Compounding Pharmacies

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“It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity, it was the season of Light, it was the season of Darkness, it was the spring of hope, it was the winter of despair, we had everything before us, we had nothing before us, we were all going direct to Heaven, we were all going direct the other way – in short, the period was so far like the present period, that some of its noisiest authorities insisted on its being received, for good or for evil, in the superlative degree of comparison only.”

A Tale of Two Cities (1859) is a historical novel by Charles Dickens. 

Although global inequality seems to be receding since its peak in 2016 we still live in a world of ‘the haves’ and ‘the have nots’. A stark reminder of this is for people living with MS and having to experience global inequality in access to effective MS therapies.

My memory of a relatively wealthy young woman with MS in Banglore, India, who I met back in 2014 when on sabbatical, reminds me that we have so much still to do. This woman was having to raise money from her extended family, and her social network, to purchase her weekly Avonex injection one syringe at a time. If she couldn’t raise the necessary money she would simply miss that week’s injection. Her neurologist informed me that since developing MS her family was facing financial ruin. The question I asked myself later was ‘Why wasn’t her neurologist treating her with an alternative DMT that she could afford?”. Therein lies the problem, i.e. how do we get the neurology community and wider MS community to accept that there are cheaper, effective, alternatives for managing MS in resource-poor environments. 

Please note that I prefer using the term resource-poor environments and try to avoid using the term resource-poor country. This is deliberate because even in rich countries there are pockets of disenfranchised people without access to healthcare, for example, refugees, immigrants and the medically uninsured.  Britain may soon be included. In the event of a no-deal Brexit, a large number of foreign EU nationals with MS living in this country may have their free-access to the NHS withdrawn. At present, there is no clarity on how the EU and the UK will deal with healthcare coverage in the event of a no-deal Brexit.

As an MSologist with a large number of EU nationals under my care, the prospect of a no-deal Brexit gives me sleepless nights. How will we respond to a scenario of a home office and/or NHS official demanding that we stop prescribing high-cost DMTs to some of our patients? Rebound MS disease activity on withdrawing natalizumab or fingolimod is potentially life-threatening. 

It is essential that the MS community seek solutions for treating people with MS in resource-poor environments. This is why we are exploring different solutions including prescribing low-cost off-label DMTs, developing compassionate access schemes, creating low-cost generics and buyers clubs. Another grass-roots solution is to use compounding pharmacies.  

In short, compounding refers to the process of creating a pharmaceutical preparation or drug by a licensed pharmacist to meet the needs of a community when a commercially available drug does not meet those needs or is too expensive. When you look at our list of essential off-label DMTs we could add dimethyl fumarate to that list. There will criticism from Pharma that compounded, or home-brew, DMF formulations are inferior. But when it comes down to a choice of either bankrupting your family due to the high-costs of innovative treatments or taking a chance on a compounded formulation of the drug I know which one I would choose. 

We have previously covered the topic of a DIY DMF formulation on this blog and you can read how to make your own DMF tablets via this website. I am not advocating that individual pwMS do their own compounding, but this could be done centrally via a licensed compounding pharmacy. The quality of the compounded formulations could then be tested using an international quality control laboratory. The latter could be funded by the global MS community (MSIF) or charities with a vested interest in finding solutions to this problem, for example, the Melinda and Bill Gates Foundation or the Wellcome Trust. 

Obviously, Pharma will object and produce papers such as the one below claiming their product is superior and that compounded formulations are inferior, but maybe this will nudge them to do something about the hundreds of thousands of untreated people living with MS in resource-poor environments. To be fair to Biogen they were the only Pharma company who responded to my call-to-arms a few years ago about trying to find a solution to treating MS in resource-poor environments and I note that one of their senior executives has already signed up to our Grass Roots Off-Label DMT Initiative (GROLDI). To do this is bold and I suspect brave, but their action shows you that even Pharma executives are prepared to acknowledge that access to DMTs is a global problem.

Please note our Barts-MS Essential Off-label DMT list has just been expanded to include compounded DMF and the generic version of DMF that is used to treat psoriasis. 

  1. Azathioprine*
  2. Cladribine
  3. Cyclophosphamide*
  4. Fludarabine*
  5. Leflunomide
  6. Methotrexate*
  7. Mitoxantrone
  8. Rituximab*
  9. Generic dimethyl fumarate (Skilarence)
  10. Compounded dimethyl fumarate
  11. HSCT

        *on the 19th WHO Model List of Essential Medicines (April 2015)

Compounding pharmacies could be one way of improving access to DMTs in low-income countries. Do you think compounding pharmacies will address the problem of access to DMTs in resource-poor environments? Let us know your thoughts. 

If you are interested in helping address the issue of lack of access to MS DMTs in resource-poor countries and environments post please sign-up to our Grass Roots Off-Label DMT Initiative (GROLDI)

Thank you.

Boulas P (Biogen, Cambridge, MA, USA). Compounded Formulations of Dimethyl Fumarate Show Significant Variability in Product Characteristics. Drug Res (Stuttg). 2016 May;66(5):275-8.

BACKGROUND: Pharmacy compounded products are not regulated to the same standards as commercially available, approved products, increasing potential safety and efficacy risks to patients. This report describes an in vitro study examining consistency of content and release profile of compounded dimethyl fumarates.

METHODS: Samples of compounded dimethyl fumarate (cDMF-A, cDMF-B, cFumaderm) from separate Austrian compounding pharmacies were analyzed for drug content, uniformity of dosage, impurity, and in vitro release.

RESULTS: The average dimethyl fumarate (DMF) content ranged from 102.5 to 96.7% of the 120 mg content listed on the product labels. While the DMF capsule-to-capsule content of cDMF-A was somewhat uniform (~20% difference), there was greater variability amongst cDMF-B and cFumaderm capsules (> 30% difference). Impurity testing revealed 2 and 4 unknown components within cDMF-A and cDMF-B, respectively, with levels ranging from 0.05 to 0.81% of total drug content. In in vitro testing of cDMF-A,>10% (12 mg) of DMF was released after 120 min in simulated gastric fluid and 17% (20 mg) released in simulated intestinal fluid after 60 min. While minimal amount of DMF was released from cDMF-B in simulated gastric fluid, 50% (60 mg) of DMF was released after 60 min in simulated intestinal fluid. Similarly for cFumaderm, a fraction (< 20 mg) of the 120 mg target dose was released after several hours in simulated intestinal fluid. The uniformity of release rates across capsules varied significantly.

CONCLUSION: These results demonstrate that compounded fumarates are not equivalent to licensed products and may present unknown safety, efficacy, or quality risks.

CoI: multiple

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.

12 comments

  • Interesting point about the woman in India. For the record, India has the second largest army in the world (1.4 million soldiers), it has nuclear weapons, a space programme (recently tried to land a craft on the moon), and has more billionaires than the U.K. India has no trouble training huge numbers of doctors – many are happy to ply their trade overseas. Surely it’s up to India to decide how to treat it patients – including MS patients. This is a country which the U.N. estimates to have 250 million people in extreme poverty. India has a different culture with regard to healthcare and social security (in effect there is none for those in need). You need to focus on your own backyard and let countries such as India deal with its own issues – do you think our neurologists are inferior to those in Europe? I would suggest that the country you left has even greater problems than India. Why not set up a neurology practice in Jo’burg or Cape Town to provide free care to those in need? Inequality will continue to get worse if the highly skilled workers (doctors, IT specialists etc) keep chasing the dollar abroad rather than working in the countries they were born in. As an Indian doctor I know this all to well – Indian children trawling through rubbish in Mumbai while Indian doctors make millions in the UAE.

    • Rav as a white British woman who has only ever travelled out of this country a handful of times I acknowledge I’m not in the strongest position to response, however I feel compelled to do so.
      I am a middle aged woman desperate to avoid the ever increasing catastrophic thinking that seems to come with ageing. However in every regard I think we need to be wary of adopting the approach that consists of each to their own / let each person and each country be responsible for their own affairs. Without repeated efforts to engage internationally on the matter of climate change for example, what hope will there be of ever effectively addressing the issue?
      I am mortified by the idea of any person anywhere going without a DMT and now most especially here in the UK with the potential ramifications of a no-deal Brexit. I want to praise ProfG for being motivated to try and improve things internationally for PwMS and reiterate my reply to one of his earlier posts on the subject: good luck and I hope you have lots of volunteers and now perhaps some elements of Pharma coming on board too.

    • Rav, we note your IP address is based in England. I assume like Prof G and more than half the Barts-MS team that you are a migrant as well. Any chance of you returning to India anytime soon to practice what you preach?

      • Why should he return? His point is that Prof G needs to remember that he, like him, is an economic migrant.

        The British have given them both a sanctuary. They are welcome guests in our country.

  • As someone who has been through the process of managing the manufacture of a drug for a Phase I clinical trial according to Good Manufacturing Processes (GMP), I have a new appreciation for the level of scrutiny that goes into making sure that drugs are safe. Compounding pharmacies just don’t have the resources to develop methods and perform the analytical testing to measure the manufacturing impurities that may be present in non-GMP synthesis of drug substance. Instead, compounding pharmacies rely on the whatever the manufacturer tells them the impurity profile looks like. So you may see toxicities that you wouldn’t see normally.

    Then there is the issue of drug product manufacturing. The Active Pharmaceutical Ingredient (API) is often blended with excipients (binders, fillers, emulsifiers, etc) that contribute to absorbance and the exposure that the person taking the drug is going to see. The pharmacokinetics can be totally different and that will lead to differences in pharmacodynamics.

    As this conclusion of the article you cite points out, DIY formulations of DMF are not equivalent to licensed products and represent unknown safety, efficacy and quality risks. The picture of the bottle of DMF, capsules and a scale really bothers me. It portrays a relative simplicity and straightforwardness to the process, but does not accurately represent the risks to health and life.

    So, Prof G, I’m surprised that you would advocate DIY formulations of drug product. But I also never understood why people would ever take street drugs either–yet people take them all the time.

  • What does the cost-effectiveness model show for HSCT or Campath/alemtuzumab (prior to being recycled for profits as Lemtrada) Dr. G.?

    Surely these are 2 treatments have got to be cost-effective for under privileged nations. They have a fixed one time cost rather than ongoing ludicrous costs with zero to minimal effectiveness with respect to progression. They actually seem to prevent progression if given early enough unlike any of the CRAB drugs that this unfortunate young lady is receiving.

    Should it not be their government’s job to negotiate reasonable costs of these effective drugs on behalf of their people? I do agree with your prodding cost-effective treatments with these governments through WHO possibly as everyone deserves a chance against this horrible disease.

By Prof G

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