Prescription for Success

PHARMACEUTICAL COMPANIES ARE LEVERAGING ENHANCED STANDARDS TO EASE THE VALIDATION PROCESS

By Joseph C. Panettieri

The validation of packaging machinery for pharmaceutical end-users has become something of a cottage industry. It’s a process that’s required by the Food and Drug Administration (FDA) and can be onerous, in both time and money. But handled correctly, and with enough pre-planning, medical validation can save companies—both equipment manufacturers and end-users—millions over the long haul. To some extent, though, the process is still shrouded in mystery.

While each pharmaceutical company has its own specific standards for validation, the process provides a road map that will chart the best route to ensuring a particular machine will operate as envisioned. Some manufacturers, like MGS Machine Corp., in Minneapolis, Minn., offer a “standard package” that establishes a baseline for the validation process. Starting from that baseline, end-users can then specify their own needs. “In general, [machinery] manufacturers are starting to better understand what it is the pharmaceutical companies need,” says MGS chairman Mel Bahr.

Fill'er up: The FLC vial filler from Bosch Packaging Technology

Adding to that understanding are organizations such as the Joint Equipment Transition Team (JETT) and the Open Modular Architecture Controls (OMAC) Users Group. These groups, working together with machinery manufacturers and end-users, are, according to Bahr, “facilitating the whole validation process. And that’s just good business. Who wouldn’t want that?”

Despite that overwhelming business logic, validating packaging machinery for the pharmaceutical industry can give managers migraines. Indeed, some pharmaceutical companies struggle to make sure their equipment and processes meet the FDA’s complicated validation and documentation requirements.

Rather than tempt the government’s wrath, savvy machinery managers have joined JETT, a consortium of pharmaceutical companies, equipment suppliers and consultants. JETT (www.jettconsortium.com) seeks to improve communication among its members and, in turn, empower its participants to more effectively meet validation requirements within the pharmaceutical industry. JETT’s membership reads like a “who’s who” of pharmaceutical companies and original equipment manufacturers (OEMs), ranging from Abbott Laboratories to Vector Corp.

Consortium members have high praise for JETT. “My personal opinion is that the JETT team is making valuable contributions to the validation process by improving communications, expectations and establishing good documentation practices between end-users and the original equipment manufacturers,” says Patrick Cashman, a project engineer at Abbott Laboratories of Abbott Park, Ill. “If I were an OEM working in the pharmaceutical industry, I would certainly want to be aware of the JETT recommendations. I would think there could be some competitive advantage in knowing what documentation would help my pharmaceutical client simplify and enhance its validation efforts.”

That’s for sure. JETT members MedPointe Inc. and MGS Machine, for instance, have a close working relationship, which ensures that MGS equipment more easily achieves validation for use at MedPointe Pharmaceuticals. “The whole idea of JETT is to get more of the validation process completed during the equipment testing stage at the OEM’s plant,” says Karl Bovyn, a production manager at MedPointe of Somerset, N.J.

Toward that end, JETT supports GAMP (Good Automated Manufacturing Practice Guide), Version 4.0, a standard published by the International Society of Pharmaceutical Engineering. JETT’s work, coupled with the GAMP guide, helps pharmaceutical companies and their machine suppliers outline and define user requirement specification (URS), installation qualifications (IQ), operational qualifications (OQ) and performance qualifications (PQ), Bahr notes.

“Virtually all of our pharmaceutical customers use our validation services in some format,” Bahr says, referring specifically to his own company rather than JETT. “I think JETT has done a really good job with the URS portion of validation. We [JETT members] are taking a serious look at the IQ and OQ areas.”

Pharmaceutical companies that haven’t joined JETT may be in for a struggle. According to broadly accepted industry estimates, of every dollar spent by pharmaceutical firms, 36 cents is tied to manufacturing costs. Even worse, those costs can skyrocket if the validation process sputters, stalls or requires unexpected machinery changes.

Skeptical? Consider that the validation process can drive costs about 40 percent higher in a typical packaging machinery deployment, according to Keith S. Campbell, former executive director of the OMAC Packaging Workgroup and former director of automation and integration at Hershey Foods Corp. The validation process can be painful for both the vendor and the customer because of extensive time delays and the potential cost of tweaking/enhancing machines that have failed validation and must go through the process again.

Even when systems are humming along, the need to track documentation so that procedural changes and line updates meet reviewer requirements is ever present. “User requirements provide the foundation for the validation process,” notes JETT member Bret Fisk, an associate engineering consultant within Eli Lilly Co.’s Global Automation Delivery division. “But some users never really put together a good user-requirement document.”

With these potential pitfalls in mind, some (though certainly not all) packaging suppliers are steering clear of the pharmaceutical market. “I’ve heard anecdotal accounts of [compliance] limiting vendor choices,” Campbell concedes. “Some vendors just won’t bite on pharmaceutical opportunities.”

FOLLOW THE LEADERS

Still, there’s no need to panic. Informed pharmaceutical firms and machinery makers are banding together to avoid such setbacks. Together, customers and suppliers are designing and adopting key standards that ease the validation process. The standards address such areas as open hardware, networking, software, development methodology and documentation.

The McBrady Orbit bottle cleaner/rinser was on display at last year's PACK EXPO

Not sure where to start? In addition to reaching out to JETT, pharmaceutical machinery managers should explore GAMP (www.ispe.org/gamp), the International Society for Pharmaceutical Engineering (www.ispe.org) and the OMAC Users Group.

Active standards advocates include JETT member Pfizer Inc., where employees—including automation engineer Robert Martell—work to ensure that the $45.2 billion company’s packaging machines meet FDA regulations for pharmaceutical plants.

Instead of worrying about validation challenges, Martell faces them head-on. “Validation of pharmaceutical machinery is too often an open-ended process with unpredictable time frames that can range from 10 to 40 percent of total project costs,” he lamented during a presentation at PACK Expo Las Vegas 2003. “However, there are proactive steps you can take to help control those costs.”

Indeed, the four steps for success, according to Chris Roerig, manager of business development at Voest-Alpine Industries Inc., are:

1. Establish approved user requirements;
2. Plan for validation before specifying a system;
3. Continually align approved specifications with system features throughout development; and
4. Prove document-to-system alignment in commissioning and qualification.

Still, companies that successfully clear these four hurdles haven’t finished the validation race. Roerig points out that validation is “a state, not a task.” To remain validated, a system needs to be part of a company’s Master Validation Plan for each site. The plan should include efficient change control processes and periodic reviews, he notes.

That sounds simple enough, but many companies need external handholding as they try to navigate the validation minefield, which is where standards bodies enter the picture.

OLD RELIABLE

Some standards efforts aren’t quite so new. GAMP has European roots that date back to 1991. The organization’s North American arm, GAMP Americas, includes key working groups such as JETT, which specializes in the validation of process control systems. The organization’s primary goals are to:

• Provide a common technical language base, bid package formats and validation test plan examples that will be widely accepted by the pharmaceutical industry;
• Promote communications between end-users and vendors that serve the pharmaceutical industry; and
• Streamline time-to-market projects by incorporating GAMP guidelines and validation requirements up front in major projects.

Admittedly, JETT’s goals are ambitious, but the organization is making rapid progress. From Abbott Laboratories to Eli Lilly and Vector Corp., big-name pharmaceutical companies and their vendors are very active in JETT. Says Fisk from Eli Lilly, “JETT has made great progress, and I expect more progress in the near future.” He points to ongoing discussions between FDA representatives and pharmaceutical executives. Most of the chatter involves a heightened focus on quality practices rather than process documentation.

The reason: Too often, pharmaceutical firms hesitate to change their quality practices because they fear it will take too long to adjust their documentation, notes Fisk without referring specifically to Eli Lilly.

MAJOR MIGRAINE?

Despite this progress, validation challenges remain. The thorniest issue typically involves the Code of Federal Regulations, Section 21, Part 11 (more commonly known as 21 CFR Part 11). The specification, enacted by the FDA in 1997, defines how pharmaceutical companies must manage documents, electronic data and digital signatures. It applies to any data related to research and development, clinical studies, manufacturing and the distribution of pharmaceutical products.

“With the rise of e-business, the government had to design legislation that protects data from being altered, deleted or misused,” says Max Famili, vice president of software quality assurance (SQA) and validation at Novatek International, a software consulting firm that serves pharmaceutical companies.

To comply with 21 CFR Part 11, pharmaceutical firms must adhere to procedural (notification, training, etc.), administrative and technical controls.

Meeting these three key criteria isn’t easy. “When you consider the number of people making money by selling training and other programs [related to 21 CFR Part 11], there must be a problem,” Campbell says.

At best, application vendors can bring a customer up to technical compliance, but customers often have to look elsewhere for administrative and procedural help, according to ADN, a London-based consulting firm that specializes in regulatory compliance within the pharmaceutical industry.

Not by coincidence, consulting firms are ramping up business practices that specifically address 21 CFR Part 11 and validation processes. Just ask BusinessEdge Solutions Inc. of East Brunswick, N.J. BusinessEdge recently recruited compliance veteran Kate Townsend to oversee the firm’s compliance services. Although BusinessEdge declines to discuss its customers by name, the firm claims to serve primarily pharmaceutical and health-care organizations.

Software companies also are assisting the 21 CFR Part 11 compliance effort. Johnson & Johnson uses EduNeering ComplianceWire to clear some CFR hurdles. The software package also supports the rules and regulations specified by GAMP and Good Manufacturing Practices (GMP), including the management of certifications, notifications, tracking, records and reporting. According to a spokeswoman for the company, Johnson & Johnson employees can maintain and access training documentation to demonstrate their compliance with FDA and other regulatory agencies.

Sounds like a case for validation.

Joseph C. Panettieri has covered Silicon Valley since 1992.