What in the world is a MINOR CRL, Amphastar?
Former FDA commissioner Scott Gottlieb once flirted with the idea of illuminating redacted versions of complete response letters (CRLs), although his interest in doing so eventually waned. Had that initiative been implemented — we may have understood exactly what Amphastar meant when it issued a press release characterizing the rejection letter it received for its formulation of epinephrine as a “minor” CRL.
Presumably, the company meant to suggest the CRL was in response to a minor deficiency in its ANDA application. Amphastar highlighted the word minor in all-caps to emphasize ostensibly just how minor the CRL was.
The company said it had received the CRL on January 24, and responded three days later. On Tuesday, the California-based drugmaker said it expected the FDA to address the response within three months.
Endpoints News reached out to Amphastar and FDA for comment on what a “minor” CRL entails.
FDA guidance suggests that minor amendments to ANDA’s often consist of responses to deficiencies that typically require relatively less extensive assessment by FDA — such as minor issues in the drug master file, incomplete dissolution data, or labeling errors that have not been adequately addressed in response to an information request. It was unclear whether Amphastar was referring to this scenario.
Critics have long highlighted that the CRLs either in part or whole should be made publicly available in the interest of transparency, but the FDA (which does not publish CRLs due to privacy concerns around unapproved applications) has traditionally maintained companies can reveal the contents of the CRL if they wish to do so. The EMA, however, does publish data from refusal assessment reports.
Five years ago, a handful of FDA executives conducted a study highlighting the discrepancies between 61 complete response letters (CRLs) issued by FDA between August 2008 and June 2013, and the press releases that accompanied them.
The data were damning. No press release was issued for 11 CRLs, and 13 press releases did not match any statements from the letters. In addition, of 32 CRLs that called for a new clinical trial for safety or efficacy, 19 had matching press release statements. Seven CRLs reported higher mortality rates in treated participants — but only one associated press release mentioned this fact.
After coming under fire from angry lawmakers in the wake of its recent decision to more than double the price of its emergency opioid overdose drug, naloxone, Amphastar in 2017 also received a CRL for an intranasal formulation of the compound. At the time, the biotech was somewhat more forthcoming in its press release.
Without revealing too much, the company cited the agency’s questions about a “user human factors study, device evaluation, and other items.”