Outsourcing Pharmacy Asks Court To Restrain FDA From Shutting It Down Over Contamination

 A Little Rock, Arkansas, outsourcing pharmacy continued to defy FDA even after the agency went to court for an injunction to shut down the pharmacy's drug compounding operations over continued lack of sterility. Cantrell Drug Co. could have accepted proposed consent decree terms but instead countered in federal bankruptcy court with an injunction request of its own.

An outsourcing pharmacy in Little Rock, Arkansas, has responded to a request by FDA and the Justice Department for a federal district court to issue a preliminary injunction against its manufacture and distribution of adulterated drugs with an injunction request of its own.

Rather than avoid the injunction by agreeing to proposed terms for a consent decree, Cantrell Drug Co. has asked a federal bankruptcy court to grant a temporary restraining order against FDA and consider issuing a preliminary injunction against the agency. That way, Cantrell could stay in business compounding and selling drug products that FDA is warning healthcare providers not to use because they are potentially dangerous due to evidence of microbial contamination.

The firm claims that FDA does not have the authority to bring enforcement actions against 503B outsourcing facilities and that the GMP regulations that cover traditional pharmaceutical manufacturing under 21 CFR 211 do not apply to it. Further, it says it's filling gaps in supply of critical medicines like injectable morphine sulfate.

A federal complaint alleged that the firm continued to distribute purportedly sterile drugs even after it was warned that these drugs were being made under unsafe and insanitary conditions. Cantrell joins a growing list of companies to feel the wrath of FDA’s beefed up enforcement targeting drug compounding pharmacies. Cantrell is registered as an outsourcing facility under Section 503B of the Food, Drug and Cosmetic Act, which subjects it to drug GMP requirements

If Cantrell were to agree to FDA's terms, it would become the seventh drug compounder to sign a consent decree since October 2012, when the New England Compounding Center crisis occurred. The others are: Isomeric, Medistat RX LLC, Med Prep Consulting, Main Street Family Pharmacy, Downing Compounding Pharmacy and Franck’s Compounding. (Also see "Isomeric Enters Drug GMP Consent Decree As FDA's Crackdown On Drug Compounders Continues" - Pink Sheet, 7 Aug, 2017.)

The federal complaint and proposed order were filed March 1 with the US District Court in the Eastern District of Arkansas against Cantrell and its CEO, James McCarley. Besides asking the court to order Cantrell to stop manufacturing and distributing drugs, the proposed order also would require Cantrell to recall all non-expired drug products from the market. These drugs include injectable sodium bicarbonate used in the treatment of metabolic acidosis for patients with severe renal disease or uncontrolled diabetes. Cantrell distributes most of their drugs to hospitals and other health care entities throughout the US.

The federal complaint and motion for preliminary injunction both cite a cascading level of complaints that government officials says were either ignored or not taken seriously.

According to the motion for injunction, “despite repeated inspections by FDA highlighting insanitary conditions and failures to comply with manufacturing practices required by law, defendants have failed to successfully remedy their operations to the standard required by federal law. Not only have defendant’s attempts at corrective action been unsuccessful, but they have refused FDA’s repeated requests to temporarily cease operations until they become compliant with the drug safety provisions in the act.”

It adds that “defendant's serious violations of the act, and the likelihood that violations will continue without court action, demonstrate that preliminary injunctive relief is necessary to protect the public.”

FDA said it inspected Cantrell’s facility June 12-29, 2017, to see whether the company fixed the deficiencies observed during a previous inspection conducted in 2016. The 2017 inspection revealed that that many of the problems were not fixed.

For example, during the 2017 inspection, FDA investigators observed that Cantrell repeatedly recovered several types of microorganisms in the air and on surfaces used for sterile processing, which demonstrated that products were made under insanitary conditions. On “at least” 12 different occasions between January and May 2017, Cantrell’s environmental monitoring detected microbes in excess of action limits. The microbial contamination identified by Cantrell consisted of bacillus oleivorans, staphylococcus epidermitis, micrococcus luteus and bipolaria spicifera. According to the complaint, if any of these organisms are present in an injectable product and administered to patients, “they are capable of causing serious adverse effects to patients.” Yet drugs were released anyway.

Also during the 2017 inspection FDA investigators observed that the company did not accurately record data on microbial growth that on at least nine occasions had been detected in air and on surfaces used for sterile processing, as well as on equipment and personnel. The company asserted that it found no colony forming units, or visible microorganisms, present in environmental and personnel monitoring plates, while FDA investigators observed a range of one to 26 CFUs  on the same plates.

After the most recent inspection, Cantrell voluntarily ceased manufacturing operations but then resumed compounding eight days later without waiting for the agency to see if their manufacturing operations had been brought into compliance. On at least six different occasions, FDA advised defendants to refrain from distributing products.

Cantrell filed for Chapter 11 bankruptcy on November 7, 2017, yet announced that “after exiting reorganization” it plans to continue operating with a planned extension of a second production facility.

Cantrell initiated voluntary recalls of drug products in 2016 and 2017. The 2016 recall involved 29 lots of unexpired sterile drug products, while the 2017 recall covered all lots of unexpired sterile drug products that were compounded and distributed between Feb. 16, 2017, and July 19, 2017. Cantrell received a warning letter for noncompliance with GMP requirements in its making of sterile drugs in January 2015  (Also see "FDA’s FY 2015 Drug GMP Warning Letters" - Pink Sheet, 29 Jan, 2016.).  

FDA issued an alert on March 1 warning health care professionals and patients not to use compounded drugs from Cantrell.

In announcing the alert, FDA Commissioner Scott Gottlieb condemned the company’s “reckless” attitude in continuing to produce sterile drugs even when informed of their potential public health risks.

Gottlieb said that “a key aspect of the FDA’s mission to protect public health is creating a regulatory framework that helps ensure that compounded drugs are made under appropriate quality standards to reduce their risk of patient harm, and to take action when those important standards are forsaken. Despite the FDA’s concerns about egregious conditions observed at Cantrell’s facility, during several inspections, with the most recent in 2017, the company continued to compound and distribute drugs without adequately addressing their potentially dangerous conditions. This reckless activity threatened patient safety and will not be tolerated.”

From the editors of The Gold Sheet.