Rigid-wall isolators improve productivity of sterility testing.


Sterility testing in an isolator helps avoid false-positive or false-negative results, and Getinge-La Calhène’s Isotest stainless-steel, rigid-wall isolators are designed to improve the workflow for sterility testing of injectables. The Isotest is equipped with one or two workstations in the same chamber, an attached fast decontamination chamber, and Getinge’s DPTE transfer system to evacuate the test canister and solid/liquid waste. The Isotest integrated bio-decontamination system is self-contained. Isotest can bio-decontaminate either the working chamber or the fast-decontamination chamber using the Isotest PLC control-system touch screen. Hydrogen peroxide is delivered from a canister that includes an RFID chip, which allows the PLC to monitor the volume and remaining shelf life, thus providing full traceability. 

MG America
 Versatile capsule filler with multiple dosing units is designed for small runs.


 MG America’s FlexaLAB capsule filler, which can produce up to 3000 capsules per hour, is designed for research and development, clinical trials, and small-batch production. The FlexaLAB can function with either continuous or intermittent motion. Installing multiple dosing units allows the FlexaLAB to manufacture capsules with combinations of products. The machine can fill powders, pellets, microtablets, tablets, liquids, and certain low-dosage powder inhalants and can perform capsule-into-capsule functions. The machine includes a touch-screen panel and PLC for machine-functions control. Machine speed can be adjusted from the monitor.

Articles

PharmTech's monthly newsletter, Equipment and Processing Report, reviews the Editor's Picks for the August 2012 edition from Getinge and MG America.

August 2012 Editor's Picks: Products from Getinge and MG America

Q. Our company wants to upgrade its single-product semiworks facility to a midscale production facility capable of producing a variety of regulated products. How can we implement a flexible solution without increasing our project budget?

A. Other companies in similar situations have implemented flexible, cost-effective solutions. For example, a small-molecule API manufacturer wanted to upgrade its single-product semiworks facility to a midscale production facility capable of producing a variety of products. The company needed a scalable solution that would meet regulatory requirements and increased security demands for producing regulated materials and controlled substances. Unfortunately, the existing control infrastructure was based on a hard-coded control system from the 1990s that limited its ability to quickly and easily adjust programming and production, which was a requirement for the company as it moved the facility to multiproduct production. The company worked with its automation partner to identify the best control solution. 

Some modern control systems allow users to program batch sequencing and use the controller independently of application servers and software. This independent function allows companies to avoid costly, engineering-intensive custom code or additional server infrastructure associated with large-scale batch solutions. Software is available to configure recipes and formulas directly in the controller without requiring code changes to the system, which helps streamline the implementation of approved changes. 

Companies today would like to reduce their use of manual, paper-based batch sheets for detailed processing instructions, but API manufacturing processes often require a high level of detail. In this company’s process, for example, removing a kill solution that deactivates a volatile chemical too soon could significantly impact the entire process. Automated solutions that take these detailed instructions into account can be embedded directly into the control system, which can improve the quality and consistency of APIs and avoid the delays that naturally occur during manual operations.

—John Párraga, global process technical consultant at Rockwell Automation.

If you have a problem with your equipment or process, an industry expert may have the solution. Please send your question to 

, editor of Equipment and Processing Report, and we may be able to provide an answer in a future issue. All questions will remain anonymous.

Troubleshooting

Flexible, scalable control systems use program batch sequencing.

Implementing a Cost-Effective Cure for Batch and Sequence Management

Implementing highly reliable energy solutions at research and manufacturing facilities is a significant challenge for pharmaceutical companies. The traditional model has been to run a facility with the company owning, operating, and maintaining all equipment itself, thus assuming exposure to risk on issues such as equipment durability, fuel volatility, and maintaining the expertise required to keep the system working properly in-house. Pharmaceutical facilities, however, are increasingly embracing the outsourcing model, in which whole functions are contracted to a third-party vendor. Outsourcing services is a proven solution to optimize efficiency. 

The outsourcing service provider can be contracted to operate and maintain complex energy plants and ancillary equipment, such as:

On-site generation and cogeneration assets

Steam, hot-water, and chilled-water systems

After the outsourced service provider has been selected, the client and service provider should agree on a well-defined scope and clear objectives, which should be captured in a service level agreement (SLA). Using a risk-based approach, the scope and responsibility of the service provider can be built up over time, which will ensure client satisfaction, specifically around regulatory compliance. However, it is important that the client does not relinquish all responsibility, as the ultimate regulatory responsibility lies with the product manufacturer. 

Identifying a key subject matter expert to serve as a liaison between the service provider and client will ensure compliance to quality and regulatory systems. The expert should also design escalation and process flows for change controls and equipment deviation, which pose the most risk to the pharmaceutical manufacturer. For the service provider, customer satisfaction and adherence to quality systems in this highly regulated industry are essential. 

The client and service provider can develop a performance scorecard that is linked financially to the service agreement contract. Key Performance Indicators (KPIs) can include areas such as safe systems of work, system availability, and performance against schedule. Each line item can be linked to a performance metric, and each metric can be weighted with agreed-upon scoring criteria that is reviewed and scored on a periodic basis (e.g., monthly, quarterly). Linking the score to contract payments, by withholding an agreed-upon percentage each quarter, drives performance from the service provider’s point of view and ensures client satisfaction. As the relationship between the service provider and client evolves, or as business expands, it is common to review and adjust the KPIs.

Outsourcing maintenance allows the client to reduce costs without reducing core-business company headcount and, as the pharmaceutical company becomes the customer of the service provider, to more easily drive change and continuous improvement. Outsourcing also allows management to focus on developing and manufacturing the product rather than on the non-manufacturing activities involved in facilities engineering. 

is business development director for Veolia Energy North America

is client operations manager at Dalkia Ireland’s Pharmaceutical & Healthcare division.

In the Mixer

Service agreements, expert liaisons, and scorecards are important to consider.

Outsourcing Energy-Infrastructure Operations

The increasing use of single-use (i.e., disposable) systems (SUS) in biopharmaceutical manufacturing is causing manufacturers and users to consider whether recycling is a viable alternative to landfill disposal or incineration. While the overall environmental footprint of disposables has already been shown to be lower than multiple-use systems in some cases, due to factors such as savings in cleaning water, industry members are taking a close look at disposal options that can further improve the sustainability of SUS. 

Many facilities send their SUS-waste to landfill and others incinerate, either in their own facilities or offsite, and even use cogeneration facilities to produce power, say SUS suppliers. Cogeneration (i.e., waste-to-energy) is considered more environmentally preferable than traditional incineration. Plastics components have a high energy value and can be burned, for example, in cement kilns, which require large amounts of energy and do use alternative fuels, such as plastics or vehicle tires. 

More recently, SUS suppliers and users have been moving toward recycling, which has become a more viable proposal now that the volumes of plastics used in SUS have increased, comments Jeffery Lee Craig, global director for business development and marketing at ATMI LifeSciences. A life-cycle analysis of SUS showed that recycling does reduce the carbon footprint, even over cogeneration, comments Johanna Jobin, sustainability manager at EMD Millipore.

Recycling can, as expected, be used for nonhazardous waste, such as in upstream media and buffer preparation. Downstream components that have come into contact with biohazards, such as viruses, must go through a kill cycle, such as an autoclave, before disposal, notes Ken Baker, CEO of New Age Industries. Once decontaminated, however, these components can also be recycled, says Jobin. 

Both thermoplastic (e.g., polyethylene, nylon) and thermoset (e.g., silicone) components can be recycled although in different ways. Thermoplastics can be melted and reformed into new plastic parts like pallets and plastic lumber. Silicone, however, can be recracked and used in caulk, for example, says Baker. 

A big challenge for recycling has been the lack of infrastructure for collecting and disassembly, says Jobin. EMD Millipore began a pilot program this past year to identify the requirements for successful recycling and to better understand the logistics needed to develop a recycling infrastructure. EMD Millipore partnered with a third-party recycler, which collects and disassembles waste and recycles the plastic materials. Because many of the systems are made out of multiple plastic components that are difficult to separate, disassembly is currently done by hand, says Jobin. Although some of the bags and films are multiple layers (e.g., polyethylene, nylon, and ethylene vinyl alcohol copolymer), this has not presented a problem in the current recycling system. Other components, such as woven filter membranes attached to plastic frames, are a challenge to the disassembling and recycling process.   EMD Millipore, however, has been taking the lessons learned from these challenges and applying them in the company’s design for sustainability program.   “We have learned more about types of materials to use for easier recycling and how to design assemblies for easier disassembly at the end of life,” says Jobin. EMD Millipore’s pilot recycling program has had positive results so far, and the company hopes to scale up from the current East-Coast US operation to the rest of the US, and perhaps eventually to Europe. “The end-of-life aspect of SUS is particularly visible to the company’s employees and management and plays a role in its acceptance,” comments Jobin. Recycling also impacts each customer’s own sustainability programs. EMD Millipore estimates that one of its customers could recycle 11,000 lbs of SUS waste per month, which would boost its annual recycling rate by 5-7%.

At the recent Bio-Process Systems Alliance (BPSA) International Single-Use Summit in Washington DC, BPSA members agreed that recycling is important because it can have a significant, positive impact on sustainability. Now that volumes of SUS have increased and are expected to continue to grow, the industry needs to develop recycling as an option. 

Production Lines

Recycling is becoming a viable option for disposal of single-use systems.

Equipment and Processing Report-08-15-2012

August 2012 Editor's Picks: Products from Getinge and MG America

Implementing a Cost-Effective Cure for Batch and Sequence Management

Outsourcing Energy-Infrastructure Operations

Waste Management of Disposable Biopharmaceutical-Manufacturing Components