Selection of starting material for synthetic processes based on ICH Q11

[@pavankumar-ky2sy]

Good explanation.I want to learn ICH quality and multidisciplinary guidelines from you. Case study examples were superb

[@go4growthsllimited]

What an explicit content. Clearly explain. I love this great content

[@sufiyanqureshi5201]

Impressive explanation

[@ernanipinto6038]

Congrats!! I enjoyed pretty much! Nicely done Fernanda!

[@Lilac66]

Excellent explanation! Thank you!

[@nileshbawane842]

Excellent.. Could you please share more video on Key starting materials

[@amitgupta-yr5pl]

Excellent explanation Fernanda

[@FernandaWaechter]

thank you!

[@dabursunny]

Nice information.ation , thank you Madam.

[@edwardkenway2372]

Why impurity F is not defined as another starting material?

[@FernandaWaechter]

Hi Edward, this is because there is only one transformation step from compound F to the API. So generally this would not be considered a justified starting material, since the steps immediately upstream of compound F may impact the API impurity profile - and in this case would need to be included in the route of synthesis. Ideally, a precursor of compound F would be the second starting material in this case. However, if compound F is a commodity it could be justified as a starting material.

[@virenkhivsara6223]

Dear fernanda, thanks for the explanation. I had a quick question on this! Can the compound F, can be considered as starting material, if is sold as commodity in non-pharmaceutical market? As this rules out to evaluate the part 2 of the decision tree!! Hope to hear from you soon!

[@FernandaWaechter]

Dear Viren, you are correct. If compound F was sold as a commodity is could be justified as a starting material, as described in Q11 Q&A 5.6: "It can be acceptable for a starting material that is demonstrated to be a commercially available chemical to enter late in the synthesis, e.g., in the last chemical transformation prior to the drug substance". It is important though to ensure that it complies with the requirements described in Q11 Q&A 5.12, 5.13 and 5.14: database.ich.org/sites/default/files/Q11_Q%26As_Q%26As.pdf

[@virenkhivsara6223]

Thank you so much for the clarification. I follow all your videos and would love to see more from you. Thanks again. Regrads Viren K

[@masaobobu]

@@virenkhivsara6223 In Japan, PMDA can not accept F as starting material even if it is commodity. Starting material should be e. “Significant structural fragment” . On this case, Starting material are C, or A and B.

[@FernandaWaechter]

@@masaobobu Thank you for contributing about the perspective from Japan!

[@bhushanborse917]

Hi madam, u r sharing perfect knowledge, one humble request, can you plz make video on impurity profile department, how there work starts, identification of impurities, main guidelines for impurity control

[@henryifeanyi5056]

explain why starting materials are important

[@rajalakku4137]

Hai Fernanda...! Please refer below principle from Q11. Manufacturing steps that impact the impurity profile of the drug substance should normally be included in the manufacturing process described in section 3.2.S.2.2 of the application. If we control control imp which is formed at step 2 in Structure E, Shall we control Structur D as Starting material?

[@FernandaWaechter]

Hi Raja! If it is shown that this impurity generated from step 2 does not impact the API impurity profile (not >30% of limit if mutagenic or not above identification threshold if non-mutagenic), then yes, you could consider compound D as starting material. In the video, compound D was not considered appropriate as a starting material because impurity C generated in step 2 was impacting the API impurity profile.

[@andyandy234]

Thank you!!

[@tsrinivas676]

Good Explanation

[@venkateshkota8693]

Genotoxic impurity, i.e., impurity C formed in Step-1, it is not formed in step -2 as mentioned in presentation. Please elaborate Persistent impurity subject I think you should relook the presentation one more time for this.

[@FernandaWaechter]

You are correct to interpret that the origin of the impurity is the step where it is generated. This is usually applied to impurities which are by-products, for example. However, in the example presented, all impurities described are starting materials or intermediates intentionally added to the process. Hence in Step-1, Compound C is our desired product, while in Step-2 it is considered an impurity if this step does not fully convert it to Compound D. This is the reason why we consider that the origin of Compound C - as an impurity - is Step-2.

[@FernandaWaechter]

Regarding persistent impurities, the definition as per ICH Q11 Q&A is: “Impurities that persist may or may not react in subsequent steps, but are not removed to the extent that they would no longer be considered to impact the drug substance impurity profile.”

[@appandiasipha4809]

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