Novo Nordisk, the Danish pharmaceutical firm that manufactures the favored weight-loss drug Wegovy and diabetes medicine Ozempic, has requested authorities in the USA to cease the compounding of those merchandise saying that this might pose security dangers.
US Meals and Drug Administration (FDA) laws permit human drug compounding — by which licensed pharmacists or physicians can mix, combine, or regulate the substances of a drugs — to satisfy affected person wants when common branded formulations are in brief provide.
Wegovy and Ozempic, each of which comprise semaglutide, have been in heavy demand for months, and lots of compounding pharmacies within the US have created their very own variations to deal with this.
Beforehand, American drugmaker Eli Lilly had sought to cease compounded variations of its diabetes and weight problems drugs Mounjaro and Zepbound. The FDA is but to decide on the purposes.
Considerations over semaglutide
Over the previous 12 months, Novo Nordisk has filed not less than 50 lawsuits in opposition to clinics and pharmacies which have produced compounded variations of its medication. These copies might be harmful, the corporate fears — Chief Monetary Officer Karsten Munk Knudsen mentioned final week that reviews had linked not less than 10 deaths and greater than 100 hospitalisations to compounded variations of Wegovy and Ozempic.
On October 22, Novo Nordisk requested USFDA to place semaglutide on the Demonstrable Difficulties for Compounding (DDC) record, which restricts pharmacies from compounding a drug, particularly when industrial variations can be found.
The FDA considers a drug for the DDC record if components akin to its stability, dosage necessities, bioavailability, or crucial sterile dealing with make it troublesome to create a secure and efficient compounded model.
In its software for DDC itemizing, Novo Nordisk has flagged 4 particular issues to the FDA.
COMPLEX FORMULATION: The complicated construction of semaglutide is tough to duplicate precisely. The drug is manufactured utilizing yeast and recombinant DNA expertise, which supplies it particular properties important for its efficiency and security. Replicating it synthetically may end up in variations in purity, stability, and total effectiveness.
The FDA-approved model of semaglutide consists of particular parts — such because the fatty acid — that decide how lengthy it stays efficient within the physique, and artificial variations could not carry out equally.
It has additionally flagged that compounded variations have led to reported opposed results, which have been recorded within the FDA’s Hostile Occasion Reporting System (FAERS).
DELIVERY MECHANISM: The supply mechanism of a drug refers back to the approach it’s despatched and launched into the physique in order that it really works successfully.
In response to the corporate, the FDA-approved semaglutide makes use of subtle supply strategies, the precision of which helps the drug work successfully and safely. Compounded variations typically lack these superior supply mechanisms, which may result in the drug not being launched within the correct dose, and scale back its effectiveness and put affected person security in danger.
A secure and efficient supply mechanism is particularly necessary as a result of sufferers administer the drug themselves. The FDA-approved model of semaglutide, made by Novo Nordisk, is available in a single-use pen injector, which supplies the precise dose, and consists of clear directions that guarantee in opposition to sufferers by chance taking an excessive amount of of the drug. The compounded variations, then again, typically are available multi-dose vials or prefilled syringes, with inconsistent directions that improve the chance of dosing errors.
Novo Nordisk has cited examples of sufferers who overdosed on compounded semaglutide. In a single case a person by chance took 10 instances the dose, leading to extreme nausea and vomiting.
BIOAVAILABILITY: This refers back to the diploma to which the energetic ingredient in a drug reaches the bloodstream and turns into usable by the physique.
The corporate has mentioned that semaglutide has naturally low bioavailability — and a compounded model that isn’t absorbed correctly could not produce the supposed results. Ineffective remedy of weight problems and diabetes may end up in coronary heart assaults, strokes, nerve harm, kidney illness, and should even require amputations.
Compounded semaglutide could not meet the necessities for efficient bioavailability, the corporate has advised the FDA.
CONTAMINATION, STABILITY RISK: The corporate has underlined that compounding semaglutide requires specialised services and tools, and that the chance of contamination is a serious concern. Contamination with different substances can probably happen if the tools isn’t sanitised completely.
In response to the corporate, in March 2022, the FDA discovered points with sterility at a compounding pharmacy that had had 5 sterility failures with injectable medication in a single 12 months, and had launched merchandise earlier than confirming they have been sterile. Greater than 15,000 injectable semaglutide items have been recalled, the corporate mentioned — and one other recall had adopted in August 2023 for a similar causes.
Novo Nordisk has additionally mentioned that semaglutide is a temperature-sensitive drug and storing it at temperatures increased than 30 levels Celsius can compromise its stability.
The corporate has flagged an occasion of a pharmacy instructing sufferers to maintain a sublingual (under-the-tongue) resolution at room temperature, and one other advising them to freeze semaglutide merchandise.
