Helmut
★★★
avatar
Homepage
Vienna, Austria,
2014-09-19 19:09
(3478 d 01:34 ago)

Posting: # 13543
Views: 3,968
 

 EMA: GL on bioanalytical method validation Rev.1 [Regulatives / Guidelines]

Dear all,

on Sep 15 EMA updated its Guideline on bioanalytical method validation.
The new document reference is EMEA/CHMP/EWP/192217/2009 Rev.1 Corr.*

Changes:
  1. Section 4.1.5. ‘Accuracy’
    • old
      […] around 50% of the calibration curve range (medium QC)
    • new
      […] around 30 – 50% of the calibration curve range (medium QC)
  2. Section 6 ‘Incurred samples reanalysis’
    • old
      The concentration obtained for the initial analysis and the concentration obtained by reanalysis should be within 20% of their mean […].
    • new
      The concentration obtained for the initial analysis and the concentration obtained by reanalysis should be within 20% of their mean […]. The following equation should be used for the cal­cu­lations:
                                 (repeat value – initial value)
           %difference = ──────────────────── ×100
                                            mean value
  3. Section 7.1.1.11. ‘Stability of the samples’
    • old
      In addition, long-term freezer stability should be studied at each temperature at which study samples will be stored. A bracketing approach may be considered.
    • new
      In addition, long-term freezer stability should be studied at each temperature at which study samples will be stored. A bracketing approach may be considered.
I’m fine with #1/#2. But why #3? If one has already shown stability at –80 ℃ and –20 ℃ – intending to store samples at any temperature in between – that’s an unscientific formalism, IMHO (yes; I’m aware about some Crystal City Conference discussions).
If you are referring to certain sections in your SOPs/protocols/reports (quoting a page-number), beware. The GL has been reformatted (now 23 pages instead of 22). :-D

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

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

Denmark,
2014-09-19 19:39
(3478 d 01:04 ago)

@ Helmut
Posting: # 13545
Views: 3,438
 

 EMA: Guideline on bioanalytical method validation Rev.1

Thanks Helmut.

Very important.

But I wonder how on earth are you supposed to know about this update: It is not mentioned on the EMA mainpage, it is not mentioned on the page listing guidelines which is often also listing revisions along with dates, and the document itself makes no -absolutely zero- attempt at indicating when the asterisked changes are made or when they are coming into effect. For the latter, I assume the effect is immediate, but that isn't my point.

Perhaps I was overlooking something, but how was I really supposed to figure out a change had been made?
:confused::confused::confused::confused:

Pass or fail!
ElMaestro
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2014-09-19 20:02
(3478 d 00:41 ago)

@ ElMaestro
Posting: # 13546
Views: 3,410
 

 EMA: NSA-approach

Ahoy ElMaestro,

❝ But I wonder how on earth are you supposed to know about this update:


I subscribed to EMA’s respective RSS feed. If you [navigate] steer your vessel to the “Scientific guidelines”, in the top right hand corner (behind the [image] icon) you find the link to EMA’s RSS feeds.
My SeaMonkey automatically checks for updates every two hours. ;-)

❝ It is not mentioned on the EMA mainpage, it is not mentioned on the page listing guidelines which is often also listing revisions along with dates,…


Yes, that’s really clever.

❝ …and the document itself makes no -absolutely zero- attempt at indicating when the asterisked changes are made or when they are coming into effect. For the latter, I assume the effect is immediate,…


Yep. Brilliant.

❝ Perhaps I was overlooking something, but how was I really supposed to figure out a change had been made?


In Adobe Reader:
Document-Properties ⇒ Created on: 2014-09-15 14:26:07, Changed on: 2014-09-15 14:26:18
If your curiosity is still not satisfied, check the User-defined Properties as well.
The document was published on 2014-09-16 14:40…

Other stuff to try: [image] 1, [image] 2

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

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

Denmark,
2014-09-19 21:28
(3477 d 23:15 ago)

@ Helmut
Posting: # 13548
Views: 3,317
 

 EMA: NSA-approach

Thanks again Helmut.

I hope EMA would apply a bit of change control if they force others to use it. The EMA home­page with guidelines has a column with "remarks". It wouldn't hurt if someone at EMA actually used that column to write e.g. "Hi mom!" or "Updated Sept 15. 2014, change enforced as of the same date." or something.
Otherwise applicants could later (once the entry slips off the rss feed) come into a situation where they cannot prove that they fulfilled the requirements at the time of submission and at the time of bioanalysis.

Pass or fail!
ElMaestro
nobody
nothing

2014-09-19 21:41
(3477 d 23:02 ago)

(edited by Dr_Dan on 2014-09-20 11:53)
@ ElMaestro
Posting: # 13549
Views: 3,294
 

 EMA: NSA-approach

..do a print-out of the internet on a regular basis! Excluding pr0n and spam, it fits on 20 pages, more or less... :-D

Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Dr_Dan]

Kindest regards, nobody
ElMaestro
★★★

Denmark,
2014-09-20 23:41
(3476 d 21:02 ago)

@ nobody
Posting: # 13550
Views: 3,264
 

 EMA: NSA-approach

❝ ..do a print-out of the internet on a regular basis! Excluding pr0n and spam, it fits on 20 pages, more or less... :-D


That's the kind of wisdom I treasure!:ok:

Pass or fail!
ElMaestro
nobody
nothing

2014-09-21 18:59
(3476 d 01:44 ago)

@ ElMaestro
Posting: # 13553
Views: 3,199
 

 EMA: NSA-approach

❝ ❝ ..do a print-out of the internet on a regular basis! Excluding pr0n and spam, it fits on 20 pages, more or less... :-D


❝ That's the kind of wisdom I treasure!:ok:


You'r wellcome <3 !

Kindest regards, nobody
Ohlbe
★★★

France,
2014-09-19 21:20
(3477 d 23:23 ago)

@ Helmut
Posting: # 13547
Views: 3,415
 

 EMA: GL on bioanalytical method validation Rev.1

Dear Helmut,

❝ 2. Section 6 ‘Incurred samples reanalysis’

old

❝ The concentration obtained for the initial analysis and the concentration obtained by reanalysis should be within 20% of their mean […].

new

❝ The concentration obtained for the initial analysis and the concentration obtained by reanalysis should be within 20% of their mean […]. The following equation should be used for the cal­cu­lations:

                 (repeat value – initial value)

   %difference = ────────────────────────────── ×100

                      mean value


The text actually changed from
The concentration obtained for the initial analysis and the concentration obtained by reanalysis should be within 20% of their mean for at least 67% of the repeats

to

The percent difference between the initial concentration and the concentration measured during the repeat analysis should not be greater than 20% of their mean for at least 67 % of the repeats


which may be a bit clearer. The initial wording could be interpreted as allowing a 40 % deviation (20 % below the mean, 20 % above it).

❝ 3. Section 7.1.1.11. ‘Stability of the samples’

old

❝ In addition, long-term freezer stability should be studied at each temperature at which study samples will be stored. A bracketing approach may be considered.

new

❝ In addition, long-term freezer stability should be studied at each temperature at which study samples will be stored. A bracketing approach may be considered.


❝ But why #3? If one has already shown stability at –80 ℃ and –20 ℃ – intending to store samples at any temperature in between – that’s an unscientific formalism, IMHO (yes; I’m aware about some Crystal City Conference discussions).


This is only for large molecules (section 7 of the guideline), not small molecules. The deletion removes the contradiction between 7.1.1.11 (which allowed bracketing) and 4.1.9 (which allows bracketing for small molecules, but excludes it for large molecules). If I remember correctly the discussions in Brussels in 2010, this was due to possible problems with the structural conformation of proteins, right ?

Regards
Ohlbe
Helmut
★★★
avatar
Homepage
Vienna, Austria,
2014-09-22 18:34
(3475 d 02:09 ago)

@ Ohlbe
Posting: # 13556
Views: 3,120
 

 THX!

Hi Ohlbe,

❝ The text actually changed from

:blahblah:

❝ to

:blahblah:


❝ which may be a bit clearer. The initial wording could be interpreted as allowing a 40 % deviation (20 % below the mean, 20 % above it).


Thanks for pointing that out. I missed that. Definitely clearer now.

❝ ❝ 3. Section 7.1.1.11. ‘Stability of the samples’


❝ This is only for large molecules (section 7 of the guideline), not small molecules.


I missed that one as well…

❝ If I remember correctly the discussions in Brussels in 2010, this was due to possible problems with the structural conformation of proteins, right ?


Possibly yes. These discussions were on the second day in the afternoon when by brain was already in idle state – I don’t remember and I didn’t take any notes.

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz
[image]

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

Italy,
2014-09-23 19:52
(3474 d 00:51 ago)

@ Ohlbe
Posting: # 13559
Views: 3,021
 

 EMA: GL on bioanalytical method validation Rev.1

Dear Ohlbe,

In my post of 2013-12-09 12:52, i discussed the calculations and had arrived at the conclusion that now appears in this correct version of the GL.

Roberto


Edit: Post linked. [Helmut]
UA Flag
Activity
 Admin contact
22,957 posts in 4,819 threads, 1,636 registered users;
85 visitors (0 registered, 85 guests [including 9 identified bots]).
Forum time: 19:43 CET (Europe/Vienna)

Nothing shows a lack of mathematical education more
than an overly precise calculation.    Carl Friedrich Gauß

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5