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Regulatory Focus™ > News Articles > 2020 > 8 > Study: FDA details high global drug quality

Study: FDA details high global drug quality

Posted 24 August 2020 | By Kari Oakes 

Study: FDA details high global drug quality

A quality improvement study led by the US Food and Drug Administration (FDA) found that over 200 difficult-to-manufacture drug product samples met US standards for dosage unit uniformity and dissolution.
The 252 products that were sampled in the largest such study to date included 35 innovator and 217 generic drug samples. In all, the products contained 17 different active pharmaceutical ingredients (APIs) and the samples originated from 46 firms.
Adam Fisher, PhD, and his colleagues at the FDA’s Center for Drug Evaluation and Research (CDER) examined drug products from the US, Canada, Europe, India and the rest of Asia. The study was important, they said, because patients and those caring for them “must have information to support their confidence in the quality of prescription pharmaceuticals.”
“Some [health care practitioners] have been vocally skeptical of the quality of certain drug products, seemingly using limited or anecdotal evidence,” wrote Fisher and his colleagues, citing a recent survey of health care providers that “showed biases associated with drug quality.” In the survey, three quarters of health care providers either did not know or were not sure they believed that “drugs manufactured outside the US and legally marketed in the US adhere to strict manufacturing standards and regulations required by the FDA.”
A similar number, found the survey, reported that patient requests for brand name drugs prompted them to issue “dispense-as-written” prescriptions.
Although all the products sampled met US Pharmacopeia dosage uniformity and dissolution standards, 11 different manufacturers had products that fell below 4-sigma capability level standards for the process performance index (Ppk) for dissolution. The samples falling below the 4-sigma threshold, meaning they had more than 1 error in 1,600, came from generics in four of the five regions from which samples were drawn – including the US.
Fisher and his coauthors also performed a retrospective analysis of the study data. Manufacturers whose results fell above the median Ppk for all samples for either dissolution or dosage unit uniformity also submitted fewer reports of product quality defects.  
The mean number of field alert reports for dissolution problems was 0.22 for the above-median manufacturers, compared with 2.1 for the below-median manufacturers. Similarly, a mean 0.63 reports for problems with dosage unit uniformity were submitted by manufacturers making higher-performing products, compared with 1.7 for those falling below the median.
The list of immediate-release solid oral dosage drug products included such antibiotics as amoxicillin and amoxicillin with clavulanic acid, hypertension medications such as metoprolol tartrate and hydrochlorothiazide, and diabetes and cardiovascular medications such as metformin and simvastatin, along with others.
The highest dissolution variability was seen in products containing amoxicillin, hydrochlorothiazide, pravastatin, simvastatin and venlafaxine. FDA is heightening its monitoring of stability data for these products, it said.
The authors observed that “Several conclusions potentially drawn from these data run counter to established biases,” noting that Indian and Asian manufacturers had similar to higher manufacturing consistency to US manufacturers.
“Although quality is often viewed as a manufacturing issue, the impact on patient use based on the perception of quality is a clinical issue,” wrote Fisher and his coauthors. They noted that the study was completed before FDA implemented several additional measures to improve drug quality, and the findings are not applicable to any counterfeit drugs or drugs purchased online.

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