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Ohlbe
Hero

France,
2018-05-21 16:28

Posting: # 18793
Views: 1,853
 

 New FDA BMV guideline [BE/BA News]

Dear all,

The FDA have just published their revised guidance on bioanalytical method validation.

Strange, considering that the ICH M10 guideline is on its way. I somehow thought that the FDA guideline had been put on hold.

Regards
Ohlbe
Helmut
Hero
avatar
Homepage
Vienna, Austria,
2018-05-21 17:47

@ Ohlbe
Posting: # 18796
Views: 1,673
 

 What a monster!

Hi Ohlbe,

THX! What a monster!
At least replaced “Concentrations below the LLOQ should be reported as zeros.” in the 2013 draft by “Study samples with concentrations listed below the LLOQ should be reported as below the LLOQ (BQL).” Someone was quick enough responding within the 90 (!) days consultation period… :-D
Looked over the fence and realised that is a good idea to assess carryover. Still the whacky recovery…

» Strange, considering that the ICH M10 guideline is on its way. I somehow thought that the FDA guideline had been put on hold.

Politics strategy to strengthen the position in the upcoming negotiations? Better to have a final guidance instead of only the 2013 draft (mentioned in the ICH’s concept paper).

Cheers,
Helmut Schütz
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jag009
Hero

NJ,
2018-05-24 03:19

@ Helmut
Posting: # 18808
Views: 1,426
 

 What a monster!

Hi Ohlbe and Helmut,
»
» THX! What a monster!

I kinda like the format with the requirements being tabulated. Easier to find things...
I knew that 7% ISR is not enough and they admitted it in a seminar later.

John
Obinoscopy
Regular

Nigeria,
2018-07-29 18:13

@ jag009
Posting: # 19114
Views: 921
 

 Two Versions: May 21 & May 24

Hi guys,

I noticed there are two versions of the guidance on the internet. One is dated May 21, 2018 while the other is May 24, 2018.

Could it be that the May 24 version is the updated and thus the recommended version to use? Was also wondering what was the modification done :ponder:.

» I kinda like the format with the requirements being tabulated. Easier to find things...

Yea me too. Makes reporting a bit easier for both the CRO and the assessors. Hopefully other NMRAs will follow suit.

Regards,

Scopy
ElMaestro
Hero

Denmark,
2018-05-22 00:17

@ Ohlbe
Posting: # 18797
Views: 1,638
 

 Repeats as part of investigations, ja oder nein?

Thanks Ohlbe,

» The FDA have just published their revised guideline on bioanalytical method validation.

for this document.

Now a million dollar question:
Are you on basis of the wording on page 13 allowed to do a repeat analysis as part of an investigation? Is for example absent or low IS response (without obvious poor chromatography) itself an assignable cause? If it is, then that would negate the need for an investigation, right?

If taken literally I am inclined to think the guidance does not allow repeats as part of investigations (to me, investigations are done when root causes are not known but potential root causes are being sought).
Common sense takes me a bit in the opposite direction and I would any day prefer to talk about reported repeats and unreported repeats on basis of the presence of a cause.

if (3) 4

Best regards,
ElMaestro

"(...) targeted cancer therapies will benefit fewer than 2 percent of the cancer patients they’re aimed at. That reality is often lost on consumers, who are being fed a steady diet of winning anecdotes about miracle cures." New York Times (ed.), June 9, 2018.
Ohlbe
Hero

France,
2018-05-22 12:02

@ ElMaestro
Posting: # 18798
Views: 1,578
 

 Repeats as part of investigations, ja oder nein?

Dear ElMaestro,

» Are you on basis of the wording on page 13 allowed to do a repeat analysis as part of an investigation?

I don't think it would prevent to re-analyse samples as part of an investigation (e.g. to identify a root cause or an explanation for anything weird) as long as:
- the repeat result is not used for PK calculations
- the repeats are clearly identified in advance as being investigation repeats, not to be used for PK
- the whole process is described in a SOP.

» Is for example absent or low IS response (without obvious poor chromatography) itself an assignable cause?

Well... Yes and no...
You may not find an assignable cause for the IS variation (was it a spiking error ? Blocked or dysfunctional SPE column ? Strict application of Murphy's Law ?). But IS variations could be considered an assignable cause for analytical repeats.

Unfortunately I was not able to attend the WRIB this year. They had a full day on IS variation, with folks from the FDA and EU Agencies. Last year there was a presentation from the FDA who talked about the importance of monitoring the IS response. Actually the guideline states An SOP should be developed a priori to address issues with IS variability.

Regards
Ohlbe
Obinoscopy
Regular

Nigeria,
2018-07-30 20:41

@ Ohlbe
Posting: # 19117
Views: 859
 

 Two Versions: May 21 & May 24

» But IS variations could be considered an assignable cause for analytical repeats.

Yes it is, but I think there is need to determine assignable cause for IS variations.

» I noticed there are two versions of the guidance on the internet. One is dated May 21, 2018 while the other is May 24, 2018.

» Could it be that the May 24 version is the updated and thus the recommended version to use? Was also wondering what was the modification done :ponder:

I have skimmed through both documents. I did not notice any difference except for a very negligible formatting difference: the May 24 document seemed a bit narrower.

If they are same, I wonder what the FDA did on the document for it to change from a size of 373KB to 386KB. I also wonder why the update if there were no changes made. My pondering continues :confused: :ponder:

Scopy
Helmut
Hero
avatar
Homepage
Vienna, Austria,
2018-08-01 11:12

@ Obinoscopy
Posting: # 19120
Views: 803
 

 Requirements ⇒ recommendations

Hi Scopy,

» » Could it be that the May 24 version is the updated and thus the recommended version to use?

Yes.
» » Was also wondering what was the modification done :ponder:

Unfortunately most regulatory documents are published without track changes. Not uncommon that older versions are overwritten (worst example: the EMA’s 15 versions of the Q&A document).

» I have skimmed through both documents. I did not notice any difference …

Not surprising. I used an online tool. Requirement(s) in the version of May 21 changed to recommendation(s):
  • Page 5, 5th bullet point (⇒ Table 1)
  • Page 8, 5. Sensitivity (⇒ Table 1)
  • Page 9, 7. Stability (⇒ Table 1)
  • Page 10, 8. Dilution Effects (⇒ Table 1)
  • Page 12, C. Validated Methods: Expectations of In-Study Analysis and Reporting (⇒ Table 1)
  • Page 13, last bullet point (⇒ Table 1)
  • Pages 20–27, VII. Appendix, Table 1.
Not unusual for the FDA to give recommendations rather than requirements. However, changing the wording was not consequent. In many places we still read e.g., “the requirements for […] are listed in Table 1.” – where only recommendations are given.

VIII. Glossary, Batch
old:

A batch is a number of unknown samples from one or more patients in a study and QCs that are processed at one time.

new:

For purposes of this guidance, a batch is a number of unknown samples from one or more pati­ents in a study and QCs that are processed at one time.


Cheers,
Helmut Schütz
[image]

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

Nigeria,
2018-08-02 22:59

@ Helmut
Posting: # 19129
Views: 765
 

 Requirements ⇒ recommendations

» Not surprising. I used an online tool. Requirement(s) in the version of May 21 changed to recommendation(s):
  • Page 5, 5th bullet point (⇒ Table 1)
    »
  • Page 8, 5. Sensitivity (⇒ Table 1)
    »
  • Page 9, 7. Stability (⇒ Table 1)
    »
  • Page 10, 8. Dilution Effects (⇒ Table 1)
    »
  • Page 12, C. Validated Methods: Expectations of In-Study Analysis and Reporting (⇒ Table 1)
    »
  • Page 13, last bullet point (⇒ Table 1)
    »
  • Pages 20–27, VII. Appendix, Table 1.

» VIII. Glossary, Batch
» old:

A batch is a number of unknown samples from one or more patients in a study and QCs that are processed at one time.


» new:

For purposes of this guidance, a batch is a number of unknown samples from one or more pati­ents in a study and QCs that are processed at one time.



Wow, thanks. Now I know the reason for the update. No more pondering. Mucho Gracias

Scopy
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