Knapp Test for Vial Testing

GOOD VALIDATION PRACTICE (cGVP)
1

Dear all,

I’ve heard about ‘Knapp Test’ for vial checking. Can anybody lead me to some of the references?

Thanks.

2

hi,
Knapp test is to ensure that the manual inspection is similar to the automated process of inspection. It is very lengthy process but this is generally asked document if you qualify an automated machine for inspection by an auditor. I had some article on this will forward to you within 2 days as i have to search for the same.
tx,
kalyan.

3

hi,
Knapp test is as follows

Firstly the USP states that “all parenterals will be 100% visually inspected.”

Secondly, below are my oponions only (experience) and if I fail to identify anything that a regulator may be looking for, or if someone with more experince can add to anything or correct anything I will truely value the feedback as I am relatively new to the qualification and parenteral inspection subject.

When developing a method in which to qualify operators it is important to develop a process for qualifying that you can easily defend.

The following discussion is something we can call the ‘pseudo Knapp method’

The PDA presents papers on Julius Knapp’s methodology to use when validating a semi-automated inspection method (eg. siedenaders) or fully automated inspection machines (eg. EISAI) so these can be used for reference.

  1. The best thing to do is collect particulate rjects from various batches (keeping the characteristics of the product the same - eg. viscosity, clear or yellowish, fill volume, etc…) (However particulate seeded sets can be manufactured a company called MML can help with this)

  2. After collecting X numbers of particulates rejects from various batches, these vials should be blindly placed into Y number of uninspected vials from various batches.

  3. Now with X + Y, have inspectors (lets say three different inspectors) manually inspect these vials 10 times each (3 inspectors times 10 times each vial is 30 inspections each vial) . Using Knapp’s probablistic methodlgy, anything with a probablity of 0.7 is classified as a reject. Thus from the X + Y, any vials that were rejected 21 out of 30 times would be considered a reject. Using these vials classified as rejects and using vials that are classified as good vials (anything witha probablity of 0.3 and less) a standard qualification set can be created.

Note: it is best to get reject vials that have a reject probabilty of 1.0 (30/30) to make things easier in the end.

  1. Lets say for example we create a set of 100 vials with 30 vials being rejects, and 70 being good vials classified per Knapps probabalistic model.

There are some other terms that I need to define
RZE - Reject Zone eficiency = sum of reject probabliity of the 30 reject vials / 30 reject vials
RAG - Reject Accept/Grey = sum of probability of rejecting the 70 Accept and Grey vials / 70 vials
(NOTE: I did not discuss grey vials, don’t see a need but this can be incorporated)

  1. Now we should determine the RZE of the set. Adding up the probablities of rejection from the 30 reject vials, (eg. lets say its 28) Thuse the RZE = 28/30 = 0.93. J. Knapp states that an RZE of 0.80 and 0.95 is what is normally seen in industry, so determine an RZE that suits your business, also business would also want a low RAG (RAG should be less than 0.10, but is aslo based on what you sets RAG is) which is considered how your operators will react to good product.

  2. Now you can test your operators using this set and calculate the RZE and RAG values to identify operators for inspection.

After writing this, I know that there are many things that I left out, like you need to verify the visual acquity of your inspectors (eye test done during hiring). Also your product set may degrade over time causing it to form particulates so you may need to store the set at the product rquirements to impede degradation, or replace the set on an on-going basis.

Like I said there is a lot I left out but if you have any questions just post and I’ll try to respond.

Hope this is useful. This is taken from this site for reference of my work and the same is posted here for u.

Tx,
kalyan.

4

Kalyan,

Excellent post. It was great help. Can you please also post anykind of link of the company(MML) who can help in making a sample set for the Knapp study. I googled it but i didnt found anything related to this. If you can post some more companies for making samples set, and some more literatrue on knapp test i would really appreciate that. My email is kapoor.nipun@gmail.com.

Thanks Kalyan!

5

Here is a paper which talks about Knap Test

Knapp test.pdf (73.7 KB)

6

Good post & literarture on Knapp test.

Keep rocking !

7

Excellent article the one in the PDF. i’ll keep looking on the Knapp method. keep up.

8

hi

i just have a question about when planning a knapp test - is it neccessary each filling size of bottles (10ml , 20ml, 100ml) or do i just have to do the knapp assay if the density of the product is different (oily, not oily liquids)??

would be nice if anyone can help me

Thanks

9

Its applicable to all types of parenterals.(Liquid, semisolid, Oily, Freeze dried , Suspensions etc).

10

So, I just have to test 100ml flasks of same type of glass only once - not depending on the solution filled? I can then use it officially for all other 100ml products?

thank you

11

No
You have to do 3 times with atleast with 1000 bottles each time.
This is an important qualification procedures.
These is wide test methodology and statistics involved in this test.

12

[quote=DURGA PRASAD]No
3 times[/quote]

yes, the procedure is clear what i ment was if it is neccessary for each vial size:

1 knapp for 10ml
1 knapp for 100ml
1 knapp for 500ml

or is it enough to do 1 knapp test and just adjust the parameters to the other sizes as it can be said that the automatic machine works as well as the operators?

thank you so much

kind regards

13

First thing is refer to regulatory guidelines.
What is that saying?
And then make an action plan.
Then refer to Knapp test fundamentals.
I really do not know from which geographical area you hail from.
Its difficult to comment at the moment.
If you come back with some answeres atleast I can guide you.

14

[quote=DURGA PRASAD]First thing is refer to regulatory guidelines.
What is that saying?
And then make an action plan.
Then refer to Knapp test fundamentals.
I really do not know from which geographical area you hail from.
Its difficult to comment at the moment.
If you come back with some answeres atleast I can guide you.[/quote]

I just got the information that every size of every product must be tested with knapp test.
I am from austria, but we need to be FDA conform, so i would decide to do knapp for each size (50ml, 100ml)
I just wanted to know if there would be a possibility to reduce the effort, like a bracketing system or anything.

Anyway, thank you for your answer

Best regards

15

In KNAPP test bracketing is not a good practice.

16

Well, I also decided not to do any bracketing for this assay
so thank you for your information, was great

best regards
eka021

17

Dear all,

I have a question about knapp test. Is anybody know the acceptance criteria of the efficiency of automatic Vs visual so that the automatic machine can be considered as valid? if anybody has information and reference (literature) about this, please let me know. I would really appreciate your help. Thank you very much.

Regards

18

please mail me on shailendra.ramgol@seidenader.de. I will let you know. We have inspection m/c

19

Can you share here so that we too can see and understand?

20

Whether the size of each of the necessary filling bottles, or do I have to do Knapp detection, if the density of Kodak 10

the product is different?