Centaur Pharmaceuticals, Inc.

Intas Pharmaceuticals’ write-up formed part of a cascade of warning letters the FDA released this week. Intas Pharmaceuticals’ new warning letter from the U.S. FDA reads like a checklist of what not to do when the regulator pays a visit to your manufacturing facility. The FDA handed Intas a five-observation write-up after inspecting the company’s Sanand, India, production plant from Nov. 22 to Dec. 2, 2022. The company got dinged for lapses in quality control, incomplete lab records, testing shortfalls and more. Chief among Intas’ slights, the company “failed to ensure reliability of data relating to the quality of medicines produced at your facility,” the FDA said in its warning letter. This included “inadequate” oversight of original manufacturing documents, poor control over computer systems and insufficient lab investigations, the agency continued. The FDA explained that its investigators found plastic bags filled with torn and discarded manufacturing documents in the quality control scrap area under a stairwell and on a truck outside the facility. Among the documents, the FDA discovered engineering checklists, analytical test reports and more. To make matters worse, FDA staffers caught an Intas analyst destroying manufacturing records “by pouring acetic acid in a trash bin containing analytical balance strips,” the agency said in its report. Intas faced problems with computerized controls, too. The company’s electronic batch records allowed changes to be made to manual entries prior to saving, the FDA explained, citing one instance in which a production employee was seen manually altering the reported time that an operation was performed. Meanwhile, this isn’t the first time the FDA has rebuked Intas for using the "douse it in acid" routine. This week’s warning letter follows Intas’ receipt of a Form 483 at the same Sanand plant back in January. In its 11-observation reproof, the FDA laid onto Intas for problems with record-keeping, poorly defined procedures and controls, plus issues pertaining to microbial contamination risk and environmental monitoring. Notably, the FDA said it uncovered a “cascade of failure” related to lack of oversight on the control and handling of critical production documents. Intas’ write-up formed part of a series of warning letters the FDA released this week. Other companies caught in the regulator’s crosshairs included Centaur Pharmaceuticals, Baxter Healthcare and over-the-counter drug manufacturer Medgel. In the case of Centaur—which just recently got slapped with a separate warning letter outlining quality and cleaning lapses at the company’s Maharashtra, India, drug ingredients plant—the FDA issued its warning despite a prior wrist slap in the shape of a Form 483. The FDA chided Centaur for issues related to cleanliness and sanitization and the failure of its quality unit, according to the letter. Baxter, for its part, is in hot water over failure to investigate batch discrepancies, poor cleaning procedures and subpar written procedures around production and process control. The company also “failed to use equipment in the manufacture, processing, packing or holding of drug products that is of appropriate design, adequate size, and suitably located,” the FDA said in its report.

The FDA approval for Daiichi Sankyo's Vanflyta, a protein degrader deal between Astellas and PeptiDream, and a Takeda trial flop made our news this week. Daiichi Sankyo's FLT3 inhibitor overcame FDA rejection to win an approval. Astellas signed another protein degrader deal, this time with PeptiDream. Takeda's enzyme replacement therapy flunked a mid-stage trial in a rare neurological disorder. And more. 1. After FDA snub, Daiichi's Vanflyta gains US approval and tees up AML clash with Novartis, Astellas About four years after an initial FDA rejection, Daiichi Sankyo has finally won approval for its FLT3 inhibitor quizatinib as a treatment for acute myeloid leukemia. Now marketed as Vanflyta, the Daiichi drug will compete against Astellas’ Xospata and Novartis’ Rydapt. Vanflyta’s label only covers cancers with FLT3-ITD mutations, while its rivals' approvals cover any FLT3 mutations. 2. Astellas notches another protein degrader pact with $21M upfront for PeptiDream Astellas has put down 3 billion yen ($21 million) up front to tap PeptiDream’s peptide discovery platform to develop protein degraders. PeptiDream will also be in line for potential milestone payments up to 20.6 billion yen ($145 million) per target, plus single-digit percentage sales royalties. Astellas has previously inked protein degrader deals with Cullgen and Fimecs. 3. Takeda suffers setback as promising neuroscience prospect flunks phase 2 Takeda’s TAK-611, an enzyme replacement therapy proposed for the rare genetic disease metachromatic leukodystrophy, has failed in a mid-stage trial. The phase 2 trial didn’t meet primary or secondary endpoints, according to Takeda. The readout was listed as a potential inflection point for Takeda’s late-stage neuroscience programs for this fiscal year. 4. Takeda hypes up dengue vaccine launch progress as Vyvanse generics loom Takeda is touting the progress of its dengue vaccine Qdenga despite a recent decision to pull its application in the U.S. The company is now focused on some endemic markets, which make up about 80% to 85% of the vaccine’s peak sales projection of $1.6 billion to $2 billion, CEO Christophe Weber said on a confererence call. Takeda is getting closer to having end-to-end in-house production capability for Qdenga by 2025, he said. 5. Lawmakers propose federal database to track supply chain vulnerabilities Sen. Gary Peters (D-MI), chair of the Homeland Security and Governmental Affairs Committee, has teamed with Republican Sens. James Lankford (R-OK) and Mike Braun (R-IN) to introduce a bill to create a federal database to track supply chain vulnerabilities. The Mapping America’s Pharmaceutical Supply Act would catalog the origin of each drug, quantities available and the location of their manufacturing facilities. 6. Centaur Pharmaceuticals slapped with FDA warning letter outlining quality, cleaning lapses Centaur Pharmaceuticals’ drug ingredient plant in Maharashtra, India, got an FDA warning letter with two observations about quality deficiencies and lapses in cleaning protocols. The agency is demanding Centaur completely assess its documentation systems and manufacturing standards training program. Other News of Note 7. AstraZeneca enlists SK Chemicals to produce diabetes combo drug Sidapvia 8. India’s pharma exports continue to rise despite manufacturing scandals, trade body says (Reuters)

Centaur’s quality unit failed to make sure active ingredients manufactured at the Indian plant complied with current manufacturing standards, the FDA said in a warning letter. While the famous half-horse, half-man of classical lore is often the one shooting the arrows, it's Centaur Pharmaceuticals that recently found itself in the FDA's crosshairs. In a warning letter published last week, the FDA chided Centaur for production shortfalls found during an inspection of the company’s Maharashtra, India, drug ingredients plant. Centaur’s active pharmaceutical ingredients (API) rebuke centered on just two observations about quality deficiencies and lapses in cleaning protocols. The latter problem carried the risk of API contamination, the FDA said. On the whole, Centaur’s quality unit failed to make sure API manufactured at the Indian drug ingredients plant complied with current manufacturing standards, the agency said in its first observation. The FDA cited three major examples of Centaur’s quality lapses. For one, the inspectors uncovered analytical worksheets, incident report forms, batch release copies and other production documents stored in laboratory drawers and cabinets with “unrestricted access and inadequate controls.” In another shortfall, the FDA said that some original manufacturing documents were “discarded and shredded without a review and a meaningful description in the logbook.” Centaur told the regulator that employees involved in those situations had either been reassigned or removed from their duties, according to the warning letter. Still, the FDA is demanding Centaur take further action, including a complete assessment of documentation systems used throughout its manufacturing and laboratory operations. Centaur is also on the hook to weigh its manufacturing standards training program effectiveness as it pertains to quality control lab operations, the FDA said. As for Centaur’s second observation, the FDA said the company failed to clean equipment and utensils to prevent contamination or carry-over of material that could alter the quality of the company’s API. Among other remediation efforts, Centaur is expected to chart appropriate improvements to its cleaning program. While Centaur’s document shredding maneuvers seem more like a lapse in judgment rather than intentional obfuscation, similar behaviors have landed other manufacturers in hot water in recent months and years. Look no further than India’s Intas, which the FDA blasted for a “cascade of failure” after it found employees destroying documents related to medicines sold in the United States. Despite last week’s wrist-slap, Centaur has largely avoided FDA scrutiny in recent years. Back in 2019, for instance, Centaur got the regulator’s OK at its Pune finished dosage facility to expand in the U.S. market after successfully completing an FDA audit with a “No Action Indicated” tag. Founded in 1978, Centaur says it offers a mix of capabilities across the pharma value chain, including producing APIs, formulation, contract research and manufacturing. As of 2019, the company billed itself as a $100 million Indian drugmaker with exports to 110 countries.