Enhanced Wet Milling Technology for API Size Reduction

Active pharmaceutical ingredient (API) milling is a key step in many drug development processes. Traditional dry milling technologies (i.e. media mills, pin mills) used for this application have come under increased scrutiny due to yield losses, hygiene concerns, process train portability as well as physical property instability due to surface defects, amorphous phase generation, and more. Wet milling equipment such as high pressure homogenizers and media mills overcome many challenges associated with dry milling, but are still restricted by low capacities, high energy consumption and frequent maintenance requirements. Continue reading

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Production of Polymer Nanoparticles Using a Microfluidizer

Over the last decade, biodegradable polymers have been of increasing interest due to their many benefits.  These benefits include the ability to deliver a combination of varying therapeutic ingredients, the capability to include targeting moieties, and to protect APIs from degradation, as well as controlled release and terminal sterilization via filtration.  The Microfluidizer™ has been widely accepted as an ideal technology for the generation of polymer nanoparticles. Continue reading

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Modern Press Technology

Tablet press technology is evolving as rapidly as the speeds at which the presses themselves are capable of running. While the old, industry assertion that “all presses make tablets in the same fashion” does have a kernel of truth to it, the real truth is that press manufacturers are, to an ever-increasing degree, engineering technologies and features that are truly novel. Continue reading

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The VarioSys® Evolution Continues –

It all started in 2013 with Boehringer Ingelheim (BI) requesting a flexible filling line for high value parenteral biopharmaceuticals.  BI contacted Bausch+Stroebel and SKAN and asked for us to team up and to meet the following requirement:  Design and build the first of its kind highly flexible portable filling skid to fill various containers in a pre-sterilized configuration (syringes, cartridges and vials) with the filling operation taking place in an isolator, different from the traditional way of thinking with individual filling and closing machines installed permanently in an isolator for each type of container.  Further, BI requested for the line to be cost effective with a small footprint to keep facility costs to a minimum.  A challenge, to be sure!  Continue reading

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Modularization Process in Project Delivery (Part III)

By Gene Martini, Design Vice President – IPS

If you read the first two installments of this series, you know that we are discussing the process of modularizing the delivery of a pharmaceutical facility. We want to avoid recursion; we want a process that builds in proven modularization concepts from the beginning.

The key to this process lies not in its steps but in the structure of the organization executing it. To optimize modularization, an Integrated Project Delivery (IPD) approach is required.

Traditional project delivery models separate the construction and CQV functions from the design function, as in design-bid-build, or restrict the owner’s involvement with the process, as in design-build. In IPD, all of the required skill sets are deployed on the project as they are needed and in collaboration, and if the entire project team has strong experience with Life Sciences Industry facilities, the combination of deep specialization and timely application yields the most efficient project execution.

In the IPD model, the owner and design professionals collect and document requirements and constraints and develop a conceptual design. On completion of the concept, procurement, construction and C&Q professionals are added to the team to develop and evaluate modularization options. The expertise applied by these team members is required to estimate the cost and schedule impacts of different options without incurring the cost to the project of fully developing those options. As the advantages of specific modularization approaches become apparent, the IPD team adjusts the course of the design and execution strategies to fully exploit these decisions.

IPD presents certain procurement and contractual challenges to the owner. However, throughout the course of an integrated project delivery, the owner is fully engaged, understanding the costs and benefits of each modularization decision, and fully supported by all of the expertise required to deliver the specified quality at the lowest possible cost and in the prescribed time.

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

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

By: Tom Piombino, Process Architect – IPS-Integrated Project Services, Inc.

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.


INTERPHEX

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Going with the Flow: Ensuring Integrity of Single-use Systems

Helene Pora, Vice President of Single-Use Technologies
helene_pora@europe.pall.com

Going with the Flow: Ensuring the Integrity of Single-use Systems

Single-use technologies for formulation and filling have revolutionized the clean manufacturing of small molecule and biologic pharmaceuticals, cutting costs and making production lines simpler, safer and more cost effective. However, these single-use systems can be damaged during storage, installation or use. To protect the end users, and give them confidence in the system, manufacturers need a simple, robust and reliable point-of-use test, confirming that there are no leaks before and/or after use.

There are a number of key user needs for a point-of-use leak test:

  • It needs to be simple to fit and must maintain the sterility of the system
  • It should be fast, so that it doesn’t hold up the manufacturing process
  • It should have a small footprint, so that it does not affect the layout of the production line
  • It should be flexible, in order to be able to test all configurations of systems
  • It should be validated and comply with CFR21 part 11 for audit purposes

Pall’s Palltronic Flowstar LGR test instrument, specifically designed for use in the vaccines, biotech, and pharmaceutical markets, meets all these criteria. It allows true point-of-use leak testing of single-use systems up to 200 L, including testing the integrity of the filters within the system, in only around 15 minutes. It is small and easy to use, and can be connected into the single-use systems via Stäubli fittings without breaching the sterility, and without the risk of additional handling.

The flexibility of the Palltronic Flowstar LGR test instrument means that it can test single-use systems with and without biocontainers, using air or nitrogen (for oxygen-sensitive applications). Their different test pressure increases its sensitivity, with high-pressure tests for simple tubing sets, and low pressure for 3D and 2D biocontainer systems. Finally, the test instrument is fully validated and CFR 21 part 11 compliant with a full audit trail. It allows end users to test endless configurations of single-use systems and filters, with a single test device.

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