Modularization Process in Project Delivery (Part 1)

By: Gene Martini, Design Vice President – IPS

Modularization has been explored and exploited in the delivery of pharmaceutical facilities for many years; the concept can now be considered mature. The objectives are unchanged: reduced time from decision to delivery, reduced risk of cost escalation, and transfer of risky construction activities away from the field and into the fabrication shop where safety and quality can be better controlled.

The solutions have been tried and tested too; process systems have been modularized as “skids.” Sheetrock wall construction once requiring numerous steps, widely varying skills, controlled conditions, and two weeks of work just to complete a single room has yielded to modular wall panel installation that requires a single craft and a quarter of the time in the field. Stick-built pipe racks, chiller buildings, and air handling systems have been replaced by drop-in modules. And structural modularizations have diverged into a wide range of solutions such as box-in-box designs and portable shipping container laboratories.

The most recent development in modularization is the implementation of design, construction, and commissioning processes that result in optimal modularization decisions at the optimal points in the project life cycle.

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Developing Flexibility and Efficiency in Biomanufacturing Facilities

By Jeff Odum, IPS-Integrated Project Services

Manufacturing Life CycleCurrent developments in the biopharmaceutical industry have added significantly to the challenges of designing, building, and operating biopharmaceutical manufacturing facilities.  With increasing insights into product requirements and product characterization, the critical path for the development of new products is shifting to process development and manufacturing timelines where speed and flexibility are now more critical than ever.  Future manufacturing systems must be agile enough to deliver more types of products in a shorter time frame.

The traditional business model of highly integrated facilities does not allow for this needed increase in operational effectiveness.  A new business model is emerging that focuses on flexibility, operability, and utilization where companies can adapt rapidly to changing market conditions.

Manufacturing simultaneous, short multi-product campaigns to supply clinical material, run conformance lots, build initial inventory, and supply commercial material only adds to the complexity of running a biopharmaceutical manufacturing enterprise.

The new generation options of facility design involve the implementation of single-use technologies and new platform technologies along with a flexible approach to facility integration. With QbD as a significant foundation of facility design, these facilities will be “designed to operate” in order to provide a higher level of flexibility, utilization, and operational excellence.Developing Flexibility and Efficiency in Biomanufacturing Facilities

These facilities implement modular delivery approaches that include rapid deployment options, interchangeability of suites, and smaller footprints that respond to the demands of the new business model of the industry.  The ability to move processes in and out of the facility quickly and efficiently can greatly increase the throughput of the facility and permit flexibility in responding Developing Flexibility and Efficiency in Biomanufacturing Facilitiesto changing manufacturing requirements or deal with process problems. Capacity can be significantly increased by cloning the process equipment and installing additional production trains in available spaces.

At Interphex 2015, IPS will focus on these new technologies and approaches that support this new generation of biomanufacturing assets.

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Single Use Disposables: Risk Reduction AND Operational Flexibility – Too Good to be True?

By Robert Roy, IPS-Integrated Project Services

The past several years have witnessed a significant increase in the rate of adoption for single use disposable systems for aseptic fill/finish applications. Paralleling recent advances in flexible aseptic filling lines, single-use disposable systems (SUDS) for aseptic fill/finish facilities promise increased flexibility and streamlined operations. SUDS also offer significant reductions in facility risk profile, by eliminating the risk of cross contamination and by offering increased sterility assurance.

The technology adoption curve is moving from the innovator phase to the early adoption phase, with more and more companies choosing to adopt single use technology. These technologies are being deployed for scale up and clinical operations as well as for commercial operations. Flexibility in size for these process systems facilitates scale-up and tech transfer activities and reduces capital investments. Unknown design factors such as the final production quantities required are easily addressed using these systems, since the scale of the system can be easily adjusted once these factors are defined.

As we saw during the IPS Interphex tours in 2014, equipment vendors in recent years have made significant progress in tailoring their systems to incorporate SUDS. A great example is the development of improved, integrated peristaltic filling systems for commercial scale applications. These filling systems readily incorporate single use components, eliminate manual cleaning and sterilization steps, and reduce up front capital costs associated with multiple re-usable fluid path set-ups.

Like the old saying, “Anything worthwhile requires hard work”, adoption and deployment of SUDS requires cross functional organizational alignment, planning and execution. For single use technology, areas of focus include the following:

  • R&D and QA/QC activities to select primary and alternate vendors, to test product compatibility, and to develop and qualify test methods.
  • QA activities to audit and qualify potential vendors and to develop In-Process test methods and limits for use of single use systems.
  • Supply Chain and Operational activities to ensure supply security and to identify cost shifting from capital equipment costs to operational costs.
  • Engineering and Validation activities to specify, select, test and validate appropriate equipment and systems.

In spite of the organization effort required, SUDS offer compelling advantages for aseptic fill/finish operations. Implementation of these technologies is no longer a question of “will this technology work?”, but rather a question of “is our company capable of developing and deploying this technology?”

The answer to the first question, based on the number of systems successfully deployed, is a resounding Yes!! The answer to the second question is one that every company needs to answer for itself.

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Small Scale Flexible Packaging Lines

By Tina Gushue, Len Pauzer and Kevin Swartz, IPS-Integrated Project Services

Small Scale Flexible Packaging Lines INTERPHEX BlogManually packaging small lot and volume products is a common practice within the industry. A lot size of three thousand units may make up a total annual volume of only a hundred thousand units. The turnaround of a mid to high speed line is inefficient since running the lot requires only a fraction of the time required to set up the line. Because of this, a common practice is for a supervisor to assemble a group of operators in a large open room with tables and components and manually assemble the packaged product. The problems with this method are that it depends heavily on the individual operator and SOPs to define the process. By utilizing automated machines, the process becomes repeatable and measurable, in addition to removing the human error.

How do you remove the human error without breaking your budget? One solution is to use the Flexible Spine Concept to create packaging lines for contract packagers and small scale, clinical packaging operations. This concept creates a spine of utilities, communications and material conveyance which allow a number of smaller scale machines to be docked into the line. The line has basic “plug & play” features for equipment allowing for fast and easy changeover times.  It results in a multi-purpose line within one room that has the advantages of digital communication within the packaging line and facility (i.e. batch record information, metrics and serialization information) and removes human rate variability.

Interconnecting automation with manual techniques may seem like a contrast, but when planned and executed properly, it maximizes the potential of both methods. As products begin to target individuals rather than the masses, lot quantities decrease yet efficiencies need to remain high. A creative look at manufacturing and packaging lines can increase output without wasting capital or sacrificing quality.

To learn more about the Flexible Spine Concept, contact IPS.

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Don’t Forget the WIP! The Impact of Work-in-Process (WIP) on Oral Solid Dosage (OSD) Plant Design

By Andrew Christofides, P.E., Lead Engineer, Process Architecture and Technology – IPS

WIP is partially completed product either undergoing or awaiting processing.  For OSD manufacturers, WIP accumulates between all unit operations and may represent a substantial percentage of a company’s total assets.  Lean Manufacturing principles promote the reduction or elimination of WIP to minimize cycle times, inventory costs and waste, thereby improving operational throughput and profitability.  In OSD processing, the effective management of WIP is especially critical because of the potential for cross-contamination, particularly in multi-product facilities.

Overlooking any aspect of WIP staging is a serious pitfall in the design of OSD facilities, which overwhelmingly feature batch processing.  Undersizing a WIP staging area can constrict material flow and exacerbate a bottleneck.  This could occur downstream of a manual dispensing area, where ingredients are pre-weighed in batch quantities and assembled in kits, to be delivered to a blending or granulation process.  If dispensing is forced to stop until downstream staging is available, then the start of a subsequent batch may be delayed, jeopardizing production goals.

Improper design of WIP staging can also result in starving a critical process.  If dispensing is the constraint, then it is critical to plan for adequate staging of raw materials upstream of dispensing, to ensure that the operation is never forced to wait for the delivery of components.  Consideration must be given to material storage and handling methods and area adjacencies, as well as scheduling philosophy.

Oversizing is not the answer because WIP staging areas that are unnecessarily large could encourage the creation of excess WIP, which will drive up inventory carrying costs, make the material handling inefficient and increase the risk of cross-contamination.

OSD plant managers will feel the effects of poorly designed WIP staging areas long after the design firm hands over the keys to the facility.  It is crucial that the facility designer and the manufacturing expert form a partnership at the inception of every OSD capital project to ensure that proper consideration is paid to WIP.

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Bioprocessing Facilities: New Technologies are driving a Deeper Understanding of the Entire Process

Tom Piombino

While most architecture in the world is devoted to creating environments for human occupancy, who is tasked with designing facilities that manufacture drug products to occupy humans?

If you have been immersed in the business and/or science of developing a new drug for the last 20 years and are fortunate enough to be thinking about a manufacturing facility for your new Phase III blockbuster biotherapeutic, trying to navigate the sea of starting point options may be your next big life challenge. Depending on the size of your organization, your experience and perhaps your geographical location, you may or may not have access to the resources needed to kick this effort off. As you embark on finding a firm to guide you through the process and design your facility, you might hear confusing terms like Lab Planners, AE (big A, little e or big E little a), healthcare/institutional architects, EPC, EPCM, EPCMV, Design Assist, Design Build, ……and the list goes on. All these terms may be relevant to your quest at some point, but if you really need to build an FDA compliant bioprocessing facility, there is a term that you may want to focus on first, Process Architect. Not the type that designs IT infrastructure or commercial office complexes or stadiums, but one with the highly specialized skills and experience required to design a facility to make drug products that are safe for one of the most intricate and sensitive communities in the world, the human body.

Billions of dollars are spent each year to research and develop new and improved therapies meant to defend, mend and extend human life. Once your therapy advances to a stage that inspires commercial development and investment, it’s critical that the facility where that therapy will be manufactured be designed to mirror the level of sophistication of its final human host. Therein lies the role of the Process Architect and “their process” to extract, understand and organize the volumes of requirements into a compliant matrix of logical compartments that emulate regulations, unit operations, safety and efficiency. A qualified Process Architect applies the appropriate regulatory requirements, engineering data points and process information available to make sense of your process, architecturally and operationally.

In the recent years, the art of bioprocess facility design and the experience that was needed to understand its many fundamentals was thrown against a wall and smashed into hundreds of small parts. To make the change even more profound, the parts move and more often than not, get replaced by many other parts that must be received, stored, cleaned, serialized and organized to avoid confusion and cross contamination. Flow through the corridors of a highly utilized facility has become a congested super highway of materials that were once hidden in “the process” and are now ushered by human hands to their interim destinations. The process architects for the next generation of manufacturing facilities will need to breathe in these new operating dynamics in order to engineer solutions that integrate hybridized platform bioprocesses and reduce the boundaries of clean travel. They will need to understand more than architecture and the published regulations; they will become experts on the technologies themselves.

At INTERPHEX 2015, the subject matter experts and process architects at IPS will again be organizing technology tours to assist you with where to start your project. They will provide introductions to the many new technologies in bioprocess that are shaping future manufacturing environments for drugs that will occupy humans.

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The Flexible Filling Line: The Crossover Vehicle for Aseptic Manufacturing

Paul Valerio, IPS-Integrated Project Services

People want it all, don’t they?  The type of cars many drive is one indicator.  Crossover vehicles have become a very popular vehicle segment.  They offer: practicality while still maintaining a cool factor; spaciousness with decent fuel efficiency; and car-like handling with the safety of all wheel drive for slippery conditions.  In much the same way, parenteral manufacturers are seeking availability of filling lines to do the equivalent of the routine drive to work, as well as the weekend camping outing on the unpaved road.

Flexibility has become a strong business driver, especially for clinical and small scale operations.  Having the ability to fill vials for liquid or lyophilized products, as well as filling syringes and cartridges all on one line, enables clinical operations to support product pipelines and contract manufacturers to handle whatever small manufacturing requests may come their way.

As we saw during the IPS Interphex tours in 2014, equipment vendors in recent years have made significant progress in developing their designs for flexible filling lines.  It is an exciting time when some of the first lines are being validated.  Increases in orders and inquiries for new lines are proof that flexible configurations will become more of a standard offering and are here to stay.

Flexibility is a good thing but we know that, like the crossover vehicle, a flexible filling line may not offer sports car performance or the ability to plow through a foot of snow with confidence.  Some important points to understand when considering a facility with flexible technology include:

  • Most designs today are using nested, pre-sterilized components in tubs. Vial suppliers have started offering the most common vial sizes but are still catching up with the full size range.
  • It is not feasible to perform 100% check weighing on systems that maintain vials in the nested format, similar to syringes.
  • Designs with most flexibility usually end up bigger and more expensive.

As with any solution, it is important to understand the benefits and challenges of flexible filling technology.  The good news is that several quality vendors offer sound solutions.

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