Sterilization Re-Validation after Manufacturer Change

[Qara123]

The first lot of products from the new manufacturer will be tested for bioburden as part of a routine lot release. The question is whether it's enough or would you suggest anything else?

In all likelihood, bioburden testing of the first lot of products will not be even close to the 10^6 cfu neighborhood. If an overkill method is used, there will be an even lower likelihood that the product is non-sterile. Furthur, the bacteria identified will not be bacillus atrophaeus so your bioburden test requirement should be easily met. This looks like a step towards justifying a reason for not re-validating a sterilization process that has not been changed since there is no change to validate.

If you can show that bioburden at the previous and new manufacturers are similar and are very low, and that the devices from the new manufactuer meet all release specifications (including EtO residue, & endotoxin levels) you may have a fighting chance.

Do you plan to include your justification (or sterilization validation if you proceed with re-validation) in your submission to the FDA or have you already notified FDA about the subcontractor change?

Also, you mentioned that there is no change to the packaging subcontractor. Are products sent "naked" to the subcontractor who then packs the devices in Tyvek pouches? If so, at what stage do you perform bioburden testing since your devices could easily pick up some bugs while packaging.

Q

 

[gitgiv]

Thank you very much Qara123 for the informative (and reassuring) answer!
We already notified the FDA. For you second question - with both manufacturers - the former and the current - the catheters were/are being put in Tyveks in the clean room at the end of assembly and sent to the packaging sub-contractor for closure, so nothing has changed in terms of packaging. You're right to think that bugs can enter on the way, but it has been proven before that even then the sterilization is valid.

 

[Qara123]

If possible, could you let us know whether FDA requested a sterilization re-validation or FDA accepted your rationale for not re-validating?

It would be valuable (non-proprietary) information that we can add to our knowledge.

Hope you get the FDA response that you want.

Q

 

[csterling]

Hello guys,

This discussion is in perfect timing for me, because we are in the same process of changing manufacturing site, but keeping the sterilization site. We have being debating if a rationale for not doing a full sterilization revalidation is enoug or not.

Has the FDA responded back to you on this issue?
It would be great to receive feedback on this.

Thanks in advanced.

 

[medwise]

In addition to DougTrof statement "Per ISO 11135-2, a requalification study may be required if a change has been made in materials, manufacturing location, or processing method which may impact the product bioburden resistance. The study results should determine the extent of physical or microbiological requalification required, i.e. full qualification, no requalification, or reduced microbiolocical performance qualification (fractional or half cycle exposures). It is common to do an annual validation review to ensure inadventant process changes have not occurred. " I will do bioburden test on 3 different batches produced by the new manufacturer and compare it with the old manufacturer.

In my opinion, the manufacturer of this device in your case is just a raw material supplier not a legal manufacturer. Therefore, the onus of risk management is on you as you are releasing the finished sterile product in the market. In the risk assessment, if you can establish that raw material made up of same material, design is identical, manufacturing process is similar including supplier's environmental monitoring, same packaging material with same packaging process and your ETO process is as per the validated method. Then you have a good case of not performing the re-validation for now. This should all be covered when you do you annual/ periodic validation.


Hope I have been of help.

Regards
Romit

 

[MIREGMGR]

A numerically comparative bioburden study comparing two different-manufacturing-site product versions, by itself, is not a valid way to determine their comparative sterilizability.

Numerical bioburden studies do not establish the character of the bioburden...only its numbers. Some kinds of bioburden are much more difficult to sterilize than other kinds. You cannot assume, without evidence, that two manufacturing sites, likely with different material suppliers, different layouts and housekeeping procedures, different personnel, etc., have qualitatively similar bioburden environments.

Only a numerical comparison plus a comprehensive type-characterization (i.e. microbial identification and quantitative apportionment) would support a conclusion of comparable sterilizability...and that would be at least as difficult, and still less reliable, than just doing a mini-re-validation in the first place.

 

[JulieChisholm]

Has your new CMO provided any guidance? I've found that some of my vendors work with many, many companies and have seen the gamut in terms of what people are doing when they make the switch. Recently I had one that provided a suggestion to mitigate risk without adhering fully to a standard.

 

[iamtroll]

Has your new CMO provided any guidance? I've found that some of my vendors work with many, many companies and have seen the gamut in terms of what people are doing when they make the switch. Recently I had one that provided a suggestion to mitigate risk without adhering fully to a standard.

Along the same line of thought that Julie has taken, consider consulting with your sterilization provider. If you have a good relationship with them, they should be able to point you in the right direction as I'm sure that they have also seen many variations of re-validation or justification not to re-validate.