Karthikeyan
☆    

India,
2013-09-02 07:55
(4677 d 21:21 ago)

Posting: # 11400
Views: 12,831
 

 Russia Guidance – BE [Regulatives / Guidelines]

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Dear All,

To become generic in Russia, is it enough to perform Bioequivalence study or it needed to perform / provide toxicology or clinical trials data. :confused:

please help me out and let me know where i can read the complete requirements. :-)

Regards,

Karthikeyan
 
drgunasakaran1
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2013-09-02 08:14
(4677 d 21:01 ago)

@ Karthikeyan
Posting: # 11401
Views: 11,968
 

 Russia Guidance – BE

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Dear Mr Karthikeyan,

❝ please help me out and let me know where i can read the complete requirements. :-)


Please see Guidelines/Guidances section of the Forum.
—
Dr Gunasakaran Sambandan MD
Disclaimer: The replies/posts are my personal opinions, and they do not represent my company's views on the same. LinkedIn
 
Karthikeyan
☆    

India,
2013-09-02 08:21
(4677 d 20:55 ago)

@ drgunasakaran1
Posting: # 11402
Views: 12,079
 

 Russia Guidance – BE

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Dear Dr. Gunasakaran,

i have gone through that and got to know their requirements to conduct BE study.

i am in need of information, whether that is sufficient or we need additional toxicity or clinical trials....

Thanks and looking forward,

karthikeyan
 
Helmut
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Vienna, Austria,
2013-09-02 12:31
(4677 d 16:45 ago)

@ Karthikeyan
Posting: # 11404
Views: 12,040
 

 Russia: Toxicity data required

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Hi Karthikeyan,

❝ i am in need of information, whether that is sufficient or we need additional toxicity or clinical trials...


You need toxicity data of the formulations (test + reference!) – not only of the API – before you start a BE study. The idea behind is a complete mystery to me. Anyhow, according to federal law #61 (aka “Lex Putin”) BE studies have to be performed by Russians CROs only. AFAIK, no way to do it in India.
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mittyri
★★  

Russia,
2013-09-02 16:18
(4677 d 12:58 ago)

@ Helmut
Posting: # 11407
Views: 11,923
 

 Russia: Toxicity data required

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Hi Helmut & Karthikeyan!

Helmut knows (almost) everything ;-)

❝ ❝ i am in need of information, whether that is sufficient or we need additional toxicity or clinical trials...

❝ You need toxicity data of the formulations (test + reference!) – not only of the API – before you start a BE study.


At this moment - yes. I would pay your attention on new amends prepared by MoH and experts. They are going to be approved soon.
According to this draft it will be allowed only to post a literature review of originator's preclinical trials.
It's discussed now about data exclusivity of this data. May be it would be possible only with originator's permision (or 6 years after Originator's registration)

No one knows how would it works :confused:

❝ Anyhow, according to federal law #61 (aka “Lex Putin”)

:-D
—
Kind regards,
Mittyri
 
Karthikeyan
☆    

India,
2013-09-03 10:48
(4676 d 18:28 ago)

@ mittyri
Posting: # 11412
Views: 11,914
 

 Russia: Toxicity data required

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Dear Mittyri,

❝ According to this draft it will be allowed only to post a literature review of originator's preclinical trials.


I understand that earlier we need to go for toxicity studies for generics and now the current draft tell to provide literature review of the product.

is my understanding is correct. Please correct me if i'm wrong. :-)

Regards,

Karthikeyan
 
mittyri
★★  

Russia,
2013-09-03 11:26
(4676 d 17:50 ago)

@ Karthikeyan
Posting: # 11414
Views: 11,794
 

 Russia: Toxicity data required

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Dear Karthikeyan,

❝ I understand that earlier we need to go for toxicity studies for generics and now the current draft tell to provide literature review of the product.

❝

❝ is my understanding is correct. Please correct me if i'm wrong. :-)


Absolutely right. Current draft allows to provide literature review only.
We are waiting for approval and first law enforcement practice because there could be some pitfalls.

to ALL:
Are new requirements in this draft (see above) closer to EMEA GL?

Best regards, Mittyri
—
Kind regards,
Mittyri
 
Helmut
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Vienna, Austria,
2013-09-03 15:02
(4676 d 14:14 ago)

@ mittyri
Posting: # 11416
Views: 11,931
 

 Toxicity data: why?

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Hi Miityri,

❝ Are new requirements in this draft (see above) closer to EMEA GL?


Since EMA doesn’t require anything – yes, closer. ;-)

I still fail to understand this requirement at all. Animal models are – only models. The innovator’s drug is on the market for years – administered to humans (the target species), not animals (a model species). Pharmacovigilance data show that the drug is safe or – more precisely – its benefits outweigh its risks. These safety data are available to regulators. It is beyond my intellectual reach how short term toxicity data in say 24 Sprague Dawley rats could give more information than ADRs collected in millions of patient-years.
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Karthikeyan
☆    

India,
2013-09-04 08:46
(4675 d 20:30 ago)

@ mittyri
Posting: # 11423
Views: 11,686
 

 Russia: Toxicity data required

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Dear Mittyri,

❝ Absolutely right. Current draft allows to provide literature review only.


Thank you very much for the clarification :-D:-D...

can you please share where i can access the draft guidance (english translated) or can u provide me link / copy. :-)

Regards,

Karthikeyan
 
mittyri
★★  

Russia,
2013-09-04 10:58
(4675 d 18:18 ago)

@ Karthikeyan
Posting: # 11425
Views: 11,792
 

 Russia: Toxicity data required

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Dear Karthikeyan,

❝ can you please share where i can access the draft guidance (english translated) or can u provide me link / copy. :-)


Unfortunately, I can't find any translations available for federal law #61 (main guide for registration) and new draft for it :-(.
—
Kind regards,
Mittyri
 
Helmut
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Vienna, Austria,
2013-09-05 02:09
(4675 d 03:07 ago)

@ mittyri
Posting: # 11440
Views: 11,835
 

 Federal Law # 61–FZ “On circulation of drugs”

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Hi Miityri & all,

❝ Unfortunately, I can't find any translations available for federal law #61 (main guide for registration) and new draft for it :-(.


See the website of the ACTO (Association of Clinical Trials Organizations). Some regulatory documents (including #61) here. A lot of drafts; none in English…
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Karthikeyan
☆    

India,
2013-09-05 15:52
(4674 d 13:24 ago)

@ Helmut
Posting: # 11442
Views: 11,742
 

 Federal Law # 61–FZ “On circulation of drugs”

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Dear Miityri & Helmut,

Thank for the link and got the english version.

http://acto-russia.org/en/index.php?option=com_content&task=view&id=7

As per page no. 20/67 & 37/67, the law tells,

"Generic medicinal products intended for medical use are subject to trials for bioequivalence and/or therapeutic equivalence in the procedure established by the authorized federal executive body"


Please confirm it is in draft stage or it is published.

Sorry for troubling more and thanks for the help.

Regards,

Karthikeyan
 
Helmut
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Vienna, Austria,
2013-09-05 17:21
(4674 d 11:55 ago)

@ Karthikeyan
Posting: # 11443
Views: 11,816
 

 # 61–FZ adopted 24 March 2010

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Hi Karthikeyan,

❝ As per page no. 20/67 & 37/67, the law tells, …


I find this statement only on page 37 (Chapter 7, Article 38/2).

❝ Please confirm it is in draft stage or it is published.

  • The law is in force; adopted by the State Duma on 24 March 2010.
  • Amended a couple of times; the linked document is an unofficial translation of the consolidated version (including 93–FZ of 25 June 2012).
  • Official translations don’t exist (see also the last paragraph of this post). If you distrust the translation, get the Russian original and go for a certified translation.
  • BTW, why does this statement bother you? Generics have to demonstrate equivalence by standardized procedures everywhere.
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Karthikeyan
☆    

India,
2013-09-06 08:32
(4673 d 20:44 ago)

@ Helmut
Posting: # 11444
Views: 11,527
 

 # 61–FZ adopted 24 March 2010

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Dear Helmut,

❝ • BTW, why does this statement bother you? Generics have to demonstrate equivalence by standardized procedures everywhere.


i just want make sure the toxicity data is not required for generics from this law.

Regards,

Karthikeyan
 
mittyri
★★  

Russia,
2013-09-06 09:22
(4673 d 19:54 ago)

@ Karthikeyan
Posting: # 11445
Views: 11,680
 

 # 61–FZ adopted 24 March 2010

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Dear Karthikeyan,

❝ i just want make sure the toxicity data is not required for generics from this law.


Helmut replies to you absolutely correct:
At this moment

❝ You need toxicity data of the formulations (test + reference!) – not only of the API – before you start a BE study. The idea behind is a complete mystery to me. Anyhow, according to federal law #61 (aka “Lex Putin”) BE studies have to be performed by Russians CROs only. AFAIK, no way to do it in India.

—
Kind regards,
Mittyri
 
Dr_Dan
★★  

Germany,
2013-09-03 16:40
(4676 d 12:36 ago)

@ Karthikeyan
Posting: # 11417
Views: 11,912
 

 Russia Guidance – BE

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Dear Karthikeyan
If your product satisfies the criteria of having the same qualitative and quantitative composition in terms of active principles, of having the same pharmaceutical form and of being equivalent then the generic nature is given and it is evident that all data available for the original product also apply for the preparation of your application. The whole information on pharmaco-toxicological and clinical experience can be transferred from the originator product to the Test product. This is the basis for generic applications. Please be advised that information on toxicology refers to the drug entity itself and not to the formulation of a drug. There will be no gain in scientific knowledge if you repeat toxicological tests for your formulation. However, you need to provide evidence that no new toxicologic data are available since marketing authorisation for the reference product was granted.
I hope this helps.
Kind regards
Dan
—
Kind regards and have a nice day
Dr_Dan
 
Helmut
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Vienna, Austria,
2013-09-03 16:45
(4676 d 12:31 ago)

@ Dr_Dan
Posting: # 11418
Views: 11,931
 

 Russia Guidance – BE

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Hi Dan,

Full ACK in the rest of the world. :-D Do you have actual experience with Russian authorities accepting such an argument?
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Dr_Dan
★★  

Germany,
2013-09-03 21:27
(4676 d 07:49 ago)

@ Helmut
Posting: # 11419
Views: 11,830
 

 Russia Guidance – BE

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Hi Helmut
Does anybody have experience with Russian authorities? :confused: I never met anybody who submitted a dossier but there are a some people who like to discuss what would happen if......
Out of curiosity: have you ever tried to find a phase I CRO in Russia? I could not identify one site which could conduct bioequivalence studies in a way we are used to it. And I am not the only one who tried. IMHO the whole business is like a black hole.
Kind regards
Dan
—
Kind regards and have a nice day
Dr_Dan
 
Helmut
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Vienna, Austria,
2013-09-03 23:16
(4676 d 06:00 ago)

@ Dr_Dan
Posting: # 11421
Views: 11,893
 

 ги́бкость

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Hi Dan,

❝ Does anybody have experience with Russian authorities?


A little bit. I know one of the scientific advisors responsible for the BE guidance. Very knowledgable person, mathematical statistician, and specialised in Population PK.

❝ I never met anybody who submitted a dossier but there are a some people who like to discuss what would happen if......

❝ Out of curiosity: have you ever tried to find a phase I CRO in Russia?


Not personally but I know one company succeeding. Took them two years, opening up an office in Moscow, a lot of site visits, mock-up inspections, and trainings. The clinical phase of the first study ran last autumn.

❝ I could not identify one site which could conduct bioequivalence studies in a way we are used to it.


Define “the way you are used to it”. :-D An important term in Russia is “flexibility” – which has a long and valuable tradition.
  • If the axis of Mr Putin’s truck breaks in the middle of a snowstorm in Siberia he gets out the welding equipment and fixes it. Mr Obama would just sit there, complain that his mobile gets no connection, and freeze his butt off.
  • [image]The Мир space station was in orbit for 15 years – at its end of service more or less sticked together by duct tape, cable ties, and twine. Cosmonauts enjoyed the space toilet developed in the СССР at a time where astronauts had still to face a future of shitting in diapers for years to come.
As you see from these examples this tradition of flexibility sits deep and you can expect to receive surprised looks when talking about the formalisms of GxP.
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Dr_Dan
★★  

Germany,
2013-09-04 12:20
(4675 d 16:56 ago)

@ Helmut
Posting: # 11429
Views: 11,788
 

 Flexibility

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Hi Helmut,
The European generic industry looks for legal certainty and does not like "flexibility". They want to stick to fixed and transparent rules in order to evaluate the risks and to assess the efforts and time to spend for a certain project. What you call "flexibility" is the reason why companies refrain from conducting studies in Russia. You could translate flexibility also by discretion, intransparancy and helplessness.
Russia is a very big and interesting market. Guess why so few generic companies try to enter this market.
Kind regards
Dan
—
Kind regards and have a nice day
Dr_Dan
 
Helmut
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Vienna, Austria,
2013-09-04 16:30
(4675 d 12:45 ago)

@ Dr_Dan
Posting: # 11434
Views: 11,854
 

 Cultural ∆

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Hi Dan,

reasonable points. Some desultory thoughts:
  • AFAIK most (all?) Russians CROs are closely related to clinics / University hospitals. Have you ever talked to a professor in a (Western-)European hospital? GCP? Gods in white coats over here as well.
  • GLP was introduced in the US in the late 1970s and by OECD in the 1980s. In Russia still in the nursery. That’s a fact.
  • Language barrier. At a conference last year in Moscow simultaneous translation was provided since ~90% of attendees didn’t speak English at all. If you want to inititate business in Russia you have to be fluent in Russian. Even if the management of CROs knows English, you cannot assume the same for the personnel – and you want to talk to them during site visits. Methods/SOPs are in Russian. Then the usual story if you meet somebody with limited knowledge of English. Most will not tell you that they didn’t understand your question and – if in doubt – answer “yes” rather than “no”.
    BTW, in Japan “yes” (by definition!) means “Yes, I understood your question” even if the answer should be “no”. Example: The CRO doesn’t have an archive. “Do you have an archive?” – “Yes.”
    Expect similar issues in Russia.
  • National pride. Without the support of the Russian space agency, the IIS should have been shut down years ago. Russia considers itself a superpower – not a developing country. Easily innocent questions are judged as Western arrogance or interpreted as a hostile interrogation.
  • …

❝ Russia is a very big and interesting market. Guess why so few generic companies try to enter this market.


See here.

  In 2012 the Ministry of health issued 915 approvals to conduct clinical trials, which is more than 60% excess over the 2011 rate. This was also an absolute record for the entire period of keeping records.
  The significant growth in the number of approvals issued was primarily due to a real boom in bioequivalence studies. The number of this kind of studies of foreign medicines increased by a factor of nearly six, totalling 107 approvals set against just 19 in 2011.
  An analysis of the local efficacy and safety trials sector revealed that the majority of the trials were those of generics. On the whole it can be concluded that the Russian market for clinical trials previously indisputably innovative, has over the course of one year veered sharply towards generics. In our opinion, these structural changes on the market are the result of the law “On Circulation of Medicines” passed in 2010.

So somebody goes there.

An interesting comparision here. Funny enough:

The Legal Department of the Ministry of Health and Social Development (MHSD) has no English translations of the relevant legislative documents available, nor does it certify/approve translations. Consequently, the experts retrieved English translations from the Internet, in particular from the website of the Association of Clinical Trial Organisations (ACTO).

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mittyri
★★  

Russia,
2013-09-04 11:15
(4675 d 18:01 ago)

@ Dr_Dan
Posting: # 11426
Views: 11,750
 

 Russia Guidance – BE

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Hi Dan,

❝ Does anybody have experience with Russian authorities? :confused:


Nice to meet :-D

❝ I could not identify one site which could conduct bioequivalence studies in a way we are used to it.


Very strange to read it
Could you clarify what do you mean?
—
Kind regards,
Mittyri
 
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