FDA’s Draft Quality Metrics Guidance, Version 2.0

December 5, 2016By Mark I. Schwartz

Last month, FDA announced the publication of a revised version of the Draft Quality Metrics Guidance that it had published back in July of 2015. We had blogged about the original Draft Guidance at that time (see prior posting here).  Below we provide a brief summary of the some of the more noteworthy changes.

Overall, the document has been substantially revised. That said, the agency’s stated objectives for the quality metrics program have remained pretty consistent, though perhaps they are explained in greater detail in the revised Draft Guidance, namely:

1/ establishing a signal detection program as one factor in identifying establishments and products that may pose significant risk to consumers;

2/ identifying situations in which there may be a risk for drug supply disruptions;

3/ improving the effectiveness of establishment inspections;

4/ improving FDA’s evaluation of drug manufacturing and control operations; and

5/ identifying potential shortage signals and engaging with manufacturers to mitigate the likelihood of their occurrence.

Intriguingly, the Notice of Availability (NOA) for the revised Draft Guidance states that:

After evaluating the results of the voluntary phase of the quality metrics program in 2018, FDA intends to initiate notice and comment rulemaking under existing statutory authority to develop a mandatory quality metrics reporting program.

So it appears that the agency has changed course as, to the best of our knowledge, it had not previously stated its intent to utilize notice and comment rulemaking to implement this program. The program was supposed to be implemented simply upon the finalization of the Quality Metrics Guidance.  This also explains why the Legal Authority section of the document has been removed.

One has to wonder whether the agency’s confidence in its legal authority for this program (i.e., the combination of sections 706 and 711 of FDASIA) has waned somewhat since the initial publication of the original Draft Guidance in July of 2015. After all, the right to request “…any records or other information that the Secretary may inspect under [Section 704 FDCA]…,” together with a firm’s responsibility for “…oversight and controls over the manufacture of drugs to ensure quality [Section 501 FDCA]…” do not necessarily constitute legal authorization to demand that regulated industry create new records in order to satisfy the agency’s curiosity that a firm’s manufacturing process is in a state of control.  Far from it.

Perhaps with an eye to eliminating that legal line of attack, FDA added the following in the revised Draft Guidance section entitled “Quality Metrics that FDA Intends to Calculate:”

FDA used the following selection criteria in developing the set of data that it is inviting covered establishments to submit: (1) objective data to provide consistency in reporting; (2) of the type contained in records subject to inspection under section 704 FDCA; and (3) a valuable component in assessing the overall effectiveness of a pharmaceutical quality system. [Emphasis added]

No doubt the decision to engage in notice and comment rulemaking will strengthen the agency’s hand should industry decide to contest the FDA’s statutory authority to require such quality metrics, as courts generally offer more deference to an agency’s statutory interpretations when they are backed up by an administrative record, and after the agency has sought formal public input.

What is unclear is whether the agency changed course in favor of notice and comment rulemaking before, or after, the November 8th Presidential election.  While engaging in notice and comment rulemaking strengthens the agency’s hand in the event of litigation, President-Elect Trump has often emphasized his aversion to “excessive regulation.”  For the record, we do not know whether the President-Elect would consider this program to constitute excessive regulation – however that would need to be an agency consideration at this point.

So, by engaging in rulemaking, the agency is likely reducing the probability that the quality metrics reporting program will be dismantled by a court; however, this formal elevation of the program through the rulemaking process also likely increases the probability that it will be placed on the chopping block by the incoming administration.

Back to the changes brought about by this revised Draft Guidance. The document explains that FDA is initiating a ‘voluntary reporting phase’ of the quality metrics reporting program, whereby FDA expects to learn more about a limited set of quality metrics, associated analytics, and to generally improve the FDA quality metrics reporting program.  During this voluntary phase, FDA will accept submissions of data from owners and operators of human drug establishments.  The revised Draft Guidance describes two types of quality metric data reports that can be submitted: product reports and site reports.

The document goes on to add that FDA may not be able to accomplish the overall goals of an FDA quality metrics reporting program (i.e., the five objectives summarized above) from voluntary reporting alone. For example, if, during the voluntary reporting phase, FDA does not receive a large body of data from the establishments that fall within the ambit of the program, the utility of the data obtained will be limited.  Hence, the expectation is that, during the voluntary reporting phase, the information collected will be primarily used for the more narrow purposes of:

1/ working with establishments towards early resolution of potential quality problems and to reduce the likelihood of a disruption in supply (i.e., no signal detection program per se and no commitment to be able to broadly identify situations in which there may be a risk for supply disruptions);

2/ helping to prepare for, and direct, FDA inspections; and

3/ using the calculated metrics as an element of the post-approval manufacturing change reporting program.

The revised Draft Guidance adds that FDA intends to accept reports with quality metrics data that are “inconsistent with the metrics and definitions” in the document, as well as reports about establishments and products that are not the focus of the voluntary reporting phase of the quality metrics program, with the caveat that the agency does not intend to include these inconsistent reports on the quality metrics reporters list (see explanation below), and may not be able to integrate the submission of the report into FDA’s risk-based inspection model.

Furthermore, FDA intends to publish a list of the names of establishments that voluntarily report all, or a subset of, the quality data described in this guidance (i.e., both product reporting establishments and site reporting establishments). FDA believes that there is a public benefit to sharing this information because, through their participation, establishments demonstrate a willingness to proactively engage with the agency in pursuit of the agency’s goals.  Also, participation contributes to improving quality monitoring.  FDA also suggests that such public information might be useful to pharma when selecting contract manufacturers and component suppliers, and the information could also be helpful to healthcare purchasing organizations, healthcare providers, patients and consumers in sourcing drugs.

In the revised Draft Guidance, FDA has reduced the scope of the quality metrics program from the four proposed metrics in the July 2015 Draft Guidance (i.e., lot acceptance rate, product quality complaint rate, invalidated out-of-specification rate, and product quality review on time rate), down to three proposed metrics. It thus proposes to eliminate the product quality review on time rate, which wasn’t likely to provide much useful information to the agency to begin with.  FDA has also removed the three optional metrics from the prior draft, including CAPA effectiveness and the percentage of corrective actions that involve retraining of personnel.

Also, now explicitly included within the ambit of the quality metrics program are both non-recombinant and recombinant versions of plasma derived products, as well as transgenic versions of same, and explicitly excluded from the program are in vitro diagnostics and all biological products that meet the definition of a device under section 201(h) FDCA.

The NOA states that FDA anticipates that the electronic submission platform will be available to test in 2017, and that FDA expects to ‘encourage’ reporting establishments to submit quality metrics data reports where the data is segmented on a quarterly basis throughout a single calendar year. The agency intends to open the electronic portal in January 2018 to receive these submissions of data.

Also new, reporting establishments will be able to submit 300 word text comments to provide an explanation of submitted data, and in order to report improvement plans. The NOA states that FDA may refer to the comments if unusual data or trends are identified, or as preparation for an onsite inspection.

The NOA also states that, in the context of the voluntary reporting phase, FDA is proposing a common timeframe to facilitate publication of the quality metrics reporters list, particularly given the need to identify duplicate data if both the product reporting establishment and the site reporting establishment (for the same product) submit data. FDA had considered supporting flexible data collection timeframes for the purposes of reporting, but the agency concluded that such flexible timeframes would only be feasible in the context of a program that mandated product-based reporting (i.e., under the current scenario, subsequent to the notice and comment rulemaking).

In conclusion, the modifications made to the revised Draft Guidance are substantial (indeed, even the name of the document was changed). It will be interesting to see whether the quality metrics reporting program, a cornerstone of FDA’s framework for building quality into drug products, advances as planned.  The path for the program over the next few years is perilous, whether the agency seeks to finalize it via notice and comment rulemaking or simply via guidance.