Академический Документы
Профессиональный Документы
Культура Документы
Journal No. 3
Summary
Point of view
Lab news
Focus on a laboratory
Research
Methods
Agenda
Introduction
Equation 1
x T
Equation 2
Objectives
The provision of objective evidence generally involves the use of
statistics. However, these statistics are not always used properly
because they are not discussed together ahead of time by the
analyst and the statistician. Different points of view have to be
addressed:
an analyst who knows from experience whether or not his
method is sound, and then sees it accepted or refused during
the statistical analysis;
the statistician who wants to ensure that the method is sound
from a statistical perspective;
the customer who wants a sound result and expects the
method to be guaranteed as such.
To reconcile these three points of view, the analyst needs a tool
which is easy to use, which can guarantee the results obtained,
and which is acceptable to the customer.
Based on this realisation, a commission from the French Society
of Pharmaceutical Science and Technology (SFSTP) has
developed a validation concept based on the total error and the
accuracy profile (Hubert et al., 2004; Hubert et al., 2007a; Hubert
et al., 2007b; Hubert et al., 2008; AFNOR 2010).
< x T <
x T<
Equation 3
(x T< )
Equation 4
, { [x T< ]/ ,}
Accuracy profile
where E stands for the expected value calculated at the
moment the measurements are taken depending on the
Point of view
Lab news
Focus on a laboratory
Research
Agenda
3,500
+ 25
3,000
2,500
Are
2,000
1,500
Validation standard
1,000
25
500
0
Domain of validity
Concentration
500
Concentration (ng/mL)
Domain of validation
June 2010
Methods
Bias (%)
Journal No. 3
Summary
30
25
20
15
10
5
0
-5 0
- 10
- 15
- 20
- 25
- 30
- 35
- 40
- 45
- 50
- 55
- 60
- 65
- 70
500
1,000
1,500
2,000
2,500
3,000
3,500
4,000
4,500
5,000
Concentration (ng/mL)
10
Point of view
Lab news
Focus on a laboratory
Research
Methods
Agenda
4,000
y = 0,686x + 1,983
R = 0,9982
3,500
3,000
2,500
2,000
1,500
1,000
500
0
- 500 0
1,000
2,000
3,000
4,000
5,000
6,000
References
AFNOR. 2010. Standard NF V03-110:2010. Protocole de caractrisation
en vue de la validation dune mthode danalyse quantitative par
construction du profil dexactitude [Protocol of characterization for the
validation of a quantitative method of analysis by construction of an
accuracy profile], AFNOR, Paris
Feinberg M. 2009. Labo-Stat, Guide De Validation Des Mthodes
Danalyse. Tec & Doc Lavoisier, Paris, France: 361 pp.
Hubert P, Nguyen-Huu J, Boulanger B, Chapuzet E, Chiap P, Cohen N,
Compagnon P, Dewe W, Feinberg M, Lallier M, Laurentie M, Mercier
N, Muzard G, Nivet C, Valat L. 2004. Harmonization of strategies for
the validation of quantitative analytical procedures. A SFTP Proposal
Part1. J. Pharma. Biomed. Anal., 36 (3): 579-586.
Hubert P, Nguyen-Huu J, Boulanger B, Chapuzet E, Chiap P, Cohen N,
Compagnon P, Dewe W, Feinberg M, Lallier M, Laurentie M, Mercier N,
Muzard G, Nivet C, Valat L, Rozet E. 2007a. Harmonization of strategies
for the validation of quantitative analytical procedures. A SFSTP
proposal Part II. J. Pharma. Biomed. Anal., 45 (1): 70-81.
Hubert P, Nguyen-Huu J, Boulanger B, Chapuzet E, Chiap P, Cohen N,
Compagnon P, Dewe W, Feinberg M, Lallier M, Laurentie M, Mercier N,
Muzard G, Nivet C, Valat L, Rozet E. 2007b. Harmonization of strategies
for the validation of quantitative analytical procedures A SFSTP proposal
Part III. J. Pharma. Biomed. Anal., 45 (1): 82-96.
Hubert P, Nguyen-Huu J, Boulanger B, Chapuzet E, Chiap P, Cohen N,
Compagnon P, Dewe W, Feinberg M, Lallier M, Laurentie M, Mercier N,
Muzard G, Nivet C, Valat L, Rozet E. 2008. Harmonization of strategies
for the validation of quantitative analytical procedures: A SFSTP
oroposal. Part IV. Examples Of Application. J. Pharma. Biomed. Anal.,
48 (3): 760-771.
June 2010
Journal No. 3
Summary
30
25
20
15
10
5
0
-5 0
- 10
- 15
- 20
- 25
- 30
- 35
500 1,000 1,500 2,000 2,500 3,000 3,500 4,000 4,500 5,000
Concentration (ng/mL)
The method is not validated for the studied domain, as the lower
bound of the accuracy profile is beyond the acceptance limit set
Table 1. Results of calculations of the accuracy profile after correction of raw data
Level of theoretical concentrations (ng/mL)
10
20
50
500
1,000
Lower
6.98
16.52
44.93
192.5
894.8
Limit of the -expectation tolerance interval
Upper
12.26
24.16
60.07
223.0
1,145
Lower
30.18
17.40
10.14
3.77
-10.52
Limit of the relative -expectation tolerance
interval (%)
Upper
22.59
20.82
20.15
11.50
14.48
Standard deviation of repeatability
0.61
0.43
1.62
5.78
32.26
Standard deviation of intermediate precision
0.99
1.31
2.81
6.32
48.01
Repeatability RSD (%)
6.08
2.14
3.25
2.89
3.23
Intermediate reliability RSD (%)
9.92
6.57
5.63
3.16
4.80
Inverse predicted concentration (ng/mL)
9.62
20.34
52.50
207.7
1,020
Absolute bias (ng/mL))
0.38
0.34
2.50
7.73
19.78
Relative bias (%)
3.80
1.71
5.00
3.87
1.98
Recovery (%)
96.20
101.7
105
103.9
102
11
5,000
4,482
5,515
10.35
10.30
136.7
199.2
2.73
3.98
4,999
1.35
0.03
99.97