Unlicensed liothyronine FOI request

[helvella]

For your interest:

17 July 2024

MHRA reference: FOI2024/00210

Dear ,

Thank you for your information request, which we received on 18 June. You asked

for:

“I am a medical researcher looking into the use of Liothyronine in the

UK and I have published papers on this see attached, I am currently

interested in the development in use of unlicensed Liothyronine.

Please would the MHRA provide the following information about the

importation of unlicensed liothyronine into the UK from 1 January 2004

to December 31 2023 (or for as long as records permit). This data is

requested should be on an annual basis (i.e. data for each calendar

year) and to include for each application:

Name of company and registration number applying to import

unlicensed liothyronine

AND the number of licences granted

AND number of units packs / quantity of tablets tablet by size (e.g. 25,

20, 10, 5mcg and any other).

If available MHRA is also requested to provide the overall/aggregate

figure of the actual volume of liothyronine tablets imported per year

broken down by (i) dosage; and if possible by (ii) pack for each dosage

(stating pack sizes).”

We have dealt with your request under the Freedom of Information Act 2000 (FOIA).

We confirm that we hold some of the information you have asked for; however, we

consider that the information is exempt from disclosure because Section 12 of the

FOIA applies.

The MHRA does not receive applications nor does it issue licences for the

importation of individual unlicensed medicines. The MHRA receives notifications

of intent to import unlicensed medicines by UK-based licensed importers. Importers

only notify the MHRA of their intent to import the unlicensed medicines and not of the

physical importation. Therefore, it is possible that MHRA is notified by an importer of

their intent to import an unlicensed medicine, but subsequently the import does not

import the medicine.

Prior to the importation taking place the importer must notify the MHRA of their intent

to import the medicine and provide a set of supportive documentation to allow for our

assessment of the request. The MHRA may decide to object to the importation of the

unlicensed medicine if significant safety risks are identified that may potentially

outweigh the benefits for the patients. If the MHRA does not object to the

importation, a letter will be issued to the importer stating the conditions under which

we do not object that a certain unlicensed medicine is imported.

Each import request is assessed on a case-by-case basis, taking into account not

only the product to be imported but also the special needs identified by the

prescriber.

Further information on the supply of unlicensed medicinal products ("specials") can

be found below:

assets.publishing.service.g...

ment_data/file/373505/The_supply_of_unlicensed_medicinal_products__specials_.p

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In addition to the above, MHRA does not hold information before 2010 as our current

database only provides reliable data from 01 January 2010 and as such the data we

are providing below does not date back tbefore this date.

Please note that the data had to be manually compiled to provide you with the

response, our records do not currently allow for the data to be extracted in the format

you have required. The numbers below include all presentations and strengths of

medicines that contain liothyronine by all importers that have notified the MHRA in

each calendar year.

mhra.disclosurelog.co.uk/do...

[helvella]

Under Section 16(1) of the FOIA, help and assistance, we expect that the table

provided above will provide you with some useful insights into the number of

notifications for unlicensed medicines containing liothyronine processed by MHRA.

However, you are welcome to submit to us a refined request for information bearing

in mind the details given above i.e. related to the earliest retrievable timepoint in our

records (01 January 2010) and the details of records that we hold versus those that

we have stated are not held. Any new request should be as precise as possible,

asking for information on specific importation applications received, Larger requests,

e.g. those with broad questions, or multiple questions covering a wide range of

records, are more likely to exceed the Section 12 limit/threshold.

If you have a query about this response, please contact us at

[e-mail].

Please remember to quote the reference number at the top of this letter in any future

communications. Details of your appeal rights are below.

Yours sincerely,

Healthcare, Quality and Access Group

Medicines and Healthcare products Regulatory Agency

I note the big increases leading up to 2018, then the falling off since. Launch of Morningside and Teva liothyronine was around 2017...

Screenshot of table in MHRA reply

[RedApple]

My instinctive reaction to this is to ask who is this 'medical researcher' and why are they asking the question?

[helvella in reply to RedApple]

Glad you said that. Because it was my immediate reaction as well.

Unfortunately, the days when redaction was so poor you could often "look under" the black marking to see what was supposed to be hidden are long gone.

[JGBH in reply to RedApple]

I agree too. How odd? What could possibly be his intention ?

[Alanna012 in reply to JGBH]

To make all our lives even harder is my instinctual and admittedly very pessimistic frame of thought.

[JGBH in reply to Alanna012]

No doubt ! What perverts these people are…

[QUE6T-33 in reply to RedApple]

Yes, me too

[TSH110]

Could a foi request unmask them?

[helvella in reply to TSH110]

No - the MHRA expressly say that the identity will be redacted. And, from a personal point of view, I think that is right. No-one should have to reveal their identity just in order to ask a question. However, I think our curiosity it understandable.

[TSH110 in reply to helvella]

I suspected that would be the case.

I know of one anti T3 researcher, and anti t4 for the elderly…the very ones who need them - could it be him?

[helvella in reply to TSH110]

I don't think it is possible to identify from what we know. Whilst I wouldn't have worded it like that, and certainly not pushed that I was a medical researcher (I'm not in that sense), the basic question is one I might have asked.

The intended use could go in any direction.

[Framboise]

Fascinating! This could be someone taking T3 and hoping to prevent it being withdrawn from them. It's a shame there's no way of seeing the published paper which the person attached.

[BB001 in reply to Framboise]

I wish. I admire your optimism. Given that it is a medical researcher and the poor odds of that medical researcher also having hypothyroidism and also being a poor converter of T4 to T3, the chances are low, unfortunately.

[BB001]

Initially upon reading this post, I thought you, Helvella, had written this foi request. Once it; became clear that you hadn't, my interest was piqued (I love a mystery). So the first thing I did was a Google Scholar search, viz:google.com/search?q=Google+...

The first result on the list is this research

'Liothyronine prescribing in England: costs versus need' thelancet.com/journals/lanc...

By

∙ Adrian Heald (a,b),

∙ Mike Stedman (c)

∙ Buchi Okosieme (d)

∙ Lakdasa Premawardhana (d)

∙ Peter Taylor (d)

∙ Colin Dayan (d)

Who declare the following affiliations:

a) The School of Medicine and Manchester Academic Health Sciences Centre, University of Manchester, Manchester M14 4PX, UK

It also gives his email address.

b) Department of Diabetes and Endocrinology, Salford Royal NHS Foundation Trust, Salford, UK

c) RES Consortium, Andover, UK

d) Thyroid Research Group, Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff, UK

The other search results are:

'Liothyronine and levothyroxine prescribing in England: A comprehensive survey and evaluation'

onlinelibrary.wiley.com/doi...

'Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement'

thelancet.com/journals/land...

Liothyronine cost and prescriptions in England

thelancet.com/journals/land...

My apologies of I've misaligned titles and links.

All this tells us though is which researchers have an interest in this area and are potential candidates for being the 'medical researcher' in question.

helvella RedApple

I've tagged you, as I've edited my reply since you 'liked' it.

[helvella in reply to BB001]

Have to say, I didn't search because I assumed that with the request only being in June 2024, any resultant paper(s) would yet have been published.

[BB001 in reply to helvella]

True, I too thought that. However, from their comment about having published a paper, I then thought it likely that the researcher in question had an historic interest.

[RedApple in reply to BB001]

I agree, it could well be this team. Perhaps trying to add to their research with more costing analysis.

[TSH110 in reply to BB001]

But a year earlier Pearce published one too

[BB001 in reply to helvella]

Unfortunately the list of possible researchers includes at least one who is anti T3. By the way, sorry for the edits in my first reply, I'm on my phone and flicking back and forth through tabs on Google and I didn't want to lose what I had written so far.

[Wua13262348 in reply to helvella]

Like BB001, I thought initially you had requested the information. The request seems to be in the same sort of time frame as a question mark being raised about the prescriber at Roseway labs prescribing T3 , going forwards. A forum member clarified their position a few days ago, in that they cannot prescribe T3 in the first instance, going forward. They will continue T3 if initially instigated by an Endocrinologist.

I did read a while ago that a well known retired from the NHS- Endo , based in Oxford, well known researcher in Wales (I think), and maybe someone from UCL ??? had had a meeting and come to the conclusion that the NHS needed to build their own manufacturing factory or something of that ilk, to keep the price of medicines down and to ensure sufficient supplies always available. I believe T3 was the prime example used for their way of thinking, and the previous price debacle with T3. The Oxford based Endo is pro T3, not anti T3.

I wondered if the scenario with the NHS factory-type thing they believed needed to be set up, had actually come to fruition? The reason being that , after Labour came to power, and possibly maybe the day after the budget?????( ish), Rachel Reeves was shown visiting a new Manufacturing Accord Facility in Newcastle, and I think it was referred to as NHS???? It was either a photograph in a Saturday issue of the Daily Mail, or on TV. Although I believe NHS was mentioned, it was an Accord factory, and definately in Newcastle. If I can summon up the energy I'll have a look and see if I can find anything.

EDIT:

If you Google "New Accord NHS Factory In Newcastle", there are articles written at the start of this month re." Government -backed deal will enable Accord to manufacture autoimmune and oncology medicines to the NHS".

[helvella in reply to Wua13262348]

NHS manufacturing does look like an appropriate response to some parts of price gouging by companies. But I think an awful lot of us here think that importing Thybon Henning would have been an excellent step.

That product has remained at a stable price (in Germany) throughout the over-charging scandal.

Yes, Accord did buy a manufacturing facility in Newcastle (area). Though when journalists get into saying what the company's plans are, I become even more sceptical than usual.

I have no idea about the actual layout and buildings. The Fawdon site was a Sanofi facility, so is this a new building, or newly fitted out? I suspect Accord got it at a relatively low price. And now £50 million of our money, they seem to be doing OK! (No criticism intended - I don't know enough to take a view on the issue.)

Going back to liothyronine, Accord did apply for and receive approval for their own product - back in 2022. (And why I added it to my UK medicines document.)

mhraproducts4853.blob.core....

Would be interesting if they launched it.

Ingredients of *possible* approved Accord liothyronine

[Wua13262348 in reply to helvella]

Re. you saying Accord have a license for 20 mcg Lio- that is disturbing. I am splitting 20 mcg Thybon Henning Lio. The sole importer in the UK , I think is Clinigen? A forum member posted quite recently that , I have a funny feeling, might have been that Clinigen are no longer importing Thybon Henning Lio, T3. For this to happen it may be that the Accord 20mcg Lio you refer to will be the forced alternative, which avoids importing a product.

There have been a few members looking to continue Thybon Henning T4 , which I know you personally liked on past use. They may have been Irish. This seems to be no longer imported. BUT, I think someone did say Clinigen , who will likely be the supplier of Roseway Labs-supplied, Thybon Henning T3, will no longer be importing it. Perhaps they are no longer allowed to import, as Accord T3 20 mcg will be the forced alternative.

[helvella in reply to Wua13262348]

Accord have had a licence since 2022. It is difficult to second-guess what is happening. But I agree that we have reason for some concern but until we know more, it is difficult to see what we can usefully do or say.

Their T4 product is usually called L-Thyroxin Henning.

An irony in here - that the new Accord plant was purchased from Sanofi who own Henning.

[Wua13262348 in reply to helvella]

Yes, I thought from previous posts you have made, that Sanofi own Henning!

I know the Australian female testosterone product which is unlicensed in the UK, has been going through the process of getting MHRA approval for years now. I think I read something to the effect that the MHRA have to invite the company to apply for approval of the product in the UK, rather than the company itself being able to apply to the MHRA???

If this is the case, Thybon is unlicensed in the UK because the MHRA would need to invite them to go through the process of having it approved in the UK. As Accord is normally supplied by Boots as Almus, as well as ACCORD in its own right (rebranding), it seems to be being allowed too much dominance in the market, through the back door. Perhaps Henning don't want the hassle of seeking approval, even if invited to apply for approval.

[helvella in reply to Wua13262348]

No - companies can apply to the MHRA but the MHRA doesn't go out and ask companies to apply. (There may be special circumstances where funny things happen. I wish we had some members who really knew these things instead of us having to try to divine what happens.)

[Wua13262348 in reply to helvella]

We know Glenmark T4 would likely be universally tolerated, and could effectively corner the market. I pointed this out to Glenmark in correspondence. Despite this , it has only been available for a few months in two separate years. They must have a quid pro quo agreement re. supply with other drug companies/suppliers/ manufacturers(you scratch my back, I'll scratch yours).

Perhaps Thybon have a similar , quid pro quo agreement with other manufacturers , where they have agreed not to seek MHRA approval in the UK for T3, in exchange for favourable market conditions elsewhere, or with another drug. It is the way of the world , nowadays.

I think Thybon T3 is about to become unobtainable in the UK , as Accord T3 will be seen to be an available "suitable licensed product . " BUT, we still shouldn't be expected to change products , as we know only too well.

[helvella in reply to Wua13262348]

I was under the impression that Glenmark might return in the closing weeks or next year. But I'll only believe it when I see it!

I'm pretty happy on Aristo Vencamil - and it seems quite well accepted though there are some who do not get on with it. (Isn't that always the case? )

[Wua13262348 in reply to helvella]

I have just gone through the ingredients of Accord T3 and Thybon T3 to see if they are like for like. The ingredients/ excipients are not all the same, unless some are alternative names for the same thing? Of those which are different:

Accord has Light Magnesium Oxide, Sodium Starch Glycolate, Sodium Stearyl Fumarate.

In Thybon, not Accord: Cornstarch( also has the pregelatinised Cornstarch), Sodium Carbonate, In German: Natriumthiosulfat 5 H2O (Ph.Eur), Silica,fumed, Castor Oil, hydrogenated.

Looks as though the excipients in Accord are different from Thybon???

Edit: 7 years ago , Thybon had Disodiumthiosulfate-5-water ( Dinatriumthiosulfat-5-wasser). It is currently, in German, Natriumthiosulfat 5 H2O (Ph.Eur).The translation is Sodium thiosulfate 5 H2O. This might be the same thing, or different????

Edited: Current box of Thybon Liothyronine hydrochloride :

Pregelatinised starch(maize),maize starch,microcrystalline cellulose, sodium carbonate,, sodium thiosulfate5H20(Ph.Eur), highly -dispersed silicon dioxide,hydrogenated castor oil

Sorry, having a brain foggy day! Current box of Thybon from Roseway came from Mawdsleys International Services. Don't know if Mawdsleys' get it from Clinigen or can import in their right, or not.

[helvella in reply to Wua13262348]

Yes - Accord and Thybon are different!

And yes, Sodium thiosulphate! (Pentahydrate, if you wish to add that.)

And Thybon is still the only one that has Liothyronine hydrochloride.

And I think Mawdsleys is nothing to do with Clinigen and will be doing their own importation.

[Wua13262348 in reply to helvella]

Ah, good to know! So if Clinigen stop importing, Mawdsley's may still be able to import. Phew!