Taking a Hard Look at Software

Despite FDA�s recent lenience, software for compliance is more important than ever.



Ben Van Houten

Pharmaceutical and medical product manufacturers breathed a sigh of relief this past August when FDA eliminated several of its guidances on 21 CFR Part 11. The agency wrote that it is reexamining the regulation, which covers electronic records and signatures, and intends to narrow its scope and formally revise it. 

The upshot for companies? Less-intense FDA focus on software compliance. �That was a sight for sore eyes,� says Shawn Gould, software compliance specialist for pharmaceutical manufacturer aaiPharma (Wilmington, NC). �Before they changed Part 11, we were scrambling to try to comply. Nobody really knew how far to go, and which software applications were affected. The changes allow us to make decisions based on risk analyses instead.� 
Alan Kusinitz, president of consulting firm Software CPR (Boston), agrees. �FDA�s reduced focus on technical requirements for computerized audit trails in particular has lowered the urgency,� he says.

FDA�s new stance is part of its �Pharmaceutical CGMP Risk-Based Approach� initiative, which includes a reexamination of 21 CFR Part 11. However, some experts say, FDA is poised to become more stringent than ever in its regulatory governing. In fact, most technical controls mandated by the original 21 CFR rule remain unchanged. �FDA enforcement is still growing,� says Kusinitz. �There is more scrutiny surrounding mislabeling of packaging, for example.�

In addition, the agency�s Process and Analytical Technologies (PAT) initiative, which employs computer systems for on-line reporting and data analysis, is expected to soon get a big push. Considering that many processes, including packaging, are still driven by software, most agree that it�s more important than ever to look at software that enhances compliance.

Indeed, software is necessary for packaging companies to organize collected data and to link to other systems such as patient care, warehouse management, transportation management, and enterprise resource planning. By using electronic solutions, packaging engineers and plant floor managers alike can have more internal evaluation and quality control. Quality assurance and information management department personnel can also exchange information quicker and reduce data-entry errors and storage space costs. Software also allows them to automate recording temperatures and pressures, enforce the right sequence of operator workflow, and maintain an audit trail showing that everything performed as expected.

And that is why many companies are still taking a hard look at their software solutions, whether for testing, audit trails, archiving, or security. �One thing to remember is that if you�re going to go electronic, you still need a very good way of validating your systems, regardless of Part 11,� says Joe Schenk, president of software vendor QA Edge (Wilmington, DE). �There are many good reasons to invest in software that does that.� 

Chris Parsons, vice president of Pilgrim Software (Tampa, FL), seconds the notion. �Software is about controlling production, efficiency, and compliance, and those will always be important to packagers and manufacturers,� he says. 

Part 11: Compliance Still Needed

So why did FDA change its approach to Part 11? In its guidance, the agency wrote that it felt some interpretations of the rule would restrict the use of electronic technology, increase the costs of compliance, and discourage technological advances. Ultimately, FDA now wants a more �risk-based� approach from pharmaceutical and medical companies. �When FDA issued the guidance, it was saying it wants companies to be risk-focused and do the right thing based on risk such as testing systems and making sure they work,� says Milan Bhalala, director of marketing at Camstar Systems (San Jose).

Yet that doesn�t mean the need for compliance will magically disappear. �FDA is trying to reemphasize some things, but I doubt the actual regulations will change much,� says Schenk. 

�The recent reinterpretation changes things for companies, but not as much as you�d think,� adds Kent St. Vrain, vice president of sales and service for software provider Paxonix (Parsippany, NJ). 

Carl Accetura, senior vice president of client services and FDA solutions for Document Control Systems (Salt Lake City), has even stronger words. �It is important that this new guidance not be overinterpreted to imply a relaxation of validation requirements,� he says. �There are so many other regulations to comply with, and validating computer and software systems is critical to achieving that compliance.�

Shawn Gould from aaiPharma says FDA will likely renew its focus more on validating software now that it has relaxed the Part 11 requirements. �So companies like ours need to take a good look at our software, specifically software that deals with testing. We need to chart batches, for example, using software that measures the temperature and other aspects of a room�s environment.�

Among the companies still making a strong pitch for Part 11 compliance software is Werum America Inc. (Towaco, NJ). Werum offers PAS-X, for example, a software program that features production planning and scheduling, materials flow control, warehouse management, packaging-line control, and calculation of key performance indicators. The company also recently collaborated with Uhlmann Packaging Systems Inc. (Towaco, NJ). That collaboration resulted in the creation of Netmaker 5.1, software that automatically downloads all product and production data required for process optimization.

Steve Cagle, manager of operations for Sparta Systems Inc. (Holmdel, NJ), touts his company�s TrackWise software, which is especially useful for packaging-plant managers. �It allows users to manage quality issues,� he says. �The packaging industry has gradually employed electronic tracking, and there�s a huge need for a solution to manage that. Companies want a single solution that allows them to have a workflow system in one database.� 

He also claims the product reduced cycle time on batch release by 35% in one case, and typically results in a 30-day closeout on investigations. Also, since GMPs are still within the scope of Part 11, �companies still need to be compliant in many ways. This program is set up to handle that,� he says. He adds that the document management system is designed to accommodate other regulated documents, such as SOPs, test methods, and batch records. TrackWise also stores each electronic record with its audit trail. It then illustrates when and why each change was made. 

Bhalala from Camstar sees an increase in the availability of manufacturing execution systems (MES). Such systems provide a method of interfacing between enterprise resource planning systems and plant-floor control systems. �The reinterpretation of Part 11 gets to the heart of what MES was intended to do,� he says. �That is to eliminate paper, create electronic batch records, and keep all the records of the manufacturing process on a database. FDA still wants complete device-history records, testing, and sampling to be done a certain way. That�s why paperless batch records will always be important.� Camstar�s InSite software provides packagers with a tool to help manage equipment on the production floor.

One critical aspect of all compliant systems, according to St. Vrain of Paxonix, is a method of �point verification� for electronic signatures. This verifies who is requesting an action, thereby preventing unauthorized people from using the system. Paxonix� PaxPro Toolset system also allows users to work from off-site locations. �This is important, because the people who are involved in approval and validation are always traveling,� he says. 

Additional Software Applications

Part 11 notwithstanding, there are numerous other manufacturing and packaging systems that benefit from the use of software. �The main goal in the pharmaceutical industry is to try to find every possible way to increase the speed to market,� says St. Vrain. �The question you have to ask is, �Does the software put too much structure into the process?� You don�t want to incorporate so much structure into the software that they can�t use it.�

Additionally, software vendors say that packagers in particular want ease of use in whatever system they incorporate. �Packaging people are traditionally not software people,� says Steve Pulsifer, vice president of marketing for GE Fanuc Automation Americas Inc. (Charlottesville, VA). �In addition, most companies no longer have the information technology staff they used to. It�s a constant struggle for these companies, due to lack of time and money. However, it should be as simple as possible. With packaging, you simply need to track what goes on and see whether there are performance deviations from one line to the next.�

Pulsifer says GE recently developed change management software for that purpose, which controls programs and file structure. The software is designed to help companies track changes and control versions of automation software, devices, and equipment used on the factory floor. It provides electronic recordkeeping, electronic signatures, audit trails, and record security, and can connect to an installed base of different plant-floor systems. The system organizes and automatically tracks every element of a plant�s automation/software system, according to Pulsifer. �This allows configuration of electronic signatures at key points in the change operation,� he says. �Any system changes are then managed and tracked automatically.�

Arbortext (Ann Arbor, MI) is another software provider that offers solutions for packaging companies. The company uses extensible markup language (XML) software that helps streamline the process of publishing package inserts, leaflets, and labels. Joe Jenkins, marketing director, explains that XML offers companies the ability to reuse a single component. �Packaging is definitely a solid candidate for XML, because each component, whether foil or cotton, has its own specifications,� he says. �For example, foil must be of a certain thickness. So the packaging engineer can create a bill of materials in XML that the specific item can have a direct link to.�

Companies also need to remain focused on validation, software vendors say, in spite of the Part 11 change. �Companies will have to take greater responsibility for process capability control,� says Carl Accetura of Document Control Systems. �With the change in Part 11, they now have to validate based on risk assessment and potential of the software system to affect product quality, safety, and record integrity. And that validation needs structure.�

He urges companies to maintain a validation documentation tool kit. According to Accetura, that should include the following: formal risk management and validation plans, user and functional requirement specifications, and operational and performance qualification controls.

Bhalala from Camstar says his company�s InSite software program incorporates prevalidated core technologies and a configurable layer that companies can use to model their processes. �This gives the product an 80%-finished validation when purchased,� he says. He adds that companies can reduce the cost of compliance with the system because it mirrors processes that FDA finds important.

The Road Ahead

No matter what transpires in the regulatory arena, most agree that software will be a factor in the immediate future. In fact, there are signs that FDA is setting its sights on other areas where software will play an integral part. For example, the PAT initiative is poised for increased emphasis. �That initiative deals with moving off-line systems in-line,� says Bhalala of Camstar. �That trend toward in-line production and packaging means that companies will be increasingly looking to consolidate applications, through software.�

GE Fanuc�s Pulsifer agrees. �All the pharmaceutical guys are looking at PAT,� he says. �Our customers are definitely concentrating on it. It is a good initiative, in that it provides a framework in which companies can be more secure.� He says PAT affects products that are developed in a real-time flow method, such as medical gases.

PAT reflects an even bigger trend, some say: integration. �More and more packaging companies are looking to integrate between systems,� says Steve Cagle of Sparta. �They want to use software to retrieve information, such as lot and batch information, from other systems.�

Package-design software company Cape Systems (Dallas) has also noticed the integration trend. �More and more companies are not only concerned with designing the packaging with a software program, but they need to integrate that information with specifications programs and other larger systems,� says Heidi Larsen, director of marketing. �They are still trying to reduce material costs, design safer packaging, and calculate more-efficient methods of transporting their items.�

Integration is also increasingly required when it comes to traceability. �From design, all the way through product, everything needs to be collected, identified, and managed,� says Brian Thompson, vice president of sales for software company AssetSmart (Santa Monica, CA). �Even at the design stage, packaging engineers have to have the correct SOPs. Our software offers integrated compliance from design through manufacturing. The integration is important, because if something goes wrong, changes can be made in real time and you don�t have to scrap entire lots.�

Another growing trend is compliance with the Sarbanes-Oxley Act of 2002. The federally mandated regulation, formally known as the Public Company Accounting Reform and Investor Protection Act, was set up in the wake of the Enron scandal to make companies meet strict financial accounting and reporting requirements. �Many pharmaceutical companies are focusing on complying with this, and they are looking for software to help them do that,� says Thompson. �Being able to accurately identify key financial information like total assets is critical to ensure compliance, as these figures are also used to calculate ratios for industry comparisons and are widely used by analysts to determine shareholder value.�

To that end, software provider Iconics (Foxborough, MA) recently announced a partnership with security firm Saflink in which Iconics� Genesis32 Automation Suite software supports Saflink�s Biometric Identity Assurance Management software. This provides users of Iconics software with the option to use biometrics for operator authentication. �This is critical for companies wanting to meet the business and security requirements of additional government regulations like Sarbanes-Oxley, which uses biometric authentication,� says Tim Donaldson, Iconics� marketing manager. 

There is also the possibility that the original, stricter version of Part 11 could make a comeback. �There is a chance that FDA will reinstate the guidelines,� says Kusinitz of Software CPR. �They are planning to have a public meeting on that soon.�
Even if Part 11 stays the same, �companies will need a very good way of validating their processes through software if they are going to go electronic,� he adds. �And I think companies are generally staying conservative, since they don�t want to be burned down the road if FDA changes its mind again.�

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