averroes1304
☆    

Morocco,
2019-03-27 11:55
(edited by mittyri on 2019-03-27 13:51)

Posting: # 20091
Views: 978
 

 importance of bioanalytical validation [Bioanalytics]

Dear all,

could you explain to me the importance of bioanalytical validation in bioequivalence studies? is it really critical and important to perform the bioanalytical validation exercise? knowing that the purpose of bioequivalence studies is only to highlight differences in bioavailability between the test and reference drug and that this difference will be highlighted in all cases even with an invalidated analytical method and that chance cannot be the only factor in case of bioequivalence between two drugs with an invalidated analytical method..... is it scientifically acceptable to use analytical methods published in the literature?

Best regards,


Edit: Category changed; see also this post #1[Mittyri]
ElMaestro
★★★

Denmark,
2019-03-27 12:08

@ averroes1304
Posting: # 20092
Views: 928
 

 importance of bioanalytical validation

Hello Averroes,

if you cannot reliably determine the concentrations in PK samples, then you cannot reliably evaluate bioequivalence. At the end of the day the comparative evaluation of rate and extent of absorption is based on quantification in PK samples.

Thus, in highly regulated markets you will not see products approved unless the reliability of the assay has been confirmed by a validation. Check also ICH E6 e.g. §2.2 and §2.5 or similar entries in WHO's set of practices.

I could be wrong, but...
Best regards,
ElMaestro
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2019-03-27 14:41

@ ElMaestro
Posting: # 20093
Views: 898
 

 OT: Your signature

Hi ElMaestro,

x=c("Foo", "Bar")
b=data.frame(x)
typeof(b[,1]) ##aha, integer?
b[,1]+1 ##then let me add 1


[image]Lemme explain:

x <- c("Foo", "Bar")
is.character(x)
[1] TRUE
b <- data.frame(x)
is.character(b)
[1] FALSE
is.data.frame(b)
[1] TRUE
print(b)
    x
1 Foo
2 Bar

  So far, so good. What else?
str(b)
'data.frame':   2 obs. of  1 variable:
 $ x:
Factor w/ 2 levels "Bar","Foo": 2 1

  Implicitly you are using the default of data.frame() like here:
c <- data.frame(x, stringsAsFactors=TRUE)
  Check #1
identical(c, b)
[1] TRUE

  Check #2
c == b
        x
[1,] TRUE
[2,] TRUE

  See the point?
typeof(b[, 1]) ##aha, integer?
[1] "integer"

  Correct. Factors are always coded as integers internally.
  Check #3
is.factor(b[, 1])
[1] TRUE

  Note also the output of str(b) above where factors are given in lexical order.
  However, since we defined x <- c("Foo", "Bar"), "Bar" gets the level 2
  and "Foo" the level 1 in b.
b[, 1]+1 ##then let me add 1
[1] NA NA
Warning message:
In Ops.factor(b[, 1], 1) : ‘+’ not meaningful for factors

  Well roared, lion!
  On the other hand:
d <- data.frame(x, stringsAsFactors=FALSE)
print(d)
    x
1 Foo
2 Bar

str(d)
'data.frame':   2 obs. of  1 variable:
 $ x:
chr  "Foo" "Bar"
typeof(c[, 1])
[1] "character"

  Is this what you expected?
d[, 1]+1
Error in c[, 1] + 1 : non-numeric argument to binary operator

  Sure. Rubbish in, rubbish out.
  Personally I prefer a straight error over a warning producing NAs.

:cool:

Cheers,
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. ☼
Science Quotes
ElMaestro
★★★

Denmark,
2019-03-27 15:35

@ Helmut
Posting: # 20094
Views: 879
 

 OT: Correct as often

Hi Hötzi,

yes you are right as most often.
It reminds me of the good old days when Delphi was a thing. Borland wrote a very comprehensive manual spanning across 5 million gazillion pages. Only problem was, you had to be a Delphi expert in order to understand any word of it. This was a standing joke in the programming community back then, around 1998-2003 or so.:-D

I could be wrong, but...
Best regards,
ElMaestro
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2019-03-27 18:48

@ ElMaestro
Posting: # 20095
Views: 845
 

 OT: Nerds chatting

Hi ElMaestro

» It reminds me of the good old days when Delphi was a thing. […]

Oh dear, already the pointers in Pascal drove me nuts. BTW, Delphi – what a name! Only topped by a company marketing databases called Oracle. What about “I will consult the Delphic oracle!”
I still have Sobell’s “A practical guide to UNIX System V” in my bookshelf. 700 completely incomprehensible pages. You have to be a nerd with horn-rimmed glasses living from pizza, burgers, and Red Bull to value vi or EMACS.* Given, powerful stuff but for an average person like attempting to climb the K2 in shorts and sneakers.


  • Quoting wiki: “Emacs has over 10,000 built-in commands…” Wow! Close to 說文解字.

Cheers,
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. ☼
Science Quotes
nobody
nothing

2019-03-27 19:01

@ Helmut
Posting: # 20096
Views: 839
 

 OT: Nerds chatting

vi is cool... and absolutely sick at the same time. But after 5 min you will get the basics with the two modes etc.

Btw: Bioanalytical method validation is very important, if you want to do your study not only for the rubbish bin (or a poster at some congress) but plan to market the formulation you test for human use.

Kindest regards, nobody
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2019-03-27 19:16

@ nobody
Posting: # 20097
Views: 832
 

 OT: Nerds chatting

Hi nobody,

» vi is cool... and absolutely sick at the same time.

Yep, I used it on HP-UX those days. Concerning the latter quoting wiki again:

Due to the unintuitive character sequence* to exit vi, hackers joke that there is a proposed method of creating a pseudorandom character sequence by having a user unfamiliar with vi seated in front of an open editor and asking them to exit the program.


» But after 5 min you will get the basics with the two modes etc.

Sure but the basics will not help too much.


  • If you are in insert- or append-mode, press Esc
    :
    q!

Cheers,
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. ☼
Science Quotes
nobody
nothing

2019-03-27 19:38

@ Helmut
Posting: # 20098
Views: 831
 

 OT: Nerds chatting

...to create a new system file somewhere on the root partition or copy&paste sumefink to a config file (if there is no nano or alike) it's OK ;-)

Kindest regards, nobody
Shuanghe
★    

Spain,
2019-03-28 13:59

@ Helmut
Posting: # 20102
Views: 737
 

 OT: Nerds chatting

Hi,

» Due to the unintuitive character sequence* to exit vi, hackers joke that there is a proposed method of creating a pseudorandom character sequence by having a user unfamiliar with vi seated in front of an open editor and asking them to exit the program.

Saw one similar on Reddit but far from random. The generated texts would be like "quitquitexitqescapequit!q()fuck!ESCgetout()...." you get the idea... :-D

» » But after 5 min you will get the basics with the two modes etc.

I use vi only on my home PC where only Linux in installed, and only occasionally. for a few editting on system config files, even nano suit me. vi is terrible, and EMACS is not anything better for me. Don't understand why each time you search best text editor those two are always on top.

All the best,
Shuanghe
ElMaestro
★★★

Denmark,
2019-03-27 22:07

@ Helmut
Posting: # 20099
Views: 813
 

 OT: Nerds chatting

Hi Hötzi,

»
  • Quoting wiki: “Emacs has over 10,000 built-in commands…”

This is much like my former girlfriend. One for every occasion you could think of, plus bonus rounds with added aggression. To me this all resulted in syntax errors.

We aren't together any more.

I could be wrong, but...
Best regards,
ElMaestro
Ohlbe
★★★

France,
2019-03-28 10:28

@ ElMaestro
Posting: # 20100
Views: 762
 

 OT: Nerds chatting

Hi there,

» »
  • Quoting wiki: “Emacs has over 10,000 built-in commands…”

» This is much like my former girlfriend. One for every occasion you could think of, plus bonus rounds with added aggression. To me this all resulted in syntax errors.
»
» We aren't together any more.

Apart from the first two, I think this is the only post in this thread which I'm able to understand :-D

Bioanalytical method validation can have consequences not planned in the ICH M10 draft.

Regards
Ohlbe
nobody
nothing

2019-03-28 11:14

@ Ohlbe
Posting: # 20101
Views: 766
 

 OT: Nerds chatting

...and even worse (re Danish footer)

The FDA ordered AbbVie to stop recruiting multiple myeloma patients for a Phase III trial of its anti-cancer drug Venclexta/Venclyxto.

Forty-one out of 194 patients taking AbbVie’s Venclexta (venetoclax) in the company’s trial have died, the FDA found, nearly twice the percent of the patients in the trial’s placebo arm.

Kindest regards, nobody
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