- While AmerisourceBergen has made strides to correct violations in its compounding business, the drug distributor doesn't know when regulators will allow commercial operations there to resume, according to a document recently filed with the Securities and Exchange Commission.
- PharMEDium, a drug compounder and subsidiary of AmerisourceBergen, received a series of Form 483s over the last year as regulators observed issues at several of its manufacturing plants. Some of the more common issues included failing to have procedures that adequately protect against contamination or ensure quality control.
- AmericsourceBergen said PharMEDium has tapped experts of current Good Manufacturing Practices to audit the subsidiary's largest compounding facility in Memphis, Tennessee, as well as implemented third party compliance monitors at all sites.
Drug compounding, a practice where pharmacists mix drug ingredients to create a custom medicine suited to an individual patient's needs, has come under increased scrutiny since 2012. In that year, a fungal meningitis outbreak caused by contamination at a New England compounding site killed north of 60 people and sickened hundreds more.
To that point, the Food and Drug Administration in January put out a list of compounding policy priorities. Included in those priorities were final guidance on several top-of-mind issues for compounders, such as what restrictions there are for compounded drugs that are essentially copies of approved medications.
Still, there appears to be more regulatory work needed on the compounding front. A Pew Charitable Trust report released just one month after the FDA's priorities list came out found that, in 2017, less than half of U.S. states required routine inspections of compounding pharmacies at least once a year.
The report also identified more than 50 instances of potential or reported compounding errors from 2001 to 2017. Those errors were linked to nearly 100 deaths and another 1,100-plus adverse events, according to Pew.
At PharMEDium facilities, violations ranged from inadequate training programs to deficient aseptic processing areas. Multiple observations also determined that drug product was released, only to be recalled later after the discovery that it failed quality tests.
In the Form 483 for PharMEDium's Memphis plant, regulators noted that the person in charge of review assurance on final batch records said "their department does not 'verify the validity of the data' contained within the batch records for potency, identity, sterility, and endotoxin prior to QA final release for distribution."
AmerisourceBergen said in a company filing that PharMEDium has been talking to the FDA and, more recently, a branch of the Department of Justice, about remediation efforts. The subsidiary has also agreed to not resume commercial operations at the Memphis plant until regulators give an all-clear.
Still, the update leaves PharMEDium in an uneasy spot.
"Currently, PharMEDium cannot determine when the FDA will consider its observations to be fully resolved, whether the FDA will impose additional requirements as a condition to the resumption of compounding for commercial distribution at the Memphis facility or whether the DOJ will initiate any enforcement actions on behalf of FDA against PharMEDium, which could include filing of a civil complaint, entry of a consent decree, or imposition of other penalties," the company said.