Making T3 chemically: The producers currently... - Thyroid UK

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Making T3 chemically

diogenes profile image

The producers currently being fined for the skyhigh price of T3 have alleged that the high cost is through difficulty in production of T3 chemically. I looked up the accepted procedure for making T3 and it didn't seem unduly difficult. Making T4, you leave all the sites of tyrosine molecules to be iodinated - 4 are, giving T4. For T3, all you do is to react the correct one of the sites with a chemical that masks it from iodine binding, but which can be simply removed after the iodination step. All that is done therefore is to mask the site, react the molecule with iodine and then remove the blocking agent. It's a well known step in making substances like T3.

70 Replies

Diogenes your Brilliance amazes me Endlessly. We ought to clone you so that the thyroid community globally can rip the benefits of your knowledge. Thank You for being a cut Above The Rest. It's our gain.

helvella profile image
helvellaAdministrator

Funnily enough, I was composing a screed which included reference to manufacturing costs - I'll paste it below.

If Glaxo could make it in 1956, I'd have expected improvements in chemical/pharmaceutical industry technologies would have made it even easier to make! And to analyse and assay.

In 2009, Midas funded by HgCapital acquired Goldshield.

In 2012, Goldshield rebranded as Mercury Pharma.

In 2012, Cinven acquired Mercury Pharma from HgCapital.

In 2015, Concordia acquired Amdipharm Mercury (owner of Mercury Pharma) from Cinven.

In 2016, Concordia renamed as Advanz.

In 2021, Nordic Capital acquired Advanz.

The CMA fine applied to the period from 2009 to 2017. Across multiple owners.

At each step, due diligence should have identified any potential for CMA action, especially once the CMA started looking around.

If liothyronine is a difficult-to-manufacture product, how come Morningside got there from a standing start and launched their own make – and in 10 and 5 microgram dosages as well?

If Advanz could justify almost 250 pounds for 28 tablets, how come they are still supplying the market at around 100 pounds? Are they not now making a huge loss?

If MHRA standards are so hard to comply with, how come Teva managed to launch their product manufactured in Hungary?

How can Advanz claim cost-savings to the NHS when the best thing they could have done would have been withdraw their own product and import another company’s liothyronine product? Why did they de-brand the product (from being Tertroxin) when, according to Advanz’s claims, they could justify every penny of the price they were charging? In that case, they would not have needed to de-brand.

On what basis do Advanz think that the price of liothyronine should represent the cost of future investment in a new factory as they claimed? Especially as the factory is not owned by Advanz but by a contract manufacturer. Companies are expected to gain a return from investment, not charge the customer in advance and then (possibly) invest.

Without knowing how much it costs Advanz to get the product contract manufactured, we can say little about the profit they make. But I assume the CMA know how much Advanz were charged so as to come up with their fine and their statement that cost of manufacture did not change significantly.

tattybogle profile image
tattybogle in reply to helvella

lots of awkward questions... squirm .

Musicmonkey profile image
Musicmonkey in reply to helvella

Perhaps worth sending these questions to the CMA to get responses from the companies involved?

marigold22 profile image
marigold22 in reply to helvella

I can buy Mexican Cynomel T3 at $13 for 100 25mcg tablets

helvella profile image
helvellaAdministrator in reply to marigold22

Trouble is, no-one is going to get any of these non-UK products prescribed for them within the UK. (One or two European products such as Thybon Henning might be prescribable but not from Mexico.)

marigold22 profile image
marigold22 in reply to helvella

I was too hasty to reply, without reading down the replies below. My reply was saying that T3 can be made cheaply.

It would appear that T3 production difficulty is only an issue in the UK. I wonder why? Could it be that our wonderful NHS is so inept that it takes years before a scam is detected (even when thousands of patients are telling them that they're being scammed)? To boot, the NHS response to the situation was to try and deprive patients of the much needed medication. Didn't anyone in the NHS think to check out the low cost of T3 in other countries when the price started to escalate in the UK? It wouldn't surprise me if the companies involved get off scot free on appeal on the basis that the NHS acquiesced to the price increases.

TSH110 profile image
TSH110 in reply to tcpace

It smacks of corruption to me

Hennerton profile image
Hennerton in reply to tcpace

I wrote to my MP about the massive price increase of Liothyronine in 2013. He sent my letter to someone in the House of Lords, who wrote back that it was caused by transport costs and difficulty of manufacturing. Hmm, really?

A few years later I wrote again. This time he told me that it was all connected with a deal the NHS made to receive branded medicine at a specially advantageous price but on the basis that non-branded treatments such as Liothyronine, could be any price the Pharma company wished to charge. So there you have it. The terrible deal that ruined people’s lives.

tcpace profile image
tcpace in reply to Hennerton

If true that is absolutely outrageous given that the NHS then proceeded to stop GPs prescribing T3 because of the cost. In other words, if true, our wonderful NHS deliberately colluded with third parties to deprive patients of medication critical to quality of life. Do you have any documentation to substantiate what John Howell told you?

jsy_girl profile image
jsy_girl in reply to tcpace

That is indeed shocking if true. But I can well believe it because it’s the only kind of explanation that you could imagine for why they didn’t just find a cheaper source

Hennerton profile image
Hennerton in reply to tcpace

I must have but will need to trawl through hundreds of emails to find it. I will start tomorrow….

Hennerton profile image
Hennerton in reply to tcpace

I have found a letter in response to one I wrote to Jeremy Hunt. It is from Jane Spencer from the department of Ministerial Correspondence and Public Enquiries of the Department of Health. She explains with regard to prices of medicines “that the department is aware that there have been a number of increases of certain medicines, including thyroid medication. These include instances where a product previously marketed as a brand has been subsequently marketed as generic and an increase in price has been applied in view of the lack of a competitive market for that product.

There are systems in place to ensure that the NHS obtains the best value possible from the purchasing of medicines. There are voluntary and statutory schemes in place to consider the prices of branded and generic medicines, rather than consider each product individually.”

I take this to mean what we know happens in practice that the branded are at a low price but are paid for by a high price on generics,

tcpace profile image
tcpace in reply to Hennerton

Typical weasel wording, probably intended to conceal what arrangement had been put in place. I'm just wondering whether a Freedom of Information request might get to the bottom of how the NHS came to accept the exorbitant price increases. The NHS must have been fully aware that patients on T3 (or hydrocortisone) would be seriously disadvantaged and they appear to have colluded in this by trying to stop prescribing of T3.

Hennerton profile image
Hennerton in reply to tcpace

Yes, maybe a Freedom of Information might throw up something but to whom is it to be directed? The government has changed since this letter came to me in 2017. I will look into it.

The letter goes on to mention what we know then happened about the NHS “leading a review of low-value prescription items and introducing new guidance for CCGs with a view to substantially saving money in this area….regarding over the counter medication like indigestion, travel sickness coughs and upset stomachs”. T3 was then classed with all those. Truly amazing!

Bluespots profile image
Bluespots in reply to Hennerton

Since when could you get T3 from a supermarket medicine aisle ? Prescription only, how would we know how much to take if it was available like that......do they not mean that some medical needs, will be Private only in the future, not NHS ????

Hennerton profile image
Hennerton in reply to Bluespots

That is the anomaly. They included T3 in all those over the counter products but must have known it would mean desperate patients would not be able to obtain it. That is exactly what have been fighting. So many patients have been forced to buy from abroad or pay an exorbitant price in the U.K. for a private endocrinologist to give them a prescription.

Last time I visited Mexico I got Cynomel 25mcg (T3) for £7 for a bottle with 100 tablets. So, surely it is not costly to make if at that price the manufacturers and the chemists are making profits. Furthermore, I was told they often had it on 4 for 3 types of offers (seemingly it's quite common for medication for lifelong conditions that such offers and loyalty schemes operate over there). People in this forum have also mentioned Tiromel and other foreign brands of T3 at much cheaper prices.

Surely, if the UK manufacturers cannot produce it more cost-effectively, the NHS should purchase it elsewhere.

Sybilla14 profile image
Sybilla14 in reply to Kitten44

Indeed, the Unipharma T3 price printed on the box of 28 tabs is €2.30.

Marz profile image
Marz in reply to Kitten44

I only paid €1.40 for T3 OTC in Greece back in 2019. Why didn't the NHS bods give Uni-Pharma in Athens a call and buy from them. Am sure they would have been delighted at receiving €10 a box for a 30 x 25mcg. UK brands only 20mcg I believe so an even better deal ...

It would seem that contracts for mates is a popular choice - and reciprocal favours no doubt. It does need looking into in more depth.

Musicmonkey profile image
Musicmonkey in reply to Marz

I bought it last year for €1.30 per box.

Marz profile image
Marz in reply to Musicmonkey

Yes the price can vary by a cent or two ! I remember when I paid €1.10 ....

In agreeing to enter a contract to supply this stuff there would have been two informed parties,namely the seller and the buyer. So I am now interested in the buyer who I don't want to hide behind the impersonal "NHS" name because there are actual individual people here; people who have names and pay slips with NHS stamped on them. People who have meetings and must keep records of who said what during the negotiation process to buy and increase the price of this stuff. Who are these NHS people and who said "yes, even though the price has sky rocketed we still are going to buy it". I also am curious asto the exact individual(s) who attended the meeting which decided to (a) keep paying the price and (b) order GPs etc not to prescribe it.

DippyDame profile image
DippyDame in reply to Tythrop

Who are these people that have ridden off into the sunset?

Are they not accountable for responsible use of public money?

From an article in The Times...

"The Times has previously obtained emails showing that NHS officials waved through large medicines price rises imposed by Advanz Pharma when known as AMCo without asking for a justification."

Why is there a loop hole allowing this price hiking to happen? Who missed that?

Who said what to whom?

There should be no hiding place for the negotiators who let this slip through the net!

This is about much more than the scandalous price if T3 methinks!

Localhero profile image
Localhero in reply to DippyDame

I totally agree. I really hope someone is on the case of understanding why these NHS jobsworths thought it was acceptable to just nod through such scandalous increases.

LindaC profile image
LindaC in reply to DippyDame

Said for years, 'Even a couple of A Level Business Studies students could have negotiated better than... ". Heads need to roll on this... ah, they usually 'move them sideways or up'.

DippyDame profile image
DippyDame in reply to LindaC

Promoted above their ability!

LindaC profile image
LindaC in reply to DippyDame

Across the board it would seem!

diogenes profile image
diogenes in reply to DippyDame

"The Times has previously obtained emails showing that NHS officials waved through large medicines price rises imposed by Advanz Pharma when known as AMCo without asking for a justification."

Simple to do. It wasn't their money. An expensive waving of the pen.

DippyDame profile image
DippyDame in reply to diogenes

Indeed! Accountability is an unknown concept...

It's blatant profiteering and greed. Turkish Tiromel is made cheaply. I bought a supply OTC. One year of 75mcg per day cost me around £25. One day equivalent when liothyronine was at its most expensive would have cost more than £27. One year at £25 versus one day over £27.Someone became extremely rich at the expense of a subset of thyroid patients becoming extremely unwell.

Unforgivable

Every penny of the £100m fine is justified.

They’re just a bunch of lying psychopaths intent only in their own gain, sadly at our expense in more ways than one.

I see from an article in The Guardian just now that shareholders were paid £400m. Also that they avoided paying corporation tax.

theguardian.com/business/20...

Completely criminal.

TSH110 profile image
TSH110 in reply to Localhero

Lowest of the low

On a more elementary level Tiromel can be sold for little over a penny a tablet in Turkey and that price includes manufacturing, testing, packaging and dispensing with fair profits all along the way.

Also, UK liothyronine was (still is?) exclusively manufactured by Custom Pharmaceuticals. When I looked a couple of years ago their total turnover was £13m a year. This included sell lots of different medicines to lots of companies, so the manufacturing cost of UK liothyronine would be very little indeed. I passed this information onto the CMA as it proves that UK liothyronine is not expensive to manufacture.

(Their 2019 annual turnover was £15m, see find-and-update.company-inf... ).

As of 2018 two out of three liothyronine products were manufactured outside the UK and no doubt marketed in Europe at a fraction of the price whatdotheyknow.com/request/... .

helvella profile image
helvellaAdministrator in reply to jimh111

Morningside and Teva is not made by Custom Pharmaceuticals. Only Advanz (Mercury Pharma).

jimh111 profile image
jimh111 in reply to helvella

Yes, they are both made in Europe, one in Hungary I think but can't remember which. Mercury were making more than £13m from liothyronine before the other two came along.

I very much doubt these two European varieties are modified for the UK market.

Glaxo-SmithKline (GSK) made Tertroxin way back in time. It was the first T3 in the UK that I was put on. It was not a generic then and they were the only UK supplier.

GSK made a profit out of Tertroxin (I know this for a fact as my sister-in-law was a VP at GSK). I can't recall the exact price of it, but I think it was about 4 times more than the Levothyroxine - something of the order of £25 for 100 pills - ish, because I asked my GP and pharmacist at the time out of curiosity So, it is possible to make it cheaply and still make a profit.

If Advanz is using that argument then they are either:

1) Extraordinarily bad at making drugs

OR

2) Lying through their teeth. Allegedly! :)

I only see one likely option!

Thanks again Diogenes!

Paul

jimh111 profile image
jimh111 in reply to PaulRobinson

In 2007, the last year liothyronine was branded 'Tertroxin' in the UK it was £15:92 for 100 tablets. (I purchased BNF 53 March 2007 on eBay for 3p plus a few quid postage). I did this to calculate the percentage increase for Sheila at TPA as she had a journalist contact, the percentage increase was 6,000%. I remember that round about 2005 Tertroxin was £13 for 100 tablets.

helvella profile image
helvellaAdministrator in reply to jimh111

Many editions of the British National Formulary are available on the Internet Archive (Wayback Machine).

archive.org/search.php?quer...

You might have to sign up for an account to view them.

Are you sure that was 100 tablets? And not 28?

jimh111 profile image
jimh111 in reply to helvella

Absolutely certain, I remember the pots and the 2007 BNF says it’s 100. The round plastic Tertroxin pot used to contain 100 tablets. When they started putting 28 in the same pot I asked Goldshied if this was in preparation for using bubble packs. They just said no, they didn’t tell me the smaller packs were a staging post for debranding and drastically increasing the price.

PaulRobinson profile image
PaulRobinson in reply to jimh111

Getting old! So, my exact memory of the price is a bit grey. But it was cheap as chips compared to now, and it was not a barrier to any CCG or endo or doctor who wished to prescribe it.

Thanks for the more exact info Jimh111

Framboise profile image
Framboise in reply to jimh111

I remember these low prices for Tertroxin too Jim, when Dr Skinner used to prescribe it for me in the early 2000s and I collected it from the local Boots. I took 40 mcg a day and was new to having to pay for meds but didn't flinch at the prices then.

I've also often bought the Unipharma version in Greece when I've been there, and the price has been even lower. I've shown the boxes, with price stamp, to my GPs and endocrinologists many times. I wrote to some NHS authority concerning it in about 2009, but I don't remember who that was. They weren't interested and nothing came of it.

If those manufacturers could, and still can, make it so cheaply then so can the current manufacturers. I suspect they've been happier making a huge profit assuming no-one would notice, or think to compare with other manufacturers.

jimh111 profile image
jimh111 in reply to Framboise

Wonderful Gordon Skinner.

I brought it to the attention of doctors in 2015 bmj.com/content/351/bmj.h51... . I also brought it to the attention of the British Thyroid Association. I had to try twice and the second time they said they didn’t know about it and will look into it. It took them about a year to take the first tentative steps. My view is that most endocrinologists want liothyronine to be expensive because if they have to prescribe it they will have to admit they are wrong and will no longer be able to treat on auto pilot by blood test results.

DippyDame profile image
DippyDame in reply to jimh111

I also think the younger generation of medics are afraid of T3!

helvella profile image
helvellaAdministrator in reply to PaulRobinson

Tertroxin was originally launched by Glaxo on 1956/06/23.

Advanz keep claiming that it is because MHRA requirements are too stringent - at least, more stringent than others.

Reading between the lines it looked as if every batch had to be submitted to MHRA for analysis before release. But I strongly suspect that was because they had actually failed to conform to the required standards on more than one occasion.

The price of Tertroxin in Australia was further evidence that Advanz's claims were rubbish - somewhere I have posted that price.

ADDING

For 100 20 microgram Tertroxin tablets (supplied via Aspen but I am sure it is the Advanz product):

Prescription Type

Private + $78.69

PBS + $40.30

Concession + $5.60

pharmacyonline.com.au/tertr...

Advanz's claims are total rubbish as you so rightly state Helvella! Just pathetic. They have such a 'front' that they can even say that it is really hard to manufacture. It beggars disbelief that they think they can get away with that argument.

jimh111 profile image
jimh111 in reply to helvella

The MHRA introduced batch approval for a while because the quality was so poor. If it was as good as Turkish liothyronine it would have retained approval.

So it's like doing Batik ? (wax resist dying) ... well that's not so difficult at all .. i might have a go.... take some 'T ' ....put some wax on one corner .. dip it in some iodine.

If it works you can all buy it off me .

i'll only charge 50p/tablet this year ... then £2 next year ... then £486 in 2024.

Can i have an OBE now please ?

nellie237 profile image
nellie237 in reply to tattybogle

Yes, and when you've donated what to you is a small portion of your multi-million £ profit that you've purposefully made extortionately and at others distress, you can have a building named after you, and be called a philanthropist.

Tale as old as time unfortunately.

tattybogle profile image
tattybogle in reply to nellie237

perfect .. can i have tea and cake at the Palace too... or would that be taking the piss ?

nellie237 profile image
nellie237 in reply to tattybogle

Oh, it's definitely taking the piss, but hey, why not have a day off......you deserve it.

tattybogle profile image
tattybogle in reply to nellie237

☎️📞got to go.... somebody called Matt Hancock ? on the phone , want's to know if his friend can be a director of my company....

nellie237 profile image
nellie237 in reply to tattybogle

🤣🤣🤣

Actually, I've got a few candidates you should be very interested in. Looking to move from Senior posts at the Department of Heath & Social Care

DippyDame profile image
DippyDame in reply to nellie237

One of them has already received a 'gong" can't remember the wording but philanthropy was mentioned in the citation.

Tythrop profile image
Tythrop in reply to nellie237

...and clain Tax relief foryour incime you put in your own personal charitable institution

I have a friend who works in a different profession, for a large company and where she must buy products from an agreed list only.

Some of these products have very seriously inflated prices but she is not allowed to source elsewhere as at the end of the financial year her company get a ‘kick back’.

It certainly makes you wonder how many over priced medicines there are on the nhs list?

CCG's do this all the time............there are quite a few 'Freedom of Information Requests' out there on this subject ie Patients wanting to make sure that their meds haven't been changed for this reason. Insulin is a big one because there isn't any generic insulin.

Will they get away with that lie about it being very difficult when it is nothing of the sort? It beggars belief I hope they are well and truly taken to the cleaners. It makes me mad to think of all the people their despicable greed has impacted.

i dont think that MP's have been particularly interested to push for answers on any of this until the CMA ruling. Now that they have ruled all these questions about the NHS involvement should be investigated.

I dont know if people should contact their MP's individually or if this should be a joined up effort with a pre-written email from this charity or the group that have been involved with the Lord Hunt campaign, that we can all send individually to make an impact. Either way we need to strike while this is fresh in everyone's minds and more importantly while the press are asking questions too.

knitwitty profile image
knitwitty in reply to Star13

I spoke to my MP in January 2020 just before the pandemic kicked off, she was newly elected and keen to help, I specifically asked if she could look into the CMA situation, but then covid hit and I haven't been in touch with her since. She didn't like the suggestion the other forces might be at work regarding the price hikes of T3 .

I might get back to her again now that we have a ruling from the CMA and see what she has to say.

Thank you Diogenes. Your logic surpasses that of the manufacturers!

Reminds me a bit if the recent criminal action against postmasters/mistresses where, until a persistant investigative journalist got stuck-in no one in "officialdom" ever challenged the word of the Big Cheeses and their dodgy computer.

knitwitty profile image
knitwitty in reply to Tythrop

That was another disgrace , people had their lives ruined over that disaster.We seem to suffer from a lot of incompetent people in this country who all seem to get very good positions and who control everyone beneath them. What's even worse , when they discover their mistakes they do their utmost to cover up rather than admit they messed up and put things right and help those they have neglected.

I’ve written to Stella Creasy MP and asked her to champion an investigation. I’ve written to her a couple of times about the price and she hasn’t responded, but she did help my daughter to gain an NHS prescription so who knows?

Just a thought:- The Women's Health Strategy: Call for Evidence Results are due this autumn.

I might feel the need to submit my 1st ever Freedom of Information request if Thyroid patients don't get a reasonable mention.

humanbean profile image
humanbean in reply to nellie237

Do you have a date for any results from the Women's Health Strategy being published?

nellie237 profile image
nellie237 in reply to humanbean

No I don't, but I remember that the blurb said that they hoped to get the results out this autumn.

I will be surprised if we even get a mention.

humanbean profile image
humanbean in reply to nellie237

Yes, my hopes for anything useful coming out of the survey are almost non-existent.

I think Hennerton received the answer that this is how prices are viewed in the brand/ generic scenario. That the pharmaceutical companies have to develop new drugs and will be funded by NHS pricing across the board so that they will continue to make enough to continue bringing out new and better remedies. Mercury Pharmacy/ Concordia blew a hole through this laissez-faire arrangement and Jeremy Hunt’s bill conveniently had to sit and wait for CMA outcomes. Will anything happen once this case has gone through appeal ? A complete overhaul of the pricing system to counter pharmaceutical profiteering might bring T3 back to affordability and to patients who desperately need it .

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