## Significant difference in Cmax of Reference drug product [Study Assessment]

Hi Mehul,

» Can anybody please tell what may be the probable reasons behind significant (more than 20%) difference in mean Cmax concentration of Reference product of a same batch number in two different studies conducted at same CRO and on the similar kind of population but different sample size?

I guess you had also the same batch of the test? Was the

» Is it correct to compare and expect Reference product's behavior same for all repeated studies?

A few reference products (dasatinib is an infamous example) show extreme batch-to-batch variability. However, generally batches are expected to be similar.

You could compare the references of the two studies as a paired design (assuming to period effects). For a quick estimate calculate \(\small{\widehat{PE}=PE_1/PE_2}\), with \(\small{PE_1=\frac{T}{R_1}}\) and \(\small{PE_2=\frac{T}{R_2}}\), where \(\small{R_1}\) and \(\small{PE_1=\frac{T}{R_2}}\) are the reference batches of the two studies.

» […] Can 6 months old (frozen) samples yield significant different results as compared to freshly analyzed study samples?

If long term storage was validated for this duration, no.

» Can anybody please tell what may be the probable reasons behind significant (more than 20%) difference in mean Cmax concentration of Reference product of a same batch number in two different studies conducted at same CRO and on the similar kind of population but different sample size?

I guess you had also the same batch of the test? Was the

*AUC*different as well?» Is it correct to compare and expect Reference product's behavior same for all repeated studies?

A few reference products (dasatinib is an infamous example) show extreme batch-to-batch variability. However, generally batches are expected to be similar.

You could compare the references of the two studies as a paired design (assuming to period effects). For a quick estimate calculate \(\small{\widehat{PE}=PE_1/PE_2}\), with \(\small{PE_1=\frac{T}{R_1}}\) and \(\small{PE_2=\frac{T}{R_2}}\), where \(\small{R_1}\) and \(\small{PE_1=\frac{T}{R_2}}\) are the reference batches of the two studies.

» […] Can 6 months old (frozen) samples yield significant different results as compared to freshly analyzed study samples?

If long term storage was validated for this duration, no.

—

Helmut Schütz

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*Dif-tor heh smusma*🖖Helmut Schütz

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

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### Complete thread:

- Significant difference in Cmax of Reference drug product Mehul Patel 2021-08-17 10:00 [Study Assessment]
- Significant difference in Cmax of Reference drug productHelmut 2021-08-17 11:57
- Significant difference in Cmax of Reference drug product Mehul Patel 2021-08-17 12:02
- Different products → different BA Helmut 2021-08-17 15:36
- Significant difference in Cmax of Reference drug product dshah 2021-08-21 10:48

- Significant difference in Cmax of Reference drug product Mehul Patel 2021-08-17 12:02

- Significant difference in Cmax of Reference drug productHelmut 2021-08-17 11:57