We have a lyophilize of BOC Edward having chamber capacity 200Kg , with 10 + 1 shelves with inbuilt CIP and SIP cycles , pl guide me for validation of lyophilizer with respective to No of cycles , biological indicators and no of probes shall be used for heat distribution , heat penetration, studies. and CIP SIP cycles and additional test to be performed for complete validation of lyophilizer
Hi There ?
You have a big task on your hands, one that needs careful planning. I know these machines very well indeed. You need to break down the tasks, as trying to handle them all in one document would be messy and difficult. I would suggest the following.
Raise a Validation Plan for the whole task - Validation of Lyophilizer No. xxxx. In this VP, document how and why you are separating and scoping tasks.
Raise a User Requirements Specification (URS)
Extract from the production process exactly what parameters are used and how many production cycles are used (there is usually one cycle per product). Enter all this into your URS as the criteria that the validation task has to verify.
Raise IQ – OQ – PQ for the CIP-SIP system and include your temperature mapping and heat studies in it. (number of t/c’s and positioning of them, I have documented in a past post to this forum). During the PQ replicate what was done during the original process validation.
Raise IQ-OQ-PQ for the Lyophilizer itself. There are a lot of inspections & verifications to be carried out in the IQ, far too much to list here, so go to our site and copy out the standard IQ and OQ tests and inspections. Include in these documents the electronic controls, this machine had quite a variation of PLC’s, but they are usually quite straight forward to validate.
Regulators hit list. (Critical items):
Make sure production has a product process acceptance criteria. Sounds silly, but so often they lyophilise through a cycle and do not test or inspect. There should at least be a weight or volume change. (This you need for the PQ)
These machines are susceptible to RFI so do include RFI studies.
The stoppering mechanism on the roof tends to twist, requires inspection and verification.
Stoppering arms must be verified as acting uniformly on all product containers.
Lubricants used around seal and doors must be cGMP compliant.
During chamber ballasting air is drawn in to chamber to equaliser pressures before unloading cabinet. The ballasting valve admits plant room air - unless it has been specially piped back to only admit room quality air. This is critical to product quality.
As I said at the start, it is a big one, but all large tasks are only a series of small tasks put together. If you tackle it in this manner you’ll get there. If you do get stuck do hesitate to ask again.
Do you have any advice on cleaning validation for lyo CIP’s? I am aware that current guidelines suggest that there be data available for residual product, but should there also be microbial testing as well?