36 Comments

  1. Hello, may I use your material as base for instructional purposes?

  2. Massimo De Angelis says:

    I usually perform calculation of MAC using PDE for liquid sterile drugs. An inspector made a recommendation saying that we have to compare the results with minimum dose and choose the lower.
    Why do I have to use a less scientific method when there is nothing more scientific than PDE?
    I’m sure using PDE, that the toxicological aspect are considered. Why do I have to put limits lower if my calculation has a scientific and toxicological basis?
    At this point I can choose the LOQ of the method if I have to obtain the lowest!

  3. Mr. Francisco Luis Cano Echeverri. says:

    Dear Sir. Thank you so much for the well writen document on Cleaning Validation.

  4. Ravindra Bansode says:

    Hello Sir,
    If our products are only excipients and it does not have specificity for analysis,
    please suggest what to do.
    Is it necessary to perform recovery test?

    1. Hi Ravindra, as far as you only produce excipients and specificity for analysis isn’t applicable, similarly recovery test isn’t applicable too.

  5. venkateswararao says:

    It is really great work Mr. Saket,

    can we consider the stopper bowl and chute in equipment grouping while perform the dirty equipment. as per guidelines product contact parts will be consider for equipment grouping but stopper bowl and chute are not direct product contact parts.

    1. Hi Venkat, your two comments (this one and previous one) looks contradictory. Please confirm you question properly.

  6. venkateswararao says:

    it is great work, during dirty equipment hold, we consider the product contact parts like manifold, filling pumps and nozzels, can we consider the stopper bowl and chute in equipment grouping while perform the dirty hold? My concern is the stopper bowl and chute are in direct product contact parts.

  7. This article was really helpful. Could you specify how to clean an equipment after defined clean hold time runs out (it is not used for 20 days but the clean hold time is 10 days). Should we do the whole cleaning procedure again or can we just take a sample for microbiology and clean it with alcohol on the surface it the test is good (no bacteria found). Thanks in advance

    1. Thanks, Mikasa for the appreciation. Regarding your query, it clearly looks a case of deviation where you need to log the deviation, investigate the failure to meet dirty hold time requirement, assess the impact, analyze, propose CAPA and close the same with sound rationale. Because, the whole purpose of the dirty hold time study would have been compromized.

  8. Great article on cleaning validation. What are your thoughts regarding cleaning validation requirements on reusing a previously dedicated line for a new product. The line would now only be dedicated to the new product. What are the expectations in this situation. Both products have established cleaning validations for dedicated equipment. There would be that initial time where equipment was previously used for and dedicated for product A, but now dedicated to only new product B.

    1. Thanks, Mary for the appreciation. Regarding your question: As you are talking about product changeover for the existing facility, you will need to perform entire cleaning validation activity. Ensure that the product A traces are removed entirely eliminating chance of cross-contamination. Suggest you to follow this article for detailed break-down of activities.

  9. ayu asmoro ningrum says:

    Hi Mr. Saket, thanks for sharing this clear and detailed article, glad to read this. I have question about the maintaining cleaning validation state, should we conduct routine validation or such periodic cleaning verification to ensure the validation state is well maintained? Could you please share any guideline talk about this part? Thanks a lot.

    1. Thanks for your appreciation. Regarding your question, FDA talks about Continued Process Verification that also applies to your cleaning procedures.
      There are various guidelines that explains how to ensure the consistency of your already validated cleaning process. You can search for:
      – FDA, Guide to Inspection of Validation of Cleaning Processes
      – EC, EudraLex Volume 4, EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use
      – PIC/S, PIC/S Validation-Master Plan, IQ, OQ, Non-sterile Process Validation, Cleaning Validation (PI 006-3) (September 2007)

      Let me know how it goes.

  10. Wonderful information Saket. Could you pls clarify if cleaning verification needs to be performed after every cleaning to ensure lproper cleaning, specially in case of multiproduct equipment?
    Thankyou
    Vaishali

    1. Thanks, Vaishali! Regarding your query, verification is a different thing.
      You must verify if the cleaning you performed between batch to batch of the same product. Of course, with the reduced efforts than the cleaning validation since your cleaning process is already established as an effective one.

      To give you simple example, you perform cleaning validation for batch to batch and steps roughly should be:
      1. Defining cleaning goals
      2. Strategy and draft SOP
      3. Protocol
      4. Execution (Actually monitoring the cleaning parameters)
      5. Verifying the cleaning termination conditions
      6. Summarizing the findings
      7. Conclusion via report and making SOP effective.

      Whereas, once this is done and while you are doing routine cleaning batch to batch.
      1. Following the cleaning SOP
      2. Verifying the cleaning termination conditions are met.

      Hope this explains your doubt clearly.

  11. It’s really very useful information to better understand the process. Can you please make one on equipment qualification as well?

  12. Rama Krishna Atmakuri says:

    Wow… Great job… Excellent Material… Thanks very much!

  13. Mahesh Urdhwareshe says:

    It’s very useful, well explained with observations received from FDA. Thank You for such an article on cleaning validation…

  14. HEBA MOHAMED says:

    Clear and interesting. Can you please let me know which guidelines clearly states the cleaning level type?

    1. Thanks, Heba for admiring the content. However, I don’t think if such types of levels are mentioned in any guidelines. Rather, regulations like FDA do mention the types of sampling, methods of analysis, and establishment of limits.

  15. Mona Shamshe from Iran says:

    The content was great. I enjoyed it and thank you

  16. Vilas Alte says:

    The article written by you gives the great information collectively. It is very informative and helpful to everyone.
    I really enjoyed reading this article.

  17. R Srinivasa Rao says:

    I enjoyed a lot while reading the article. Good theory. Thank you for sharing such data with us…

  18. Exceptional work, thoroughly enjoyed reading it.

  19. Rakesh Jakkashetty says:

    Really an excellent effort Mr. Saket. I can say you are the library of your profession! 😊 I relished the reading.

  20. Musbau Lasisi says:

    I enjoyed the write-up on Cleaning Validation. More power to your elbow.

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