By the time a patient picks up a prescription from a pharmacist, the drug has likely passed through the hands of nine other entities in the pharmaceutical supply chain. The US Food and Drug Administration intends to automate and enhance the safety of the pharmaceutical supply chain by establishing electronic pedigrees (ePedigrees) for drug products. An ePedigree is an electronic log of all parties at all points in the supply chain that possessed a given drug. The goal is to track drug products at the unit level as they are manufactured, packaged, sold, returned, and recalled. 

To help ensure the accuracy of the system, the pharmaceutical industry is considering two machine-readable automatic identification methods-barcodes and radio-frequency identification (RFID) tags-to store ePedigree data. Regardless of which technology is selected, packagers and label designers will need to plan for the day when a manufacturer or distributor is required to add ePedigree information to the unit-level package.

Some firms prefer barcodes because they are familiar with the technology, and because barcodes are inexpensive to print and apply. A two-dimensional barcode stores more data than do other formats, but reading barcodes is sometimes a labor-intensive process. A barcode must be applied at a position where it is visible and can be easily scanned. A variable-data printer could be used, either on an in-house printing line or at a contract partner’s facility, to generate barcodes with data that are unique to each individual dose, compared with preprinting the same barcode on every package for a particular product. Especially with variable printing, the packaging line should include a vision system to confirm the barcode’s readability at the time of printing.

Other firms prefer passive RFID tags, which cost more than barcodes but do not need to be visible to be read. This characteristic reduces the amount of handling. RFID readers can also write data to a tag, thus data can be added or changed at any point in the production line. In addition, RFID tags can store more data than a barcode and can include digital signatures to prevent the data from being read, modified, or copied by unauthorized personnel. A summary of public comments submitted to FDA in 2008 shows that RFID is the preferred technology (1). Passive RFID tags, which vary in size, shape, and style, can be embedded into a cap, wrapped around a vial, or printed on a label. Liquids and metal can influence the movement of radio waves, so RFID tag placement would have to be tested during the package-design process to ensure maximum read rates when items are packaged at the case or pallet level.

Part of a packager’s inspection and verification process should include barcode scanners or RFID readers linked to a middleware solution, which applies filtering, formatting, or logic to the data captured by a reader, thus enabling software applications to process them. Packagers should confirm the content of the recorded data, look for duplicate codes, and capture the ePedigree information in their own databases to meet possible regulatory requirements and assist with recalls. 

The pharmaceutical industry must answer the following questions before it can select and implement an ePedigree solution:

As a drug product moves through the supply chain, will the ePedigree information generated at each ownership transfer be stored in a central database or in the RFID tag on the product itself?

Who would own, manage, maintain, and protect the data in a centralized database of ePedigrees? How would participants in the supply chain access this information securely? What would happen if the database becomes inaccessible? 

If the ePedigree information is stored on the RFID tag, what security will be implemented to protect it from unauthorized readers?

Should anyone be allowed to access and use ePedigree information for purposes such as marketing? Should a manufacturer or packager be able to monitor how its drug is distributed? How is consumer privacy affected by ePedigree systems?

What scanning equipment or network access will be required at each point in the supply chain, including pharmacies, hospitals, and clinics?  How will this affect the shipping, receiving, and distribution processes?

How will the costs to establish a system to record and read ePedigree data be shared among members of the pharmaceutical supply chain? 

Patients may still be years away from knowing what other entities handled their prescriptions as well as they know their pharmacists. The California ePedigree plan is expected to become the model for FDA’s national efforts to identify, validate, authenticate, track, and trace prescription drugs, but the California State Board of Pharmacy delayed its deadline to track dangerous drugs electronically within the state. The new plan is for a staggered implementation from 2015 to 2017. 

 
  1. FDA, “Technologies for Prescription Drug Identification, Validation, Track and Trace, or Authentication,” 

http://www.regulations.gov/fdmspublic/component/main?main=DocketDetail&d=FDA-2008-N-0121

Louis M. Parks, is chief executive officer of SecureRF Corporation, 175 Post Road West, Westport, CT 06880, tel. 203.227.3151, ext 1301, LParks@SecureRF.com.

Articles

In the Mixer

The US Food and Drug Administration intends to automate and enhance the safety of the pharmaceutical supply chain by establishing electronic pedigrees (ePedigrees) for drug products.

Pharmaceutical Packaging and ePedigree Requirements

Automation has been part of pharmaceutical processing for some time, but robotics have not yet found wide acceptance among drugmakers. Recent concerns about quality control, efficiency, and cost reduction should spur the industry to reexamine the potential advantages of robotics. Robots can be particularly helpful in sterile-manufacturing applications, which are important at a time of strong demand for cytotoxic and biopharmaceutical drugs.

Shibuya Kogyo’s (Ishikawa, Japan) CellPRO system could replace human operators in processes that carry the risk of contaminating sensitive products or harming personnel. The system includes two M-430iA/2PV robotic arms created by FANUC Robotics America (Detroit) with Shibuya’s technical support. The arms are installed in Shibuya’s isolator. The robots are designed to work in International Organization for Standardization (ISO) 5 environments and do not contribute a significant amount of particulates under typical working conditions. The arms move on six axes and carry a maximum payload of 2 kg. Design features such as enclosed electric cables, triple seals, and a lack of retention areas help resist bacterial growth on the machines and reduce the potential for contamination. The robots have the International Electrotechnical Commission’s International Protection rating of 67 and are designed to withstand decontamination with vapor-phase hydrogen peroxide. 

The FANUC robots can be controlled in several ways, including manually or with a standard programmable logic control. Shibuya’s Manipen controller enables personnel to operate the robots from a separate room or another facility. Jim Akers, president of Akers Kennedy and Associates and a member of 

’s editorial advisory board, likens the Manipen to a more sophisticated version of the Nintendo Wii controller. The Manipen works through push-button and accelerometer operation and vibrates when a robot contacts a solid object, similar to the way a Wii controller functions. A user can step on a foot pedal to move the robots’ grippers into a horizontal position to pick objects up easily. The robots also can be programmed to operate automatically.

The CellPRO system’s control software has the ability to record human operators’ movements, save them as a set of instructions, and repeat them exactly. Using this feature, personnel can train the robots to perform specific tasks. After several days of practice, an operator can learn to control the robot arms well, and the arms’ trainability makes control relatively straightforward.

Manufacturers could incorporate Shibuya’s system into many pharmaceutical applications. The CellPRO system has potential to increase operator safety by compounding potent drugs, manufacturing radiopharmaceuticals, or handling cytotoxic ingredients. The robots also could help to reduce contamination risk in aseptic environments by replacing humans in cell-culture, sterility-testing, and aseptic-processing applications. The CellPRO system is appropriate for research applications, packaging, and small-scale clinical manufacturing as well, says Akers. 

As it has for other industries, robotics can bring speed, repeatability, and flexibility to pharmaceutical operations. The CellPRO system is one example of the technological advances that could improve the safety, quality, and efficiency of small- and large-molecule production. As software and robots become more sophisticated, drugmakers have less reason to shy from adapting them to their processes. Robotics could become an integral part of the industry’s strategy for the 21st century.

Production Lines

Automation has been part of pharmaceutical processing for some time, but robotics have not yet found wide acceptance among drugmakers.

Teaching a New Robot Old Tricks

Continental Disc
 Rupture disc withstands severe conditions


 Continental Disc (Liberty, MO) has added the MP unit to its SanitRX series of rupture discs. The product was designed for applications during which conditions frequently change between positive pressure and vacuum. The company moved the disc’s score line from the contact side to the downstream side so that it is subject to less stress when pressure changes. The new position also improves the disc’s cleanability. The disc can be cleaned or steamed in place.

The disc complies with the American Society for Mechanical Engineers’s bioprocessing equipment criteria for process-side surface finish and fully traceable metal and elastomer materials. The component also is free of polishing compounds, release agents, and animal derivatives. The disc’s flow-resistance values are 1.13 for gas and 1.60 for liquid. The disc is appropriate for pressure-vessel applications such as autoclaves, fermenters, and heat exchangers.


 Filamatic’s (Baltimore, MD) AdaptaFil semiautomatic filling machine now offers interchangeable peristaltic, gear, lobe, and piston pumps. Pump changeover does not require tools and enables users to adapt the device to run new products. Changeover also reduces operators’ need to learn how to use new equipment, says Jack Chopper, chief electrical engineer for Filamatic.

The unit can operate at production scale and can be incorporated into an automatic filling line. The filler’s human–machine interface allows operators to save and retrieve recipes by name and number, copy recipes to other machines, and change fill setups easily. The machine’s software system provides control over fill speeds and delay time between fill segments. Users can calibrate a fill with the push of a button. 

PharmTech's monthly newsletter, Equipment & Processing Report, reviews the Editor's Picks for the May 2009 edition from Continental Disc and Filimatic.

Equipment and Processing Report-05-20-2009

Pharmaceutical Packaging and ePedigree Requirements

Teaching a New Robot Old Tricks

May 2009 Editor's Picks: Products from Continental Disc and Filimatic