3 STEPS TO PREPARE FOR FDA’S FINAL QUALITY METRICS GUIDANCE

Reacting to industry trends, including drug shortages and plant inspections that increasingly question manufacturing data integrity, FDA’s revised draft guidance from November 2016 - Request for Quality Metrics promotes a quality-driven corporate culture as one of its goals. It prescribes a sequence of steps for life sciences companies and contractors to follow to improve and demonstrate process understanding and control of quality — a valuable goal that benefits patients and manufacturers alike.

The revised guidance document states, “In order to both inform FDA’s risk-based drug inspection scheduling and to better detect manufacturing conditions that may lead to a shortage, FDA intends to collect and use quantitative quality data to calculate certain quality metrics....” It recommends these key quality metrics, and, after taking into account industry’s feedback, FDA expects to publish the final guidance with exact metrics soon:

• Lot acceptance rate

• Product quality complaint rate

• Invalidated out-of-specification (OOS) rate

Some organizations see the guidance as an added burden to the industry. The Pharmaceutical Research and Manufacturers of America (PhRMA) said that, while it agrees that reporting quality metric data has benefits, the group “is concerned that FDA is substantially underestimating the burden that manufacturers will encounter in collecting and reporting such information.”1 The International Society of Pharmaceutical Engineers (ISPE) responded to draft guidance with suggestions including a targeted, “phased introduction that will maximize learning, minimize burden on both the industry and FDA….”2

In an already heavily burdened industry dealing with consolidation and increased use of third-party contractors, there is certainly a call for help in how to approach new requirements. When drafting guidance in the public’s best interest, FDA looks to research from ISPE and others, as well as to the best practices of successful companies that embrace good manufacturing practices (GMPs) and already have offset “the burden.” Successful companies don’t have manufacturing quality metrics (MQM) initiatives in place because they’ve been told to from the outside, but rather because they know the benefits and they see results.

These role models treat quality as a way of life in their cultures, in which everyone shares outcome responsibilities, rather than describing quality as an autonomous department. They have processes and systems in place for data collection and sharing — among their owned sites and contract manufacturing organizations (CMOs) — that are well-aligned with FDA’s goals. Not only are they meeting regulatory compliance requirements, but they are also providing sustainable patient benefits through the availability of safe drugs and business improvements that make the burden worth the effort.

Companies who aren’t already monitoring quality metrics can begin to do so in advance of FDA guidance becoming expected best practices. As first steps to adopting similar best practices for MQM, companies can focus on these three areas:

1. Building quality monitoring into processes. Model organizations already have many MQMs in place, often more than just four. They gain insight to trends and trouble spots they can address before product outcomes fail to meet quality or regulatory inspection requirements, or customer demands. Looking to continued process verification (CPV) guidance helps monitor processes based on sources of variability. FDA describes CPV as assurance that a manufacturing process is in a continued state of control.

This isn’t a simple request for many companies that encounter technological and cultural barriers to implementing CPV, so leading companies typically enlist

FDA REVISED GUIDANCE RECOMMENDED QUALITY METRICS AND DEFINITIONS

Lot acceptance rate1 – x (x = number of specification-related rejected lots in a timeframe divided by the number of lots attempted by the same establishment in the same timeframe)

Chemistry Collection UpdatesNumber of product quality complaints received for the product divided by the total number of lots of the product released in the same timeframe

Invalidated out-of-specification (OOS) rate

Number of OOS19 test results for the finished product invalidated by the establishment divided by the total number of OOS test results divided by the total number of tests performed by the establishment in the same timeframe

Source: FDA’s Request for Quality Metrics: Draft Guidance for Industry

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an internal task force to oversee program implementation. Its first assignment is outlining necessary changes, from software systems to work habits. Identifying and removing such roadblocks leads to improved data analysis and better understanding process variability to improve quality.

2. Establishing open collaborative relationships with contractors. FDA considers contractors as extensions of manufacturers’ organizations with shared responsibility for product quality. Implementing communication plans that outline how deviations will be relayed and resolved are critical to MQM and realize valuable business benefits. Since processes — and therefore quality — can vary from site to site, this can be especially challenging unless systems are in place to effectively manage process validation data throughout tech transfer and outsourced manufacturing processes.

To facilitate consistent quality, sponsors and contractors can look to manufacturing analytics to identify critical quality parameters (CPPs) and key performance indicators (KPIs). Employing real-time monitoring and controls across the global manufacturing network, including contractors, enables better data sharing and helps make product and process quality comparisons that better prepare all parties for MQM.

3. Improving report creation, editing, tracking, auditing, archiving, and retrieval. There is an enormous amount of data — residing in disparate systems — that’s needed in real time to leverage metrics for running businesses, not to mention to be able to transmit reports to the FDA. Digitizing operations now will help prepare for future expectations. As starting point, it’s critical to incorporate process and quality data stored in disparate locations as both electronic and paper records.

Companies outside of life sciences are running their businesses this way, so why not use these same methods to also improve the costs and time involved in getting drugs to market for society’s benefit? Increasingly, regulators — and the public — will make choices based on a manufacturer’s reliability. FDA says it will consider ways to reward manufacturers who exceed minimum requirements, so putting MQM monitoring initiatives in place sooner rather than later will help companies not only prepare for the final guidance, but stay ahead of the curve, reaping significant business benefits as well.

REFERENCES1. Bronwyn Mixter, Pharmaceutical Law and Industry Report, “Drug Industry Has Concerns With Quality Metrics Guidance,” BNA Bloomberg, Dec. 4, 2015.2. James Hale and Scott Fotheringham, PhD, ISPE’s Pharmaceutical Engineering, “Responding to the FDA Federal Notice on Quality Metrics,” January-February 2016