
 ABB’s (Québec, Canada) MB3600-PH Fourier transform–near infrared spectrometer is designed for pharmaceutical quality-control and at-line process analytical technology applications. The instrument is designed to have an exceptional signal-to-noise ratio. It uses a solid-state laser that has a lifetime of more than 20 years, according to Frédéric Despagne, the company’s industry manager for life sciences and fine chemicals. The spectrometer’s optics are designed for pin-in-place positioning so that the interferometer’s field of view is precisely aligned along its optical axis. This technique provides a reproducible line-shape function.

The instrument uses flex-pivot bearings to perform rotary scanning of the interferometer mirrors, thus permitting reliable and precise scanning. This design eliminates friction, mechanical wear, and the need for lubrication. The design also enables the interferometer to be compact and robust.

The analyzer’s sample port accommodates various accessories such as a diffuse-reflectance rotating vial for powders, a universal temperature-controlled vial holder for liquids, and a hand-held diffuse-reflectance pen-probe for 

The David Round Company 
 Trolley products maintain sterility


The David Round Company (Solon, OH) offers its SSPT series of stainless steel trolley products for pharmaceutical cleanrooms. The trolleys, intended for loading and unloading raw materials and finished product, are designed to prevent contaminants from being introduced into cleanrooms. The products are not painted and do not incorporate carbon steel parts. These design features are intended to reduce the potential for particulate generation. In addition, the trolley products are available with crack- and crevice-free surface finishes to avoid entrapment.

The SSPT series withstands washdown operations. The products’ sealed bearings are suitable for high- and low-temperature applications. Manual, hand-geared, and motorized versions of the products are available. Certain models include articulating wheels that can negotiate curves and switches along monorails without requiring great operator effort. The trolley products can be provided to fit customers’ required capacity ratings. The company can design the products to fit beams of any size. 

Articles

PharmTech's monthly newsletter, Equipment and Processing Report, reviews the Editor's Picks for the February 2010 edition from ABB and David Round.

February 2010 Editor's Picks: Products from ABB and David Round

Implementation of the California ePedigree legislation, now scheduled for 2015, has been postponed many times, and some pharmaceutical manufacturers have delayed preparations for compliance. This strategy, however, may be shortsighted. Large challenges, including dwindling pipelines and an increasing focus on reimbursements, require pharmaceutical manufacturers to improve operational efficiency and reduce risk. Serialization solutions may help companies achieve both goals.

The California ePedigree initiative, designed to ensure that only authentic pharmaceutical products are distributed through the supply chain, requires manufacturers, distributors, wholesalers, and retailers to track, trace, and authenticate the entire chain of drug custody. It also requires manufacturers to track their products at the serialized salable-unit level—a significant change in an industry that has never tracked beyond the lot level.


Pharmaceutical manufacturers that launch ePedigree and serialization initiatives today will improve their competitive positions in the short and long terms. First, ePedigree and serialization initiatives yield greater inventory visibility and traceability that can support business operations at several levels. These capabilities can help improve patient safety and protect brand integrity by reducing fraud and identifying counterfeit drugs before they reach the public. In addition, pharmaceutical manufacturers that undertake ePedigree and serialization initiatives can avoid much of the financial loss associated with diversion, counterfeiting, and recalls, which, according to some analysts, cost the industry more than $30 billion annually.  

Furthermore, the increased level of transaction detail captured through ePedigree and serialization initiatives helps reduce chargebacks and improve their reconciliation, thus strengthening a pharmaceutical manufacturer’s financial position. Several manufacturers have discussed novel approaches that could enable access to better inventory information. The approaches, which would rely on improved access to downstream supply-chain data and the adoption of serialization, would help prevent overproduction, eliminate waste, and improve on-hand inventory levels.  

Achieving these benefits, however, will require fundamental changes in the relationship between manufacturers and wholesalers. In the United States today, pharmaceutical wholesalers are the manufacturers’ biggest customers, and they control sales to pharmacies and other outlets. Wholesalers possess the lion’s share of market data, which they guard closely because selling the data to the manufacturers brings them significant profits. It remains to be seen whether ePedigree requirements will put an end to this data-sharing impasse.  

Also, ePedigree and serialization enable efficient and accurate returns management. Industry sources estimate that returns cost the pharmaceutical industry approximately $2 billion annually. Lot-level product tracking does not enable manufacturers to verify which returns are legitimate. It is most cost effective to write off returns without additional verification, even though some returns could be counterfeit, returned at a higher price than the invoice price, purchased from another manufacturer or distributor, or even expired. Serialization initiatives provide a link between the return receipt and the original shipment and invoice. Supported with the right technology solutions, ePedigree and serialization can provide returns-repudiation functionality that will enable manufacturers to verify that the returned products are the same as those that were shipped. This verification can improve accuracy and increase cost savings.  


  Information technology is at the core of ePedigree and serialization initiatives. Although regulations do not require specific technologies, the realities of unit-level serialization, item-level tagging, and the resulting capture and management of massive amounts of transactional data make technologies such as radio-frequency identification (RFID) and two-dimensional (2D) barcodes practical requirements.

Many core technologies are available to companies embarking on ePedigree and mass-serialization initiatives, but few business-applications solutions can support them. Some manufacturers have launched Electronic Product Code Information Service pilot projects only to find that this technology requires the company to build an additional business application to use the data.

To gain the flexibility and agility necessary for a successful ePedigree initiative, pharmaceutical manufacturers require business applications that are built on an open, standards-based, service-oriented architecture (SOA). The applications must generate, transmit, and authenticate drug-product serial data and electronic pedigrees when pharmaceutical products move within the enterprise and across the supply chain. An SOA-based mass-serialization and pedigree-management application provides a scalable and flexible infrastructure for efficient forward and reverse logistics by integrating with existing back-end transactional systems.

Existing business applications can become overburdened quickly because they were not designed to manage the additional data generated by mass serialization. SOA enables the legacy business applications and the serialization application to coexist. The serialization application generates, stores, and analyzes the massive quantity of serialized data with minimal or no effect on the existing transactional systems. Because SOA enables a loosely coupled approach to enterprise-application integration, it allows one system to experience disruptions without halting the whole business process. SOA enables business processes to operate across a multinode network, which makes the process more fault-tolerant and protects existing investments against potential business and technological disruptions.

SOA also facilitates the integration of ePedigree solutions with existing manufacturing, shipping, and receiving transactional systems by relying on standards-based web services and reusable business objects, thus extending a pharmaceutical company’s investment in information technology. In addition, a standards-based architecture offers more flexibility at less risk than a tightly coupled approach, thus facilitating interactions within the enterprise and throughout the supply chain. SOA also facilitates the adoption of new technologies more than tightly coupled architectures do. Thus, SOA protects against obsolescence caused by disruptive techniques and technologies.

Little more than five years ago, the pharmaceutical industry had hardly considered serialization. Similarly, the disruptive trend of personalized medicine has fostered the emergence of companies such as Genzyme (Cambridge, MA) and Myriad Genetics (Salt Lake City) that can change the way they manage information. These and other companies have excelled at accessing and using many disparate patient-related data sources, including genomic, proteomic, clinical, and molecular artifacts, to focus the drug-development process on an individual’s predisposition to a particular disease or condition. Companies that can adapt quickly and embrace serialization will be the first to reap its business benefits. Companies that are less nimble will struggle to comply with evolving regulations in time for enforcement deadlines.

Pharmaceutical manufacturers that meet ePedigree and serialization requirements without delay will be better prepared for the new regulatory environment. These companies will be able to improve their operational efficiency and will reduce their risk now and in the future.  

John Danese is director of life-sciences product strategy, and Arvindh Balakrishnan is vice-president for the life-sciences industry, both at Oracle, 500 Oracle Pkwy., Redwood Shores, CA 94065, tel. 800.ORACLE1, 

In the Mixer

Pharmaceutical manufacturers that launch ePedigree and serialization initiatives today will improve their competitive positions in the short and long terms.

Resist the Rain Check: ePedigree Solutions Have Immediate Value

Rising titers in biopharmaceutical processes have enabled companies to produce highly concentrated liquid drugs. As concentrations have increased, fill volumes have decreased. The lower limit of a dose has dropped from 10 mL to 0.1 mL, and even smaller volumes are needed sometimes. Drugmakers have many incentives to avoid overfilling their containers, including the scarcity, and correspondingly high cost, of certain cells and ingredients. These concerns highlight the need for techniques that can fill small volumes of product with great accuracy. Many strategies are available to the industry, but which one works best?  

Bosch Packaging Technology studied the accuracy of various fill techniques and concluded that positive displacement remains the most accurate, according to Jeff Jackson, the company’s North American pharmaceutical sales director. A positive-displacement pump traps a given amount of fluid and forces it into a discharge pipe. Piston pumps, diaphragm pumps, and peristaltic pumps are different types of positive-displacement pumps, which are less sensitive to a product’s viscosity than other pumps.  

The traditional method of filling is with a piston pump that incorporates an O-ring seal. “The injectable pharmaceutical requirements for clean, accurate filling changed this design to a lapped-piston design that has a piston-to-cylinder clearance of one-hundred-thousandth of an inch without an O-ring. This has been the normal method of parenteral filling for several decades,” says Jack Lysfjord, principal consultant for Lysfjord Consulting. Though accurate, these devices also are delicate. “If you drop it just slightly or damage the piston, they won’t work anymore.” They’re also expensive.  

Rolling-diaphragm pumps, which were introduced later, do not exhibit the slight leakage that lapped piston pumps do. These pumps also reduce the shear effect on biological products and proteins, compared with piston pumps. They also equal the accuracy of the lapped piston pump. The rolling-diaphragm pump is one of the most accurate pumping systems available, says Jackson.  

A peristaltic pump, which typically is used in clinical applications, incorporates a rotating roller or series of rollers. An operator inserts flexible tubing into the rollers, connects it to the nozzle, and feeds product into it. The rollers compress the flexible tubing and force the liquid out the discharge, thus dispensing the desired volume. Peristaltic pumps have not performed as well as other types, but their accuracy has been improving as new designs emerge. “I would say their accuracy is approaching that of piston pumps,” says Jackson.  

Other filling techniques are less common, but still used for certain applications. Time-pressure filling, for example, uses air, nitrogen, or gravity to create a slight overpressure that pushes the product through an orifice. This filling method has fewer parts than other kinds, but the simplicity of design has its tradeoffs. Time-pressure technology is sensitive to product characteristics such as viscosity, says Jackson. The accuracy of time-pressure filling varies depending on fill volume. At low volumes, time-pressure filling is not as accurate as piston pumps are.  

In optical filling machines such as Millipore’s (Billerica, MA) Acerta system, sensors trained on the tubing trigger a valve to shut when product reaches the desired height or fill volume. Optical filling is about as accurate as time-pressure filling, according to Jackson.  

In the fill-by-weight technique, an empty vial is weighed on a scale. Next, a valve is opened to begin the fill. The valve must be closed in time so that the last drop of product does not overfill the vial. The accuracy of this technique varies, says Jackson. The weight keeps changing during the fill, so the system must stop filling, let the product settle, then read the weight to get an accurate measurement. This method is impractical for filling commercial quantities, so a company might choose to weigh one vial and use it as a guide for the others. “If you’re doing it at production speeds, fill-by-weight is probably the least accurate of any of the techniques,” says Jackson. On the other hand, the technique provides data about every container filled and allows underfilled units to be rejected.  

The mass-flow technique uses a sensor built around the product dosing tube. As product flows through the tube, the sensor measures its fluid mass. Mass flow is growing in popularity in the pharmaceutical industry because the accuracy of the flowmeters has improved. “It’s pretty accurate on big fill volumes, it’s not as accurate on small fill volumes,” explains Jackson. In addition, the flowmeter must be cleaned and sterilized on the filling machine because it’s part of the fluid path.  

Each filling technology is susceptible to certain product characteristics that can affect its accuracy or performance. “From my perspective, no one filling technique does everything, although the rolling-diaphragm pump is one of the better ones,” says Jackson. Current filling technology can accurately fill common dose volumes. Bosch has successfully filled 0.03-mL volumes accurately with rolling-diaphragm, piston, peristaltic, and time-pressure pumps. The company controlled fills to fractions of a drop. Drugmakers can rest assured. Apparently, it will take even higher titers and rarer products to challenge the accuracy of the filling techniques available to the industry. 

Production Lines

Drugmakers have many incentives to avoid overfilling their containers, including the scarcity, and correspondingly high cost, of certain cells and ingredients. These concerns highlight the need for techniques that can fill small volumes of product with great accuracy. Many strategies are available to the industry, but which one works best?

Equipment and Processing Report-02-17-2010

February 2010 Editor's Picks: Products from ABB and David Round

Resist the Rain Check: ePedigree Solutions Have Immediate Value

Turn Down the Fill Volume