## Is ƒ2 dead as well – always bootstrapping? [Dissolution / BCS / IVIVC]

I’ve read the Q&A again. Here the last paragraph in all of its beauty:

Any approach based upon confidence intervals for ƒ_{2} would, however, be considered appropriate whether the validity criteria outlined in CHMP guidance are met or not [CPMP/EWP/QWP/1401/98 Rev. 1/Corr**]. Similarity could then be declared if the confidence interval for ƒ_{2} were entirely above 50. However, regardless of whether the conditions to adequately apply ƒ_{2} in a dissolution experiment are fulfilled or not, the properties of the ƒ_{2} sampling distribution do not allow the derivation of exact confidence intervals to adequately quantify the uncertainty of the ƒ_{2} estimate. To address this, bootstrap methodology could be used to derive confidence intervals for ƒ_{2} based on quantiles of re-sampling distributions, and this approach could actually be considered the preferred method over ƒ_{2} and MD.

Do I get this right? Bootstrapping is preferred over ƒ

_{2}even if the validity criteria* are met?

I expect ‘regulatory creep’.

*Preferred*will turn into

*mandatory*. Will it be required retrospectively? I know some minor variations supported by ƒ

_{2}, where it was say, only 53 in one pH. Will not pass the lower confidence limit.

IMHO, the only way to decrease the CV – and hence, the width of the bootstrapped CI – is to substantially increase the number of units.

`CV units`

────────

♫ 12

¾ 21

⅔ 27

½ 48

⅓ 108

- ≥12 units of T and R, CV ≤20% at ≤15 minutes, CV ≤10% at >15 minutes, not more than one mean value of >85% dissolved for each formulation.

Cheers,

Helmut Schütz

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

Science Quotes

### Complete thread:

- EMA: Mahalanobis distance is dead... Helmut 2018-11-09 18:01 [Dissolution / BCS / IVIVC]
- EMA: Mahalanobis distance is dead... ElMaestro 2018-11-09 19:12
- Is ƒ2 dead as well – always bootstrapping?Helmut 2019-10-06 15:27
- Is ƒ2 dead as well – always bootstrapping? ElMaestro 2019-10-06 17:54
- Ahem – number of units? Helmut 2019-10-06 18:14
- Ahem – number of units? ElMaestro 2019-10-06 22:45
- Ahem – number of units? wienui 2019-10-07 19:11

- Ahem – number of units? ElMaestro 2019-10-06 22:45

- Ahem – number of units? Helmut 2019-10-06 18:14

- Is ƒ2 dead as well – always bootstrapping? ElMaestro 2019-10-06 17:54

- Is ƒ2 dead as well – always bootstrapping?Helmut 2019-10-06 15:27

- EMA: Mahalanobis distance is dead... ElMaestro 2018-11-09 19:12