Skip-Lot Testing and the FDA - Reduced Testing Plan for Raw Materials

[ConnieH]

I need help!

I'm trying to establish a reduced testing plan for raw materials involved in the production of API (Active Pharmaceutical Ingredients).

I've done some online research and have tracked down some possibilities. The term skip-lot testing keeps popping up but I can't seem to determine if it's a viable option as far as the FDA is concerned.

I'm also confused as to whether our current sampling plan (square root of N+1) can be used with skip-lot testing.

I'd really appreciate any help anyone would be able to offer.

 

[Rick Goodson]

Hi Connie,

Welcome to the Cove!

I don't have any background with the FDA so I can't tell you if skip lot is acceptable. There is an excellent description of skip lot sampling on the web at http://www.itl.nist.gov/div898/handbook/pmc/section2/pmc27.htm

Hope this helps. If you need further information please ask, we are here to help.

Rick

 

[Dave Strouse]

ASQ Booklet

Connie -

ANSI-ASQ S1-1996 entitled An Attribute Skip-Lot Sampling Program is another reference you may find useful.

I think you are already in some jeopardy with your square root of N+1 plans. I have not been involved foir soem years but CFR-21 used to say "Sampling plans, if used, will be statistically based"

Square root of N+1 sure sounds ad hoc to me. Do you have any kind of statistical rationale written?

Good Luck -

 

[CarolX]

or try this

You can get a copy of MIL-STD-105 here


This was the Department of Defense standard on Attribute Sampling and has instructions for skip lot inspection. The FDA use to accept sampling plans to this standard, but that was 10 years or so ago.

Go to the DOD Index of Specifications and Standards page and type in MIL-STD-105 in the field for the DODISS ID Number. You will need Adobe Acrobat Reader to view it.

CarolX

 

[Aaron Lupo]

Re: Skip-lot testing and the FDA

ConnieH said:

I need help!

I'm trying to establish a reduced testing plan for raw materials involved in the production of API (Active Pharmaceutical Ingredients).

I've done some online research and have tracked down some possibilities. The term skip-lot testing keeps popping up but I can't seem to determine if it's a viable option as far as the FDA is concerned.

I'm also confused as to whether our current sampling plan (square root of N+1) can be used with skip-lot testing.

I'd really appreciate any help anyone would be able to offer.

It depends on a lot of factors:

1) How many pieces per lot?
2) What is the risk, i.e.. sterile vs., nonsterile product?
3) What does the customer require
4) What is the past performance? Is it a stable process? how many have been rejected in the past?
5) What is the recall process?

 

[Al Dyer]

Very true ISO GUY,

And I think the most importand aspect would be the function of the final product.

If a company is making steel blocks with a tol of +/- 1" as opposed to a substance/drug that could kill somebody, it needs to be taken into account. In past experience this can be documented on a FMEA study. Although some people disagree, FMEA is a tool for all processes, not just automotive.

Al...

 

[v9991]

Re: Skip-lot testing and the FDA

Guess, you might have already found suitable references .... just to close the loop for FDA references... further, my interpretation is that if its discussed in the context of human/veterinary drugs then, its certainly relevant for devices as well!

as Aaron has indicated, the protocol depends on comprehensive evaluation product specific requirement. System & Process has to demonstrate superior control on meeting the system requirements.

(system - define a criteria for identifying & evaluating the feasibility of skip testing, define the roll back procedure, further, it has to closely monitor the implementation )
(process - capability - consistency - predictability )

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm134966.htm
http://www.fda.gov/downloads/Animal...Enforcement/GuidanceforIndustry/UCM052487.pdf

2.1 Periodic or Skip Testing
Periodic or skip testing is the performance of specified tests at release on preselected batches and/or at predetermined intervals, rather than on a batch-by-batch basis, with the understanding that those batches not being tested still meet all acceptance criteria established for that product. This represents a less than full schedule of testing and should therefore be justified and presented to and approved by the regulatory authority prior to implementation. This concept may be applicable to, for example, residual solvents and microbiological testing for solid oral dosage forms. It is recognized that only limited data may be available at the time of submission of an application (see section 2.5). This concept should therefore generally be implemented postapproval. When tested, any failure to meet acceptance criteria established for the periodic test should be handled by proper notification of the appropriate regulatory authority(ies). If these data demonstrate a need to restore routine testing, then batch-
by-batch release testing should be reinstated.

 

[v9991]

heres another reference but this one too is for herbal products (not a human drug products)
http://www.ema.europa.eu/docs/en_GB/...C500003393.pdf
2.4. Periodic/skip testing
Periodic or skip testing is the performance of specified tests at release on pre-selected batches and/or at
predetermined intervals, rather than on a batch-to-batch basis. This represents a less than full schedule of
testing and should therefore be justified and presented to the regulatory authority prior to implementation.
This concept may be applicable to, for example, dissolution, residual solvents, and microbiological
testing, e.g., for solid oral dosage forms. This concept may therefore sometimes be implemented postapproval
in accordance with GMP and approval by the Regulatory Authority.

 

[AAA211]

Re: Skip-lot testing and the FDA



It depends on a lot of factors:

1) How many pieces per lot?
2) What is the risk, i.e.. sterile vs., nonsterile product?
3) What does the customer require
4) What is the past performance? Is it a stable process? how many have been rejected in the past?
5) What is the recall process?

Do you know some example of skip test plan or where I can find it? Which kind of method I could use to decide if I could reduce the number of test for that raw materiel in coming?