	Attendees found innovations for all points in the packaging line at the inaugural Pharma EXPO and the co-located PACK EXPO International, Nov. 2-5, 2014, at McCormick Place, Chicago.  

	In preparation for filling, an Ionized Bottle Rinser from Paxton Products neutralizes static cling and uses blower-driven air, instead of more energy-intensive compressed air or water, to remove foreign material from glass or plastic containers. Rated at up to 1200 containers per minute, the unit handles sizes from 20 ounces to 3 L.

	The TE 20 tablet elevator from NJM Packaging feeds tablets, capsules, or softgels to a tablet counter or blister packaging machine at nearly double the speed (24,000 tablets per minute) of its TE 10 model. It’s also approximately 50% smaller and locates the 113-L hopper at a relatively low height for easy loading. When demand increases, the standard hopper can be replaced in the field with a larger 198-L hopper. A push of a button releases all product contact parts for tool-free removal to expedite cleaning and minimize downtime (1).

	Self-teaching optical technology in the cutting head allows the 5D Desiccant Dispenser from AZCO Corp. to run desiccant material from any supplier. Measuring 7x12x14 inches, the compact unit is rated at up to 100 cycles per minute. Cantilevered design of the self-threading, all-electric machine provides full access to the feeding process and simplifies setup. A knife cartridge cuts blade changeover time to 30 seconds without tools (2).

	Another versatile desiccant feeder, the Rx-Desiccant PLUS model from BellatRx handles either desiccant canisters or pouches (3).

	For parenteral lines, Denso Robotics introduced a cleanroom-compatible robot with an outer coating and sealed joints, which withstand hydrogen peroxide or ultraviolet light sterilization. The VS 050 six-axis robot handles 4-kg payloads and offers a maximum reach of 520 mm with accuracy of ±0.02 mm (4).

	The FXS Combi filling and closing machine from Bosch Packaging Technology handles nested syringes, vials, or cartridges. The monoblock design includes an integrated capping station. The unit may be equipped with up to six dosing heads and is suitable for peristaltic or rotary, slide-valve piston pumps as well as Bosch’s single-use PreVAS technology. It’s also compatible with isolators or restricted access barrier systems. Integration with an ATO automatic tub opener and ABO automatic bag opener, also from Bosch, results in a fully automated line (5).

	The FLR (faulty label removal) System from Newman Labelling Systems removes bad labels before application to eliminate rework of labeled containers and simplify label reconciliation and decommissioning of serialized codes. Once detected, the bad label is immediately transferred to a secure paper web, and sensors confirm this action. Being able to view each rejected label on the paper tape simplifies reconciliation. If desired, a camera can be added to automate decommissioning of serialized codes. The FLR system handles label sizes from 12x20 mm to 108x200 mm at up to 500 labels per minute. Compatible with any of Newman’s pressure-sensitive labelers, the stepper-motor-driven unit was shown mounted on the company’s S350 labeler, set up to handle vials.

	Avery Dennison can incorporate DirectLink near field communication (NFC) tags into its pressure-sensitive labels for communicating information to consumers. NFC, a form of short-range wireless communication, transforms the package into an interactive product communicator. Tapping an NFC-enabled phone against the tagged package can deliver content such as a special offer, survey, coupon, website link, or manual (6).

		NJM Packaging, “NJM Packaging Introduces the New TE 20 Tablet Elevator,” Press Release, Nov. 2, 2014.	

		AZCO Corp., “AZCO Corp.’s 5D Desiccant Dispenser,” Press Release, Nov. 2014.

		BellatRx, “BellatRx Showcasing Several Packaging Solutions at Pack Expo Booth #S-2566,” Press Release, Nov. 2014.	

		Denso Products and Services Americas, Inc., “New Denso VS-Series Aseptic Robot,” Press Release, Nov. 4, 2014.	

		Bosch Packaging Technology, “New Filling and Closing Machine FXS Combi from Bosch,” Press Release, Nov. 2014.	

		Avery Dennison, “Interactive Packaging: The Future of Labeling,” http://label.averydennison.com/en/home/lpm-products/key-label-innovations/directlink.html, accessed Nov. 24, 2014.

Articles

Packaging

New pharmaceutical packaging equipment includes advances in automation and efficient systems.

Packaging Innovations Displayed at Pharma EXPO

	Sterilize-in-place (SIP) and clean-in-place (CIP) systems can be used in various pharmaceutical manufacturing operations to automate cleaning and sterilization. 

 spoke with Klaus H. Schreiber, marketing and sales for Pharmatec, a Bosch Packaging Technology Company, and

Klaus Ullherr, product manager at Bosch Packaging Technology

, about the key considerations for choosing and using such systems in aseptic filling.

What are the key considerations for using/installing CIP/SIP systems in an aseptic filling process?

 An SIP system is usually combined with a CIP system to ensure the final and automatic sterilization of modules or a complete system before the next batch is produced. In general, SIP systems reduce the handling of parts or modules to be sterilized. SIP may be required if the production exceeds a certain size, weight, and level of complexity. The automated SIP process with validated parameters ensures a reproducible result and at the same time monitors and records critical process parameters, which is a must in industrial pharmaceutical production.

	Aseptic handling is always critical at the interfaces between different systems or whenever human interference is required. Potential contamination by humans, as well as faulty operations or non-compliance with standard operating procedures in aseptic processing, is considered a risk. Automated processes (like CIP and SIP) can significantly reduce the need for, and thus impact of, human interference and ensure sterility. When highly potent or toxic ingredients or APIs are handled, CIP systems help protect both the operators and also the environment from exposure. Prior to disposal, any liquid waste will be chemically and thermally inactivated.

 When it comes to the actual aseptic filling process, the benefits of a CIP/SIP system primarily depend on the level of production. From a pharmaceutical point of view, it makes more sense to sterilize filling paths when they are already installed rather than to install them after sterilization. The latter has to be carried out manually and is more prone to human errors. Using a CIP/SIP system removes the operator as a cause for possible contamination. Aseptic handling is reduced and the system does not have to be dismounted.

	The use of CIP/SIP systems is recommended for the production of large batches and toxic products since the initial investment for implementing CIP/SIP systems is comparatively high. Such systems need space, and the process can require a considerable amount of time. For smaller batches, the installation of CIP/SIP systems is not efficient, as downtimes might be too long. Contract manufacturers are also less likely to use CIP/SIP systems since a large number of different products and formats require higher validation efforts.

	As an alternative, single-use, prevalidated, preassembled and presterilized parts, including hoses, product bags, filling needles, and tubing, can eliminate the loss of capacity resulting from lengthy cleaning validation as well as the risk of contamination between batch runs. They also reduce the amount of cleaning media and energy. Eventually, each customer’s decision depends on the following factors: economic evaluation, anticipated risks, and established processes.

 SMB, a Bosch Packaging Technology Company, recently introduced a patented energy-recovery concept for hot-water shower sterilizers, which is described in 

Cleaning and sterilizing in place have benefits for aseptic filling processes.

Choosing and Using Clean-in-Place and Sterilize-in-Place Systems

	With progress being made in continuous manufacturing of solid-dosage drug products, there is an increasing need for tools to aid risk assessment. In August 2014, FDA awarded a $0.5 million grant to the Engineering Research Center for Structured Organic Particulate Systems (C-SOPS) at Rutgers University and another $0.5 million grant to the University of Massachusetts, Lowell (UML) for the development of process simulation and modeling tools for integrated solid-dosage drug manufacturing processes, and work is now underway. The tools will be used for risk assessment of continuous pharmaceutical manufacturing processes, for control strategies, and to identify critical material attributes and process parameters. Continuus Pharmaceuticals, a spin-off company that launched from the Novartis­–Massachusetts Institute of Technology (MIT) Center for Continuous Manufacturing, is taking a different approach and is developing an end-to-end integrated continuous manufacturing process for pharmaceutical products.

	Dr. Seongkyu Yoon, assistant professor in the Chemical Engineering department at UML, is the head of UML's three-year project, which is the university's first project to receive official funding from FDA. The goals of the project are to develop and provide training for process models and a simulation platform, to conduct case studies for quality risk assessment and control strategy determination, and to conduct verification and validation of process models by comparing model predictions with experimental data, reported UML in a press release. Dr. Yoon also leads the Biopharmaceutical Process and Quality Consortium (BPQC) based in the Massachusetts BioManufacturing Center at UML. The BPQC has been working on continuous biopharmaceutical process design and modeling and quality by design and process analytical technology for risk assessment and control strategy determination. The solid-dosage modeling project, which will use the same engineering principles, will be an extension of this research work, notes Dr. Yoon.

	The multiyear project at C-SOPS is focusing on developing flow sheet-model algorithms that dynamically simulate an integrated process from individually developed unit operation models. FDA plans to use these models in the future for risk assessment of process submissions, including failure mode analysis in continuous drug product pharmaceutical manufacturing. 

	C-SOPS has been working on several projects associated with continuous solid-dosage manufacturing since 2006.  At the biannual C-SOPS advisory board meeting in College Park, Maryland on Oct. 29–30, 2014, C-SOPS researchers from Rutgers University, Purdue University, the New Jersey Institute of Technology, and the University of Puerto Rico reported progress on projects and obtained feedback from the C-SOPS industrial consortium, which includes more than 45 companies. Dr. Lawrence X. Yu, acting director of the Office of Pharmaceutical Science at FDA, was the keynote speaker at the meeting. Dr. Yu commended the Center for helping to enable FDA’s vision of the future of pharmaceutical solid-dosage manufacturing in the area of continuous processes, reported Doug Hausner, associate director for Industrial Relations and Business Development at C-SOPS. Dr. Yu further challenged the team to tackle the existing scientific challenges related to pharmaceutical batch manufacturing, indicating that the transition to continuous will take time and many of the scientific approaches used to develop continuous manufacturing are applicable to the challenges that plague batch manufacturing.  

	The project team at the Novartis­–MIT Center for Continuous Manufacturing successfully demonstrated proof-of-concept of its Integrated Continuous Manufacturing (ICM) technology that combines the synthesis of API and final solid-dosage form in a seamless process, and the technology was transferred in 2012 to Novartis, where development is progressing internally. Continuus Pharmaceuticals was launched in 2013 to apply ICM to the broader pharmaceutical industry, and the company has an exclusive license with MIT that is co-exclusive with Novartis. The start-up company has raised $2.5 million in the past two years, notes founder and CEO, Salvatore Mascia, who was formerly the project manager of the Novartis­–MIT Center. Earlier in 2014, the company partnered with pharmaceutical equipment manufacturer IMA Industria Macchine Automatiche, and in November, Continuus announced an alliance with New England Controls, a business of Emerson. In December 2014, Continuus moved into its new process development facility in Woburn, Massachusetts, and the company is ready to begin process development work with clients who want to investigate its novel ICM technology. "We have a pilot process and are ready to go to the next level," says Mascia. He notes that the novel process technology will require a change in operational structure and mindset, but offers significant advantages in efficiency by eliminating the corrective steps required in existing solid-dosage manufacturing. Mascia says that the concept has high-level FDA support.

FDA funded projects at Rutgers' C-SOPS and at UMass Lowell to develop flow-sheet model algorithms for use in risk assessment, and start-up company Continuus Pharmaceuticals is making progress on their integrated system.

Equipment and Processing Report-12-17-2014

Packaging Innovations Displayed at Pharma EXPO

Choosing and Using Clean-in-Place and Sterilize-in-Place Systems

Development Progresses in Continuous Solid-Dosage Manufacturing