Quality of drug copies not up to scratch

How much will the MS DMT market shrink by when fingolimod comes off patent? #MSBlog #MSResearch

“Unlike biological, or protein-based therapies, small molecule drugs are affected by their patent-life. When a small molecule comes off patent the price of an easy to make small molecule can plummet to 10% of its price as generic equivalents flood the market. Fingolimod is the first small molecule MS DMT that will come off patent in February 2019. This will have a dramatic effect on the MS market unless we have all moved onto more effective treatments, or the therapeutic paradigm has shifted. The paper below compares the purity of non-propriety fingolimod copies and shows that they are not as good a Novartis’ branded innovator compound. What this paper forgets that all the current copies are in less established peripheral markets and when the big-generic companies get involved, Novartis’ Sandoz included, the quality of generic fingolimod will soar. What the patent cliff means for MS is that many more MSers who can’t access DMTs at present due to cost will at least have the opportunity of getting their disease treated appropriately.”

“The fact that drugs come off patent is essential for two reasons; firstly, it allows poor countries and people without healthcare insurance to access effective treatments and secondly, it means pharma can’t rest on their laurels and have to continuously innovate. There are some people who are arguing for an extension of the patent-life of drugs to give Pharma more time to recoup their investment. I think the case at present for  this change is weak considering how profitable the Pharma industry is at present.”

“Roll on 2019!” 

Correale et al. Assessing the potential impact of non-proprietary drug copies on quality of medicine and treatment in patients with relapsing multiple sclerosis: the experience with fingolimod. Drug Des Devel Ther. 2014;8:859-67

BACKGROUND: Fingolimod is a once-daily oral treatment for relapsing MS, the proprietary production processes of which are tightly controlled, owing to its susceptibility to contamination by impurities, including genotoxic impurities. Many markets produce non-proprietary medicines; assessing their efficacy and safety is difficult as regulators may approve non-proprietary drugs without bioequivalence data, genotoxic evaluation, or risk management plans (RMPs). This assessment is especially important for fingolimod given its solubility/bioavailability profile, genotoxicity risk, and low-dose final product (0.5 mg). This paper presents an evaluation of the quality of proprietary and non-proprietary fingolimod variants.

METHODS: Proprietary fingolimod was used as a reference substance against which eleven non-proprietary fingolimod copies were assessed. The microparticle size distribution of each compound was assessed by laser light diffraction, and inorganic impurity content by sulfated ash testing. Heavy metals content was quantified using inductively coupled plasma optical emission spectrometry, and levels of unspecified impurities by high-performance liquid chromatography. Solubility was assessed in a range of solvents at different pH values. Key information from the fingolimod RMP is also presented.

RESULTS: Non-proprietary fingolimod variants exhibited properties out of proprietary or internationally accepted specifications, including differences in particle size distribution and levels of impurities such as heavy metals. For microparticle size and heavy metals, all tested fingolimod copies were out-of-specification by several-fold magnitudes. Proprietary fingolimod has a well-defined RMP, highlighting known and potential mid- to long-term safety risks, and risk-minimization and pharmacovigilance procedures.

CONCLUSION: Non-proprietary fingolimod copies produced by processes less well controlled than or altered from proprietary production processes may reduce product reproducibility and quality, potentially presenting risks to patients. Safety data and risk-minimization strategies for proprietary fingolimod may not apply to the nonproprietary fingolimod copies evaluated here. Market authorization of non-proprietary fingolimod copies should require an appropriate RMP to minimize risks to MSers. 

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


    • Yes, interferon-beta and glatiramer acetate. As these are biologicals the price won't drop very much. The entry level for biologicals is high therefore the companies need to keep the price high.

  • I am a chemist with MS. With fingolimod, purification of the active ingredient from any metals (heavy or not) should not be a serious problem. Furthermore, at a dose of 0.5 mg, it's hard to poison patients with relatively minor inorganic impurities. Generic fingolimod will be as good as the original proprietary drug. Interestingly, dimethyl fumarate (the active ingredient of Tecfidera) is trivial to make – but at very high doses of this drug (240 mg per dose, taken twice a day), impurities will become an issue when generic versions will become available.

  • By 2019, we hope that something substantially better than fingolimod exists. The long-term risks of fingolimod use will also be better understood and it may not look so appealing. Only time will tell, but nearly anything that reduces the cost of our medications is welcomed.

By Prof G



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