Beating the Serialization Clock

By: Optel Vision

By 2019, 80% of the world’s medication supply must be serialized, but only 30% of pharmaceutical packaging lines are currently equipped with serialization capabilities. This looming deadline ─ November 2017 in the US ─ is an enormous challenge for the entire industry, as the serialization process is a lot more complex than it initially seems.

Although the basic steps (printing codes, reading them, verifying them and ejecting non-compliant products) are relatively straightforward, that’s just the beginning. When we take a closer look, we realize that the difficulty lies not within the serialization operations themselves, but within everything and everyone required to make it happen on a daily basis. Main stakeholders include packaging, the warehouse, label control, validation, logistics, and many others, so the project can get very big, very quickly. This, of course, is in addition to the individual requirements of each packaging line and the numerous IT connections to a variety of systems, because all the data collected from the lines (like EPCIS reports, serialization results, e

tc.) must be reported to a database.

Meeting all these requirements takes time, not to mention a substantial budget, which can be yet an additional obstacle. Considering the currently low percentage of serialization-ready lines, many pharmas and CMOs might not make it in time for the deadline if they opt for a full-fledged custom system. Yet all these requirements still demand a highly adaptable solution that can be implemented in time. In response to this issue, some serialization partners have put together a line of preconfigured units, specially designed to be delivered before the deadline.

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Meeting Today’s Product and Personnel Protection Industry Requirements in Fill-Finish

By: BOSCH Packaging Technology

While today’s aseptic filling applications increasingly require the protection of both the product and personnel with elaborate air handling systems, automated decontamination processes, and the latest safety features, the growing need for specialized medicines produced in small batches means that efficient manufacturing systems also need to be flexible with short changeover times.

At this year’s INTERPHEX conference, and also part of the IPS Technology Tours (Aseptic Full-Scale & Flexible Technologies track), Bosch Packaging Technology will be presenting a case study on its FLT 1000 vial filler with Isolator, an offering designed to meet today’s increasingly challenging needs in fill-finish by providing a complete range of infeed and outfeed options to cover the wide variety of vial sizes, materials, and configurations (glass, plastic, and RTU components) handled.

Filling lines require competent management of the interaction between filling machine, barrier system, and preceding and subsequent machines. Challenges include the safe functioning of the interfaces, the simplicity of the overall controls system, and the ease of operation of the individual components. Interface resolutions between different manufacturers are often risky and time-consuming, and can delay projects by weeks, the start-up of individual subsystems failing to provide assurance that they will work properly together. The delivery of all components from a single source: isolator, machines, and processes from one provider, developed together and for each other, significantly mitigates these risks.

The Bosch FLT 1000 with Isolator fully integrated solution is a product of the close collaboration between three Bosch global sites: Bosch Minneapolis (filler technology), Bosch Crailsheim (filler and barrier technology), and Bosch affiliate Klenzaids in India (barrier technology and cost-effective manufacturing). This illustrates the depth and breadth of in-house technologies and capabilities that are necessary for adequate concept planning and successful implementation of today’s complex pharmaceutical fill and finish projects.

 

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A milestone in packing material and process development

By: Bausch + Stroebel

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KCP: The potential of this equipment has by far not been exhausted yet

With the KCP Bausch+Stroebel took the next evolutionary step into automation. Having a flexible filling platform with four configurable modular processing stations, our customers can simulate a variety of different industry standard dosing, closure placement, sealing, and inspection arrangements currently used in commercial production of parenteral products.

With two clean room robots, the filling and closing machine provides a wide range of applications for small batch production or process and product development. Virtually any customary container (vial, syringes, and cartridges; plastic or polymer or glass) can be processed on the line with minimal changeover time. Completely different work steps can be integrated in the work flow.

Up to four work stations can be integrated in the KCP as required and can easily be customized by the operating staff. To support cGMP traceability requirements and batch record documentation, Bausch+Stroebel has developed a system to verify if the selected size parts at the HMI match the size parts that are installed on the machine (HMI-prompted recipe verification of the size parts).

The two aseptically designed robot arms never cross between the laminar airflow from the RABS and an open container. They are always below the open containers, thereby ensuring first air is never broken by robot processing activities. The KCP is compatible with a RABS or isolator installation with optimized air flow verified with detailed Computational Fluid Dynamics studies (CFD).

The KCP is capable of testing the handling of a broad range of packaging material, such as plastic or glass containers (vials, syringes, cartridges), coated, siliconized or uncoated stoppers and plunger closures.

Furthermore, the KCP provides the possibility for In-Process Control (IPC) of up to 100% of the production batch or at regular predefined intervals, thereby ensuring documentation compliance of batch data.

Our customers are therefore in a position to evaluate all possibilities and risks during process development prior to production. Thus, they optimize packing material composition and product compatibility, thereby ensuring troublefree production and absolute process reliability.

The filling, stoppering, crimping and control technologies on the KCP are fully scalable to other high speed production lines. All batch parameters are transferable and applicable to high speed production.

Furthermore, a big advantage for our customer is to have that knowledge and testing possibilities at their site.

With the KCP, Bausch+Stroebel can supply an extremely flexible filling and closing machine for comprehensive development and small batches (the model at the Interphex can process up to 1,000 containers per hour).

High flexibility and time saving are the advantages for the user of the newly developed KCP.

The KCP5060 gives ultimate flexibility to test any packaging material configuration provided that the appropriate change parts are installed. Our best example of the breadth of flexibility available is the custom KCP5060 purchased by West Pharmaceutical Services. West is currently testing 7 different containers (vials, syringes and cartridges), 21 different closures (stoppers, seals, caps), 5 filling and closing processes (rotary piston, time/pressure, peristaltic, sensor filling, and vacuum filling and closing) in 98 different configurations (bulk feeding and RTU components) on their KCP. The range of processing sequences the robot-equipped KCP is able to cover is enormous. However, the full potential of this equipment has not yet been realized. New applications are continuously identified and the system can be expanded at any time for additional future processing capabilities.

Erik Anderson, Principal Product Development Engineer from West Pharmaceutical Services states how the KCP is applied at West and how it enhances the product development life cycle:

“To characterize the performance of all fill finish process variations as well as all closures, seals, vials, cartridges and syringes (commercial and prototype) requires the use of an extremely robust, innovative, and flexible filling platform. After much scrutiny via a West user requirements matrix vetted against a wide range of well-established OEMs, this project was ultimately awarded to Bausch+Stroebel because of their ability to meet the majority of user requirements, innovative culture, track record of proven performance, and technical competency.

Since project inception, multiple challenges have been overcome, processing capabilities have increased, and new applications for the use of this custom filling platform have been identified. Some of these applications include performance characterization of containers and closures, machinability performance evaluations, and testing of novel fill finish process improvements. West is very pleased with the progress to date with Bausch & Stroebel and is looking forward to continued success.”

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Cell Therapy: Process Commercialization Considerations

By: Erich Bozenhardt
Process Engineer
IPS-Integrated Project Services, LLC

Would you pay $93,000 USD to extend your life by four months and would you relocate to one of the handful of treatment centers in the US for that therapy? Questions like this continue to propagate. Innovative and effective cell therapy treatments are advancing in the R&D pipeline, but costs and logistical challenges have been limiting the commercial success of the select therapies that have been approved. The considerations on the road to commercialization for cell therapy take on a higher level of complexity than those for biopharmaceuticals. For example, cold chain logistics moves from refrigerated cases of finished product handled by a distributor to shipping individual cryogenic units of sale. Additionally, new considerations come into play like administration through a medical device or a pre-conditioning treatment that are as much part of the process as the operations in a controlled manufacturing facility.

Some companies are betting on autologous therapies as the quickest and safest route. These therapies challenge us as an industry to deliver personalized medicine in a reliable and repeatable way. While the immediate goal might be successfully completing clinical trials, developing the process for scale-up and automation early on is critical to future successes. Removing operator variability by automating manipulations is one consideration. This can be a simple jig or the process could utilize a fixed bed culture technology that has an existing scale up/automation solution like a NuncTM Cell FactoryTM or Miltenyi Biotec Prodigy®. Developing the process to use closed systems can reduce the clean room space required, as well as the cross contamination risk. Gaining a deeper understanding of culture needs and how to meet those needs without a conventional incubator can also help the commercialization. Moisture loss concerns through vent filters and CO2 control have kept several processes locked into manual operations since the culture must be loaded into a reach-in style incubator.

During the development of the process for scale up and automation, logistics need to be considered. A Fenwal AmicusTM collects and processes the donation so that the desired fraction can be shipped frozen with a significantly longer allowable storage time versus a refrigerated whole blood donation.  As those donations arrive at the manufacturing facility, the management of what will become individual lots needs to be established. Barcode readers have been standard for a number of years and workarounds have been identified for frost over issues; however, cryogenic capable RFIDs can provide a simpler solution.

While autologous therapies provide a straightforward means of patient safety, specifically addressing graft versus host disease, researchers have developed allogeneic cell-based therapies that sufficiently address the safety concerns. Allogeneic therapies relieve some of the logistical complexity as a lot can provide therapy to many patients. Although donation logistics can be complex if the number of cell expansions are limited, requiring new donor material for every batch. Induced pluripotent stem cells (iPSCs) have the potential to allow for a traditional cell banking approach on human stem cell based therapies. Some allogeneic therapies take a different approach and utilize bacteria for cell therapies. One of the common commercialization considerations for all types of allogeneic therapies is the development of the culture to use microcarriers. Culturing on suspended microcarriers instead of 2D bioreactors significantly reduces the cost of goods and capital cost of the facility.

Cell therapies have the potential to open new treatment options for numerous diseases. Our industry needs to position those processes/products for long-term success by reducing the cost to patients and developing logistical solutions. Holistically developing the process for scale-up and automation across the process of making and administrating the therapy will drive down the cost and improving logistics for cell therapies.

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In Bioprocess Design Form Follows Experience

By Carl Sexton
Sr. Process Architect, Associate
IPS-Integrated Project Services, LLC

When American architect Louis Sullivan famously proclaimed that “form should follow function” in 1896, I’m sure he had no idea of how this statement would impact the world of design and architecture forever. Sullivan was referencing his idea that a building should serve a greater purpose.  Ultimately that purpose should dictate how the building should be designed.  This was a revolutionary idea at the time as traditionally the job of a well-trained architect was to make sure that buildings adhered to the distinct style it was designed to replicate.  The function of the building was of less importance as long as it “looked the part.”   While traditional classical architects reviled this statement, modern architects embraced it and it would be the rallying cry for modernist design for a generation of young designers and would change the face of architecture and design way into the 20th  and 21st century.  At this time the industrial revolution was just getting going.  Large scale manufacturing was still in its infancy.  How could he possibly know that his statements would impact not only residential design and urban development but manufacturing for the next 100 years?

In the current climate of design in today’s biopharmaceutical industry, Louis Sullivan’s statement is more relevant than ever.   Our clients are constantly pushing us as designers to execute projects faster, cheaper and as always the quality of the design must improve efficiency.  As process architects, we navigate these waters with our zest for problem-solving, our creativity and above all our experience.   It’s the experience that sets us apart from scores of talented designers.  However, it is our experience with new technologies that needs to drive design forward.  In the ever-expanding worldwide marketplace, new technologies and processes are emerging daily.  As industry professional, we need to be technology leaders.  We need to expand our outlook about tradition design methods and embrace new ideas so that we can push our clients and our designs far into the exciting future of biologics manufacturing ahead.  Then and only then can we truly claim that our processes are driving the design and in the truest form adhere to Sullivan’s famous quote.

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Pharmaceutical Serialization: Looking beyond Regulatory Compliance

By: ACG North America

Counterfeiting of medications is a major problem faced by the global pharmaceutical industry. As per the WHO estimates around 30% of the medicines sold in developing countries are counterfeit.[i] Owing to globalization, the supply chain for medicines has become lengthier with every step offering another opportunity for counterfeiters. As a result, global track and trace requirements have become stringent putting tremendous pressure on the supply chain’s transparency.

Using Serialization as a Business Strategy

The pharmaceutical companies do believe that counterfeiting can be reduced significantly by implementing product serialization. However, serialization requires a comprehensive system to track and trace the passage of prescription drugs through the entire supply chain. Therefore, serialization is often looked upon as an effort and cost-intensive process and often a regulatory mandate. However, pharmaceutical companies are now increasingly adopting a strategic business view for overall adoption of serialization. They have started developing packaging and information technology to not only ensure regulatory compliance, but also use this for their own business gain: safeguarding brand reputation and ensuring patient safety to name a few. Serialization and traceability can also be used for effective management of the supply chain and management of medicine inventory at wholesale and retail levels.

The following are some additional benefits that companies can reap by implementing effective serialization processes:

Protecting brand reputation

Counterfeit drugs pose a huge risk to pharmaceutical companies. It not only affects potential sales, but also leads to deterioration of brand reputation and brand value. Brand reputation is of utmost importance for the pharmaceutical industry, as compromised drugs can potentially harm the patients’ health. Therefore, serialization and traceability allow pharmaceutical companies curb counterfeiting and protect the brand image.

Improved processes

Serialization and traceability can standardize and harmonize operational processes in across manufacturing units, warehouses and distribution hubs, resulting in smooth operations. It also assists in scanning and removing expired, faulty or damaged product, ensuring that only genuine product reaches the consumer. Further, it helps manufacturer by preventing revenue loss occurring due to recall of faulty or damaged product.

Ensures better control over parallel trading

Parallel trading is when goods are bought in low price and sold in the market when their price increases. This is considered as an illegal process in certain industries where the cost of the product is a cumulative of the actual cost and additional import and export taxes. Track and trace is quite useful to curb parallel trading.

Serialization is a cost-saving exercise

Serialization and track and trace projects are often perceived cost-intensive exercises owing to complex serialization framework and equipment handling. However, pharmaceutical companies often tend to overlook the amount of revenue lost due to counterfeit medicines that serialization projects can help curtail. Currently, the global counterfeit drug market allegedly makes for approximately USD 200 Billion.

Serialization also helps eliminate manual errors, such as incorrect entry of GTIN or batch numbers (prevalent in manually operated machines), that are linked with loss of productivity. Furthermore, loss of time due to human intervention adds to the loss of production and revenue. Automation in the serialization machines can minimize the loss of productivity.

In conclusion, an efficiently implemented serialization and traceability processes can offer benefits that are beyond regulatory compliance. Serialization and traceability processes can be complex to develop and implement. However, there are companies that have experience in both pharmaceutical and inspection technologies that can smoothen the process and ensure cross-country regulatory compliance. It is essential for particular pharmaceutical companies to partner with trusted and experienced solutions provider to achieve successful serialization and traceability.

ACG provides a comprehensive range of serialization and track and trace solutions that help you get ready to meet the global serialization demands. The innovative machine vision systems of ACG are designed to inspect quality, while helping maintain traceability and eliminate possible loss of revenue & reputation.

[i] Bansal D, Malla S, Gudala K, Tiwari P. Anti-Counterfeit Technologies: A Pharmaceutical Industry Perspective. Scientia Pharmaceutica. 2013;81(1):1-13. doi:10.3797/scipharm.1202-03.

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Is Continuous Manufacturing Really New?

By Ed Godek
Manager, Process Technology
Glatt Air Techniques, Inc.

Some 25+ years ago, I graduated from college with a Chemical Engineering degree, armed with the knowledge of process modeling, flow sheet analysis and statistical process control…important skills for continuous manufacturing in the chemical industry. At that time, I chose to venture into the world of Pharmaceutical Manufacturing for a career and found one.  Unfortunately, the industry was rigidly stuck in a world of batch manufacturing.  It was almost like we just took the unit operations from the old compounding pharmacists’ benches and made them bigger, while adding technology from the food and baking industry.  Not as cutting edge and revolutionary as I was hoping for.  Fast forward to the present.  We are finally trying to move the Pharma Industry into the world of Continuous Manufacturing at the urging of FDA and other Regulatory agencies.  It is a known fact that the ability to manufacture product of a very high quality hinges on complete process understanding, the ability to analyze the product “in-process”, and have the flexibility to adjust process parameters to maintain quality.  Sounds like the skills I once possessed 25 years ago.  We need to reach back into our engineering past to help bring us fully into the Continuous Manufacturing space of the future.  This is what we are trying to do at Glatt: to provide the best and most flexible continuous manufacturing systems in the industry.

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