Cleaning Validation - A Practical Approach

[@ulhasdesale2363]

Dear Sir, your process validation and cleaning validation lectures help me lot to give presentation in the company. Thanks lot for educating the pharma professional free of cost in such important areas of pharma industry.

[@hitendrakumarshah3718]

Thank you so much for your kind comments. Keep Learning !!!

[@2010dharmu]

Sir, Thanks for valuable training session. I have some queries- Q.1 Why consider minimum batch size for MACO calculation? Q.2 Any reference guideline or rational for safety factor, which are considered in this presentation. Thanks

[@hitendrakumarshah3718]

Hi; For cleaning validation, we need to have worst case approach. By referring minimum batch size of previous product, we will get worst case limit. That's why we need to use minimum batch size. There are many references for safety factor. You can refer APIC guide, safety guides, TPD guide you will get the reference. As per PDA technical report, these safety factors are not in use. But still, as a routine practice to evaluate the safety, these factors are commonly used.

[@alkasingh5417]

Sir Very informative training. Thanks.

[@hitendrakumarshah3718]

Most welcome

[@wasimiqbal9422]

Campaign manufacturing also will perform for cleaning validation with worst case product and apply to all?

[@hitendrakumarshah3718]

Thank you for your question. I will consider your question on separate LIVE training on Q&A on Cleaning Validation. We will arrange it shortly.

[@sumfung3917]

Sir, i have 2 questions. 1. For dedicated equipment, is it necessary to perform 3 rounds DEHT and CEHT? Is it acceptable if only perform 1 round DEHT and CEHT? 2. For dedicated equipment running in campaign production, is there any requirement on the inter batch cleaning? The purpose of the inter batch cleaning within the campaign should be reducing the gross contaminants. Does it need to reach the level of visual clean, means free from any residues or contaminants? Thank you.

[@hitendrakumarshah3718]

I suggest, you can have 3 runs for hold study. Further ,you can perform inter batch cleaning not up to visually clean unless it will impact on product quality. Hope, it is clear to you.

[@dedeepyagamingchanel2444]

Good knowledge and explanation

[@hitendrakumarshah3718]

Thank you

[@ashishjain412]

Very nice job sir... excellent training session

[@hitendrakumarshah3718]

Thank you so much for your kind comment. Keep learning.

[@muthinenishravankumar3581]

Pls conduct a class on CHT and DHT study for intermediates &API with detailed sampling procedure, what to evaluate and how to fix limits?

[@hitendrakumarshah3718]

Sure. I have considered this aspect in part 1 of this session. I suggest, you can go through the same. kzbin.info/www/bejne/aHrCeWiJqLmGq7M Further if you are interested in complete two days seminar, let me know.

[@sumfung3917]

Sir, i have 3 questions. 1.If there is no hard-to-clean location identified on a piece of equipment, say tablet metal detector. How can we perform a CV study on this equipment? Should we just pick a representative location from the equipment to be tested under CV? 2. What is the definition of hard-to-clean locations? By geometry or by the experience of the operator? 3. Is it acceptable to use the longest DEHT among 3 DEHT studies instead of the shortest one? Thank you.

[@hitendrakumarshah3718]

Thank you for your question. I will consider your question on separate LIVE training on Q&A on Cleaning Validation. We will arrange it shortly.

[@drx.kalpeshgayakwad6094]

One question sir If we perform cleaning validation Why required swab and rinse each and every change over. If we performing swab for chemical analysis on the basis of api solubility Using any solvent It is not possible to carry out the tracess of this solvent in next batch.

[@hitendrakumarshah3718]

We need to evaluate variability. I sugest you to refer complete cleaning validation webinars and video. kzbin.info/aero/PLq7ln35Rt1rMN52n2o3t_nH0lpmZShkZ6

[@abduls8003]

Thanks,I have subscribed

[@hitendrakumarshah3718]

Thanks

[@sreedevitv86]

Excellent

[@hitendrakumarshah3718]

Thanks

[@ulhasdesale2363]

Can worst case product selection be done only considering solubility criteria?or is it require to consider toxicity, clenability and potency combinely while selection of worst case product.

[@hitendrakumarshah3718]

You have to consider all criteria while selecting worst case.

[@manojmunjal392]

Great session. Thanks for training

[@hitendrakumarshah3718]

Thank you so much for your kind comment and active attendance in the training session.

[@wasimiqbal9422]

As per APIC guideline we perform 1st approach that basis on therapeutic dose? But MACO found high. Then we go to 2nd approach that is LD50. If high. Then we finally go to 10 ppm criteria? These step should be covered in SOP of cleaning validation?

[@hitendrakumarshah3718]

Thank you for your question. I will consider your question on separate LIVE training on Q&A on Cleaning Validation. We will arrange it shortly.

[@sumfung3917]

Sir, is it a regulatory requirement to have a worst case evaluation based on API solubility, toxicity and potency even the plant is dedicated to a single product? If yes, are the above three aspects sufficient for the evaluation? Can you recommend what other aspects should be included? Thank you

[@hitendrakumarshah3718]

For dedicated product, it is not required to identify worst case. I suggest, you can go through in detailed "Cleaning Validation Package" as per link below. You will get information about cleaning validation. kzbin.info/www/bejne/sHKYqaaNh558i5o

[@sumfung3917]

Thank you sir. What if the single product contains two or more APIs? Do we need to identify the worst case? Do we need two or more analytical methods to detect each API residue?

[@sumfung3917]

Sir, when validating a campaign length, do you recommend to control the longest equipment idle time (time between end of 1 batch and start of next batch) within the validated dirty equipment hold time?

[@hitendrakumarshah3718]

Campagin study and equipment dirty hold time is different. I sugest, to go through this video in detailed.

[@samvdio7513]

Sir What is importance of considering equipment surface area and why it is not considered im dose criteria.

[@samvdio7513]

Sir waiting for your guidance

[@hitendrakumarshah3718]

As, we are taking sample-swab or rinse from the surface, we need to have equipment surface area. It is required for all criteria. For details you can go through the cleaning validation learning package as per the link below; kzbin.info/aero/PLq7ln35Rt1rOUM4zL4X2ARTlsm5UCwDOD

[@hitendrakumarshah3718]

I have shared you cleaning validation learning package of three videos. Further if you have any questions, let me know.

[@dharmeshrabadiya5624]

Dear sir, Swab limit we derived, is it limit or carry over ?

[@hitendrakumarshah3718]

It is limit derived based on the MACO

[@alkasingh5417]

Hi sir, good afternoon. In case of any failure results observed during cleaning validation , what would be next and should QC need to perform investigation as per OOS guideline. Regards,

[@hitendrakumarshah3718]

Yes. Ofcourse

[@wasimiqbal9422]

First we do visual inspection. My Q is first we perform swab sample or first we collect rinse sample? Need also guideline reference

[@hitendrakumarshah3718]

Thank you for your question. I will consider your question on separate LIVE training on Q&A on Cleaning Validation. We will arrange it shortly.

[@komalikomali4770]

Rinse sample

[@ulhasdesale2363]

After completion of successful cleaning validation study, can we go for visual verification by skipping rinse and swab sample testing for routine changeover cleaning. For cleaning verification, can we keep limit by omitting safety factor from the MACO Sir I want guidance on how to set limit for visual verification?

[@hitendrakumarshah3718]

I suggest, you please go through in detailed - All complete cleaning validation training package. It contains three different videos. You will get the answer. The link is below; kzbin.info/www/bejne/sHKYqaaNh558i5o

[@muthinenishravankumar3581]

What is the limit to be followed for non dedicated equipments used for(both potent and non potent) intermediate(no active moety or similar stracture to API) manufacturing and what is rationale?

[@hitendrakumarshah3718]

This, I need to explain in detail. Considering your lot of queries, I suggest, you need to attend complete two days seminar. So that you will get complete clarity.

[@muthinenishravankumar3581]

Among all the non dedicated equipment matrix two of my equipments involved in the manufacturing of intermediate of product "X"& "Y"(one is potent intermediate,another is non potent intermediate with no similar final molecule stracture) and API of product "Z"(means 2 eqps used for intermediate and API manufacturing),what will be approach in this practical scenerio?

[@hitendrakumarshah3718]

This, I need to explain in detail. Considering your lot of queries, I suggest, you need to attend complete two days seminar. So that you will get complete clarity.

[@samvdio7513]

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

[@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.

[@dharmeshrabadiya5624]

Dear Sir, we have consider 100 ppm limit for 'intermediate' product. Can you give your opinion Sir

[@hitendrakumarshah3718]

You need to consider the impuriti generated at this intermediate stages. If no impact, then, no problem.

[@dharmeshrabadiya5624]

@@hitendrakumarshah3718 thanks a lot sir 👍

[@hitendrakumarshah3718]

@@dharmeshrabadiya5624 👍

[@bobby0058]

Next product batch size means input batch size or output batch size? Pls clarify sir

[@hitendrakumarshah3718]

Its standard batch size.

[@JC-qu1se]

Sir i have a query for one cleaning validation. If my product concentration is 50 MCG per ml And batch size is 275 litre. What should is acceptance criteria.

[@hitendrakumarshah3718]

We can not just evaluate by referring this information. I suggest, you refer our cleaning validation part- II for better understanding. I am sharing link for the same. kzbin.info/www/bejne/sHOvooWQaqmLjJY

[@venkatasudheerchirumamilla7255]

Is 10ppm criteria acceptable for highly hazardous drugs, injectables, inhalants.

[@hitendrakumarshah3718]

It depends on product, worst case scenario and many aspects. 10ppm is one of the criteria. Its not only criteria. Hope, you understood the point.

[@wasimiqbal9422]

03 batches taken for cleaning validation of worst case product.? Clean hold time study and dirty hold time study we need only one batch test ?

[@hitendrakumarshah3718]

Thank you for your question. I will consider your question on separate LIVE training on Q&A on Cleaning Validation. We will arrange it shortly.

[@bittusingh1853]

If one product have many ingredients, how to calculate limit of all ingredients. Need to check each ingredient carry over to another product

[@hitendrakumarshah3718]

Please elaborate your question clearly

[@raahulpotdar2620]

Sir for rinse calculation same calculation as per swab?

[@hitendrakumarshah3718]

The calculation is similar. In rinse, you consider whole surface area and rinse volume while in the swab, you consider the whole surface area and swab area.

[@leonaidus3]

How MACO calculated for insulin variants.we have dedicated equipment.

[@hitendrakumarshah3718]

The cleaning validation is not so simple. Hence, I need to understand properties of variants, what are common areas and many more. On the basis of all these information we can calculate MACO.

[@user-bo2ei3lt3g]

During DEHT Study AHU should be off or on condition?

[@hitendrakumarshah3718]

No. AHU should be on.

[@wasimiqbal9422]

We perform 100cm2 swab for chemical and 25 cm2 for micro swab ? That's ok ?

[@hitendrakumarshah3718]

Thank you for your question. I will consider your question on separate LIVE training on Q&A on Cleaning Validation. We will arrange it shortly.

[@santoshparida9766]

Sir first doing swab or rinse and what is the reason behind this??

[@hitendrakumarshah3718]

Thank you for your question. I will consider your question on separate training on Q&A on Cleaning Validation.

[@wasimiqbal9422]

If we not following PDE/ADE base MACO..is there any issue?

[@hitendrakumarshah3718]

Thank you for your question. I will consider your question on separate LIVE training on Q&A on Cleaning Validation. We will arrange it shortly.

[@raahulpotdar2620]

How to performance cleaning validation for parenteral IV fluids product?

[@hitendrakumarshah3718]

You need to put the same thought into cleaning validation. You can consider the previous product traces, detergents, endotoxin, microbiology, and also, if you are performing an aseptic fill simulation, you need to check the traces of media also.

[@musicrocks2218]

Super sir,, thank you very much

[@hitendrakumarshah3718]

Thank you so much for your kind comment and active participation in the training session.

[@sadyojathaitagi4061]

What is safety factor, why need to consider this during cleaning validation

[@wasimiqbal9422]

What is common surface area? And surface area for complete equipment train?

[@hitendrakumarshah3718]

Thank you for your question. I will consider your question on separate LIVE training on Q&A on Cleaning Validation. We will arrange it shortly.

[@navneetpathania2786]

Sir, How ADE/PDE is related to cleaning at site ??

[@hitendrakumarshah3718]

It is helpful for the identification of the worst product also. Not only worst case limit.

[@satnamom4667]

Hello Sir, I have particular case study of rounding off of figures in analytical validation. I am emailing you since it's very big data. Please reply.

[@hitendrakumarshah3718]

Only final results we need to round off

[@ilohfrancisca8010]

How do you determine volume of rinse?

[@hitendrakumarshah3718]

It has to be determined based on equipment surface, recovery and testing method

[@naveenkumarsharma2234]

Basis of selection of nos. of swabs and qty of saline in case of rinse? Also pl clear qty of saline in case of Placebo ?

[@hitendrakumarshah3718]

You need to have rationale(basis) for selection of type of method- Swab/rinse/placebo, Quantity of saline or rinse solvent, location is important parameter. It depends on type of molecule/product you are handling, type of manufacturing equipment you are using, type of analytical method to detect the residue will be followed, recovery study and so many parameters. Basically, the rationale(basis) will different for different companies besed on these ground reality.

[@JC-qu1se]

Sir how to calculate the cleaning validation if LOD is higher than least count

[@hitendrakumarshah3718]

You can refer the video. kzbin.info/www/bejne/sHKYqaaNh558i5o For further details, you can go through completely cleaning validation package. kzbin.info/aero/PLq7ln35Rt1rOUM4zL4X2ARTlsm5UCwDOD

[@aryanpant982]

Sir please tell that how we calculate tje max daily dose

[@hitendrakumarshah3718]

I will prepare separate training session on it

[@bhavikjaniPharma]

In dose based criteria why equipment surface area not consider.

[@hitendrakumarshah3718]

In dose based criteria, you have to consider equipment surface area. Please refer this recorded webinar in detailed. I have taken example with equipment surface area. you will come to know. For further clarification, you can again post your question. Good Keep Learning !!!

[@bhavikjaniPharma]

Thank you sir I refer presentation where examples are given for 10ppm and PDE but for dose based criteria example is not given. However in acceptance criteria slide calculation given without surface area.

[@raahulpotdar2620]

How to calculate rinse value?

[@hitendrakumarshah3718]

You can calculate rinse volume based on equipment size as well as the analytical method. Because the rinse should be such that, the whole contact surface area should be rinsed. While as you increase the volume, the traces get diluted also. I Hope, you understood the thing.

[@hitendrakumarshah3718]

Good evening all of you!!!

[@JC-qu1se]

Good morning sir

[@muhammedragheb2141]

can i get the slides ?

[@hitendrakumarshah3718]

I suggest, you can refer the recorded version because the discussion will be more than the slide contents. I dont keep or maintain slides with me. I am just preparing new module for each session. So that, I can ensure current information all time.