Child-resistant (CR) packaging may be middle-aged; it dates from the passage of the US Poison Prevention Packaging Act (PPPA) of 1970. Nevertheless, development efforts continue.  

In fact, a CR design developed by Ecobliss and marketed by Locked4Kids was recognized as the Best Innovation in Packaging in the Pharma Awards competition at CPhI Worldwide in October 2014 in Paris (1). The reclosable Locked4Kids carton consists of tear-resistant laminated paperboard and features a polyethylene terephthalate blister tray that locks in place (2). Available in various sizes, the pack runs on conventional cartoning machines at standard speeds (1).

Another CR carton for a blister card, the medlock compliance package EZ from Colbert Packaging, disengages a patent-pending locking mechanism when the sides of the carton are pressed and held. When the locking mechanism is released, the caregiver or patient can slide out the blister card to access a dose but cannot completely remove it. Sliding the blister card back in relocks it inside the paperboard carton. In a conversation at Pack Expo International (Nov. 2-5, 2014, in Chicago, IL), Jennifer Gross, manager, marketing and sales support at Colbert Packaging, reports the patent-pending design has achieved F=1 CR status (i.e., the strictest rating) in tests.  Colbert is working with several firms, including a major pharmaceutical company and two contract packagers, to commercialize the design. 

CPhI Worldwide also showcased CR designs from MeadWestvaco (MWV), which plans to launch its HiMark CR Nasal Sprayer early in 2015 (3). The new CR nasal sprayer was developed to meet US Consumer Product Safety Commission regulations, taking effect in December 2014, which require CR packaging for products containing imidazolines (4). SecureCap closures from Comar also meet CR standards for products containing imidazolines (5).

At Pack Expo International, Presto launched Child-Guard slider technology, which the company says is the first child-resistant slider available for pouch packaging that meets Title 16 

 1700 of PPPA with ASTM D3475 classification (6). The slider is challenging for children under five years old, but simple for adult consumers, including seniors, noted the company. The technology allows brand owners to choose a flexible-packaging format as a lighter-weight alternative to rigid packaging and still meet child-resistant mandates. 

Meanwhile, research continues on consumer preferences for CR packaging. A focus group study by TricorBraun Design & Innovation evaluated seven CR closures early in April 2014 (7). Participants considered how each felt in the hand and assessed functionality and visual appearance. After group discussion, each individual evaluated the closure according to six characteristics: 
  

I like the way this closure feels in my palm
  

 It is obvious how to open and close this package
  

 I like the way it feels when I open this package
  

 I like the way it feels when I close this package
  

 I am worried that my child will accidentally be able to open this package
  

 I like the way this closure looks (visual design).

At the end of each session, participants associated specific descriptive words such as modern, outdated, user-friendly, frustrating, innovative, or clunky, for example, with four of the closures. 

A common reaction coupled the comfort level of the closure in the hand with the relative ease and comfort of opening it. A closure with a soft-texture surface, for example, produced comments such as, “I like the way that feels; I get a better grip with that rubber top.” Closures molded with ribs around the edge for gripping elicited comments including, “It hurts my hand to turn that; the ribs aren’t high enough; I can’t get a firm grip.”

Participants were particularly concerned about how clearly each closure indicated that it was securely closed and contents were safe from children. Closures signaling “closed” with a clearly audible click rated higher. 

Bi-color closures where instructions and branding contrasted with the background color also rated higher, and graphic opening instructions won over text. Several participants noted, “I prefer pictures over words.” 

Becky Donner, TricorBraun vice president of Design and Market Insight, noted in a press release, “The primary value of this consumer research initiative is that it gives us very clear insight into consumer preferences, emotional reactions, and consumer behavior with packaging. That provides invaluable information for our design team.” 

Focus groups are conducted year round at TricorBraun’s Design and Innovation Center in Oak Brook, IL, in partnership with NSM Research, a market research group that has assessed consumer preferences for packaging since 1996. TricorBraun Design & Innovation Group is a business unit of TricorBraun, a St. Louis-based supplier of bottles, jars, and other rigid packaging components. 

CPhI, “CPhI 2014 Pharma      Awards,” Press Release, Oct. 8, 2014.   

Locked4Kids B.V.,      “Child-resistant Locked4Kids Packaging from Ecobliss Nominated for Gouden      Noot 2014,” Press Release, Aug. 5, 2014.   

MeadWestvaco, “MWV to      Present Trends in Child-Resistant Packaging Design during CPhI Worldwide      Conference,” Press Release, Oct. 1, 2014.   

MeadWestvaco,      “MeadWestvaco Hemer Facility Fact Sheet,” http://newsroom.mwv.com/sites/meadwestvaco.newshq.businesswire.com/files/press_release/additional/Hemer_Opening_Fact_Sheet_Final.pdf,      accessed Oct. 29, 2014.   

Comar, “SecureCap Closures Pass Child-Resistant      Packaging Standards Set by Consumer Product Safety Commission for Products      Containing Imidazolines,” Press Release, Mar. 10, 2014.   

Presto, "Presto      Launches Child-Guard, First Ever Child-Resistant Slider for Flexible      Packaging," Press Release, Nov. 2, 2014.   

TricorBraun, “TricorBraun      Focus Groups Assess the Feel, Functionality and Appearance of      Child-Resistant Closures,” Press Release, May 2014. 

Hallie Forcinio is Pharmaceutical Technology's packaging editor, 

Articles

Packaging

New child-resistant packaging designs meet regulatory requirements, and consumer research into child-resistant closures continues.

Child-Resistant Packaging Meets Regulations and Consumer Needs

Manufacturers of tablets have long battled a host of occasional but common issues, one of which is spots or specks, which are undesirable visual flaws that can be superficial and/or embedded within a tablet. Commonly referred to by the over-generalizing term “black spots,” these unsightly blemishes or foreign substances should more appropriately be categorized as any spots or specks that are not supposed to appear in the first place, but that in most cases are easily (and visually) detectable. Spots are generally those imperfections that reside on the surface of the tablet only, while specks can be present throughout a tablet. Specks are sometimes visible on the surface, sometimes hidden inside, or both. It is important to note that undesirable spots or specks can be gray, black, or almost any other color, even white. 

Although it often proves true that an oil-based issue on the tablet press is the culprit, the following are other potential sources:

Reactions between incompatible material combinations (e.g., certain active ingredients will turn darker when subjected to high heat or when mixed with particular tooling lubricants)

A “slinging” effect at excessively high turret speeds, where an accumulated product–lubricant mix is thrown from the punch barrel

Poor or inadequate cleaning procedures, especially between product changes

Upstream origins (e.g., contaminated raw materials, blending issues, dislodging of grease and lubricants on mixers or granulators)

Improper product-specific gaps between feeder base plates and the turret surface; too-tight gaps can cause some particle sizes to “roll” and ultimately change color

The best possible solution for an issue with spots on tablets is to consistently employ methods for avoiding them in the first place. This may appear obvious, but in reality, tablet press operators often deviate from GMP methodology, especially in terms of following recommended guidelines for cleaning and set-up as provided by original equipment manufacturers (OEMs). If not already in possession of such procedures, every company should poll their suppliers for them and implement their contents into a cohesive and all-encompassing set of standard operating procedures (SOPs).

Having stated the above as a best line of first defense, strict adherence to good SOPs cannot supersede all potential issues. Some suggested guidelines for eliminating spots when they do appear, or for helping to prevent their occurrence at all, include:

Optimizing lubrication settings, including dose rate, interval, and duration, especially for upper punches; documents and suggestions from the OEM should help here

Regular use, and replacement of, quality dust cups; they are easy to install and are disposable

Regular use, and replacement of, upper punch seals (on presses that offer them as an option)

Use of punch bellows, especially for particularly dirty products or those necessitating the use of maximum upper lubrication; bellows can actually prevent the mixing of lubricant and dust in the first place, greatly reducing the likelihood of eventual spots

Strict adherence to SOPs for cleaning and set-up

The use of equipment manufacturer-recommended vacuum settings

Judicious inspection and replacement of “contact” parts, such as feeder base plate seals and “tail-over-die” scrapers 

Regular inspection of seals and/or gaskets located within mechanical feeders

A systematic inspection of all product-contact areas within the entire manufacturing line where an oil or other lubricant may be used.

If, indeed, raw material issues are ruled out and a press manufacturer is asked to recommend a first place to look, most will generally suggest the bottom of the barrels on the upper punches, where the punches protrude from the upper punch ring. A quick visual inspection can detect any unusual build-up of material and excessive lubricant that may be contributing to a problem. If present, it should then prove easier to put a stop to the offense.

Depending on the severity of the issue and the company experiencing it, some will seek independent analysis from a third-party laboratory in an effort to determine the source and composition of the spots. It is, however, important to note that the success of such an investigation can vary considerably. Certainly there are times where the lab can shine the brightest light on a shadowy issue, while just as frequently the offending contaminant is identified and confirmed locally, at the floor level.

For further suggestions and to read how a mysterious problem of blue spots was solved, read the full article in the December issue of 

Matt Bundenthal is direct sales and communications manager at 

Troubleshooting

Although the source of spots and specks on tablets is sometimes difficult to identify, following good maintenance and manufacturing practices can help solve or even prevent the problem.

Eliminating Tablet Spots and Specks

The Dispense Works RP Series robotic dispensing system with an optional vision guided system performs pattern recognition and edge/hole detection for simpler setup and fixturing, while assuring repeatability. The robot takes a picture of the part, does any necessary offsets, and adjusts its program for precise dispensing and part placement. 

All motion, vision, and control system software is written in house. Systems are available that meet FDA and cleanroom specifications.

A robotic dispensing system has an optional vision guided system.

Robotic Dispensing System Assures Repeatability

I Holland's MF 80 automated punch polisher for tablet tooling has double the capacity of the previous version for consistent, even polishing. I Holland recommends automated polishing as part of a seven-step procedure for tooling maintenance that includes cleaning, assessing, repairing, measuring, polishing, lubricating, and storage. Polishing helps overcome tooling problems, such as sticking or corrosion. The company says it is difficult to achieve a consistent finish across a tool set with an abrasive manual polishing process. Automated polishing, however, eliminates variation and prevents premature removal of tool coatings. The automated polisher will polish dull and discoloured punches to a micro-fine, high-quality finish by using a drag finishing process. The punch is automatically rotated through media and polishing paste, which saves time and ensures a consistent result. 

The automated punch polisher for tablet tooling has double the capacity of the previous version for consistent, even polishing.

Automated Punch Polisher Increases Capacity

Automation, including automated inspection and packaging, is becoming an increasingly important part of pharmaceutical manufacturing. The many benefits of automation include efficiency, saving workers from hazardous environments or repetitive tasks, reducing training overhead, eliminating human error, increasing repeatability and reproducibility, and in cleanrooms, removing the potential for human contamination. 

A robotic system is a type of automation that has multiple axes of motion and can be programmed to perform a function. Robot types include articulated, cartesian (i.e., gantry), parallel (i.e., delta), and selective compliance assembly robot arm (SCARA). Common applications include "pick and place" operations that often use SCARA robots. There is also a new, growing use of delta-type robots for high-speed picking and packaging, noted Chris Sumner, managing director of Fanuc Robotics UK and vice-president of Fanuc Europe Corporation, in a press release (1). Merck, for example, is using a Fanuc delta robot on a bottling line to place dispenser caps onto bottled allergy medications. "Ten variants of the bottle can be run on the system, and the only robot line-change requirement is to select the appropriate program on the robot controller," explained Sumner. 

A study by the Association for Packaging and Processing Technologies (PMMI) found that robots are expected to handle 34% of primary pharmaceutical packaging operations in North America by 2018, compared with 21% in 2013 (2). An increase in the use of robots is seen in dispensing, sorting, kit assembly, and light machine-tending as well as in more traditional applications associated with packaging, notes Jonathan Ferrell, a packaging market manager at ABB Robotics. "The advantages of robotics are fairly simple: greater speed and accuracy, greater flexibility and reliability than hard automation, and they are becoming ever more affordable," says Ferrell. 

Robots for filling, inspection, and packaging


  Robotic technology is being used for vial-filling applications on slower speed applications. "Robotic vial manipulation transfers components from station to station both before and after filling and pack-off," says Walt Langosch, director of sales and marketing at ESS Technologies. The company also has experience with handling plastic and glass prefilled syringes in pre-process, buffering, and initial and end-of-line packaging. "Automated syringe assembly, inspection, and preparation for packaging is an ideal application for robotics," says Langosch. "The primary advantage in sterile environments is reduction of risk due to environmental contamination and contamination generated from human intervention during component transfer."  In addition, productivity is increased because of the accuracy and efficiency of robots, which often perform at increased speeds and produce less scrap. 

Automatic inspection, as part of a robotic system, has the advantage of enabling 100% part inspection. Vision-sensing technology can be used in pharmaceutical packaging to verify serialization numbers for compliance with track-and-trace regulations. "Robotic dexterity and accuracy combined with current and future optical technology and serialization software is the ideal technology for an automated solution," says Langosch. 

An advance in vision sensors is color imaging, which, for example, allows systems to distinguish between bottle caps of different colors, noted PMMI in a trend report (3). Vision sensors have also led to advances in end-of-arm tooling design that improve the ability of robots to accurately identify and place objects.

Robots for producing personalized medicines


Custom automation and contract-manufacturing company Invetech recently partnered with biopharmaceutical company Argos Therapeutics to develop automated manufacturing systems based on Argos' Arcelis technology platform for personalized immunotherapies.  "The Arcelis platform uses two, five-axis robotic arms in the production of the mRNA from a patient’s tumor, which is used as the antigen for loading into the dendritic cells produced in the cellular processing equipment," explains Richard Grant, director of cell therapy at Invetech. "The cellular equipment uses automation to manipulate the white blood cells throughout the manufacturing process to control their development and maturation into dendritic cells. These cells express the desired antigens, which when delivered to a patient, will trigger the patient’s immune system to produce killer T-cells that will target the metastatic tumors."

"The RNA robots manipulate closed disposables to perform the process within the common Class 100,000 cleanroom space," says Grant. "The use of the closed disposables allows multiple patients' materials to be processed in the same manufacturing space, driving the facility capital and operating costs down significantly." 

Argos' lead candidate is currently in Phase III clinical trials, and the automated technology is designed to be modular and easily scalable. Clinical processes are generally manual, skill-based processes that cannot operate practically or economically at commercial scale, notes Grant. Use of robotics, however, allows the processes to be scaled up commercially. "In addition, robotics allows new sites to be replicated around the world in a scale-out model, with minimum training for set-up and validation of new sites and minimal site-to-site variability in production processes," explains Grant.

Robotic technology is ideal for cleanroom processes, such as aseptic filling, because it eliminates human contamination risk. Robotics can provide an ISO 5 environment to preclude the possibility of microbial ingress, says Langosch. ESS Technologies partners with Fanuc Robotics for secondary packaging and palletizing of pharmaceuticals, and Fanuc has several robots that will operate in an ISO 5 environment. The Fanuc M-430iA/2PV can withstand hydrogen peroxide vapor sterilization and has a waterproof rating; all wiring and cabling is routed through the robot’s hollow arm.

Robots designed for use in cleanrooms must minimize particulate generation to maintain cleanroom classifications, typically ISO Class 5 or 6. Cleanability, including minimizing crevices and ensuring the robot is resistant to cleaning and sterilizing agents, is also a requirement, notes Grant. Operator safety must be ensured by guarding or containing the robot. Another requirement is controlling the speed of robot movement to minimize impact on airflow and particle generation and to a lesser extent, managing heat generation and its impact on the heating, ventilation, and air-conditioning system of the cleanroom, explains Grant.


  Robotics has come a long way in the pharmaceutical laboratory, notes Mike Ouren, Life Sciences manager at Precise Automation. In the laboratory, robots are used, for example, to transport microtiter plates between instruments. "Although the instruments can be loaded manually, a robot tied to a scheduling software system eliminates human error, maintains the quality of the experiment, and allows scientists to focus on the content of the experiment, instead of how they will execute it," explains Ouren. 

Laboratories differ from industrial applications in that, although tasks are repetitive, they are not as consistent and may change depending on the experiment, says Precise Automation's Ouren. The need to access equipment near the robot quickly and the space limitations of a laboratory can be met with new collaborative robots that do not require safety guarding. In 2012, Precise Automation introduced a collaborative SCARA robot (or "cobot"), the PreciseFlex (PF)400, which handles less than 1-kg loads and is designed to allow operators to work safely next to the robot without barriers. The smaller footprint of the robot reduces cost, and the space savings is useful in benchtop laboratory applications. The robot is user friendly, and the Precise Guidance Controller inside the PF400 allows laboratory personnel to "teach" the robot using only their hands. "Because there are no barriers, instead of using a complex remote-control pendant to teach the robot, the operator can show the robot what to do by simply grasping the end of the robot arm. This accessibility is unheard of in industrial automation," explains Ouren. 

Other laboratory applications for robots include vial handling. A Fanuc robot is being used in a laboratory, for example, as a single-point handling solution for vial processing. "A handling tool was designed and attached to the end of the robot to enable it to handle ten vials at a time. A variety of components were also placed around the robot cell-including indexing tables for full rack staging, a thermostatically controlled water bath for precise sample temperature, a retrieval system for dumped vials, a washing-brushing-rinsing-drying station, a preservative spray station, and a recapping station," explained Sumner in a press release.

In the laboratory and on the manufacturing floor, robots are increasingly used to improve quality and efficiency. 

PMMI Talks North American Pharmaceutical Trends at interpack

PMMI Packaging Intelligence Brief, "Trends in Robotics: Market Assessment, April 2014," 

www.pmmi.org/files/Research/2014RoboticsPIB.pdf

Production Trends

Robots are proving advantageous in filling, inspection, packaging, laboratories, and the manufacture of personalized medicine.

Equipment and Processing Report-11-19-2014

Child-Resistant Packaging Meets Regulations and Consumer Needs

Eliminating Tablet Spots and Specks

Robotic Dispensing System Assures Repeatability

Automated Punch Polisher Increases Capacity

Using Robotics In Pharmaceutical Manufacturing