Home runs are getting harder to come by in the pharmaceutical industry and drug makers know it. Innovation writ large for Pharma used to mean funneling, stadium-filling amounts of money into research and development (R&D) efforts tied to finding the next blockbuster therapy and afterwards, reaping the rewards of its patent-protected profitability. For most of Pharma’s history, those successes fueled even more profligate research spending, dollars which not only financed the development of new winners, but also plenty of losers as well. But in the wake of patent expiries (and an ever-shrinking pool of large-class disease categories), this “Blockbuster Quest” business model’s being traded for a leaner, more cost-effective R&D and manufacturing strategy designed to focus drug discovery efforts and accelerate the time it takes to get a solid hit, take it around the bases and score a run.
Gaining such competitive agility is increasingly coming from the Pharma industry’s technology and system suppliers. These companies are fielding some pretty impressive players to support big-league Pharma-style innovation. Fortunately, innovation is a competitive driver for Pharma technology providers as well, and their R&D efforts continue to deliver game-winning solutions ready to drive costs out and efficiencies in to drug manufacturing operations. These innovators deserve to be recognized. What follows are this year’s All-Star Innovators: technologies and systems introduced within the last 12 months that, based on their relative applicational and technical merits, were selected by Pharmaceutical Manufacturing’s editors and reviewers to be on this year’s All-Star Roster. Just like in the big leagues, each player, er, product is highlighted by its own card, complete with performance and other stats. What follows are excerpts from those cards, but to view them in their entirety visit our All Star Locker Room. For now, though, take your seat, grab some peanuts and find out which ones might have the potential to be on your team.
ANALYTICAL AND MONITORING DEVICES
Cobalt Light Systems’ RapID developed its competitive edge via its patented Spatially Offset Raman Spectroscopy (SORS) technology, which permits a high-quality Raman spectrum to be measured through the thick, unopened layers of packaging. Most players know significant time and resources can be spent on verifying the identity of raw materials. Accurate ID of these materials is essential, but time consuming, expensive and resource intensive. RapID allows ID through unopened plastic containers for growth media and brown glass bottles for sterile liquids. According to Cobalt, sacks of lactose can now be identified through a multilayer paper sack in 20-30 seconds without needing to open or sample the sack.
Most understand that if you have a player who can execute on fundamentals a little bit faster and more accurately, it’s likely it can make a winning contribution to an optimized process strategy. GE Power & Water’s got one, the Sievers M9 Total Organic Carbon (TOC) Analyzer. Designed to measure TOC in a broad range of samples from ultrapure water to process waters, the M9 is able to measure TOC and conductivity simultaneously, and provide accurate results in only two minutes.
Prozess Technologie developed an interesting approach that drives a bit of complexity and a lot of cost out of spectroscopic measurement with its REVEAL Measurement Appliances. This in-process spectroscopic measurement tool confirms blend conformity in real time and is easily deployable at a price that is well below industry norms. The company refers to its devices as “appliances” because unlike other measurement platforms, the unit is a single measurement device, eliminating the need for labs and scientists while delivering an accurate measurement for batch-based and continuously processed compounds. REVEAL is designed to work in virtually any manufacturing environment including hazardous materials and provides data that is accessible anytime via wired and wireless methods.
Need a player who can deliver material ID wherever it’s needed? Rigaku Raman Technologies has one ready to run the base line. Its Progeny Material ID Handheld system offers bench top analytical performance in a rugged, ergonomic and IP-68 sealed enclosure. Progeny’s fully customizable workflow software is 21 CFR Part 11 compliant, and its fast quad-core processor manages demanding search and quantification algorithms without requiring remote desktop work routines. An innovative 512-pixel InGaAs detector delivers improved resolution, analytics and signal to noise, handling the most challenging mixture analyses.
Improving HPLC/UHPLC method development productivity is an optimal strategy to speed drug development operations. Shimadzu Scientific Instruments introduced its Nexera Method Scouting System at Pittcon 2014, where it was recognized as a stand-out performer. Equipped with two pumps — each with a quaternary valve — Shimadzu’s system allows analysts to run binary gradients with 16 different solvent pairs. When combined with a robust, high-pressure resistant column selection valve, which holds up to six conventional or UHPLC columns, the system can investigate up to 96 unique separation conditions per sample. A transfer program allows ultra-high-speed conditions to be transferred to conventional conditions, making the system suitable for both R&D and QA/QC applications.
Waters ionKey/MS System integrates UPLC separation into the mass spectrometer for improved sensitivity and unparalleled compound separation and detection — something that reduces solvent consumption and costs and simplifies the user experience. Containing fluidic connections, electronics, ESI interface, a column heater, eCord Intelligent Chip Technology and 1.7 micron UPLC grade particles packed inside a 150 micron I.D. channel, the ionKey/MS System was Merck Beta tested revealing a >60-fold increase in sensitivity for GLP-1.
AUTOMATION CONTROL AND SENSING
Endress+Hauser continues to intervene at critical points in manufacturing and process control and data environments, and its CM44x Liquiline Multichannel Transmitter is a strong individual contributor to processing trains via EtherNet/IP. One CM44 transmitter in play allows access to many parameters and accepts inputs down to the sensor level, including sensor condition and diagnostics. Traditionally, devices measuring and controlling process variables rely on a process instrumentation network to transfer data, while other devices within the plant work on a completely different network. By improving this complex, multi-tier networking strategy with one standard network architecture — EtherNet/IP — users have better access to real-time information. This improves the ability to monitor overall performance, troubleshoot out-of-margin conditions and minimize downtime.
Diverse pH and ORP sensing applications across Pharma and chemical process system piping require a tough and smart player to get the job done. With its rugged Ryton body material, Georg Fischer Piping Systems’ DryLoc Sensors deploy a positive connector system to indicate a solid, water-tight connection and resist moisture/dirt intrusions. The sensors mount into standard Signet 0.50-inch to 4-inch fittings as well as into GF tees and reducing tees of ¾ inch or larger. The installation versatility makes virtually any manufacturer’s sensor simple and easy to replace when coupled with the Signet 2760 DryLoc connector, which can hook up to other manufacturers’ instruments.
Often innovation comes from understanding there’s a gap and filling it. ASI Life Sciences engineers understood that without an available high-capacity, single-use heat exchanger, manufacturing engineers were being forced to choose one of two sub-optimal options: Insert a stainless-steel heat exchanger along with its incumbent CIP/SIP infrastructure or use a jacketed mixing tote or similar technology as a stop-gap solution. Certainly not ideal. ASI’s DHX Single-Use Heat Exchanger now offers a purpose-built solution by combining the heat transfer properties of a high-capacity plate and frame heat exchangers with the advantages users can leverage from its single-use configuration. ASI’s system offers advantages for cell culture at the manufacturing scale, allowing engineers to build temperature control into their process without having to sacrifice the benefits of single-use.
On deck last September and already bringing efficiencies to downstream single-stage clarification are EMD Millipore’s Clarisolve Depth Filters. With higher titers coming from today’s upstream bioreactors, conventional approaches have posed a challenge to clarification, that is, until now. Clarisolve depth filters eliminate the need for centrifugation, which enables implementation of a fully single-use process train and reduces pre-use flushing requirements. This technology was developed to address the shortcomings of traditional downstream clarification approaches when processing high cell density and high-product titer cell cultures.
Any process operation is likely well supported by automating manual tasks. Parker domnick hunter offers its SciLog SciFlex Filter and Dispense System, a downstream solution that automates final bulk filtration and container filling, a step previously performed in a manual fashion within a vertical laminar flow cabinet. The system can perform manual filtrations, constant pressure, constant flow rate or the company’s R/P Stat Method, a hybrid method that maximizes filtration capacity. Playing for Fujifilm Diosynth Biotechnologies, the installation of the SciFlex Filter and Dispense System into the company’s cGMP manufacturing was a critical success factor in achieving compliant, right-the-first time manufacture of biologic pharmaceuticals, according to the biotech firm.
Single-use systems rely most on the disposable vessels at their heart, and Sartorius Stedim Biotech has developed its Flexsafe Single-Use Family of scalable range bags to perform better. Flexsafe enables the implementation of single-use bioprocessing throughout all steps of drug manufacture using a single polyethylene film. The innovative concept addresses key industry requirements for future-proof single-use manufacturing of commercial vaccines and drugs. The optimization of the resin formulation, the complete control of raw materials, the extrusion process and the bag assembly guarantee lot-to-lot consistent cell growth performance. Furthermore, batch-to-batch consistent extractables and leachables profiles support drug manufacturers throughout the entire lifecycle of modern biological treatments.
PACKAGING AND HANDLING
Glass ampoules, vials and other vessels have been on Pharma’s team a long time and possess many superior qualities. However, commercial-scale handling of glass in Pharma filling and handling operations is prone to create contamination issues from (relatively) rough handling. Garvy Corp.’s Infinity RX 36 Table Top Accumulator is a potential trade for traditional rotary table or turntable accumulators in product-handling environments. The Infinity RX 36 can out-feed products faster than a traditional rotary table and with less pressure and no damage, says the company, and requires the same footprint as a traditional rotary table while greatly reducing the pressure and noise associated with rotary table accumulators.
Hamilton Storage Technologies’ LabElite Benchtop Line offers users end-to-end, automated liquid sample processing, decapping, recapping and high-speed barcode reading. This innovator from Hamilton provides the market with the first system where users have the ability to positively identify the tube chosen for decapping/recapping and track it throughout the workflow. The LabElite I.D. capper enables labs to combine decapping/recapping and high-speed barcode reading within one device without additional user interaction. When sample tracking is not required, the LabElite DeCapper is ready for decapping and recapping tubes in 48-cryovial or 96-microtube racks. A new feature can automatically move the racks from portrait to landscape formats.
Process gas handling is often a critical control parameter, and the 544 Series IntelliSwitch IIv from CONCOA is designed to routinely switch between two gas sources without interruption. This team player offers reliable high-flow, high-pressure switching in the most demanding applications and environments. Economization software virtually eliminates liquid cylinder vent loss and substantially reduces residual return. Switching is actuated as inlet pressure falls below a user-defined point by means of a Web interface or a serial port. A server allows for remote monitoring and e-mail notification of events.
Conveying fragile, friable products to and from an operation along the line takes a player with a gentle touch. Flexicon Corp.’s Flexi-Disc Tubular Cable Conveyors have that touch able to move delicate pharmaceutical products gently, quietly and dust-free, horizontally, vertically or any angle with minimal space requirements. The conveyors are designed to integrate with upstream and/or downstream equipment that sources material from single or multiple locations and deliver it selectively to storage vessels, filling machines or other processing equipment. Flexi-Disc conveyor moves materials using high-strength polymer discs in 4- and 6-inch diameters affixed to a stainless-steel or galvanized cable. Systems can have single or multiple inlets and outlets, and convey over short distances or hundreds of feet/meters.
Attention to detail provides Bosch Packaging Technology’s Manesty TPR 500 Tablet Press an innovative edge. Built for commercial, high-volume line duty, Bosch’s press can produce more than 400,000 tablets per hour and features well-integrated components and an advanced HMI to deliver high throughput as well as reduced maintenance requirements. For instance, filling parameters can be reproduced to consistently support high-quality yields. To ensure the smooth delivery of tablets, its True Flow tablet discharge chute features a pneumatic gate mechanism and an optimized take-off angle, which the company says reduces product damage and increases output, especially with shaped/friable tablets.
Dosing compliance is an issue both Pharma and health care professionals are seeking answers for, and 3M is applying its vast materials and manufacturing experience to solve them. Its Hollow Microstructured Transdermal System is a patient-friendly intradermal delivery solution designed for difficult-to-deliver biologics and other therapies. Human factor refinements to the 3M hMTS include a textured grip and the capability for non-specific actuation. A cap protects the microneedle array, which patients simply remove, adhere to the skin of the thigh or abdomen, then press down to begin dosing. An audible click assures activation. The FDA-approved device is capable of delivering liquid formulations from 0.5 mL to 2 mL.
Achieving better performance per dose is something GlaxoSmithKline wanted for its FDA-approved type 2 diabetes drug and Novozymes’ VELTIS Half Life Extension Platform provided via its Veltis albiglutide technology that helps diabetes therapies achieve an extended half-life; patients are only required to inject their medication once a week. Veltis’ half-life extension platform is based on engineered albumins that enable manufacturers to define and optimize the therapeutic window of their drug candidate to help control dose frequency, dose quantity and improve drug tolerability. The platform also offers the ability to provide once-weekly, once two-weekly or once-monthly peptide or protein dosing.
West designed the SmartDose patch injector system technology to be a single-use system ready to deliver higher-dose volumes by injecting therapies slowly over a period of time. SmartDose can be pre-programmed and controlled to provide the optimal dosing rate because many injectable drugs currently on the market require repeated dosing and are intended for self-administration. West’s system is delivered in a single package; patients insert the cartridge into the device’s injector and adheres the system to the body. A push of a button inserts the needle and starts the injection, which is delivered over time, based on instructions entered by the drug company. Visible/audible indicators confirm operation of the system.
Hitting the field at Pittcon, Bio-Rad Laboratories’ KnowItAll ATR/IR and Raman ID Expert offer new technologies, says the company, that combine years of accumulated knowledge in the field of spectroscopy with advanced computational power to provide the fastest, most accurate answers possible to scientists identifying unknown infrared and Raman spectra. KnowItAll software offers users comprehensive solutions for spectral analysis, identification, search, data management and reporting. It supports multiple instrument vendor file formats and techniques including IR, Raman, NIR, NMR, MS, UV-Vis. Ready for cGMP and QbD-compliant operations, the spectral intelligence built into KnowItAll ATR/IR ID Expert, combined with the world’s largest spectral reference collection, provides a high level of expertise to any scientist.
Increasingly, mobile devices are bringing efficiencies to Pharma process and procedures, especially when it comes to paper-based SOPs in the lab. To help run down this issue and support mobile-device applications, BIOVIA, a brand of Dassault Systèmes (previously Accelrys) introduced Accelrys Capture at Pittcon 2014. Through a small mobile device, users can enter data quickly, find procedures and make instant procedural annotations at the bench without having to document changes outside the lab. BIOVIA’s technology helps ensure that laboratory data meets prerequisite requirements before being recorded, thereby reducing review time and rework loops. Automated compliance solutions include validation-ready wireless infrastructure, validation-ready handheld devices for tracking/tracing process-linked data and numerous instrument-to-procedure integrations running on handheld devices in regulated laboratory environments.
A hit at Spring Training, Biopharm’s BioSolve Process 5 process analysis and economic modeling platform provides insight that enables biopharma innovators to reduce manufacturing costs and make more informed process and operational decisions. Armed with data from a broad spectrum of sources, BioSolve Process can analyze a range of scenarios to support operations business planning, from building a business case for a fully integrated continuous biomanufacturing platform to the development of an integrated continuous purification process template for monoclonal antibodies.
Need a player who can deliver complete control over methods and SOPs from a single source, and one that combines SDMS, LIMS and LES into one integrated platform, and obsoletes paper-based systems? Thermo Fisher Scientific fielded its all-arounder Lab Execution System LES at Pittcon 2014 and is ready to play. The platform’s functionality is built on the Thermo Fisher Scientific SampleManager platform and is fully integrated with the newest SampleManager LIMS. It combines all the functionality and integration capabilities necessary to move toward a truly paperless lab, and lets lab managers automate their SOPs and methods, but with much deeper integration.
SUPPLY CHAIN TRANSPARENCY
TruTag Technologies’ TruTag microtags are inert, edible and can integrate into the fabric of a product, independent of packaging and labels, much like fingerprints. Millions of optical patterns can be embedded into a “TruTag,” which is a dust-sized particle less than the width of a human hair. It can be used for the authentication of food, drugs and other commercial/consumer products. A security platform that will help prevent counterfeiting, TruTag’s technology etches unique “spectral barcodes” into a porous silicon wafer. The codes can be measured via a portable spectrometer-based optical reader and can reference a label in a secure database, where more information about the item (including lot number, expiration date, date of manufacture, authorized customer, or country of authorized sale) can be stored as desired.
Imagine a labeling system that could provide seamless, wireless, near-field communications and data capture along with temperature and time sensing. Thin Film Electronics did, developing the Thinfilm Near Field Communication Smart Label. The platform is designed to handle a variety of sensing elements, both printed and conventional, and depending on the application, labels may be fully printed or feature a combination of printed and surface-mounted elements. Furthermore, Thinfilm’s Printed-dopant polysilicon logic allows Thinfilm engineers to significantly compress the cycle time for new designs.
WASTE STREAM AND SUSTAINABILITY
A solution that simplifies both resource management and a necessary operational chore in an innovative way is sure to find a spot on any team, in this case near a clean control zone’s locker room. CO2Nexus’ Tersus Cleanroom Laundering Solution enables simple, modular cleanroom laundry plants to be deployed virtually anywhere, liberating cleanroom garment end-users and service providers from the uncertainties associated with water availability, permitting, cost, validation and quality. Offering the world’s first CO2-based barrier (pass thru) system and the company’s cleanroom-specific process and chemistry, Tersus uses liquid carbon dioxide in place of water, 40-45 pound cleaning capacity, 30-minute cycle times, and 90-pound throughput/hour via an advanced control system.