Cleaning Validation

[bijaykmohalik]

Anyone would like suggest me the various criteria of determination of clening of residue ( method used in pharma industries).

[yogibear]

Can You be more clear?

The various methods of cleaning? or
The various methods of validating the cleaning or ensuring good cleaning?

About Methods of cleaning:
There ae various Clean in Place (CIP) , clean out of place (COP), Sterilization in place (SIP), etc. The most common method is rinsing with 5% - 20% NaOH alkaline solution at temperature range 35 - 60 degree centigrade followed by buffer solution rinse or the RO water rinse. , as far as aI know.

The cleaning is generally validated by visual inspection and by swabbing (using a standard wipe and swiping at the required location ) and then sending it to QC lab for analysis. It generally takes 24 hrs to know the result of swab if the cleaning was successful.
The location for swabbing need to be very carefully selected.

As far as I know

[jojo]

many thanks …I’d like ta ask you about
how could excute in practical way- a cleaning validation for a such blistring machines i.e( cleaning validation protocol outlines)?

[bijaykmohalik]

Hello Dear

Thanks for your valuable & prompt answer.

But I am not clear on idea that, we are validating the cleaning procedure for previous product( for the API used in manufacturing). Again for clening we are using NaOH solution. Then please tell me, after completion of clening if we are going for “Swab Method” or “Rinse Method” , then test for what to be carried out? I mean test for detection of either API or NaOH or Both to be performed ???

[mukesh_dv]

Hello Dear,

Both should be tested for residues i.e.Previous API and the cleaning agent used.

Thanks,
MUKESH VARDE

[ovais]

Dear Mr Bijaykmohalik,

I am bit confused, as both the queries raised by you are totally different. Well I try to answer both for you.

The first query is regarding the determination of acceptance criteria or limit for cleaning validation (CV) studies. There are four approaches used for this:

[LIST=1]

First approach is based on the therapeutic dose of previously manufactured product. This criterion is based on the principle that an active ingredient (API of previously manufactured product) should not be present in the maximum daily dose of the subsequently manufactured product at levels higher than 1/1000 of the minimum daily dose of the API.

Second approach (known as 10-ppm criterion) is based on the principle that any API should not be present in a subsequently manufactured product at levels higher than 10 ppm.

Third approach (known as toxicological criterion) uses toxicity data for the calculation of CV acceptance limit. This strategy is generally used in the industry when dealing with contaminants for which therapeutic doses are not known (e.g., intermediates, precursors, and cleaning agents). The calculation is same as that of "First approach" and uses "no observed effect level/safety factor" (NOEL/SF) in place of dose/safety approach.

Fourth approach is based on "visually clean criterion" which requires the equipment to be visually clean after cleaning is finished. Out of the four, the approach giving the lowest value is then selected as [b]Maximum Allowable Carry-Over[/b] (MACO). (To know more about the formulae used for the calculations please find the spreadsheet, prepared by me, at http://www.scribd.com/doc/10994609/Cleaning-Validation-MACO-Swab-Rinse-Ovais )

Coming to your second query i.e. What is to be tested? API or cleaning agent or both? Well for CV studies you need to test for (1) API (of previously manufactured product) residues; (2) Cleaning agent residues and the last (3) Microbial residues (or testing for microbial contamination).

Hope this answers to your query. Another thing, please post your issues at only respective forums (for example, relating to CV at CV forum). You posted your query at “Software Validation” forum (probably this is the reason not many members replied to it).

[rika_ndry]

[quote=ovais]Dear Mr Bijaykmohalik,

I am bit confused, as both the queries raised by you are totally different. Well I try to answer both for you.

The first query is regarding the determination of acceptance criteria or limit for cleaning validation (CV) studies. There are four approaches used for this:

[LIST=1]

First approach is based on the therapeutic dose of previously manufactured product. This criterion is based on the principle that an active ingredient (API of previously manufactured product) should not be present in the maximum daily dose of the subsequently manufactured product at levels higher than 1/1000 of the minimum daily dose of the API.

Second approach (known as 10-ppm criterion) is based on the principle that any API should not be present in a subsequently manufactured product at levels higher than 10 ppm.

Third approach (known as toxicological criterion) uses toxicity data for the calculation of CV acceptance limit. This strategy is generally used in the industry when dealing with contaminants for which therapeutic doses are not known (e.g., intermediates, precursors, and cleaning agents). The calculation is same as that of "First approach" and uses "no observed effect level/safety factor" (NOEL/SF) in place of dose/safety approach.

Fourth approach is based on "visually clean criterion" which requires the equipment to be visually clean after cleaning is finished. Out of the four, the approach giving the lowest value is then selected as [b]Maximum Allowable Carry-Over[/b] (MACO). (To know more about the formulae used for the calculations please find the spreadsheet, prepared by me, at http://www.scribd.com/doc/10994609/Cleaning-Validation-MACO-Swab-Rinse-Ovais )

Coming to your second query i.e. What is to be tested? API or cleaning agent or both? Well for CV studies you need to test for (1) API (of previously manufactured product) residues; (2) Cleaning agent residues and the last (3) Microbial residues (or testing for microbial contamination).

Hope this answers to your query. Another thing, please post your issues at only respective forums (for example, relating to CV at CV forum). You posted your query at “Software Validation” forum (probably this is the reason not many members replied to it).[/quote]

Dear Mr Ovais,
thanks for your information on scrribd that help me lot.
but the information i think its only for swab method. how about the calculation of rinse method or combined two method (rinse & swab method)?
coz i’m stil confused.
my second question, if i take combined of two test method (rinse & swab method), which should i do first, rinse method then swab method or swab method then swab method?

thanks waiting for reply

[ovais]

Dear Rika,

You can download the revised edition now at the same site (scribd). The revised version provides the details for rinse sample acceptance criteria also.

If you have an equipment for which you want to collect both swab and rinse samples, you have to estimate the acceptance criteria for both separately. The calculation (i.e. equipment surface area, batch size, LD50, daily doses etc.) used will be same. Carrying out combined swab and rinse sampling will not affect the calculation of acceptance criteria (i.e. whatever limit is set for swab method alone will also be applicable to condition where combined rinse and swab methods are used). Coming to your second question, I feel that you should do rinse sampling first followed by swab sampling. If you have selected genuine worst-case swab locations for your equipment, rinse sampling is not going to affect the amount of residue left over at the location significantly. Another reason is ease of sampling, once the equipment (such as blending tanks, mixers etc.) has been cleaned, its easy to take rinse sample first rather than swab samples, as in most of the cases equipment may require opening of the equipment or disassembly for swab sampling.

Hope this clarifies your doubts.