The purge factor - ICH M7 Option 4

No video

The purge factor - ICH M7 Option 4

Рет қаралды 23,564

Күн бұрын

This video explains and gives an example of how to calculate the purge factor to support the adoption of Option 4 control strategy as described in ICH M7.
To watch the first video about ICH M7, follow the below link:
• ICH M7 - Risk assessme...
To know more about Mirabilis, visit www.lhasalimit...
Note: There are discussions currently taking place to reach an agreement on the best practice for solubility purges. Considering these current discussions for the example presented in this video, the solubility purges immediately following precipitation purges would not be assigned any factor.
This is a conservative approach, hence tends to be more easily accepted by regulators, and it is based on the fact that the second operation - filtration stage in this case - is only a consequence of the separation obtained in the precipitation stage (which in fact separates the solid from the liquid phase).

Пікірлер: 40

@jigneshkhant7095 2 жыл бұрын

Excellent Video, Well done, covers all without any ambiguous or obvious Statment, Superb...

@bablujejurkar661 Ай бұрын

Superb cover all point great !!!! thank for edudacting.....

@sathishgandu2221 6 ай бұрын

Madam your explanation is very good and we expect more videos from you.

@FernandaWaechter 6 ай бұрын

Thank you dear :)

@harshavardhan.b2547 Жыл бұрын

Nice explanation madam, thank you so much

@FernandaWaechter Жыл бұрын

Thank you, I’m glad you like it :)

@ernanipinto6038 4 жыл бұрын

Congrats!! Very nice, well done Fernanda!

@swatikadam5294 4 жыл бұрын

Please add video for method validation expectations as per RDC 166. Very much needed. Thank you 😊

@FernandaWaechter 4 жыл бұрын

This is a really good idea! Although with the new Brazilian API regulation which will come into force in August 3rd, Anvisa will accept analytical validations as per ICH Q2 in case a CADIFA is issued. I will soon make some videos about this subject as well :)

@sheelakanugo5537 6 ай бұрын

@@FernandaWaechterCould you please arrange details for selection of the staring material. Whether ANVISA accepts CEP access of KSM.

@FernandaWaechter 5 ай бұрын

@@sheelakanugo5537 Anvisa will not automatically accept a KSM if there is a CEP, as they always evaluate the documentation anyways. However Anvisa's requirements are in line with ICH Q11 and EDQM, so in case a CEP was issued recently where EDQM have reviewed and approved the KSM selection, it's likely that Anvisa will be in line with them.

@krish_krish354 8 ай бұрын

Amazing

@nitinmehendale4656 Жыл бұрын

Want to know how values are given like for filteration and washing 03

@tushargiri5433 7 ай бұрын

Nice explanation

@yomudon2 4 жыл бұрын

It's interesting because it shows each score in each operation. And I'm wondering whether filtration score can be included in precipitation.

@FernandaWaechter 4 жыл бұрын

Since these are different operations which can separate the impurity from the API, separate factors could be applied. We should always consider a degree of conservatism in the calculation, which in this example was done through assigning factors of 3 to the next operations. However, you can also assign a single score for these two operations, which would be even more conservative. This makes sense especially if there is limited additional data such as solubility measurements to support the assigned factors.

@yomudon2 4 жыл бұрын

@@FernandaWaechter Thank you for kind explanation. I found filtration score was calculated like "physical processes", it's acceptable. However, from the point of transfer of an impurity to solvent, impurities are already eluted in solvent at the precipitation, so further purge is not difficult to be anticipated at filtration, I guess. It may be from conservatism, as you pointed out...

@FernandaWaechter 4 жыл бұрын

@@yomudon2 I have included a note in the description which refers to this question that you have raised. There are discussions taking place currently which will probably be published soon, about solubility purges best practice. The experts agree with your first comment - that precipitation + filtration scores should be counted only once. Thank you for commenting and I would recommend to stay tunned on the publications about this subject.

@yomudon2 4 жыл бұрын

@@FernandaWaechter Thank you for your kind response. It's very informative. And I really appreciate your helpful information, because purge factor of solubility has many specific cases and they sometimes bother us. I'm looking forward to getting the publications.

@sujitkumarraskar666 3 жыл бұрын

Very informative, Thanks

@ramakrishnaguttula7941 2 жыл бұрын

Good information

@nileshbawane842 2 жыл бұрын

Excellent one...

@SaiKiran-oq5oz 3 жыл бұрын

Nice

@ederlorenzatojunior5344 3 жыл бұрын

Boa noite, Fernanda. Parabéns pelos seus videos. Uma dúvida , por exemplo: Em uma reação de A+B -> C , com quantidades estequiométricas 1:1 dos reagentes A e B, é obtido um rendimento de 90% para a formação do composto C. Neste caso, podemos considerar que 10% do composto A e composto B inicialmente introduzidos não reagiram. Sendo assim, eu posso inferir que a concentração inicial dos compostos A e B, para determinar o fator purga requerido, é 10% da concentração do inicio da reação (para cada composto) ? Ou seja, eu posso utilizar o rendimento da reação como ponto de partida para a determinação da minha concentração inicial? Obrigado

@FernandaWaechter 3 жыл бұрын

Oi Eder! Sim, você está certíssimo. Pode sim considerar o rendimento da reação para calcular a concentração inicial, e nesse caso o cálculo da purga inicia a partir desse ponto.

@srinivasaraothoomu3454 Жыл бұрын

Excellent 👌

@dabursunny Жыл бұрын

Excellent

@adityakallakuri4023 4 жыл бұрын

Hi Example 1 in the article "Risk Assessment of Genotoxic Impurities in New Chemical Entities: Strategies To Demonstrate Control" shows that if, REQUIRED PURGE FACTOR * 100 > PREDECTED PURGE FACTOR preclude the need for any further investigation. This article is quoted by ANVISA during evaluation. In this article PR was not discussed. I am little confused. Can you please clarify

@FernandaWaechter 4 жыл бұрын

Hello Adity, thank you for your comment. You are correct, this article by Teasdale (2013) does mention that if "the level of a GTI is >100 times below the appropriate TTC limit, then no further action should typically be required." (i.e. PR>100) However the purge ratio concept was introduced later, by Barber et al (2017), complementing and further detailing the best practice when applying purge factors for justification of Option 4 control strategy as per ICH M7. I would suggest to consider the most recent publication when defining which additional data would be required. In this more recent publication, if PR>100, there is still no need for trace analytical data, although some experiments may be needed to support key purges.

@adityakallakuri4023 4 жыл бұрын

@@FernandaWaechter thank you for letting me know about the latest publication. Will go through it 🙏☺️

@lucylee2664 4 жыл бұрын

As you said, if the PR is higher than 1000, option 4 could be used without development of analytical method. But I can't find what you said above in ICH M7, whereas I found the sentence shown below which still need scientific data for option 4 For Option 4 approaches where justification based on scientific principles alone is not considered sufficient, as well as for Option 3 approaches, analytical data to support the control approach is expected___ICH M7 section 8.2 please advise.

@FernandaWaechter 4 жыл бұрын

Hello Lucy, Indeed ICH M7 does not mention the purge ratio rationale, as this was published after ICH M7 last revision. ICH M7 gives reference to Teasdale's paper (2013) on the purge factor, which was subsequently complemented by these other publications - mentioned in the video - which describe the purge ratio approach: Barber 2017, Burns 2019. My interpretation is that this sentence "For Option 4 approaches where justification based on scientific principles alone is not considered sufficient" refers to cases where the purge ratio is not high enough, whereas when the PR>1000 this would be considered to be a sufficient justification based on scientific principles.

@lucylee2664 4 жыл бұрын

@@FernandaWaechter Thank you for your kind explanation. Is it acceptable if the prediction purge factor is calculated according to Teasdale 2013 rather than from Mirabilis?

@FernandaWaechter 4 жыл бұрын

@@lucylee2664 Hi Lucy, you're welcome! Of course, as long as strong scientific justification is given for each purge, the paper-based calculation should be acceptable.