Cleaning Validation - Regulatory Expectations

[@pradipagarwal2946]

Shah sahab, you are giving good information to audience. Appreciate your efforts.

[@hitendrakumarshah3718]

Thank you so much

[@naushadshaikh1154]

Thanks Sir Very nice session. Particularly the question answer session was very useful

[@hitendrakumarshah3718]

Thanks. Please keep learning

[@kedarkulkarnikeke5181]

Very insightful lecture.. Thank you sir for your great help

[@hitendrakumarshah3718]

Thank you for your kind comment.

[@ajitwagh2710]

Sir what should be the acceptance criteria for degradation in DEHT?

[@hitendrakumarshah3718]

It depends on the nature of the molecule

[@bhrugupadakandi8572]

Hi sir good morning I watched your video on 19-12-2020 And I observed that some of the topic you need to explain more Like - possible contamination part Airborne Ancillary matterials Decomposition Mold etc

[@hitendrakumarshah3718]

Sure

[@kiranyekula6302]

Which sampling method is best to start first I.e rinse or swab

[@hitendrakumarshah3718]

Both sampling methods are having their own positive and negative points. You can make use of both methods.

[@narasimhaanjaneyulu5410]

Hi sir please clarify whether nitrosamines can be eliminated in cleaning during reaction in vessel?? Is it possible??or else only downstream process mechanism of chemistry can control nitrosamines

[@hitendrakumarshah3718]

Hi, I need to understand the process. I suggest, you need to take steps to avoid the generation of this impurites. For further details, please go through the FDA advise. www.fda.gov/media/122643/download

[@ramakrishnaguttula7941]

Good information sir

[@hitendrakumarshah3718]

Thanks

[@manojmunjal392]

Thanks for the great session

[@hitendrakumarshah3718]

Thank you so much for your kind comment

[@sidheswarkandhare5939]

Thanks for good information sir.

[@hitendrakumarshah3718]

Welcome. Please keep Learning !!!

[@Vikayadavbpharmhhhh]

Is it necessary for making cross change over matrix

[@hitendrakumarshah3718]

It depends on scenario. This question needs to evaluate in detail and generic answer can not be given to this question.

[@Vikayadavbpharmhhhh]

Sir If MACO calculated by help of largest equipment surface area then no need for cross change over matrix required Is it right or wrong?

[@snwani9109]

Sir what is soil condition, in cleaning validation study?

[@hitendrakumarshah3718]

It reflects the information about DEHT(Dirty Equipment Hold Time) study.

[@rajathathireddy3285]

Sir, pls plan for stability management presentation

[@hitendrakumarshah3718]

One recorded video is under editing now. This video will be available in next week, If you have activiated notification (bell) icon, you will get automatic notification about this video. Otherwise, please check in next week. Thank you so much and keep FREE LEARNING.

[@ankalreddymsc]

Hi sir, For one of oncology product pass limit for swab sample is 0.0290ppm. Based on the 0.0290ppm I have to validate my analytical method? How to perform precision, loq and lod?

[@kiranyekula6302]

Failure of cleaning sample results consider as OOS or Deviation ?

[@hitendrakumarshah3718]

The failure need to be investigated. If you are handling through deviation, the analytical error also need to be investigated and evaluated. I personally recommend to investigate as per OOS procedure.

[@samvdio7513]

Pls tell me any reference guidelines available for clean and unclean hold period of equipment and accessories used for manufactring of OSD formulation.

[@samvdio7513]

Sir pls waiting for your valuable guidance

[@hitendrakumarshah3718]

As per EU guide- "The influence of the time between manufacture and cleaning and the time between cleaning and use should be taken into account to define dirty and clean hold times for the cleaning process". I need to check FDA requirement. Hope, this will solve your purpose.

[@hitendrakumarshah3718]

Hope, you got reply

[@kiranyekula6302]

Dear sir, When ADE,PDE introduced please tell the revision history

[@hitendrakumarshah3718]

Why you need this information. Please focus on compliance and practical implementation approach. Becuase, in Pharma we always follow cGMP and also benchmarking.

[@kiranyekula6302]

@@hitendrakumarshah3718 its an interviewed question for me sir,thats why I asked you, I faced this question

[@naushadvasaya4585]

Thanks for valuable session. Qus- sir how to clean the swab area after swabing.

[@hitendrakumarshah3718]

You need to use same vehicle to clean the swab surface area. It should be specified in the SOP.

[@user-bo2ei3lt3g]

During equipment matrix API Contact equipment we have select or all the equipment used for mfg process. We are using tray dryer for excipients drying and no API is used for tray dryer, so we have to select tray dryer in equipment matrix or not?

[@hitendrakumarshah3718]

We have to perform cleaning valiadation for the equipments which are used for manufacturing of the multiple products. Tray drier is not used for manufacturing. Active ingradient or colour is not handled. Hence, we should not consider in equipment train. Otherwise, the total equipment contact surface area will be very high if we go on considering all equipments. This may result in impractical MACO limit. Hope, this clear your doubt.

[@satishdasu33]

Thank you sir nice explain

[@hitendrakumarshah3718]

Most welcome !!!

[@nighthunterism]

Hello Sir, Want a Detailed discussion on Stability study in Pharma

[@hitendrakumarshah3718]

Sure. What exactly you are looking for? For stabilty study you can go through this - kzbin.info/www/bejne/aHi8XmBoecmXj80 For bracketing and matrixing link - kzbin.info-EORYjL2Z6Y?feature=share

[@nighthunterism]

@@hitendrakumarshah3718 exactly in detail explanation of ICH Q1 specially Q1(R2) guidelines...and one more thing sir, I have been through your CSV sessions it was very helpful...but i want a brief session on SDLC Models like V, Agile, Waterfall...and a brief discussion on GAMP V...the guidline is pretty vast so it would have been better if you just summarise the guidline and give a session on its approach.

[@dharmeshrabadiya5624]

Campaign cleaning ka rational kya hona chahiy? Can u suggest please Sir

[@hitendrakumarshah3718]

Campaign cleaning should be based on the nature of the product and campaign length. It should be based on period and number of batches whichever is lower.

[@dharmeshrabadiya5624]

@@hitendrakumarshah3718 thanks sir

[@dharmeshrabadiya5624]

How to justify campaign cleaning , if I am doing periodic cleaning after every ten batches...I want to give rational for ten batches , so how to justify it's betterly.

[@hitendrakumarshah3718]

@@dharmeshrabadiya5624 Based on the business requirement and also nature of the product you can decide the campaign length. That you need to validate and justify that no impact.

[@dharmeshrabadiya5624]

@@hitendrakumarshah3718 Thank you Sir . Quality evaluation done for 1-10 batches series and found complies results, hence there is no impact . I think it is ok.

[@narasimhaanjaneyulu5410]

Can we have any regulatory guidelines on nitrosamines cleaning validation ???

[@hitendrakumarshah3718]

The nitrosamines are impurities of drug substance generated during manufacturing, processing of drug substances. These impurities are potent genotoxic carcinogens. Hence, if it is generated during manufacturing, efforts, should be made to avoid from going to next batches. It depends on the manufacturing process that you are dealing with. Please go through in detail- the FDA general advise. www.fda.gov/media/122643/download

[@9949918845]

sir, why 3 cleaning validation batches shall be considered. is there any guideline .

[@hitendrakumarshah3718]

There is no guideline states the number of batches to be considered for cleaning validation. However, for process validation, EU clearly suggest to have minimum 3 consecutive batches . So, as a routine practice, for cleaning validation also 3 batches are selected (considering it as process validation. Only the difference here is, the cleaning process will be validated instead of manufacturing process). Hope, it is clear to you.

[@2010dharmu]

For statistical evaluation minimum 03 batches are required. Hence at least 03 batches are considered for cleaning and well as process validation.

[@navneetpathania2786]

Why ADE is considered in selection of worst case and how it is related to cleaning, High or Low ADE which one is used in worst case??

[@hitendrakumarshah3718]

I suggest to refer PDE. For further details, please refer session 2 Link: kzbin.info/www/bejne/sHOvooWQaqmLjJY

[@navneetpathania2786]

@@hitendrakumarshah3718 Dear sir, ADE Or PDE both are similar.

[@venkatalaxmi6778]

Where we will take recovery study values in cleaning validatiin

[@hitendrakumarshah3718]

You can consider recovery factor either in final calculation or in QC where they are calculating and arriving on results.

[@kunalmistry5856]

Sir, is it right that for intermediate product residual substance acceptable criteria is 100 ppm and that for API is 10 ppm??

[@hitendrakumarshah3718]

Its really nice question. But, it can not be answered in straight way without understanding the details. Request you to put more details about this case. So that, I will able to evaluate and revert you correctly.

[@9949918845]

Dear sir, i have Question. My product Having Different Strength (5 mg,10 mg, 25 mg) and batch size also different. for 5 mg batch size 1 kg, for 10 mg batch size 2 kg, for 25 mg batch size 1.5 kg. so, can i do cleaning validation for each strength or each batch size ? what is the approach . please give me suggestion, and provide the Guideline for my reference. Regards Goutham

[@hitendrakumarshah3718]

Hope, you got the answer with the earlier question

[@9949918845]

Dear sir, I have Question, if batch size change can i do cleaning validation ? (we have 1 kg, 2 kg & 3 kg batch sizes) if product Strength Change can i do cleaning validation ? (we have 5 mg, 10 mg, 25 mg, 50 mg Strengths) How many cleaning validation Runs shall be performed ? { 3 Runs for each strength (or) 1 Run for each strength ? & 3 runs for each Batch size ? or 1 Run for Each batch ? ) Contact Equipment's are not changing This is NEW PRODUCT INTRODUCTION . How can i establish Cleaning validation ? what is the cleaning validation approach please provide me Reference Guidelines. Regards, Goutham

[@hitendrakumarshah3718]

Hi, I can evaluate to identify the worst case product among all the products. You have to consider one product batch size as minimum batch size below which if you go , again you need to evaluate worst case as, the limit will change after change in smallest batch size. Then, you can perform 3 consecutive runs of cleaning validation on worst case product and complete the study. Hope, this is clear to you.

[@9949918845]

@@hitendrakumarshah3718 thank you sir ji...

[@Vikayadavbpharmhhhh]

How to performed OEL study

[@hitendrakumarshah3718]

It is big topic. I will prepare separate learning session on it.

[@Vikayadavbpharmhhhh]

How to find maximum daily dose of ophthalmic

[@hitendrakumarshah3718]

You can follow the same procedure. The safety factor you can use more stringent.

[@sujitwazarkar6285]

If MACO level is very low. What to do

[@hitendrakumarshah3718]

This is a one of practical problem many are facing. I suggest, you can go through my recorded video on cleaning validation, which will guide you to move further. If still you have any problem, feel free to post. I will revert you. kzbin.info/www/bejne/sHKYqaaNh558i5o

[@Vikayadavbpharmhhhh]

Share your LOD and MACO

[@Vikayadavbpharmhhhh]

If MACO value low in compared with LOD then your MACO is LOD

[@bobby0058]

Sir which Therapeutic value to be considered for calculation of MACO....? Maximum TDD or minimum If menttion 250 mg twice a day, How much to be considered? If 10 mg/ kg mentioned, how much to be considered? Please suggest.

[@hitendrakumarshah3718]

I suggest, you can go through this video. You will get all information. kzbin.info/www/bejne/sHKYqaaNh558i5o Further I suggest you can go through the another cleaning validation webinar with practical approach. You will get all the information about your questions.

[@user-bo2ei3lt3g]

After cleaning of dirty equipment which location for sampling we have to consider, any one location or all the defined location in CV protocol?

[@hitendrakumarshah3718]

You have to sample from all "Hard to clean" locations defined in protocol after cleaning.

[@user-bo2ei3lt3g]

@@hitendrakumarshah3718 Thanks for reply sir

[@samvdio7513]

Hello sir please guide on my query

[@hitendrakumarshah3718]

As per EU guide- "The influence of the time between manufacture and cleaning and the time between cleaning and use should be taken into account to define dirty and clean hold times for the cleaning process". I need to check FDA requirement. Hope, this will solve your purpose.

[@samvdio7513]

Thanks for your valuable comments I am totally agreeed with your suggestions for unclean study since there is always chances of increase in bioburden in uncleaned equipment however why we can't go beyond 7 days frequency for clean equipment based on validation study and risk assessment. Is there any regulatoy requirement for such validation study upto 7 days only. Please advise

[@hitendrakumarshah3718]

@@samvdio7513 The guide doesnt state about actual period for the study. But, considering the lowest practical scenario we should consider. 7 days will be too long for keeping any equipment in dirty condition. QRM should not be followed to address wrong practices. Hope, you got the answer.

[@playlistajsy4486]

Tq sir 🙏🙏🙏

[@hitendrakumarshah3718]

Welcome

[@bhrugupadakandi8572]

Your voice is breaking exactly after 30 mints 21 seconds

[@hitendrakumarshah3718]

Ok.May be. But hope, the understanding is clear.

[@guru9075]

Hi

[@hitendrakumarshah3718]

Hello