Nostrum Pharmaceuticals LLC

A Missouri-based pharma company, once at the center of a Shkreli-esque generic drug pricing scandal, just lost its chance to challenge the FDA’s complete response letter for its generic drug theophylline, which is used to treat asthma and other respiratory conditions. The court ruled that it cannot take action on the suit as there’s a “statutory barrier” to the court’s review of complete response letters because they aren’t technically final. The facts of the Nostrum Pharmaceuticals case also underscore the unfinished nature of the CRL process, the opinion explained, noting that since petitioning the court for review, Nostrum has also pressed FDA to approve its still-pending ANDA. “Because neither agency action constitutes a final rejection of the application, we lack jurisdiction to hear Nostrum’s petition and therefore dismiss it,” the opinion says . In March 2021, Nostrum sent the FDA a letter disputing the CRL’s bioequivalence conclusions while also responding to “all the other issues” that the division raised. But the court explained how Nostrum sent this letter to FDA for the express purpose of “stav[ing] off” an end to agency proceedings as inaction by an applicant for a year after the issuance of a CRL may be construed as a “request by the applicant to withdraw the application.” “Those measures would make no sense if the FDA had already issued an order ‘refusing * * * approval of [the] application[.],'” the court said. The challenge for theophylline is that it’s a narrow therapeutic index drug, meaning, according to the court, “[t]here is little separation between effective concentrations and concentrations associated with serious toxicity[,]” and “[s]ub-optimal concentrations lead to severe therapeutic failure.” For these types of generics, the FDA often requires the submission of more rigorous bioequivalence studies, including a study with a fully replicated crossover design. That kind of design requires subjects to receive two doses, one each of the test and the branded drug, so that researchers can measure the difference in rate and the extent of absorption between the two doses, administered at different times to the same subject. The FDA and Nostrum went back and forth on the requirements and during a second reconsideration request, Nostrum petitioned the DC court to review the CRL, which has now concluded with this dismissal. Nostrum previously fell into the spotlight in 2018 after the company had to defend its decision to almost quadruple the price of the generic antibiotic nitrofurantoin, which can treat and prevent urinary tract infections. In an interview with the Financial Times , Nirmal Mulye, Nostrum’s CEO, said he had priced the generic according to market dynamics as the company making the brand version also increased its price. “I think it is a moral requirement to make money when you can . . . to sell the product for the highest price,” he told the FT.

It’s been a relatively quiet year for drug recalls with the FDA facing a work backlog, but that doesn’t mean the agency isn’t watching for offenders. Now, a generic diuretic maker is being forced to withdraw after mixing doses of its meds in the same bottles. Bryant Ranch Prepack (BRP) has recalled 47 bottles across four lots of spironolactone tables due to incorrect labeling of the drug’s strength on its packaging, the FDA said this week. The agency said prepackaged bottles labeled spironolactone 50 mg may contain spironolactone 25 mg tablets, and prepackaged bottles of spironolactone 25 mg may contain spironolactone 50 mg tablets. A diuretic used to treat high-blood pressure, spironolactone taken in less-than-prescribed doses may cause an elevation in blood pressure or edema over time. The FDA warned patients could experience a decrease in potassium if taking half of the expected dose, which could lead to hypokalemia, a condition associated with cardiac arrhythmias. Patients who take double their prescribed dose could experience an increase in potassium, which could be life threatening, the agency said. As of Tuesday, BRP had not received any side-effect reports. The lots and expirations dates for the recall include: It’s been a quiet year for recalls at the FDA amid an agency-wide pinch for resources and a chronic backlog of site inspections that are often the precursor for recalls. Last month, Apotex launched a voluntary recall of two batches of the blood thinner injection enoxaparin sodium this week after discovering that some syringes were mislabeled and could’ve resulted in patients accidentally getting more of the drug than needed. Blamed on a packaging error, Apotex said the discrepancy was discovered through a customer complaint investigation. A few days earlier, Nostrum Laboratories pulled one lot of metformin HCl extended release tablets, USP 750 mg, a Type 2 diabetes drug (the generic equivalent to Glucophage tablets) after testing discovered elevated levels of nitrosamine, the probable carcinogen. It was an expansion of Nostrum’s earlier recall and the latest of a string of drugmakers to pull their generic versions of the Type 2 diabetes meds off shelves based on carcinogen concerns.

Medical device and drug recalls, whether voluntary or mandated by the FDA, ensure patient safety. Here are seven reported to the FDA since early December: Apotex recalls blood thinner due to packaging error Apotex has recalled two batches of its enoxaparin sodium, a blood thinner, after finding that some syringes were incorrectly labeled as containing a higher strength of the drug. Chicago drugmaker recalls neuromuscular drug due to labeling error Meitheal Pharmaceutical has recalled one lot of cisatracurium, a muscle-relaxing drug used during surgery, after finding that some of the vials in the lot are incorrectly labeled as phenylephrine, a drug used to treat low blood pressure during surgery. Nostrum Laboratories recalls metformin after finding carcinogen Nostrum Laboratories has recalled one lot of its metformin tablets after finding levels of nitrosamine above the FDA's accepted limit. Fresenius Kabi recalls NSAID due to presence of particulate matter Fresenius Kabi has recalled one lot of its drug ketorolac after finding particulate matter in some of the vials. Boston Scientific recalls aortic valve device Boston Scientific has recalled its LOTUS edge aortic valve system, saying the delivery system for the device is too complex. There's no safety issue for patients who currently have the device. Penumbra recalls JET 7 Xtra Flex catheter Penumbra has recalled its JET 7 Xtra Flex after finding the tip of the device is susceptible to damage during use. The FDA has received more than 200 adverse event reports related to the device, including deaths and serious injuries. Boston Scientific recalls cardiac device Boston Scientific has recalled its implantable defibrillator device after finding an increased risk of the device fracturing during use. The FDA has received 26 reports of serious injuries related to the device.