How we can qualify visual inspectors in injectables?
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.
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)
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.
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.
- 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)
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.
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.
hmmm… there are two posts with the same answer… from two different persons…??? maybe someone should mention the other??
[quote=Acohen]hmmm… there are two posts with the same answer… from two different persons…??? maybe someone should mention the other??
Please explain Acohen, not sure what you mean?
what should be the minimum quantity of batch and what % of rejection to be included in this batch to qualify the visual inspector and what guideline we follow for it.
You have asked a question which can be debated in many ways.
-There is no hard and fast rule as per minimum batch size. After the advent of Oncology products the batch sizes especially in injectable varie from 2500 Vials or Ampoules to 15000 plus.(5Lts to 25 lts)
The whole issue depends up on your machine installed capacity Vs your operational capacity, Environmental and sampling controls and complexicity of the whole process.
% rejected again depend up on real percentages those have to be mentioned in records after you inspect. Normally for any organization 0.5 to max 1.5% are acceptable at this place. Beyond this if you have, it means you have serious manufacturing problems and your process is not economically vaible.
I really did not bother till this day to find out any regulatory guideline on percentage of rejection. The reason is industry always moves ahead to reduce rejections. They need to excel and reduce rejections and increase out put.
Many controls by QA are mentioned from starting to end of a process to reduce chances of rejections.