FDA Outlines 10 Data Points for Drugmakers to Calculate Quality Metrics

The FDA has identified 10 quality data points that finished dosage form and active pharmaceutical ingredient makers will need to collect to calculate four quality metrics for each product they produce.

As outlined in long-anticipated draft guidance released July 27, drugmakers will need to aggregate and report data on:

• The number of lots attempted of the product;
• The number of specification-related rejected lots of the product, whether rejected during or after manufacturing;
• The number of attempted lots pending disposition for more than 30 days;
• The number of out-of-specification 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 that are invalidated because of a lab error;
• The number of quality complaints received for the product;
• The number of lots attempted that are released for distribution or for next stage of manufacturing;
• Whether the associated annual product review or product quality review were completed within 30 days of their annual due date; and
• The number of APRs or PQRs required for the product.

These data will be plugged into formulas that will calculate the four quality metrics — lot acceptance rate, product quality complaint rate, invalidated out-of-specification rate and annual product review (APR) or product quality review (PQR) on time rate.

For example, product quality compliant rate will equal the number of quality complaints received for the product divided by the total number of lots of the product released during the safe timeframe.

Any firm involved in the manufacture, preparation, propagation, compounding or processing of a finished dosage product or API must submit quality metrics data, the FDA says. A firm’s quality control unit will be tasked with compiling the reports.

Reporting Data

Firms will need to compile the data for each FDF and API of a covered drug product and submit it to the FDA in a single report. The FDA assumes that drug companies will already have access to the data needed to submit such a report.

Once collected, the data will be used to develop a risk-based inspection schedule, predict drug shortages and increase the efficiency and effectiveness of inspections.

Companies can expect quality data to be verified during on-site inspections. If inconsistencies are found, the report’s integrity may be questioned and used as an additional factor in risk-based or for-cause inspection scheduling, the FDA says. In addition, failure to report quality data may lead to an earlier inspection, or cause products made at the site to be deemed adulterated and subject to enforcement action.

The agency also plans to use the metrics data — along with internal FDA data such as inspection results, recalls, field alert reports and biological product deviation reports — to identify quality problems that require correction or could result in a shortage, according to the draft. The FDA stressed, however, that it doesn’t plan to publicly disclose quality metrics data submissions.

Three Optional Metrics

The agency is also seeking input on whether it should allow drugmakers the opportunity to submit data on three optional metrics — senior management engagement, CAPA effectiveness and process capability/performance — as evidence of manufacturing robustness and a commitment to quality.

Under the draft guidance, senior management engagement and CAPA effectiveness metrics would determine “quality culture.” Management engagement is used to determine if APRs or PQRs are reviewed and approved by either the head of the quality unit, the head of the operations unit, both of them or neither. CAPA effectiveness asks what percentage of a company’s corrective actions involved retraining of personnel, to determine if the root cause of a deviation is lack of proper training.

Process capability and performance covers three yes/no questions: whether management calculated a process capability or performance index for each critical quality attribute as part of a product’s APR or PQR; whether management requires a CAPA at some lower process capability or performance index; and if so, what is the capability or index that triggers a CAPA.

The second phase of ISPE’s quality metrics pilot program — which kicked off in August — will continue as planned, despite differences in its metrics and the quality data the FDA plans to collect, says the co-chairman of ISPE’s quality metrics team.

There may be some “subtle tweaks” to ISPE’s metrics, but otherwise they are well-structured and it wouldn’t be prudent to make major changes, says Máiréad Goetz. The pilot included a “placeholder” metric in anticipation of the FDA releasing draft guidance, and ISPE will incorporate it into phase two, although just how hasn’t been decided, she adds.

Three of the four quality metrics the FDA plans to collect are accounted for in the eight quality metrics ISPE is collecting. The other metric the FDA announced — annual product review or product quality review on time rate — was dropped from phase two after ISPE found no correlations or outcomes. Goetz says ISPE understands why the FDA included it, as the data are readily accessible during an inspection and perhaps indicative of quality culture.

Overall, there were “no surprises” with the quality data FDA chose to collect, Goetz says, as it is consistent with the agency’s thinking.

Metrics data will need to be submitted for a one-year period that begins after the FDA begins collecting the data, which hasn’t been announced. Reports must be submitted within 60 days of the end date of the reporting period, and data should be segregated in the report on a quarterly basis.

The FDA held a public meeting on Aug. 24 at its White Oak campus to discuss the quality metrics reporting program. Comments on the draft guidance are due Sept. 26.

Stay up to date on regulatory stories like this one by subscribing to the Drug GMP Report. For over 20 years, drug manufacturers have relied on DGR for the latest on FDA’s interpretation and enforcement of cGMPs and the Quality Systems Regulation — information you need to stay in compliance.