Life-Science companies have been implementing manufacturing information systems for over 30 years. These systems were often part of automated manufacturing initiatives aimed at increasing product quality and lowering manufacturing costs. For many years, Life-Science companies have aspired to gain visibility by unlocking valuable manufacturing data to support initiatives such as Lean Manufacturing, Quality by Design and Continuous Improvement. However, the industry’s hyper-focus on compliance and its reliance on paper systems has hindered this level of visibility and intelligence and is further clouded by globalization, externalization and outsourcing.
Compliance to regulatory requirements, such as 21 CFR 210, 211, 820 and 11 just to name a few, is paramount in Life-Sciences. However, compliance should be the baseline not the objective. The primary objective for Life-Science companies should be manufacturing high quality products while simultaneously complying with all applicable regulations.
"FDA is driving industry to focus on improving product quality rather than compliance as a baseline."
REGULATORS TO THE RESCUE?
The Food and Drug Administration Safety and Innovation Act (FDASIA) provides FDA the legal authority to conduct electronic inspections (e-Inspections) and target onsite inspection based on metrics.
By shifting to a metrics based approach, the Agency would like to “encourage” industry to implement state-of-the-art, innovative quality management systems that drive industry to focus on improving product quality, rather than simply ensuring compliance to regulatory requirements.
“…we want to encourage firms to prioritize quality and encourage their boardrooms and their pocketbooks because quality costs money,” stated Howard Sklamberg, J.D., FDA’s Deputy Commissioner for Global Regulatory Operations and Policy. To support this effort, FDA released for comment its Guidance on “Request for Quality Metrics.”
GRADING INDUSTRY ON A CURVE
FDA intends to request quality metrics data reports from industry for a one-year period in electronic format through the FDA Electronic Submissions Gateway (ESG). Per the guidance document, “reports would be submitted within 60 days of the end date of the reporting period. For example, if the requests called for data for the period October 1, 2016 to September 30, 2017, data reports would be due by December 1, 2017. FDA intends to request data segregated in the report on a quarterly basis.”
The following are the data FDA is proposing industry report by product and establishment.
• The number of lots attempted of the product.
• The number of specification-related rejected lots of the product, rejected during or after manufacturing.
• The number of attempted lots pending disposition for more than 30 days.
• The number of out-of-specification (OOS) results for the product, including stability testing.
• The number of lot release and stability tests conducted for the product.
• The number of OOS results for lot release and stability tests for the product which are invalidated due to lab error.
• The number of lots attempted which are released for distribution or for the next stage of manufacturing the product.
• The number of product quality review(PQR) complaints received for the product.
• If the annual product reviews(APRs) or PQRs were completed within 30 days of annual due date for the product.
• The number of APRs or PQRs required for the product.
FDA would then use analytics tools to grade companies on a curve. Based on a specific company’s fit on the curve, the agency would direct resources to those companies who are on the lower end of the curve.
FDA would also use its analysis of Quality Metrics across the industry to develop a risk-based inspection schedule.
Establishments that show FDA their commitment to Quality and have highly controlled manufacturing processes have the potential to be inspected less often (as a lower priority for inspection occurrence) than similar establishments that demonstrate uncontrolled processes (as a higher priority for inspection frequency).
Manufacturing Execution Systems can play a key role ensuring that a manufacturer has highly controlled manufacturing processes; thereby demonstrating its commitment to quality through metrics.
In the event an establishment does not report required Quality Metrics, FDA may deem products manufactured or processed at that establishment as adulterated and subject the company to enforcement action.
REQUIREMENTS FOR NEXT GENERATION MES
“FDA is driving industry to focus on improving product quality rather than simply meeting regulatory requirements.
Axendia conducted research to identify current issues and benefits, as well as requirements for next-generation MES. The survey found that many Life-Science companies view MES primarily as a tool to solve the problem of eliminating human error and ensuring that records are complete (i.e., regulatory compliance).
Axendia grouped the respondents into four categories: Brand Owners, CMO/Supplier, Consultant and Software Vendor. Its research found that two-thirds of brand owners surveyed identified ‘improved regulatory compliance’ as the main benefit when implementing MES, while only 44 percent see improving product quality as the top benefit.
Software vendors who answered the survey had yet another perspective, with 60 percent selecting a reduction in data entry errors and reducing manufacturing cycle time as the most important benefits of MES.
The research showed a wider gap between software vendors and brand-owners regarding the top future requirements of MES. Most software vendors (67 percent) chose “Internet of Things” as a top requirement, but brand-owners selected “global visibility,” “predictive maintenance,” and “manufacturing optimization.”
This response is concerning, since vendors may be building software to support Internet of Things (IoT), but this may not be what industry says it needs. The ability of MES to support global visibility is a key requirement as industry continues to globalize, externalize and outsource.
The inability to achieve global visibility through MES is a major challenge since these systems are generally designed for one plant, resulting in the need to aggregate data for multiple sites. To optimize capacity and improve product quality, however, decision makers need to be able to compare parameters at multiple sites to identify critical to quality attributes and prepare accurate forecasting.
In addition to global visibility, MES must provide visibility across the entire supply chain. The majority of the quality metrics FDA is seeking to collect could come from MES. Visibility throughout the supply network is critical as brand owners will need to report data from outsourced processes as well as in-house manufacturing.
Improved predictive maintenance is also part of optimizing manufacturing processes. Systems must provide capabilities that enable Life-Science companies to become proactive and ultimately predictive to avoid quality issues before they happen.
However, the gap between industry and MES vendors may be semantic and in fact narrower than it seems. Brand owners indicated they want and need:
• Predictive maintenance
• Global visibility in to supplier networks
• Manufacturing optimization
These requirements could be achieved through the implementation of IoT/Industry 4.0, cloud platforms and mobile / connectivity being offered by MES vendors. In fact, the requirements and needs of both groups intersect when digital transformation occurs and are bi-products of a data-driven, smart and connected digital enterprise.
It is important for vendors to support the needs of bran downers and for brand owners to prepare their organizations for the inevitable impact of the cultural change necessary to ensure that the systems being implemented address the future needs of industry rather than merely fixing issues of the past.
By transforming the way information is accessed, Life- Science companies can continue to strive for continuous improvements and optimize their manufacturing processes while supporting regulatory compliance.
FDA’s e-Inspections program based on Quality Metrics is a key step in its objective to encourage industry to implement state-of-the-art, innovative quality management systems that drive industry to focus on improving in product quality, rather than simply ensuring compliance to regulatory requirements.
To support e-Inspections, most Life-Science companies will be forced to discontinue the use of paper batch records in favor of electronic Batch Records Systems and MES. Integration with complimentary systems like QMS, PLM and LIMS will play a key role in achieving a single source of truth to support Quality Metrics reporting.
The time to begin preparations is now. Is your company, and are your systems, ready to support e-Inspections? Are you ready to be graded on a curve.