Content uniformity

Please help me with this problems

  1. I am perform for production validation of hard capsule. Is it necessary to perform content uniformity test for semi-product (bulk product)? if any, how can i perform this test. For tablet for coated tablets, it seems very easy to assay the content in 10 individual tablets but how to perform this test for hard capsules because it is hard to transfer accurately all the content in each hard capsule for sample preparation.

  2. In testing related substances in Clopidogrel bisulfate film coated tablet. I am perform testing related substances in all production process (from granule - Tablet - film coated tablet (bulk product) - finished product). My manager told me it is only to test related substances for finished product. Is my manager true and is there any requirements for this?

Thanks you very much!

BUA(Blend Uniformity Analysis ) or homogeneity testing can be applied to all dosage forms, but is recommended for those dosage forms for which the USP requires content uniformity testing. These dosage forms include
Coated tablets, other than film coated tablets
Transdermal systems
Suspensions in single-unit containers or in soft capsules
Pressurized metered-dose inhalers
Suppositories

Under current good manufacturing practices (CGMPS), an applicant is required to perform a test or examination on each commercial batch of all products to monitor the output and validate the performance of processes that could be responsible for causing variability, which includes
adequacy of mixing to ensure uniformity and homogeneity (21 CFR 211.11 O(a)(3)).

The recommended sample size of the blend material is no more than three times the weight of an individual dose. If the firm experiences problems in collecting small samples equivalent to 1 to 3 dosage units and demonstrates that small samples give lower values for BUA due to sampling bias, larger samples (usually no more than 10 dosage units) can be collected.

Samples for BUA can be collected either from the drums or the blenders. For more than one drum or blender, analysis from each drum or blender is encouraged for the bioequivalence ard/ortest batches. The batch size, number of samples (usually 6 to 10), locations of sampling, and equipment should be specified as part of the in-process controls for BUA or homogeneity.Potential differences in mixing efficiency associated with specific types of equipment should be considered when determining sampling locations.

Container  :  Before seaming  the  container  

a) Collect 10 polythene bags filled with Tab / Cap. Randomly from each batch.

b) Cut the polythene bag.

c) Count the number of tab / cap per polythene bag / container

d) Record the number of the in the test sheet.

e) Confirm that each container is having nos of tab / cap from 98 – 102% o the labeled amount.

f) Calculate average number of units as follows

Average number of Units = Total Units / No of container = Limit not less than labeled amount.

If the above procedure does not comply please follow this:

Count the number of 10 additional containers. Average number of in 20 containers is & not less than labeled amount and the number is not more than one of 20 container is less than 98% or more than 102% of the labeled amount.