Anda di halaman 1dari 1

1) Failure to thoroughly investigate unexplained discrepancies (including a percentage of theoretical yield

exceeding the maximum or minimum percentage established in the master production and control records) or the
fa ilure of a batch or any of its components to meet any of its specifications whether or not the batch has already
been distributed. [21 C.F.R. 21 1.192). For example,

a) Aloxi (Palonosetron HCI) inj ection batches (b)(4) fa iled to meet the yield limits; no root cause was

In particular, batches (b)(4) fa iled to meet yield limits of (b)(4)%- (b)(4)%. Validation batches (b)(4) reported yield
out-of-limit (OOL) values of (b)(4)%, (b)(4)%, and (b)(4)%, respectively. You indicated that the resu lt obtained fo r
batch (b)(4) was due to a high particle per volume content documented during manufacturing and product visual
inspection of the vials. However, the root cause fo r the increased number of particles in the product remains
unclear. There is also no information regarding the overall impact of the problem in the quality of the product, or
the corrective actions implemented to prevent re currence of the problem. You identified the defect but were
unable to determine the root cause. In addition, you fa iled to assess the product yield OOL values documented
for batches (b)(4).

Because your firm was unable to determine the root cause of the yield OOL values in the first validation batch
((b)(4)), you could not implement corre ctive and preventive actions fo r the subsequent batches. Consequently,
the second and third validation batches ((b)(4)) and ((b)(4)) also rep orte d yield OOL values.