Bioequivalence and Bioavailability Forum • change in CC range

sushil.pimpare
☆

India,
2017-05-31 11:31
(2512 d 02:57 ago)

Posting: # 17429
Views: 7,569

change in CC range [Regulatives / Guidelines]

As per applicable method validation, validated CC range for Analyte X is 10.0 ng/ml to 11015.9 ng/ml, 15.1 ng/ml to 6037.2 ng/ml for Y Analyte and 0.20 ng/ml to 9.84 ng/ml for Z Analyte however during subject sample analysis CC range used is 10.0 ng/ml to 11031.0 ng/ml, 15.1 ng/ml to 6039.8 ng/ml and 0.20 ng/ml to 9.96 ng/ml for X, Y and Z respectively which is outside the validated CC range.
I just wanted to confirm whether this is acceptable or not? also wanted to know is there any acceptable % deviation mentioned in any guideline related to change in CC range which found during method validation and subject sample analysis.

Edit: Please follow the Forum’s Policy. [Helmut]

Helmut
★★★

Vienna, Austria,
2017-05-31 14:41
(2511 d 23:48 ago)

@ sushil.pimpare
Posting: # 17430
Views: 6,932

exact matching of CCs (validation’s and study’s)

Post reply

Hi Sushil,

welcome to the BEBA-Forum! Before asking for help: What are your own thoughts?
Bioanalysts should be blinded for treatment but not blind. Science first, regulations second. SCNR. :-D

IMHO, exceeding the upper limit of the CCs in the study compared to the validation by 0.12% (X), 0.04% (Y), or even 1.22% (Z) is simply irrelevant. However, I’m not aware of any GL giving a specific limit.
See also a similar thread (whether it is possible to match CCs and QCs).

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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nobody nothing 2017-05-31 15:43 (2511 d 22:46 ago) @ Helmut Posting: # 17431 Views: 6,828	exact matching of CCs (validation’s and study’s) Post reply
	Hi Sushil Can you post the FULL, original validation data for the highest concentration of all three analytes? Raw concentration data for determination of variability. While you write the post, have a look at the data. And: As Helmut wrote: Start thinking... — Kindest regards, nobody

sushil.pimpare
☆

India,
2017-05-31 16:01
(2511 d 22:27 ago)

@ nobody
Posting: # 17433
Views: 6,898

exact matching of CCs (validation’s and study’s)

Post reply

In method validation CC range proved for three analytes are as mentioned below;
For analyte X :10.0 ng/ml to 11015.9 ng/ml
For analyte Y :15.1 ng/ml to 6037.2 ng/ml
For analyte Z :0.20 ng/ml to 9.84 ng/ml

During subject sample analysis following CC range prepared for three analytes and used for subject sample analysis;
For analyte X :10.0 ng/ml to 11031.0 ng/ml
For analyte Y :15.1 ng/ml to 6039.8 ng/ml
For analyte Z :0.20 ng/ml to 9.96 ng/ml

As you can see, the ULOQ of CC range used during subject sample analysis is above the ULOQ of method validation CC range.

We can see CC range used during subject sample analysis is not within the proved method validation CC range.

As per my knowledge this is not acceptable. we have to use CC range which falls within the proved method validation CC range. If there is change in the CC range then partial method validation needs to be proved for that new range which falls outside the proved method validation CC range.

Is there any accepted % deviation mention in any guideline for this change in the cocn. during method validation and subject sample analysis?

ElMaestro
★★★

Denmark,
2017-05-31 16:11
(2511 d 22:18 ago)

@ sushil.pimpare
Posting: # 17434
Views: 6,912

exact matching of CCs (validation’s and study’s)

Post reply

Hi Sushil.pimpare,

❝ In method validation CC range proved for three analytes are as mentioned below;

❝ For analyte X :10.0 ng/ml to 11015.9 ng/ml

❝ For analyte Y :15.1 ng/ml to 6037.2 ng/ml

❝ For analyte Z :0.20 ng/ml to 9.84 ng/ml

❝

❝ During subject sample analysis following CC range prepared for three analytes and used for subject sample analysis;

❝ For analyte X :10.0 ng/ml to 11031.0 ng/ml

❝ For analyte Y :15.1 ng/ml to 6039.8 ng/ml

❝ For analyte Z :0.20 ng/ml to 9.96 ng/ml

I do not know here the limit is but here we are dealing with 1% deviations, and I think this is not a profound worry for any analyte. I am talking on basis of gut feeling not on basis of a guideline.

CROs often specify that the method is validated from approximately 6 ng/mL to 6000 ng/mL or whatever to make room for exactly this phenomenon.
Also, can you check how many significant digits you have on the CoA for the ref std.'s potency? If you specify your ULOQ as 11015.9 ng/mL then you probably had 6 digits on that CoA (and you used pippettes and glassware which was unsually precise). But you didn't. I am wiling to bet on it :-)

—
Pass or fail!
ElMaestro

nobody nothing 2017-05-31 17:38 (2511 d 20:50 ago) @ sushil.pimpare Posting: # 17436 Views: 6,778	exact matching of CCs (validation’s and study’s) Post reply
	Raw concentration data for determination of variability. ALL concentration data for ALL individual samples used to validate the method, i.e. determination of precision and accuracy. A list of 6 to 12 concentrations determined for validation of the ULOQ. And start thinking about what you are doing, while preparing the post. Please... — Kindest regards, nobody

sushil.pimpare
☆

India,
2017-05-31 15:46
(2511 d 22:43 ago)

@ Helmut
Posting: # 17432
Views: 6,850

exact matching of CCs (validation’s and study’s)

Post reply

Thank you for your reply.
Also I wanted to confirm wheteher Below reason for change in CC is acceptable or not?
Nominal concentrations obtained on the basis of weight of reference standard and purity of reference standard used during method validation and subject sample analysis and since these values, i.e. purity, water content, weight of standard etc., could vary slightly from one preparation to another, there is bound to be some difference in nominal concentrations during experiments and theoretical values. These differences are very small (less than 2.0%) and do not necessitate any partial validation.

Helmut
★★★

Vienna, Austria,
2017-05-31 16:46
(2511 d 21:42 ago)

@ sushil.pimpare
Posting: # 17435
Views: 6,830

Sapere aude!

Post reply

Hi Sushil,

❝ Also I wanted to confirm wheteher Below reason for change in CC is acceptable or not? […]

Please use you own reasoning – taking the answers of the other members into account. I’m not in the position to confirm anything.
See what Immanuel Kant wrote a good while ago:

An Answer to the Question: ”What is Enlightenment?”
Enlightenment is man’s release from his self-incurred tutelage. Tutelage is man’s inability to make use of his understanding without direction from another. Self-incurred is this tutelage when its cause lies not in lack of reason but in lack of resolution and courage to use it without direction from another. Sapere aude! Have courage to use your own reason! – that is the motto of enlightenment.
Immanuel Kant (Königsberg, Prussia, 30 September 1784)

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes