Article | August 15, 2014

Scaling Up For Biopharmaceuticals

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New treatments for patients challenge manufacturers to ramp up production; solutions can be found at Pharma EXPO 2014

Biopharmaceuticals are at the forefront of medical research, and there is no doubt that demand is increasing for bio-based vaccines, hormone- and protein-based drugs, and gene- and cell-based therapies. Dallas, Texas-based research firm Market and Markets predicts the U.S. biopharmaceutical market will reach $144 billion by 2016, having shown 11.2 percent annual growth since 2009. However, the marked increases in development and commercialization, along with increases in production yield and efficiency, mean biopharmaceutical manufacturers face challenges in processing and packaging.

Packaging environments must be meticulously designed to safeguard sterility, drug stability and efficacy. Packaging must minimize potential drug interaction with machinery surfaces on the line as well as other external contaminants. With the goal of limiting or effectively eliminating direct operator contact with product and product contact parts, the U.S. Food & Drug Administration (FDA) favors a transition from traditional clean room environments and practices to isolator technology, and is expected to audit restricted access barrier (RABS) designs to ensure barrier integrity is maintained throughout the manufacturing process. Advanced fill-and-finish machinery enables highly accurate and repeatable sterile processes, assuring the assembled sterilized drug product and packaging are uncompromised by micro contaminants. Tertiary packaging must protect temperature-sensitive drugs during storage and distribution.

As a solution, manufacturers can look to syringe, cartridge and vial fill/finish machines flexible enough to handle multiple filling options and container formats and sizes, and suited to restricted access technology for minimizing human contact through cycles of washing, depyrogenation, filling, stoppering, and capping. Therapies targeted to patient subsets based on genotype give rise to small lot sizes and small overall volumes, placing machines and lines adaptable for high-product-mix, short-run production in demand.

Farther down the line, manufacturers are implementing multiple layers of overt and covert tamper-evident solutions at every level of packaging in efforts to secure the supply chain against counterfeiters. In addition to the security seals, labels and closure systems developed to make tampering with vial and syringe products easily recognizable, companies are also moving to implement track-and-trace solutions to prevent instances of diversion and enhance authentication.

The latest capabilities in aseptic fill and finish processes designed to support these trends in biopharmaceuticals will be featured at the inaugural edition of Pharma EXPO 2014 (Nov. 2-5; McCormick Place, Chicago). Co-produced by PMMI, The Association for Packaging and Processing Technologies, and the International Society for Pharmaceutical Engineering (ISPE), the new show will co-locate with PACK EXPO, to offer solutions for the pharmaceutical supply chain as well as manufacturing innovations for nutraceutical, medical device, and biotech manufacturers. Pharma EXPO attendees can also explore the show floors of PACK EXPO and find inspiration from other industries.

Efficient Syringe Processing

Aseptic packaging is a requirement for biopharmaceuticals that cannot withstand terminal sterilization methods after packaging. Ready-to-administer prefilled syringes which can be assembled into disposable auto-injection devices and with needle safety features have been favored as supporting easier and safer self-injection than traditional vial and syringe

Bosch Packaging Technology (Booth #W-603) has extended its line of FXS syringe filling and closing machines with the introduction of the FXS Combi for processing syringes in combination with vials and cartridges. The FXS Combi features an integrated capping station for vials and cartridges where capping takes place directly after stopper insertion.

“In response to customer demand for higher flexibility in a more compact footprint, we transferred the successful FXS concept to additional pre-sterilized packaging types. The FXS Combi is the first filling and closing machine of this kind with an integrated capping station,” says Klaus Ullherr, product manager, Bosch Packaging Technology.

As a low-to-medium output machine designed for quick exchange of format parts, the FXS Combi provides a fully automatic continuous fill-and-seal process suited for integration of Restricted Access Barrier Systems (RABS) and isolator environments. The Bosch ATO tub opener and ABO bag opener can be integrated for direct loading to the filling line of pre-sterilized, nested, and ready-to-fill containers shipped from the manufacturer.

An FXS Combi filling station with up to six dosing heads supports peristaltic, rotary slide valve piston pumps, as well as Bosch’s disposable PreVAS single-use filling technology, a pre-validated, pre-assembled, and pre-sterilized, single-use system which eliminates the need to disassemble, clean, sterilize, and reconnect filling components between batches.

At Pharma EXPO, Bosch will feature a PreVAS mobile filling station supporting efficient scale up from clinical batch to full production. A mobile PreVAS pump trolley situates the product bag outside of the isolator while filling tubes are compactly and safely guided through the isolator wall for connection to the filing station via a newly developed multi-tubing port.

Flexible Vial Filling

Vial filling machines geared for smaller production volumes feature versatile filling options in designs maximizing machine access and sterility assurance.

Dara Pharmaceutical Packaging, a manufacturer of machines for aseptic filling of syringes, vials, cartridges, and small containers, is exhibiting at NJM Packaging’s PACK EXPO booth (Booth S-2130). The Barcelona, Spain-based company has developed the SX-300Lyo in-line filling system for lyophilized vials and the SFL/S for filling disposable syringes in nest.

“Our relationship with Dara Pharmaceutical enables us to expand more into biopharmaceutical and biosimilar packaging, as we see it as the larger growth portion of the pharmaceutical industry,” says Tom Kessler, regional sales manager at NJM Packaging, the exclusive sales and service representative for Dara Pharmaceutical Packaging in the US and Canada.

For the SX-300Lyo, vials are typically delivered to the machine washed and sanitized in sealed trays. In small-to-medium-batch-size production they are manually loaded to a rotary feed table then automatically fed to a servo-controlled star wheel for fill, and partial stoppering. The machine handles up to 60 glass vials of 0.1 ml to 100 ml per minute, with peristaltic and rotary piston filling as an option.

Dara Pharmaceutical integrates laminar air flow and HEPA filtration technology and RABS or isolator systems for creating controlled Class 100 and Class 1000 environments over the machine based on customer request.

NJM Packaging, a packaging systems manufacturer and integrator for the pharmaceutical, nutraceutical, personal care, and food and beverage industries, is also exhibiting a full line of equipment at Pharma EXPO (Booth #W-503), including a print-and-apply machine integrated to an Optel Vision semi-automatic packing table for serialization of individual bottles, cartons, or bundles.

Marchesini Group (Booth #W-743), a manufacturer of vial, syringe and ampule filling-and-closing machines, tube fillers, blister thermoformers, labelers and cartoners, has developed the Stery-Capsy line for aseptic vial filling of small parenteral volume vials. The line integrates the Stery-LC filling and stoppering machine with the Capsy-LC closing machine for continuous processing in a compact foot print.

A balcony design with mechanical components segregated at the back in a vertical position supports easier maintenance and optimizes the installation of RABS, isolators, or protection hoods. The design enables high laminar air flow efficiency in filling through capping processes, cutting cycle times by 50 percent compared with conventional machines. Compact machine components support cGMP-compliant transfer of size-parts to the filling core or capping station through glove ports.

The in-feed scroll for arranging vials conveyed into the system by linear belt is driven by an independent  servo motor that can interrupt the vial flow such as for component loading. Vials are transferred from the in-feed scroll to belt-inserted pucks that keep the vials centered, visible, and exposed to the laminar air flow as they are moved by walking beam conveyor to filling, where peristaltic or volumetric pump filling parameters are programed for the application.

Vials are transferred directly to a rotary tower for stoppering, then to the capping zone where the continuous-motion rotary Capsy-LC ensures process repeatability with a proportional regulator and brushless motor controlling compression force, position and cap rolling speed.

PACK EXPO exhibitor Cozzoli Machine Co. (Booth #S-2541) will feature the Mini Monoblock for intermittent filling and stoppering of liquids or powders in vials in laboratory and clinical production environments with limited space.

Designed to accommodate a LAF hood and enclosure, the compact PLC-controlled unit handles vial sizes from 1 ml to 100 ml at speeds up to 50 vials per minute. A feed screw spaces and controls the vials for filling after they are delivered in single file to the monoblock from a rotary unscrambler. A missing-vial detector ensures the vial is present prior to product dispensing. Vials are filled with a standard positive displacement fill system or alternate free-standing diaphragm, peristaltic pumps, or volumetric powder fill system. Filled vials are transferred to a star wheel where they are aligned for full or partial stopper insertion with an inclined rotary stoppering head designed to reduce particle generation and enhance LAF effectiveness.

A Cartoning Option

In secondary packaging for parenteral containers, Körber Medipak Systems (Booth #W-683) is introducing the NeoTOP X, a new generation of Dividella top-loaded cartoners, which can be easily adapted for multipacks of up to 100 items or individual products such as sprays and inhalers.

As an alternative to traditional thermoformed plastic trays in side-loaded cartons, NeoTOP machines automatically erect partitioned cartons from flat paper board blanks with inserted fluted partitions that clamp and cushion the syringes, vials, pens, and ampoules. Package materials, pre-formed components inventory, space, production equipment, and cold chain shipping costs are all reduced, resulting in reduced packaging costs.

NeoTOP X can reduce package size further with the option to insert flutes transversely for a greater amount of product in a smaller package footprint. And with its toolless format changeover (20 minutes or less) and expanding feeding options, customers can respond quickly to changing market requirements as. An optional module prints, attaches labels, and applies Braille text to the blanks before they are passed to the erecting module.

Track And Trace

Pharmaceutical packagers planning to meet the package coding and tracing requirements of the Drug Quality and Security Act will find a lineup of track-and-trace solutions at PACK EXPO and Pharma EXPO.

These coding management solutions are integrated on packaging lines for transparent tracing of uniquely coded cartons, cases, and pallets at the line, plant and enterprise levels, as the pharmaceutical supply chain develops an electronic, interoperable system for tracking prescription drugs.

Mettler Toledo (Booth #W-776) CI-Vision will feature a track-and-trace solution encompassing serialization and aggregation from single cartons through pallet load. Scanning the code on the pallet reveals the codes for each individual carton in the automatic identification solution.

The process begins with the Mettler-Toledo PCE DMS XMV Marking and Vision System, which codes packages with ink jet or laser marking. A high resolution optical camera system immediately verifies code legibility and correctness at speeds up to 90 meters per minute. The company describes the DMS XMX as the most compact, complete package serialization solution available needing only 800mm of floor space.

The Mettler-Toledo PCE Advanced Bundle Station and Mettler-Toledo PCE Shipping Case Station are control units for aggregation and labeling of bundles of cartoned products and shipping cases respectively. Bundles and cases are marked by direct print or printed label with unique serial codes after cameras read, verify, and record the codes on packages associated with each package containment level.

Pilot Line Manager software manages the camera systems, code readers, sensors, and integrated printers as all lines at a production site are monitored and controlled from a single touch screen. Order, product information and customer data can be input manually, received from the Enterprise Resource Planning (ERP) system or from web services via a new open interface.

Quality With 'Zero Defects'

The provider of checkweigher, metal detection, and x-ray inspection solutions will introduce the Mettler-Toledo ProdX Advanced Connectivity Data Management Software System for centralized monitoring and control of inspection systems at one location or multiple sites. ProdX supports security as changes to product set ups on multiple devices can be carried out simultaneously. Productivity is improved as inspection data is made available in real time and on-demand. Companies can receive early warning alerts on non-conforming raw materials, product rejection, and maintenance requests, and plan maintenance at times of lowest production activity.

Over at the Körber Medipak (Booth #W-683), Seidenader is presenting the Seidenader CS, a compact automated inspection unit for liquid or solution lyophilized packaged drugs.

Ampoules, cartridges, and vials up to 100 ml fed to an inspection carousel with up to 40 servo-driven product positions are optically inspected by up to seven cameras for particles in the product and container cosmetic defects, at speeds of up to 24,000 containers per hour. A modular design enables customizing infeed and outfeed and the addition of high voltage leak testing, head space gas analysis, near-infrared spectroscopy and polarimetric glass stress verification.

Combined, Pharma EXPO and PACK EXPO International 2014 will feature 2,000 exhibitors span more than 1.1 million net square feet of exhibit space and attract more than 50,000 attendees. For more information or to register, visit www.pharmaexpo.com or contact PMMI’s Show Department: 571.612.3200 or expo@pmmi.org.

About PMMI
PMMI, The Association for Packaging and Processing Technologies, is a trade association representing over 650 packaging and processing supply chain companies that provide a full range of packaging and processing machinery, materials, components and containers. PMMI actively brings buyers and sellers together through programs and events such as The PACK EXPO family of trade shows, packexpo.com, PMT Magazine, PACK EXPO Show Daily, networking events and educational programs.

PMMI organizes the PACK EXPO trade shows: PACK EXPO International, Pharma EXPO, co-located with PACK EXPO International and presented jointly with the International Society for Pharmaceutical Engineering (ISPE); PACK EXPO Las Vegas, PACK EXPO East, EXPO PACK México and EXPO PACK Guadalajara, connecting participants in the packaging and processing supply chain with their customers around the world. Coming Up: EXPO PACK México 2014, June 17–20 (Mexico City, Mexico); PACK EXPO International 2014, Nov. 2–5 (McCormick Place, Chicago); Pharma EXPO, co-located with PACK EXPO International 2014; PACK EXPO East, debuting Feb. 16–18, 2015 (Pennsylvania Convention Center, Philadelphia); EXPO PACK Guadalajara 2015, March 10–12, 2015 (Guadalajara, Jalisco, Mexico).

Learn more about PMMI and the PACK EXPO trade shows at PMMI.org and Packexpo.com.

About ISPE
ISPE, the International Society for Pharmaceutical Engineering, is the world’s largest not-for-profit association serving its Members through leading scientific, technical and regulatory advancement throughout the entire pharmaceutical lifecycle. The 20,000 Members of ISPE are building solutions in the development and manufacture of safe and effective pharmaceutical and biologic medicines and medical delivery devices in more than 90 countries around the world. Founded in 1980, ISPE has its worldwide headquarters in Tampa, Florida, USA and offices in Frankfurt, Germany and Shanghai, China and is publisher of Pharmaceutical Engineering magazine. Visit www.ISPE.org for more information.

Company URLs:

Bosch Packaging: www.boschpackaging.com

NJM Packaging: www.njmpackaging.com

Marchesini Group: www.marchesini.com

Cozzoli Machine Co.: www.cozzoli.com

Körber Medipak Systems: www.kmedipak.com

Mettler Toledo: http://us.mt.com

Körber Medipak: http://www.kmedipak.com

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