Process validation for new process

Quality Assurance
1

Hi sir this is Ravi

I have a observed a one observation during review .that is for so and so product there 3 batches executed in process validation according to protocol.in first 2 batches filtration was done through offline method, but in last 3rd batch filtration was done through online method parllal with offline . But in protocol there is no discussion about online method.so please clarify is there is any nessecory to validate the new process in process validation.

2

@katla_chanakya_padma
Hi Ravi,
Yes they need to establish the equivalency of both offline and online filtration. I have few questions:

  1. Was there any planned deviation/temporary change control for this?. If yes what reason was given?
  2. Is this change is covered in the intervention sections of process validation? If no, how they got authorization to change the method.
  3. Was online method was part of BMR? or is it a regular practice of online filtration, however offline was only selected for this validaiton (as per your protocol)?
  4. was any risk assessment of offline method was performed?
    see as PDA and PICS guidelines Time limits should be established for each phase of processing, and equivalency should be addressed to identify worst case scenario e.g.
  • maximum period between start of bulk product compounding and sterilization (filtration)
  • product exposure on processing line
  • storage of sterilized containers/components
  • total time for product filtration to prevent organisms from penetrating filter
  • maximum time for upstream filters used for clarification or particle removal (can support microbial attachment)

The time limit for both the processes (offline/online) should be established and validated so if there is any change in key chain of process, for establishing it…a validation is required to document and establishment of limits.

for your further reading please refer below few informative links:

https://www.google.co.in/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&cad=rja&uact=8&ved=0ahUKEwiPuMbF_fXQAhWMuY8KHWu8DeIQFggZMAA&url=https%3A%2F%2Fwww.picscheme.org%2Flayout%2Fdocument.php%3Fid%3D127&usg=AFQjCNHsRnHYEC_vwakPcrhnRSaN5EkcPA&bvm=bv.141536425,d.c2I

Intervention
7.4 Intervention Monitoring
https://www.google.co.in/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=0ahUKEwiPuMbF_fXQAhWMuY8KHWu8DeIQFggcMAE&url=https%3A%2F%2Fwww.picscheme.org%2Flayout%2Fdocument.php%3Fid%3D153&usg=AFQjCNENAJVm6NrozpQqC55w0h-jcqJetg&bvm=bv.141536425,d.c2I

3

Please elaborate stability study of cap opening for reconstituted syrups and oral Syrups

4

@jehangir
Although this question is incorrectly posted in this discussion however i request you to kindly read the following chapter of USP and FDA guideline for quick insight.

http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/ucm051556.pdf

General Chapters: <1191> STABILITY CONSIDERATIONS IN DISPENSING PRACTICE

STABILITY CRITERIA AND BEYOND-USE DATING
General Chapters: <795> PHARMACEUTICAL COMPOUNDING-NON-STERILE PREPARATIONS

STORAGE CONDITIONS
General Chapters: <659> PACKAGING AND STORAGE REQUIREMENTS

Enjoy reading…