20 years of automation

Companies have reaped large benefits in automating packaging lines and enterprises.

Higher production rates, improved efficiency, and lower operating costs are high priorities for all industries and life sciences packaging is no exception. Toward these ends, pharmaceutical and medical device packaging companies have automated manufacturing lines and enterprise-wide systems for insights on businesses’ performance.

In replacing manually performed functions with machines and using automated systems for process monitoring and control, packagers in 20 years have realized major gains in improved equipment up times, labor savings, and reduced incidents of human error.

“Where appropriate, automation can reduce costs by increasing speed and enabling automated inspection and verification of processes. Packaging can often be modified to allow for automation where an increase in packaging costs may be offset by increased productivity,” says Mel Bahr, founder of MGS Machines.

Emerging on pharma lines in the early 1990s, digital servo technology has enabled a level of control and flexibility beyond the reach of common mechanical drives and cam systems. With built-in Ethernet connections, packaging machines interface with plant networks and enterprises, yielding data for process improvement.

Automation has transformed pharmaceutical package inspection yielding benefits in lean operations and quality of finished goods. As sensors and cameras deployed on and beyond the packaging line advance efficiency, they also allay one of the pharma industry’s biggest worries: having a product misbranded out in the market place.

Primary and secondary packaging have been rendered automatic or semi-automatic for tablet, capsule, and bottle filling, and cartoning and bagging; tray packaging; label creation and inspection; vial and syringe filling and capping, and blister strip assembly for clinical trials. Programmable controllers monitor and coordinate the performance of line components within set ranges, automatically adjusting machine speeds to prevent product from building up or starving downstream equipment.

Automation milestones

2002—rommelag improves blow-fill-seal machine capacity and control with servo motors driving all major machine functions in Bottelpack BFS models.

2006—ATS Automation Tooling Systems develops the ATS Smart Vision Lyoscan inspection system for high-speed, single-pass-through inspection of lyophilized biologics and vials.

2006—Fargo Automation offers a patented robotic pack-off solution with a servo-driven reach-in device for use with FFS clip-chain machines.

2007—Advanced Scientifics develops the Automated Filling Machine, a stand alone unit for efficient low volume filling of premade bags with a sterile disposable filling system for aseptic filling.

2008—As an alternative to fully automated change over, Serpa Packaging Solutions offers Verified Changeover in which the machine monitors embedded change part sensors to verify that correct parts have been installed and positioned properly.

2009—ESS Technologies launches the high-speed Monoblock Filler/Capper for Micro-Tubes and Micro-Vials; standard features for precise control include a zero-play turret and servo-driven capping station.

2010—Pfizer automates bottle filling inspection with Optel Vision’s Slat Filler Inspector camera-based solution.

2011—Uhlmann Packaging Systems introduces the Integrated Bottle Center 120, a monoblock system for solid dose filling with features including 100% tablet count accuracy, shift register control and monitoring, and Uhlmann Track & Trace. For faster fill rates, the Uhlmann Integrated Bottle Center 240 was launched in 2012.

2011—MG America offers the Farmo Res Prima K7 Thermoformer for deep-draw syringe, vial, ampoule, and device packaging with Profibus motor monitoring system for making machine adjustments in cycle mode.

2012—The International Society For Pharmaceutical Engineering issues the first comprehensive guidance on design, construction, commissioning, and qualification of packaging, labeling, and warehousing facilities, with emphasis on a risk-based approach following Good Automated Manufacturing Practice (GAMP 5).

2012—Pharmaworks introduces all-servo-driven TF2 blister machine with features including direct-cooled tooling at the forming station and tool adjustment while the machine is running.

2012—Uhlmann Packaging Systems introduces the Blister Express Center 500 with integrated blister and cartoning machines, new Smart Control HMI, toolless change over, and integratable Uhlmann Track and Trace for inspection and tracking serialized blisters and cartons.

2013—Praxis Packaging Solutions develops primary fill and secondary packaging tablet bottling line with support for late stage ‘brite’ stock packaging. Synchronizable variable speed drivers on each machine enable efficient product flow for different pack outs.

2013—Rx Pharma Pack adopts the IMA Safe Uniline monoblock tablet counting line with IMA Safe SwiftPharm electronic counter. Shift register and positively controlled bottles pass a series of sensor-based inspections confirming product count and density with vision and bar code readers verifying label and codie accuracy.

2013—AFA Systems offers MK-DLT cartoner with integrated Delta robot, both controlled from one Allen Bradley platform.

2012—Weiler Engineering introduces the all–electric ASEP-TECH Model 628 blow-fill-seal machine with servo control on all machine motions.

2013—Baxter BioPharm Solutions launches new vial packaging line with automatic SCADA system control of variable data input and verification and 100% OCR/OCV inspection.

Faced with global requirements for unique coding of unit-level packaging, pharmaceutical companies most recently have developed line and company-level systems for serialization. These solutions will need to manage, apply, verify, and share voluminous amounts of data with a high degree of accuracy.

Machine control

Packaging machines have changed with the advent of servo technology and programmable PLCs and motion control systems. Single line shafts driving multiple functions are replaced by controllers managing sectionalized machines where local servo drives and motors perform discrete tasks.

Large panels covered with hard-wired circuits are replaced by PLCs, and more fully featured programmable automation controllers (PACs) with operator-friendly HMIs and interoperability with networks and enterprise systems.

Motion is rendered more tightly synchronized, shock and vibration is isolated, change over for different products requires less effort, and energy use is more efficient.

The advanced technology has been transformative, as MGS Machines’ Bahr describes:

“Thirty or 40 years ago an operator stepped up to a machine with a large operator panel filled with pushbuttons, “idiot” lights, and possibly a gauge or two. To start the machine, buttons, usually arranged logically, were pushed in sequence. While running you heard the clatter of relays in the panel. If you needed to change the speed you bent down to turn a hand wheel. Changeovers were accomplished by using a series of tools, loosening bolts, and adjusting a bracket to a scribe mark on a mating bracket. Changing lot and date codes was a manual type-changing process. As the machine was running, the operator would occasionally pull a product off the discharge and inspect it.

“Today the operator steps up to an HMI interface, logs in, and starts the machine with a single push of a button. The machine starts up in sequence automatically. You hear the quiet hum and hiss of servos running. The HMI provides data about the product you are running as well as operation and line conditions. Changeovers are started by pulling up a recipe on the HMI and entering lot/date code information. The changeover is done automatically with servo motors and/or a combination of hand wheels with digital readouts, possibly with feedback to the HMI. Inspection is automatic and every package is identified and verified.”

Older machines were robustly construction to withstand the forces exerted by mechanical systems, whereas modern equipment features lighter weight components, with electronic sensing to stop systems before damage can occur, Bahr says.

“Servos have improved packaging equipment tremendously because of the flexibility they offer in modularity in the design, change overs, and future conversion to new products. Machines integrated into a common control system with properly controlled smart technology can automatically adjust to conditions such as speed changes, product changes, and other line situations,” Bahr adds.

Along with easier adjustments and faster tool changes, today’s machines address print and seal registration.

“Newly loaded webs need to be registered when you pull the material forward through the machine. When machines stop and start such as during changeover or other line stops the plastic web shrinks when it cools. Using lasers that sense the position of the web we can employ active registration to sealing stations,” Ben Brower, vice president and sales director, Micron PharmaWorks said in 2009.

“There are a lot of gains to be made in the machine movement itself. Customers are looking for smart machines that employ self-diagnostics to make automatic adjustments,” Brower added.

Solutions have increased up time and production rates while vastly eliminating labor, with equipment integrated with common controls and with plant-wide systems.

In 2006, Sigpack Systems, of Bosch Packaging Technology, helped Warner Chilcott increase production of hermetically sealed birth control kits with an integrated line featuring the Sigpack HBL flow wrapping machine.

As carded blisters with birth control pills, wallet holder, patient insert, and desiccant are packaged together, a feeding control verifies the presence of each component, and adjusts feeding to the wrapper chain if any component is misfed. If sensors detect product located in the clamping area at the cross sealing station, a head with separate servo control doesn’t deploy and the pack is blown off the line. Reject and reject verification after filling and sealing ensure only correct packs go on to an integrated IWKA (Oystar) cartoner.

An Allen-Bradley ControlLogix controller is programmed to enable seamless operation of the wrapper with the line component feeders and downstream cartoner so the system acts in steady state within a tight range based on a given recipe housed in a MicroInnovation MC-2 HMI.

For a pharma firm hand-picking bottled product to cardboard boxes, packaging systems integrator R/X Automation Solutions partnered with Automated Packaging Systems to install an automated bag packing system that enabled material and shipping cost savings. Bags supplied on a roll are automatically pre-opened for operator insertion of the order, then sealed and printed. Except for operator product insertion of product and paperwork, each action is system controlled as conveyors feed product and paper work to the workstation, including bar code printing and verification of packaged materials.

Bosch’s Packaging Technology Division developed a bottle filling line for a customer with multiple different style applicators that had to be fed and inserted to a variety of different bottle sizes and configurations. An Allen Bradley Control Logix PLC controls all stations as bottles, applicators, and leaflets are staged, fed, and conveyed to an integrated Bosch CUC horizontal cartoner. Line component machines use Pack ML standard operating protocols and Ethernet communications to report their status to a single HMI screen.

Addressing efficient small-batch blistered tablet production, Losan Pharma in 2009 installed a Romaco Noack N 623 blister machine with integrated Promatic PC 4200 cartoner. A servo-based control system monitors the blistering at the sealing, perforation, and stamping stations. An adjustment system compensates for temperature-caused irregularities as a laser light barrier determines the position of the film and automatically moves the station to the required position. Blisters are passed on to a continuously working cartoner where folding boxes are grasped by servo-operated sucker arms and actively opened.

In form-fill-seal (FFS) packaging, turnkey designs featured integrated up- and down-stream equipment and advanced control systems. Multivac offered a horizontal FFS machine in a fully automated line with integrated labeler, 100% seal inspection, and Multivac robots picking product and inserts to the thermoformed cavities, removing non-conforming product, and stacking trays for final pack off.

“We consider the replacement of individual heat sealers with thermoform-fill-seal equipment to be one of the greatest impact areas for automation. Although we have a ways to go in product placement into cavities, the amount of labor spent in creating packaging has been greatly reduced by the utilization of Multivacs, Tiromats, and other TFFS machines,” says Nick Fotis, director, r&d , surgical and lab, Cardinal Health.

Robotics

The life science sector’s use of robotics has advanced as companies have become more comfortable with the technology.

Robots were embraced by a segment of the pharma industry in the late 1990’s when big pharma made a push to run factories with very little human interaction. In this scenario, robots would load the line with materials and components and then off-load finished goods when production had been completed, says Scott Wells, consultant, PharmAgility Consulting Group.

“There was a school of thought for which the holy grail was high-speed, high volume, and “lights out.” Some companies were striving for complete end-to-end automation from warehouse to production line and back to warehouse.”

“Some did manage it successfully but it did not become the new standard practice of automation that was once envisioned. In most cases using robotic material handlers in that manner proved either too costly to implement and/or too problematic to maintain efficiently. Industry kind of backed away. I think today we see a balance in technology with automated palletizers and conveyor systems that generate much of the same benefit that was being pursued through robotics back then,” Wells says.

Robots promise advantages in many applications. Companies handling a wide range of products and sizes can benefit from flexibly configured end-of-arm tooling. For those with a need for high speeds, robots perform with an accuracy that doesn’t fade.

Integrated robot control has enabled improved performance. Beckhoff in 2011 introduced a PC-based software platform that eliminates the need for a dedicated robot controller and handshaking routines among separate CPUs. Robotic and non-robotic motion is tightly coordinated from one controller and screen.

 “Manufacturers are trying to find ways to reduce production costs and provide a safer environment for employees. You are freeing valuable employees from repetitive-motion tasks,” observed Walter Langosch, director of sales and marketing, ESS Technologies in 2006.

ESS Technologies uses robots for device and diagnostic kit assembly, picking and packing vials from star wheels, case packing of tubes, bottles, and bags, cartoner in-feeding, and palletizing. In a solution developed with a Multivac blister machine, a FANUC robot performs loading, unloading, orientation, stacking, and cartoning functions.

Schneider Packaging Equipment Co. paired a Schneider case packing and palletizing system with a FANUC robot in a scant 120 sq ft footprint for a medical products company with tight space constraints. The robot presents closed and sealed cases to a print-and-apply labeler, label verifier, and on to palletizer.

For a manufacturer that was manually picking and cartoning blistered glucometer reagent cartridges, Fargo Automation built an intermittent-motion robotic top-loading solution for packing multipacks. Sensors signal the location of random flowing blisters on the conveyor as a four-axis robot picks and packs two cartridges at a time into two cartons. Product-specific calibration cards and leaflets are picked, verified, and top-loaded into the indexed cartons as bar coded components are verified. Cartons move to a custom-built checkweigher where bad boxes are auto ejected.

Plant floor

As machine automation benefited production, manufacturers reaped added efficiencies in plant floor documentation and control with manufacturing execution systems (MES) and electronic batch recording (EBR). Companies have reduced process deviations and documentation errors as operators document batch processes and results following the standard rule-enforced dialogs of MES software.

“The replacement of paper-based with computer-based control systems such as EBR has been a long journey. Compliance and validation pathways needed first to be defined and accepted before those solutions could be fully leveraged. Today, they are readily embraced as key elements to an effective automation and business optimization strategy,” PharmAgility’s Wells says.

Merck Serono expanded MES from Germany to production in Mexico in 2011. The company is deploying MES as a strategy for standardizing packaging and manufacturing processes across its global locations.

“The QA people had to be convinced they could trust the system. This mind set change was a major challenge,” said Dr. Jörg Spörle, senior vp, pharma manufacturing global market, Merck Serono, describing the year-long, change management process at Naucalpan.

“Quality assurance is one of the major opportunities of MES where the QA people do not have to review every page of batch records. The system is automatically comparing the values entered by the operators with the production parameter target values, with any deviations automatically reported. In the ideal case, the QA person just has to press a button to release the batch,” Spörle described.

MES solutions offered to the market encompass processes from manufacturing through packaging with modules covering materials work flow, process deviation reporting, data analysis, serialization data base, and overall equipment effectiveness (OEE) evaluation. Merck Serono achieved OEE gains by reducing time spent in manual documentation and decreasing manufacturing and packaging cycle times.

Through machine Ethernet connections, manual key boarding to the MES software interface can be eliminated. Factory floor production data is automatically captured and retrieved to the certified batch record and ERP system for diagnostics and planning.

Automation has advanced plant testing where testing machines feed results in real time to Laboratory Information Management Systems (LIMS), eliminating the need for manual notebook entry in updating the batch record.

“One area where we have seen significant automation progress over the years is in laboratory automation. It is becoming more and more rare that data is hand transcribed,” says Cardinal Health’s Fotis.

“Data travels electronically from test equipment to computer to engineer’s computer for analysis and to final reports. We have especially seen improvement in dimensional measurements as much of this work can be automated and results in greater accuracy. Our technicians are freed up from tedious work to focus on the method development and testing that only human beings can do,” Fotis says.

Inspection

FDA’s amended cGMP guidance of 1998 aiming to reduce the frequency of drug product mislabeling focused attention on more thorough inspection of labels, inserts, and cartons to ensure printing is readable and accurate.

Vendors have progressively introduced faster and easier-to-use digital camera technology supporting 100% automated inspection, often without putting limits on line speeds. As cameras were introduced in more compact form factors--some with on board image processing, others tied to a PC —manufacturers would expand “vision” to a host of different tasks.

“Integration of ancillary equipment such as vision systems, non-contact printing, bar code scanning, checkweighing, and other inspection devices are a must for today’s packaging equipment. These items seamlessly interfaced allow for data gathering, automatic closed loop rejection of non-conforming products, and quick if not automatic verified changeover,” says MGS Machine’s Bahr.

Inspection devices and software tools are mixed and matched in one system for on line inspection assurance, as PMPN described in 2009:

“High-resolution cameras work hand-in-hand with code readers, compact, high-performance computers, and user-friendly touch screens to identify incorrectly packaged or labeled pharmaceuticals, recognize all codes and colors, and compare them with predefined standards.”

Allowable Quality Levels in supplied materials were eclipsed by zero defect requirements as manufacturers pressed suppliers to use advanced technology to ensure all defects are corrected at the source.

“Cost avoidance is the huge issue. You are avoiding a negative impact for the patient and the company if you have the wrong medication in the wrong container or the wrong label on the product,” says Wells.

Manufacturers and contract packagers deployed vision systems to confirm the presence of package components, detect raised vial stoppers, ensure blister fill accuracy, verify the quality of human readable print, view the physical characteristics of parenteral needles, and confirm the readability of bar codes to the extent of grading bar codes to ANSII quality standards in process at line speeds.

Printing

As packagers embraced advanced inspection, printing technology had to improve. Programmable technologies such as thermal transfer printing, thermal ink jet, and laser clearly print variable data and high resolution images of the complex matrix-style bar codes and smaller Databar codes industry has favored.

As far back as the 1990s, few could print readable copy and bar codes at production speeds.

“Most of our [lines] for pharmaceuticals have vision systems so your print quality has to be very good. For a while there was no technology that would let us print at the speeds our customers wanted. They would have to go with preprinted or slow their lines down. Today we can meet customers’ requirements--even at 220 labels per minute,” said Joe Danyow, director of engineering– labeling, NJM/CLI in 2009.

Medical and pharmaceutical packagers often have two types of printers on a line: flexographic printing for repeatable print and variable-data technology. But some saw that changing as packagers planned for serialization, and on the medical packaging side, the Unique Device Identifier.

“With a full web programmable printing system you are maximizing packaging line space, reducing or eliminating downtime associated with printing plates and ink changes, and eliminating preprinted web inventory. You are not plugging in rubber slugs to accommodate variable data. I think you are going to see contact printing become obsolete,” predicted Tom Pugh, vice president of sales at Bell-Mark Corp in 2010.

Clinical trials

Automated processes have created efficiencies in clinical trial packaging. As clinical trials grew larger and more complex with growing package volumes, systems for fully automated blister strip card assembly came into use. Manufacturers then sought to get results faster and reduce costs with adaptive design trials, putting an emphasis on fast turnaround of new labeling instructions to keep up with adjusted patient dosing regimens.

Clinical trial supply management software coordinates label creation with inventory management, mating scheduled packaging jobs with approved label designs. Labels are automatically populated with imported text and trials’ randomized dosing schedules. Manual label inspection is replaced with automated label verification systems enabling improved service levels as labels are available and approved in a much shorter time.

In automated assembly of cards with blister strips with in line blister sealers, packagers increase production by four or five times compared with manual strip placement.

Zed Industries was among vendors providing trial blister packing machinery that features quality control at virtually all production stages. Blister strips are grabbed from consecutive feeding stations via vacuum pick and place and laid down on base cards automatically moved into position. Sensors and vision systems track that the right blister strips are placed in the right magazines, magazines’ fill status, proper strip placement on the base card, and confirm product in each blister cell. With assist of servo encoding, data captured on production flaws is captured in a count registry as flawed product is rejected without stopping the machine

In alternative multi-fill loading of multiple products to a formed blister, clinical trials services provider Aptuit automated the process with an Uhlmann UPS 1030 and Uhlmann Simtap feeders. A modular tool set supports a diverse set of blister configurations. For reducing lead times and costs for large trials, Aptuit further planned development of in line printing of static and variable information with a CSAT printer and Uhlmann VisioSafe for print inspection.

Track and trace

Over the past decade, the pharmaceutical industry has faced the issue of government-imposed track and trace mandates. As major manufacturers launched pilots to develop the technology internally and with trading partners, smaller companies set aside funding, while industry awaited clarity on standards and requirements for the US market and globally.

An entire industry offering traceability solutions has grown up. Machine vendors have teamed with track and track system partners, or offered “serialization ready” machines supporting integration of printers and vision systems with Ethernet ability for sending data to MES and ERP.

Pharma firms have embarked on multi-year projects to develop solutions that span every level of the enterprise, from sensors on a packaging line to ERP control, and for transferring data in a secure fashion with trading partners.

Companies have had to adapt lines to ensure that production efficiency is not negatively impacted as serial numbers are generated, applied, verified, and commissioned at unit, case, and pallet level, and containment is aggregated at each level with unique bar codes.

Industry to this day is working on best practices for handling exceptions, or how data will be rebuilt such as if a unit goes missing from a case or a case is destroyed in a pallet. The pros and cons of centralized or decentralized supply chain network models are being evaluated.

Though companies have been daunted by the large expense, industry working groups identified business benefits accruing from serialization, where detailed real time information on each serialized package promises improved supply chain visibility and control.

“There are business value opportunities we can all enjoy if we take this serialization to the next level as a strategy to reform the pharmaceutical supply chain,” Ron Guido, vp of global brand protection & supply chain integrity, Johnson & Johnson, would describe in 2013.

 “The number one reason we are doing this is for patient safety, and I don’t think we need a business case for that. Even with no laws, we should be doing this on our own,” Guido said.

Discipline integration

The output of a packaging plant comprises three things: the packaged product, documentation of the production, and documentation of quality records related to testing, describes PharmAgility’s Wells.

“We have come a long way in the automated integration of the different disciplines—the production floor, inventory management, labeling control, and quality systems—at the enterprise resource planning (ERP) system level. That was a pipe dream 20 years ago,” Wells says.

“Now the corporate suite can use real time information in 12-month forecasting of how many shifts you need to run, the product mix, economic order quantities, how many operators are needed. What you want is have the automation work for you so you can do more with less. The companies that can achieve that and do it efficiently are the ones with the competitive advantage because they are using that automation to the best benefit,” Wells adds.