Lab ware cleaning validation

GOOD VALIDATION PRACTICE (cGVP) CLEANING VALIDATION
1

Dear all,

does anyone know how to define the acceptance criteria for lab ware cleaning validation? we did a riboflavin test, but I think that is not enough. We’d like to perform a regular validation on the lab glassware washer, but don’t know how to set the acceptance level like TOC, it is not like the production line, a MAC can be calculated, any ideas from you?

thanks

2

Hi Hank,

Your ribloflavin test was basically for your coverage, so lets say that passed and you have complete coverage…that means nothing when it comes to your glassware to be honest.

What you need to do is determine within the washer ‘baskets’ how each piece of glass is going to placed in each basket. Each time you wash the glass needs to be inserted in the same place as this is how you are going to quality the washer. This needs to be captured as part of a drawing so individuals know how to load the washer and maybe a drawing laminated and placed above the washer for info.

Next step - Determine what your acceptance criteria are - temp for wash duration rinse - wash time - rinse with acid volume - wash heat drying time and temp etc etc etc (this is all depending on the configuration you have available) - then qualify the system to these parameters. It should be configurable to some sort of parameters which you need to determine and verify. What will the acceptance criteria be - visibly clean? I m sure it will need to be swabbed.

I hope these suggestions help and good luck!! Its not that difficult, its only a washer!!

Regards,
Muuray

3

Hi Muuray,

thanks for your quick reply.

Our coverage test showed that each pieces of glassware in the basket (full load) is free of riboflavin.

Now we need a performance validation of the washer to prove the factory set wash program can clean the glassware, the parameters like wash time, temp. and cycles are pre-set by manufacturer, can not be changed. We’ll take samples from the glassware (swab sample for the potential sticky soils and rinse sample for possible remaining detergent) after cleaning. This is my question, how to set the sample acceptance criteria, i.e TOC and conductivity acceptable level?

thanks for sharing your experience!

4

Hi Hank,

The water that’s supplying the Washer should be supplied by the Purified Water system or the Wifi system. Therefore TOC and conductivity for water would already be continuously monitored by that system (PW or the Wifi). What you should be sampling for is the residues of the product you wish to clean from the glass. Yes/No? If you don’t have a PW or Wifi supply then is it a distilled water system? How is your water supplied to the washer?
Regards,
Murray

5

Hi Murray,

the final rinse is using purified water from the lab. The validation purpose is to prove that there is no detectable residues on the glassware after the cleaning cycle, the most commonly monitor method is TOC and conductivity, for the conductivity, the criteria can be the same as purified water, but for TOC, not sure how to set the criteria.

thanks

6

Hi Hanks,

There is TOC specification for purified water, which is 500ppb.

Regards,

7

Hi Tangkakj,

thanks for the information. I feel that might be too tight for swab sampling. I’m looking for general lab acceptable criteria for clean glassware in term of TOC.

thanks again!

8

Hi Hanks,

For pharmaceutical or API industries, this equation is normally being applied MACO=0.001 X (PDE / DEL) X (MBS / SSA) where:
PDE = Permissible Daily Exposure of previous product
DEL = Maximum Daily Exposure Limit of next product
MBS = Minimum Batch Size of next product
SSA = Total Shared Surface Area

In lab ware cleaning context, I think it is difficult to define previous and next product batch. Hence, I recommend you to define acceptance criterion for swab sample as 10ppm, where only 10mg of residue is permitted to carry over to next maximum load of lab ware cleaning.

Hope this is making sense!

Regards,

9

Hi Tangkakj,

In PDA report No 49, there is a statement for biotech industry cleaning criteria about TOC, which is 5-10 ppm for upstream process, the same as you mentioned. I think I’ll use this criteria. The following questions are how to decide the sampling area ( 5x5 cm? or 2.5x2.5cm?) and swab dissolution volume (5mL?).
I saw a calculation formula about swab area and volume, do you use it too?

Limit (ppm) = MACO x (1000/C) x (D/V)

C = cumulative surface area of the equipment used
V = volume of solvent used to dispense swab
1000 = multiplication factor to convert value in mcg from mg
D = swab surface area

I am not clear the meaning of the multiplication factor “1000” . In this formula, a MACO is still needed, I don’t know how to apply this in my case. For the swab area and solvent volume, I think I can decide one variable first like the solvent volume, then calculate the swab area.

I appreciate very much you or any others who can help solve the problem.

10

Hi,

Sory for using your topic, but i’m also interested in this subject.

I’ve been reading around but i still couldn’t came up with a solution to my problem, which is precisely what you explained: I want to validate the cleaning procedures of CQ glassware but can’t decide my acceptance criteria…

Talking to the analysts of the lab i got the information that HPLC peaks equivalent to <0.01% were basically “disconsidered”.
Basically, the ideia was using those 0.01% on the assay of the product with the lowest concentration and use that value as acceptance criteria, but i get a very tight acceptance criteria (0.1ppm).

Can anybody share a stretegy to define the acceptance criteria?

Thanks in advance!
Best regards,
João Laranjeira

11

I used the TOC and conductivity limits for ‘Water for Injection’ which for TOC is less than 500 ppb. Just insert some beakers and go through the washing cycle. After the rinse cycle but before the drying cycle take out the beakers and test the water.

12

Thank for sharing.

In the cleaning validation of the production equipment i was able to obtain results <50ppb, so it would probably be alright also for the CQ glassware (i think).

But the thing is, does it makes sense to set 500ppb for the cleaning validation of CQ glassware when I have a higher limit for the production equipment? This is an honest question, because i know that laboratory techniques can be very sensitive, but there isn’t the problem associated with the PDE since no one will be taking the drug.

Best Regards

13

Yes. There are no production lots involved since there is no cross-contamination possible (as long as you don’t re-enter samples into the production process). All you have to show is that the water can meet the WFI specifications (it is different acceptance criteria for a parts washer used in the production process).