Even as the U.S. House of Representatives fast tracks H.R. 3, the Lower Drug Costs Now Act, as its solution to making prescription drugs more affordable, other bills aimed at drug pricing continue to roll in. Just last week, Rep. Katie Porter (D-Calif.) introduced the Freedom from Price Gouging Act, H.R. 4663, which would require drug manufacturers to pay the government back when they increase the prices of their Medicare Part B drugs. A similar measure is included in the Senate's bipartisan Prescription Drug Pricing Reduction Act that cleared the Senate Finance Committee in July on a 19-9 vote. Also last week, Rep. Peter DeFazio (D-Ore.) introduced legislation intended to end price gouging on prescription drugs, vaccines, diagnostics and medical devices developed with taxpayer support. H.R. 4640 would require federal agencies and nonprofits to secure affordable pricing agreements from manufacturers before granting exclusive rights to intellectual property stemming from federally funded research. Two other bills introduced last week are intended to make drugs more affordable for Medicare beneficiaries. The Better Transparency in Information for Medicare Beneficiaries Act, H.R. 4632, is part of the Drug Pricing Action Plan Rep. Ron Kind (D-Wis.) announced earlier this year. It would require Health and Human Services to notify Medicare low-income subsidy (LIS) enrollees about less expensive plan options to cover their prescription needs. The other bill, the More Help for Seniors Act, H.R. 4620, would use savings from Medicare prescription drug negotiations to lower Medicare Part D costs for LIS enrollees. Introduced by Reps. Joe Morelle (D-N.Y.), Max Rose (D-N.Y.) and Marc Veasey (D-Texas), the legislation would raise the income limits for eligibility under the Medicare Part D LIS program, lowering the copays and premiums for more seniors. (See BioWorld, July 26, 2019.)
The U.K.'s Medicines and Healthcare Regulatory Agency (MHRA) updated its 2013 guidance on determining whether a "borderline" product is a drug or a medical device. "Decisions about whether a product is a medical device are based on the stated intended purpose of the product and its mode of action," the MHRA said. "If the product is a medical device, the principal intended action is fulfilled by physical means." The agency cautioned against the assumption that just because a product is considered a device elsewhere, it will be regulated as a device in the EU. The updated guidance includes links to related guidances and forms, as well as to final determinations the agency has made on borderline products.
Following in the steps of other regulators, Australia's Therapeutic Goods Administration (TGA) updated the labeling for Pfizer Inc.'s Xeljanz (tofacitinib) to include information about an increased risk of blood clots and death when the JAK inhibitor is used at the higher dose of 10 mg twice daily. Although Xeljanz is approved in Australia to treat rheumatoid arthritis and psoriatic arthritis, the 10-mg dose is only approved as a second-line treatment for ulcerative colitis, the TGA said, and even then, it should be used at the lowest effective dose for the shortest time needed. The labeling change is in response to results from an ongoing safety study. The U.S. FDA added a boxed warning about the safety concern in July.
The FDA Tuesday posted a warning letter to a Torrent Pharmaceuticals Ltd. plant in Indrad, India, that manufactures losartan potassium tablets, one of the angiotensin II receptor blockers being investigated for nitrosamine impurities. The letter details several manufacturing violations, including failure to follow written procedures for production and process control and failure to adequately investigate batch discrepancies. In qualifying an alternate active pharmaceutical ingredient (API) for the losartan tablets, Torrent circumvented its approved process validation protocol that requires quality attributes to be met for three consecutive batches of an API. When the first batch failed, Torrent added a fourth batch. When that batch also failed, the plant initiated multiple out-of-specification (OOS) investigations and all four validation batches were rejected due to quality. The company closed the investigations without determining a root cause and developed an interim protocol to justify the commercial use of the alternate API, according to the FDA. It then shipped numerous batches manufactured with the new API to the U.S. Subsequently, multiple batches of the company's losartan potassium were recalled for unacceptable amounts of nitrosamine impurities, according to the warning letter. In responding to the FDA's April inspection finding, Torrent acknowledged that it didn't follow its approved written validation protocols, but it told the agency that the API change "had no impact on the manufacturing process and the quality of the finished drug." The company's improper invalidation of initial failing OOS results wasn't limited to losartan. The FDA noted that Torrent was aware that it had a high percentage rate, 60% to 70%, for invalidated initial OOS test results between January 2017 and March 2019, but it didn't adequately investigate the cause.
Lingering problems with a gritty topical cream and temperature excursions continue to plague Mumbai-based Glenmark Pharmaceuticals Ltd. "Product grittiness has been an ongoing formulation issue since 2010 and was a deficiency cited in the previous inspection of your facility," the FDA said in a warning letter posted Tuesday that was based on an April inspection of a Glenmark facility in Kishanpura, India. In response to the most recent inspection, Glenmark said the grittiness issue had been remediated with a product reformulation last year. That answer didn't satisfy the FDA, which said the company didn't "provide sufficient data to demonstrate the robustness of the new formulation." And although Glenmark, in July, recalled all unexpired batches of the product that were manufactured using the original formulation, the reformulation and market actions weren't performed in a timely manner, the FDA said. The agency also cited Glenmark for failing to adequately investigate several temperature excursions that occurred in the shipping of its drugs last year to the U.S. When the company was cited for a similar failure before, it studied the impact the elevated temperature had on the product and found phase separation in the cream. After the most recent inspection, Glenmark said it would implement new shipping practices to protect its products from thermal excursions; the FDA faulted the company for not implementing the changes in a timely manner. Other citations in the warning letter included failure to adequately investigate multiple batch failures and more than 70 consumer complaints about punctures, cracks and holes in various ointment and cream containers. Glenmark attributed the root cause for the complaints to improper consumer handling. Considering the complaint rate as insignificant, the company closed more than 50 complaints without a corrective and preventive action to prevent a recurrence of the defects, according to the FDA.