By Lisa Nadile
DURHAM, NC—Meeting FDA requirements for validating software automated operations not only will improve the quality and safety of a manufacturing process, but the validation process itself will help manage and improve contamination control strategies, say validation specialists.
The message is simple. If one improves a tool that organizes the way a company operates, the procedures used to control and prevent contamination are also improved. Less contamination means fewer recalls and corrective actions, reduced cleaning time, and liability. The lower the contamination, the lower the costs the company incurs.
The information described in this article is detailed in a draft of the FDA's software validation regulations at: http://www.fda.gov/cdrh/ode/swareval.html. Similar information was also presented at last year's CleanRooms West '99 in San Jose, CA.
Which companies should validate their software?
- The software used in medical devices requires validation as part of a company's implementation of design controls for the regulation of medical device quality systems.
- The software used to automate a production process is also used to meet the medical device quality systems regulations.
What does it mean to validate software? The FDA states in 21 CFR 211.68(b) that companies must examine and confirm all software used to automate operations have clearly outlined specifications, and they must demonstrate that the specifications are met.
Validation consists of a review of the tests performed by the software, the testing of the software's functionality, code walkthroughs, inspection of flowcharts, and the testing of software tools.
Companies must create a software design plan that:
- Describes how the software is integrated and what interaction it achieves among research, production, marketing, and other areas of a company;
- Outlines quality practices, assessment methodologies, timelines, resources, and documentation requirements;
- Creates review procedures to verify design;
- Describes criteria for creating and validating changes to the software. (Be sure to maintain a previous version of the code.);
- Specifies steps for software maintenance and the identification of improvements.
Faced with this daunting task, companies are now hiring specialists to walk them through the process. Clarkston-Potomac, a consultant company, has just hired Carol Brandt, a 20-year veteran of the software validation in the biosciences and pharmaceutical industries.
“Most companies have no idea what is entailed,” says Brandt. “Each company has designed its system, added modifications over time to meet its own needs, and created its own standards,” she says.
Brandt adds that she often sees monolithic legacy systems with no documentation. “Many companies have never even tested their systems and don't even know their accuracy,” she explains.
“Over time, the companies and the FDA have cracked down. Companies are currently installing new systems or ironing out the wrinkles in their legacy operations,” says Brandt.
“One of the most important events taken during software validation is assessing the risks with doing (or not doing) a step. Companies must ask themselves: does taking a step have an effect on product quality or efficacy?” she says. Brandt stresses a company can expect to encounter a large number of gray areas both in the FDA requirements for validation and in the company's choices in its manufacturing process.
“Just analyze a step according to its direct affect on the business,” Brandt says. Evaluating how each step will affect a company's contamination control strategy is a must. The choices revealed in the manufacturing process can reveal areas of weakness in a contamination control strategy in addition to opportunities to improve a satisfactory one.
“Most companies fail to take into account how a step affects the process indirectly. Ultimately, there can even be a domino effect if a step's interconnections with the manufacturing process is underestimated,” she says.
One example Brandt cites is evaluating human resource (HR) documentation. While such information seems innocuous at first, not taking the advantage of the resources contained in these documents can lead to unexpected problems in a cleanroom.
Companies must understand that even HR documents must be maintained according to FDA regulations. An employee's experience and training is ascertainable very quickly, preventing the placement of a person in a job for which they lack appropriate training, she explains.
This mistake could show up much later in procedural errors that can contaminate a cleanroom and result in faulty products.
The FDA requires that a company demonstrate the use of its software automation operations throughout all phases of manufacturing. To begin with, documenting the management of internal SOPs is a must. According to Brandt, a company must show a timeline.
 source: Analex Corp. |
“Most companies concentrate on the design, testing, and implementation of their software automation procedures. They fail to create and validate procedures and controls for making changes,” Brandt says. Implementing changes in sterile environments is an important and often overlooked part of the strategy.
The most important part of software validation is to get the most out of the process for your company, rather than just satisfying the FDA.