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On November 23, 2016, the Food and Drug Administration (FDA) published a revised draft
guidance for Submission of Quality Metrics Data. The guidance includes significant changes to the
earlier quality metrics draft guidance issued by the agency on July 28, 2015.
FDA's Quality Metrics Initiative, announced in April 2013, encourages pharmaceutical firms to
embrace continuous improvement and foster a culture of quality by collecting and reporting
manufacturing quality data. During the comment period for the 2015 draft guidance,
manufacturers acknowledged that the initiative has the potential to transform the way the
pharmaceutical industry approaches overall product quality and the reliability of the supply chain.
However, manufacturers and participants in ISPEs Wave 2 Quality Metrics Pilot Program,
conducted across 28 companies (83 sites, 60 products), expressed concerns over lack of clarity
regarding implementation, timelines, definitions, and evaluation guidelines.
The FDA reviewed these comments from industry and revised the draft guidance in 2016.
Following are the most significant changes that can be found in the latest draft guidance:
Drug makers can submit metrics data by product or site on a quarterly basis. While the program is
geared towards finished drug products and API manufacturing, all industry manufacturers may
report quality metrics data (e.g., atypical active ingredients and excipient manufacturers).
The program is voluntary in 2018, but most manufacturers should still assess their quality
systems, update the metrics, and prepare metrics data for submission. As a keystone initiative,
quality teams can use this program to revitalize their processes and systems.
Most CMOs may need to prepare metrics by both product and site, and submit the data to the
product owners. Contract manufacturers can expect changes to their quality agreements to address
these requirements and to comply with the Drug Supply Chain Security Act (DSCSA).
FDA intends to accept either product- or site-level reporting data from covered establishments.
However, the agency encourages product reporting because it demonstrates a further level of
oversight and control over the manufacturing of drug products across the supply chain.
Product owners need to decide if they are going to be product reporting or site reporting
establishments. Gathering the metrics by product across the supply chain will be more complex
than the site reports. For example, a product owner might be using a CMO who in turn uses a
subcontractor, and the API might be supplied through an entirely different entity. Metrics
gathering and reporting through an automated system would not be easy between site and
companies. Also, the data might reside in multiple manufacturing execution systems (MES),
laboratory information systems (LIMS), complaints management systems, and enterprise resource
planning (ERP) systems, at the least.
By taking a three-phased approach toward redesigning their quality metrics dashboard and
management review processes, manufacturers can drive consistency across the enterprise and
partners:
In addition, the following guidelines can help with the overall program:
The quality system must include policies and procedures that define the level of
management visibility to be enabled by the dashboard and that validate information is
flowing to the dashboard as intended.
All KPIs in the dashboard should include clear definitions with data standards and
training for individuals manually entering source data, and should align with FDA
guidance.
Splitting the dashboard into operational quality (e.g., out-of-specs, change controls) vs.
post-marketing quality (e.g., field reports) provides a more complete view of performance
and risk.
Include KPI tiers with index KPI(s) that cascade to lower-lever tier metrics to provide
differing levels of analysis.
Based on the industry comments to the previous draft, the FDA has reduced the scope of the
program from four primary metrics and three optional metrics (in the 2015 guidance) to three
primary metrics. Those three are:
Furthermore, the FDA has revised the metric definitions as detailed below
Covered entities will need to review their metrics management systems across the manufacturing
supply chain, identify gaps in data collection, standardize KPIs, review CMOs/subcontractor
metrics data, collate and calculate metrics, review metrics with management, and ensure
alignment with metrics program guidelines. Standardization is the key to the success of the
program.
Pharmaceutical manufacturing operations and supply chains are very complex, with each drug
product often involving numerous sites and multiple contract manufacturing (CMOs) partners.
This has significant implications on how quality metrics are collated, calculated, and reported.
Further, some reporting establishments ultimately will be responsible for submitting data for a
large number of products. Thus, reporting establishments should consider the following while
calculating the three metrics indicated in the new draft guidance:
LAR and IOOSR FDA recognizes that it may not be possible for some covered
establishments to identify started lots, rejected lots, and OOS results that are manufactured
by CMOs outside of the U.S. and then imported. The report can include data from
lots not imported along with data from lots imported, provided they follow the same process
and controls.
PQCR Product quality complaint data should be related to drugs that are imported,
intended for import, or manufactured in the U.S.
5. FDA will establish a portal for the submission of metrics data and recognize the
reporters.
FDA intends to open an electronic portal in January 2018 for voluntary submissions of quality
metrics data on a quarterly basis. A revised version of the Quality Metrics Technical Conformance
Guide will be released soon, followed by the release of guidance about the submission portal by
December 2017.
Reporting establishments may include up to 300 words of comment with their submissions,
mainly to indicate reasons for any significant variations in the data or anything else of importance
to note. The submission of comments is optional. In the future, FDA may consider establishing a
set of codes to standardize the comments.
For any other clarifications about submitting metrics, reporting establishments may email their
questions to OPQ-OS-QualityMetrics@fda.hhs.gov.
To recognize proactive engagement, transparency, and commitment to quality, the agency will
identify participating establishments on its website in following categories:
o Product reporter top tier: Supplied complete data supporting all metrics for each
covered establishment in the manufacturing supply chain for all covered drug
products or APIs for the full year
o Site reporter top tier: Included complete data supporting all metrics for all covered
drug products or APIs for the full year
o Site reporter mid-tier: Included complete data supporting all metrics for at least one
covered drug product or API manufactured at an establishment for the full year
Key takeaways for manufacturers and CMOs:
Currently, FDA has to sift through fragmented, disparate, and incompatible data sources to
understand quality. Data from NDA field alert reports (FARs), recall alerts (RAs), biological
product deviation reports (BPDRs), Medwatch 3500A forms, CMC supplements, annual reports,
complaints, establish inspection reports (EIRs), and 483s is helpful but not always a clear
indicator continuous improvement. With the new guidance, manufacturers can report quality and
show progress over time in an easier format that is comparable across the industry.
Pharmaceutical quality especially among peers has not always been readily transparent.
Compared to other industries such as automotive and aerospace, there is no ready mechanism
available for sharing quality data. This would serve as an opportunity for companies to have a hard
look at their reporting mechanisms and quality systems maturity.
Conclusion
The pharmaceutical industry is under intense pressure and scrutiny from regulators, customers,
stakeholders, and other groups. To produce quality medicines at reasonable cost and manage
supply and demand complexities manufacturers will need to run their operations vastly
different than they do today.
In a recent report, FDAs Office of Pharmaceutical Quality stated grimly that it has only limited
information about the current state of pharmaceutical quality. The success of the quality metrics
reporting program is the bedrock to FDAs grand vision for building quality into drug products. To
help achieve this vision, the agency needs the industry to shift from a culture of rules and
regulations to a culture of quality, where quality is embedded in every process.
With its new quality metrics draft guidance, FDA is nudging manufacturers to change. It will be
interesting to see how the manufacturers respond. This is an opportunity for pharmaceutical
manufacturers to see these changes not simply as a new set of rules, but as an opportunity to
demonstrate their leadership in how they manage the quality of their products.