Most pharmaceutical companies have made major inroads in applying advanced control technology to improve their manufacturing processes. However, these efforts often stop abruptly at weigh-and-dispense operations.
The weighing and dispensing of pharmaceutical ingredients may seem mundane, but it's crucial. If a mistake is made at this traditionally manual point in the manufacturing process, no matter what happens later on, the entire batch may need to be thrown out or remade.
Unfortunately, errors can occur when operators write information down or when other employees enter process data into a computer-based system, says Glenn Restivo, life sciences solution marketing manager at Rockwell Automation in Philadelphia. In most cases, a weigh-and-dispense error isn't picked up until after the fact. "By then," he says, "you have a wasted batch."
In modernizing weigh-and-dispense operations, one goal is to drive errors out of the operation, and record data properly and accurately, Restivo says. Another goal is to use data more effectively. "Weigh-and-dispense has become an integral part of a plant's electronic batch record," observes Thomas Farenholtz, director of professional services at Honeywell Life Sciences in Herndon, Va., which offers the popular POMS manufacturing execution system (MES). "Many manufacturers today are seeking to use the data from the weigh-and-dispense operation and extend this automation toward the rest of the plant," he adds.
Although new pharmaceutical plants are typically built with extensive automation and electronic controls, older plants that make established products or commodities still depend largely on manual or semi-manual data collection and record-keeping. "Most companies [use] off-line scales to prepare materials for a batch," says Janice Abel, director of pharmaceutical marketing at Invensys Production Solutions, Foxboro, Mass. "Electronic record-keeping tends to be [seen] as a want, and not a need," adds Robin Laub, account manager at Schneider Electric (Palatine, Ill.), "and record-keeping activity gets put off."
Technological Lethargy
Perceived cost savings often play a key part in this technological lethargy. As profit margins continue to be pressured, managers at leading drug firms are scrutinizing manufacturing costs as they never have before. A recent GlaxoSmithKline survey, for example, found that the 16 largest drug firms spent more than twice as much on manufacturing as they did on R&D.
Some firms resist upgrading because such changes would necessitate a fresh review and approval from regulators. "When you want to make some changes to automate certain functions, you have to revalidate the entire control system," says Mark Liston, pharmaceutical business director at Scneider.
Even the validation of the scales used for weighing materials can be problematic, says Steve Smith, applications support manager at Kistler Morse Co., a Bothell, Wash., manufacturer of weighing systems. "The cost to bring everything up to date may not be worth it to them, because they would have to revalidate the whole process."
However, manual checking, testing, weighing and recordkeeping may end up costing far more than they save, opening the door for monumentally expensive, often preventable human errors. Consider the fact that 354 prescription drugs were recalled last year, a 50% increase from the previous year and more than double 1997's figure, according to the U.S. Food and Drug Administration (FDA). Recalls can cost manufacturers several millions of dollars. In addition, observers say, five to 10 percent of the medicine currently produced in the U.S. falls short of quality or other specifications and has to be thrown out or reprocessed.
Even if companies aren't making weighing or dispensing errors, outmoded equipment can prevent them from utilizing data, or streamlining or automating processes. "Data collection goes hand in hand with analysis---the idea is to turn the data into knowledge to improve your process," says Steve Pulsifer, marketing development manager in the life sciences group at control systems manufacturer GE Fanuc in Northamptom, Mass.
Caught between a Scylla of regulation and a Charybdis of rising manufacturing costs, more drug makers are starting to modernize their weighing and dispensing functions to reduce expenses and ensure better quality control. Instead of developing software in-house, many are evaluating control vendor platforms to improve the speed and accuracy of their weighing and dispensing functions. And many are implementing this automation in phases, says John Blanchard, director of research and principal analyst for the food, beverage, and life sciences industries with the ARC Advisory Group, a manufacturing technology research firm in Dedham, Mass.
"These improvements make good business sense," says Jim Marshall, engineering team leader with Eli Lilly (Indianapolis). "Better data integrity helps the plant with uptime and to run better."
FDA is providing added incentive for modernization as it revamps its manufacturing guidelines. "FDA is putting incentives in place so that pharmaceutical companies can improve the efficiency of their manufacturing operations," says Bob Lenich, business development director at Emerson Life Sciences in Austin, Texas.
Weigh and dispense begins with an operator getting a bill of materials for ingredients that make up a recipe for a batch to be manufactured. Each material must be gathered from a warehouse or other storage area. Then it must be verified as the proper material, carefully weighed, checked again, and finally readied for mixing in the recipe. Sometimes the mixing occurs immediately upon assembly of the various ingredients, and sometimes it occurs later on, with the materials being chosen, weighed, and removed to a staging area in advance.
Traceability an Issue
At each step, checks must be observed to ensure that the operator, the equipment, the materials, their weights---and even the scales they are weighed on---are up to snuff. All must be verified to conform with manufacturing specifications and regulatory requirements.
Drug manufacturers also benefit from an all-electronic solution by having faster and more accurate data records for traceability purposes down the line. "The idea is to be able to go dock to dock with complete traceability" for a particular batch and the materials used to make it, says Daren Moffatt, pharmaceutical industry business manager for Invensys. For many companies, it would take days to get that information, adds his colleague Janice Abel.
While an operator is required to handle most of the actual weighing and dispensing functions, the process automation surrounding the weigh-and-dispense routine can itself perform most, if not all, of the associated record-keeping. By moving this process to an electronic data recording system, manufacturers can eliminate the chance that an operator maintaining paper records may skip a step or erroneously duplicate a step in the process.
Also, the need to collect data stored on paper records can be so time-consuming that some companies avoid analyzing the results, a decision that allows inefficiencies in the process to continue unchanged. "Invensys can capture that information at the source---at the weigh scales---and feed it back into the system electronically," says Richard Howells, vice president of marketing at Invensys Production Solutions, Newton, Mass. Invensys' Wonderware Factory Suite's Intrac component handles the weighing data.
Last but not least, an effective process control system or MES at this shop-floor level can be tied into the company's enterprise resource planning (ERP) system. By contrast, traditional methods used to convert paper records to computer data often are not cost-effective, requiring a clerical person to manually enter the data into a spreadsheet program for later uploading to the corporate materials management and inventory system.
Electronic collection of the data associated with the weigh-and-dispense manual process goes a long way toward eliminating such errors, and by extension, waste in the manufacturing process. Electronic record-keeping ensures that operators are efficient, prevents errors, and provides a more careful check of quality at each juncture in the process.
"Saving a batch because the operator was going to add the wrong material otherwise can save a company anywhere from $50,000 to $2 million,"says Lenich of Emerson, which integrates Decision Management International's software into its process automation system to offer a turnkey application for drug firms.
Similarly, Rockwell's Restivo notes that his firm's RSBizWare eProcuredure MES system automates these manual procedures while both managing and documenting the process. Adds Lorenzo Majewski, product manager at Rockwell Automation headquarters in Milwaukee, the system also can be set up "to create instructions to operators to guide them through the operation."
E-signatures Important
One area where most manufacturers are finding significant benefits to be gained via automation is the electronic signature. Basically, instead of having the operator who selects the materials and weighs the amount of each that goes into a batch sign his or her name manually---long a requirement of the FDA--- the operator now can use a computer to perform the verification.
"The operator is asked to identify himself at least with his user name and password before he is allowed to do the action he is supposed to do," explains Robert Fretz, head of corporate manufacturing execution systems at Hoffman LaRoche (Nutley, N.J.).
This kind of electronic audit trail can also be a productivity tool, Fretz adds, because the traceability of a specific batch no longer requires manual searching for paper records. The Rockwell Automation system, for example, automatically enforces the electronic signature, both at operator log-in and sign-off according to the FDA's 21 CFR Part 11 standards.
Integration a Concern
An obvious area where pharmaceutical manufacturers are concerned is data integration. What with a compendium of different technologies to be dealt with on the plant floor, it's a wonder companies are willing to take on the sometimes monumental challenge of making every piece of hardware and software speak the same language---and smoothly.
"There is a variation in the spectrum of vendors," Marshall of Eli Lilly explains. "A lot of vendors have very good standalone systems, but the difficulty is integrating them with other vendors' solutions."Fretz of Hoffman LaRoche agrees, adding, "The nightmare is that most of our systems are composed of components of different vendors. The dream is to integrate all these systems," he says.
"Drug firms need to develop a strategy for integrating all these different control systems," suggests Schneider Electric's Liston. "This coordination issue is a significant burden for our customers in the pharmaceutical industry," he says.
Very simply, one reason for the common lack of data coordination is that most process automation vendors tend to come into a plant, install their own system, and then leave, without concern for how well or how poorly it interacts with other existing hardware and software in the plant and at the company offices.
As Liston points out, "Project management gets it on site and gets it running, but takes no responsibility to come in and fix everything and make everything work." Usually, these kinds of integration headaches become the purview of the pharmaceutical company's validation team, which must address data integration problems after the fact.
Another related issue is changing old systems and old procedures to mesh with the new technologies. "Basically all the procedures in place in a pharmaceutical manufacturing facility are in place to make it difficult to change anything," says Fred Doubleday, CTO of Decision Management International (Bradenton, Fla.). "It's always easier to implement automation into a new plant than an existing one."
Still, weigh-and-dispense processes and systems are on the verge of significant modernization. "Now that the FDA has accepted electronic record-keeping, more manufacturers will start automating these processes," says Invensys' Howells. "Or they will be forced to do so from a competitive and regulatory standpoint."
