use the prefabricated coating and encapsulation can be added without approach, for an oral solid-dosage application, re- interrupting the existing structure.
This facility, which can be used for one or several companies. In the latter example, for small lot production all the way up to mil- companies can share administrative resources such lion tablets per year, was designed and built in 18 as using the same quality control, purchasing, op- months, saving two or more years.
The total cost erations support, etc. Resources are more efficiently used. Facilities, such as the process equipment will become the building blocks to standardized inside, will become reusable commodities. Concep- platform approaches for well-defined processes. A tual design costs would also decrease substantially. The pro- to design a standardized L mAB site as well. These suppliers have created being reinvented over again. Meeting the aseptic filling challenge These unit operations can be placed into cleanroom Smaller volumes within bioprocesses, the need containment systems and once again interconnected for more robust containment, and new therapies to an entire facility layout.
In the past, it would be left have led to new, compact fill line designs. The result would be significant man human interventions. And if the the end-user site. The prospective owner needs to consider whether the option will be a turnkey solution that will operate efficiently over the lifetime of the prod- uct being produced as well as what the value of that enclosure is after the product lifecycle has come to an end.
Table I reviews some of the parameters that should be considered in capital projects. New opportunities for facility design In short, facility design requirements are evolving, just as bioprocess technologies did as they moved from stainless steel to flexible and agile single-use second barrier, compact designs for both, and the process technologies 4, These innovative tech- possibility of sanitization with vaporized hydrogen nologies have created new opportunities for facil- peroxide, filling can now stop being the most criti- ity design, and modular solutions offer potential cal step in the manufacturing process and become benefits in boosting flexibility.
More els , and some are starting to work together. At least examples like this are sure to be seen in the future. Modular challenges Whenever modular options are brought up, they References 1. Shanley and P. Jornitz, Pharmaceutical Processing, April 14, , www. Parameter Considerations Does the facility option require owner personnel on site during the build?
Construction personnel needs at the site, including supervision and security are often not considered or underestimated. From a Personnel needs safety standpoint, if the personnel density allowance is reached, the project timeline can be adversely affected.
Build-in-place options often require custom redesigns of available space leading to significant Design time and costs engineering, permitting, and construction costs. Off-site built modular options are pre-engineered and repeatable leading to significantly less costs in this regard.
Laydown area larger than the cleanroom space is needed in on-site built options. It is not uncommon Construction site space that such space is as large as the actual cleanroom space. Off-site prefabrication reduces the space required. Offsite built modular systems utilize repeatable designs that lead to a more streamlined regulatory Validation costs review. Onsite built systems are typically custom leading to no such streamlining. Traditional sites require large mezzanine areas to run miles of process piping and ductwork.
This is space, and the cost of the HVAC system and piping needs to be added into the overall project cost Superstructure and calculation. In offsite built options, compact and decentralized air distribution systems reduce the mezzanine levels space needs and the need for separate contractors to run such ductwork and piping. In addition, the more compact and contained ductwork reduces the possibilities of leaks and pressure losses leading to a more efficient system.
The costs of low quality components generate risk of not meeting the required quality standards on a Quality materials short-term and long-term basis. Future manufacturing needs to be considered at the outset to determine whether the chosen option allows for scaling without interrupting the existing process. The costs of production interruptions Scalability should be accounted for when making facility design choices. If each cleanroom enclosure is autonomous, scaling up without interruption is possible.
How fast the facility can be deployed is a crucial factor in the facility decision. Days lost in product Time to first product run manufacturing leads to lost revenue for products with a limited life.
The potential for such losses should be considered in the decision making process. Onsite built options must be depreciated as a long-term capital asset. Offsite built options that are Depreciation moveable can be considered equipment and therefore depreciated on a much shorter schedule. In the latter example, a 5- to 7-year depreciation is typical compared to 30—40 years for long-term assets. Onsite built options require construction insurance and bonding, which can add significantly to the cost Insurance of the project.
Offsite built do not require such. Cleanability of the options should be considered at the outset. An area that cannot be properly cleaned may lead to shutdowns or product contaminations. Some options use gypsum board, plywood, etc. Sanitization The cleanability of these options is questionable, especially long term, as cleaning agents can deteriorate such finishes over time.
If the cleanroom can be repurposed when the product lifecycle ends, the efficiencies are apparent. Langer and R. Rader, Pharmaceutical Technology, September 9. Pralong, Biopharma Asia, 2 1 , Levine et al. Boisvert and P. The editions are the result of a systematic review and include changes made in response to requests by users and experts in the clean- room community. Because Part 2 is closely aligned with Part 1, the committee reviewed both parts together. To see our hands-free, sterile manufacturing process in action, visit www.
No assumptions are made regarding the distribution of the actual particle counts over the Sampling changes area of the cleanroom or clean zone; while in ISO The primary changes to Part 1 involve the number an underlying assumption was that the of samples and the selection of sampling locations.
If contracting out the classification activities, you According to ISO, the new method for selecting the should make sure that your contractor is now sites and number of sampling collections uses a more using your new, representative sample locations. She notes that risk-based sample site a classification tool for their Grades A at rest and op- selection is crucial for environmental monitoring. The new document does not address nano-scale It is important to be able to identify all of the po- particles, which were formerly defined as ultrafine tential contamination sources in each cleanroom particles in ISO , but will address and to select environmental monitoring sample these under a new Part 12, notes Farquharson, locations in close proximity to these sources.
These particles are not generally of interest the responsibility for review to the pharmaceutical and life-sciences industries. The standard addresses airborne particle concentration, airflow, and device pressure Pharmaceutical cleanrooms typically already difference. New topics include monitoring of criti- have monitoring plans, which are required by cal parameters and setting action and alert alarms.
She The revised standard now allows companies to notes that users should, however, check with their use risk management to set their periodic classi- cleanroom contractors to determine whether a con- fication testing schedules, notes Hardiman.
Because air handling accounts membranes, and ePTFE filters have higher dust-holding capability for a significant percentage of energy costs, filters represent with a lower pressure drop. This pressure-drop difference equates to an opportunity for savings. BioTechnique, a division of PSC energy savings. The main disadvantage of an ePTFE filter is its higher Biotech and a sterile injectable contract manufacturer, sought to initial investment, but total lifecycle costs are typically lower.
We predict that, for our facility, this could result in a Clapham: Filters typically fail due to a combination of poor kWh energy savings. Clapham: We are currently performing in-situ tests to measure Laminate filters constructed with a ePTFE membrane and a filter reliability and energy savings, using our production filling and supporting nonwoven layer have an advantage because the ePTFE capping rooms to compare approximately 70 microglass HEPA filters fibers are stronger and less easily damaged than glass fibers.
We expect that ePTFE filters will require strength results in fewer leaks during use. ISO, ISO , Cleanrooms and associated controlled environments—Part 1: Classification of air cleanliness by bility for review and approval of their results and particle concentration Geneva, Play Video www.
This staircase narrows examples show. The results of this spiral are seen today in pharmaceutical regula- tion, where the principle of erring on the side of safety is now so in- grained. The authors support the idea of erring on the side of safety, but can find no data to support treating a recall as prima facie evi- dence of patient risk, and there are no available data to suggest that aseptically produced drugs and biologics manufactured in facilities engineered and built in the past 25 years cause undue risk to patients.
Unfortunately, the result of aseptic regulatory spirals has often been drug shortages and other problems that pose real threats to patient health. William Whyte 2 shows how this value arose, and addressed. The number 90 only at Sandia Laboratories in New Mexico, showed up in the first two revisions of Federal this value was theoretically calculated Standard , last appearing in version B 5.
Subsequently, full of implications European Union GMP Annex 1 for Sterile Medici- nal Products, which appeared in , inserted the but lacking in clarity, metric conversion of 90 into the regulatory spiral, is common in the and to make matters even more confusing, its au- progression of thors decided not to harmonize with ISO regulatory spirals. This seems to avoid prescrip- which defined the cleanroom classification stan- tion, but FDA, unfortunately, introduced an un- dards Class , Class , etc.
Both of these statements rooms, and there is less linear distance between the and concepts feed the idea that velocity is, by itself, HEPA-filtered air entry point and the work surface, a noteworthy air quality attribute.
Industry objections to its Studies have found that there is no advantage to air inclusion were ignored. Thus, the FDA statement velocities as high as 0. It should be noted lated to cleanliness. This kind of imprecise lan- that in many isolators an air velocity of 0. This common in the progression of regulatory spirals is enormous ventilation for systems with intrinsi- and the myth-building associated with them.
Like the filter. This translates to higher energy costs and a undead of popular media, it has taken on new higher carbon footprint. Others suggested that the powers and continues to plague the living. Air sition that air velocity should not fall below 0. Others suggested that firms should impose room air balancing for decades. This technique, known as the L-R how it started out.
Unfortunately, the smoke test Method, is based on the use of electronic particle has numerous complicating factors. Videos have been pro- The L-R Method is different from the other tests duced to illustrate this point, in which dry ice was done in cleanroom certification in which particu- used to generate smoke and this cold smoke sinks late is generated upstream of a HEPA filter to test even with the air supply turned off.
In filter efficiency tests, the particulate smoke, one would start with smoke that is isother- challenge is put into the air stream above the filter mal, which is to say the same temperature as that and then the face of the filter is scanned to detect of the room that is being evaluated.
It lays out the basic concepts definitions methods and applications of bioprocessing. A single volume comprehensive reference developed to meet the needs of students with a bioprocessing background; it can also be used as a source for professionals in the field. Download PDF. You may also like.
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