FDA has been encouraging drug manufacturers to tackle their batch-to-batch quality requirements for years, but is now getting serious about it. Historically reactive in its enforcement actions, FDA is now looking to proactively improve quality in the life-sciences industry. For example, rather than just punish companies for quality missteps, FDA is making plans to incentivize high-quality manufacturing in hopes that this will ensure better overall drug quality and a reduction in drug shortages. While FDA is still unclear on how this can be done, it knows which sort of initiatives it wants to reward."[We are] looking at ways the FDA, using our existing authorities, can recognize manufacturers that do a particularly valuable job," said FDA deputy director of regulatory programs Dr. Douglas Throckmorton.
One major step has already been taken. The Center for Drug Evaluation and Research has created a new Office of Pharmaceutical Quality that will support these efforts by collecting performance metrics and conducting trend analysis. Ostensibly, the office will focus on metrics such as manufacturing defects, cycle times, and overall batch quality. This makes sense except that these are all lagging indicators that measure the outcomes of what has already happened. Leading indicators, by contrast, provide information that may directly aid in predicting future outcomes so companies can potentially prevent errors or identify bottlenecks before the damage is done. While they can be more difficult to capture, leading indicators can be spotted early on—before molecules are processed, capsules are formed, and batch reports are run. Months before the quality management system starts processing data, life-sciences companies can get a sneak-peak into potential quality problems by looking at the leading indicators hiding in the document management process further upstream. In other words, by taking one step back, organizations can jump two important steps forward.
Document lifecycle metrics
Today, especially with the high volume of quality assurance (QA) related documents (standard operating procedures [SOPs], training manuals, etc.), life sciences companies can uncover trouble spots and bottlenecks just by looking at their documents from the authoring process to related training impact. Document lifecycle metrics (e.g., how much time it takes to review a change in training SOPs) can pinpoint various key leading indicators of quality discrepancies and compliance risk.
If there is a spike in the number of corrective actions and preventive actions (CAPAs) submitted in a particular month (say a 25% increase compared to the typical run rate), for example, a company could expect an increase in the number of days to update affected SOPs or work instructions. Changes to these documents require a change-control process, and delays prolong completion of the documentation updates. This delay postpones checking the effectiveness of the resolution to the original problem and closure of CAPAs. An organization that has an internal goal to speed closure of change controls and CAPAs could find their metric has trended adversely. If the company, however, had been monitoring the status of documents in process and rebalanced document control resources to accommodate the influx of documentation updates, it might have been possible to avoid a performance decline, thereby closing change controls and CAPAs more quickly.
Looking proactively at the document lifecycle can reveal many leading quality-indicating metrics, such as how long it takes for a document to be routed from draft to review to approval and distribution to staff; or the amount of time it takes to train staff on a new or changed SOP. If a document gets snagged somewhere along the way, it could cause a production delay downstream, and if this is a common bottleneck, it could suggest a much bigger problem. If an organization must amend an equipment calibration SOP to meet new standards, but approval is stalled, staff training is likewise postponed, which directly impacts manufacturing. Such delays could even shut down drug production. But, if a company sees this bottleneck in the document management system, it can immediately take corrective action. Further, if the QA manager determines that a calibration SOP needs revision to improve manufacturing, but knows that SOPs traditionally ‘get stuck’ for two weeks longer, he can monitor the process and work to remedy the problem in advance, or otherwise expedite the review. Long term, the company can address the root cause to improve overall processes.
Cloud-based management system
Horizon Pharma, a specialty pharmaceutical company that has developed and is commercializing products to primary care, orthopedic surgeons, and rheumatologists, adopted a cloud-based electronic quality document management system enterprise-wide in late 2012. Horizon had been using paper-based processes but needed a new, more efficient solution that was also scalable and accessible globally, to support its rapid expansion. Since implementing its cloud system, the company has leveraged it to identify areas that need process improvements, by tracking and monitoring product deviations. “We route all quality data and documents through our document management system for review and approval and then house all of this content in the same system, so everyone has visibility and access. With everything in one place, we can spot key performance indicators and improve the overall manufacturing process,” said Cara Weyker, Horizon’s vice-president of CMC Regulatory and Quality.
Weyker continued, “For annual product reviews, as an example, we look at how many investigations we’ve had, the types of investigations, and any recurring deviations by category and location. Running a simple report gives us immediate insight into a potential glitch, and we can remedy the situation before it turns into a real problem. Fortunately, we haven’t had any major quality problems since implementing the new system.”
With an electronic quality document management system, the manager can easily run a quick risk assessment on documents in process, monitoring various metrics across the enterprise. Similar assessments can trigger a red flag so QA managers can help ensure effective documents are produced rapidly, and people are trained thoroughly and quickly, both leading to an efficient production line for a quality output. Configuring the system to automatically generate ‘read-and-understood’ reports broken down by user, department, and facility assessments gives a quick, visual demonstration that proper training has been completed to meet compliance audits, and provides valuable metrics by role and by function. In addition to driving more comprehensive compliance reporting, this creates transparency for all parties across all levels, empowering staff with performance data they need to identify areas that still need improvement.
By focusing on document lifecycle states and identifying bottlenecks or process anomalies found at different stages in the lifecycle, companies can also cross reference against other documents and processes to determine reasonable internal benchmarks for use across the enterprise. If one particular manufacturing plant is noted for having the lowest risk of non-compliance, for instance, and their standard for reviewing critical SOPs is four days, then ‘four days’ can become your organization’s benchmark. When using a cloud-based electronic quality document system, specifically, the scope of these quality performance reports is compounded, because the application is easily accessible worldwide. At this level, drug manufacturers can compare SOP performance between different locations around the globe and gain meaningful insight.
Additionally, because the cloud is so ubiquitous, cloud-based systems enable life-sciences companies to establish universal quality and measurement standards, even when it comes to taxonomy, for continuity across the organization. Process data can, therefore, be compared side by side. If two or three other locations take six days to accomplish the same quality assurance review, the centralized quality group can examine the circumstances more closely and potentially solve a problem, or open up a roadblock. “Since implementing a cloud-based quality document management system at Horizon, we’ve been able to harmonize across the organization globally,” added Weyker. “What used to be a manual process is now handled in a single, centralized system so that processes and document templates can be standardized. This reduces the risk of making errors or duplicating efforts and helps to ensure that the right people are reviewing the right documents at the right time.”
GenomeDx, a genomic information company based in Vancouver and San Diego, recently migrated to a cloud-based electronic document solution to help improve manufacturing efficiency and quality. “Our document management system makes it easy for us to understand where a document is in its lifecycle, who’s touched it, who has yet to do something about it, and where the bottleneck resides. It does so in a way that is intuitive and easy to follow,” said Andy Katz, PhD, chief operating officer of GenomeDx.
Cloud-based electronic document management systems are also designed with a modern framework and consumer-like user interfaces (think Amazon) rather than legacy architectures that are notoriously clunky and difficult to use. An easy-to-use system encourages higher adoption and, therefore, captures more data, resulting in in improved accuracy and increasingly reliable leading indicators. It also aligns with the business world’s move away from the desktop for greater flexibility and mobility—managers can review and approve documents from wherever they are, whenever they want, from any device, to improve efficiency. And, external partners such as contract manufacturers and subject matter experts who write SOPs can access and work with documents conveniently in a centralized repository, further fostering system use and greater data capture. With more data, companies gain visibility into leading indicators to thwart problems before they cause non-compliance or worse.
“We run reports on a wide range of document lifecycle metrics across the enterprise and are now able to anticipate potential bottlenecks or compliance risk well in advance,” concluded Horizon’s Weyker.