TOPIC:

Does anyone know - are indian dac generics "licensed" (like sof and harvoni generics licensed by Gilead) or not? Was transfer of technology from BMS to indian dac producers performed or not yet? If transfer of technology did not performed, is this correct that indian dac generics are not "licensed" yet, like dac generics made in Bangladesh? If i correctly understand, all indian generic dac is manufactured by two companies (Hetero and Natco) and is marketed under various brand names by various companies - hepcasia.com/wp-content/uploads/2016/03/...mmary_7-March-16.pdf But, different dac generics have different storage conditions (for example, Natdac below 25 celsius degree, Daclahep - below 30 degree). Thus, is this correct that technology or manufacturing is different between various brands?
Indian dac generics were launched in December 2015, but sublicenses between BMS and 4 indian dac producers (Natco, Hetero, Emcure, Cipla) and medicine patent pool was announced only at 20 January 2016 - www.medicinespatentpool.org/the-medicine...edicine-daclatasvir/ . There are no marks "manufactured under license from BMS" on many packs of dac, made by Natco and Hetero. But packs of HepcFix, made by Dr.Reddys have mark "sold under license from BMS and MPP", despite Dr.Reddys probably did not signs sublicense with MPP and BMS. I am a little bit confused...

Good question Serg as am also puzzled about this...

I am also wondering whether there is any difference between "sold under license from BMS and MPP" & "manufactured under a license from BMS and MPP". "Sold" doesn't mean being manufactured under licence from BMS/MPP....? And I haven't seen any news re. Dr.Reddys entering into direct agreement with BMS/MPP to either produce or sell DAC.

"Sold under license from BMS and MPP" doesn't make any sense provided that Dr Reddys's HepcFix - 60 is actually manufactured by Hetero who did sign the agreement with BMS/MPP back in Jan....

Virtuose
Hi!
Yes, it seems like "puzzling" questions...

Can anyone clarify these things? What do you think about it? Thanks.

The Medicines Patent Pool Signs First Sub-licences for Hepatitis C Medicine Daclatasvir

Four companies to help speed access to curative direct-acting antiviral in 112 low- and middle-income countries

Geneva, 20 January 2016 – The Medicines Patent Pool (MPP) announced its first round of sub-licences for the generic production of Bristol-Myers Squibb’s daclatasvir, a novel direct-acting antiviral that is proven to help cure multiple genotypes of the hepatitis C virus. Generic companies Cipla, Emcure, Hetero and Natco have signed non-exclusive, royalty free agreements with Bristol-Myers Squibb and the MPP to produce and sell daclatasvir in 112 low- and middle-income countries.

www.medicinespatentpool.org/the-medicine...edicine-daclatasvir/

Yes. But does it mean that transfer of technology was already completed to these 4 companies under supervision of BMS? If yes, how to explain different storage conditions for different brands and absence of "manufactured under a license" marks on many packs?

Serg wrote: Indian dac generics were launched in December 2015, but sublicenses between BMS and 4 indian dac producers (Natco, Hetero, Emcure, Cipla) and medicine patent pool was announced only at 20 January 2016 - www.medicinespatentpool.org/the-medicine...edicine-daclatasvir/ .

Thank you Dr Freeman but you just repeated what Serg had said in his initial post...

Gilead gets its APIs from Chinese manufacturers. India exports more sofosbuvir than it manufactures. I think the "licensing" deal really amounts to Gilead allowing the word "licensed" to appear in advertising and marketing strategies.......for a fee, of course and probably some kind of agreement to restrict exportation.

In this case, what is about "quality control" and "transfer of technology" from Gilead/BMS to generic manufacturers (for example, recently mentioned by Dr.Gane for ledipasvir)? Is this correct that different generic producers may develop their own different technologies of manufacturing, then Gilead/BMS give them rights to put on packs "under a license" marks without transfer of technology and "quality control"?

Hi Serg,

Just a few thoughts on this. I'll start by saying I don't know all the Indian laws that need to be complied with nor fully understand how this sort of international licensing agreement involving the MPP would work. My comments are based on some understanding of generics manufacturing processes and licensing agreements (food, additives, cosmetics rather than pharmaceuticals) and a quick scan through of one of the agreements attached to your links. I am not endorsing or criticising anything, just commenting on what I can see and speculate about.

- The licenses may not be very similar to Gilead ones in that while they allow manufacture of product and sharing of IP there are no fees and a third party involved (MPP) so there are likely to be very different clauses regarding responsibilities and liabilities.

- There are four Indian manufacturers licensed but from what you say only two of them are currently using that right. Anything made by them for their own sale would not need the "manufactured by" bit but probably requires the "sold under license from".

- There are multiple agents/distributors such as Dr Reddy/Mylan who sell products under their own brand names that are produced by the four (two?) manufacturers. I would expect that their packaging would need to carry "manufactured by" and "licensed from" information either under Indian law or the licensing agreement but this may vary a bit depending on whether they were a tied agent (part)owned by the manufacturer or an independent distributor.

- As Dac was being made in India prior to the signing of the licenses, there may be stock in the market that does not fully comply with whatever the final rules and agreements are. I would suspect that if this is the case there may be a fair amount of it as the manufacturers were getting ready to launch new products. Normally this would be a manufacturers worst nightmare as all the packaging would need changing but in this case, in the spirit of cooperation and distribution of affordable lifesaving medicines, it may have just been agreed that the old packaging could be used until it ran out then the necessary changes made.

- Technology handover in the license seems to amount to electronic and hard copies of BMS technology that were handed over during signing of licence agreements. Dac is not that complex (and it wouldn't surprise me if they are buying in the APIs anyway) so could be made prior to this happening without a lot of difficulty. It is more likely a symbolic "we are all on the same page" thing than resulting in any great revelations.

- The 25°/30° Storage temp split is likely along manufacturing lines and may be due to different binders or other incipients in the pills. But it could also be to give different shelflife for different markets or a purely marketing decision.

Anyway, those are my thoughts on the situation. I suspect that most of the anomalies will disappear with time as the market settles. But as always with generic HCV medications, Supply Chain integrity is vital and caveat emptor (buyer beware).

Edit: hehe, took so long to type that, the story has mostly moved on.

Gilead is one of Gane's largest funding sources. What is he supposed to say?

The path to market for Gilead's Harvoni looks like this;

China->India->Saudi Arabia->Jordan->Ireland->USA

Nobody starts with raw carbon, oxygen, hydrogen, nitrogen, fluorine, sulfur and phosphorus. People start with intermediates part of the way there.

Okay, on the question of quality control the licence requires that the products are manufactured in compliance with:

1. World Health Organisation requirements

2. Any other relevant authorities (e.g. Indian health requirements, GMPs, ISO9001, HACCP, local council by laws, etc, etc.)

So BMS and MPP expect the manufacturers to have standard quality control procedures in place.

Edit: I will note here that while I haven't seen the Gilead licenses (has anyone?) I would expect they would be very similar in what they stated with regard to Quality Control. This isn't rocket science, manufacturing is global these days as are quality standards. And no company is going assign it's own "policemen" to oversee compliance by a licensee.

Incepta is approved by WHO.

Gaj
Hi! Gilead license agreement is there - www.gilead.com/~/media/files/pdfs/other/..._agreement.pdf?la=en