Terminal Sterilization


I have terminal sterilization process for small volume and large volume can i know reference for terminal sterilization, as we are using 108/106 degree temperature (Super heated water spray) for 60 mintutes sterilzation, is this ok.

These super heated spray autoclaves have evolved from Retorspray chambers which is called retort sterilization. These are generally good for packing of precooked food materials.

All you need to know that after sterilization you have to prove that there was a minimum 3-5 log reduction of bioburden.
If you can test a vial prior to sterilization and then after sterilization you can prove it yourself at lab.
If you prove it is performing as per guideline its very good.

Which guideline preferred for the same can you provide the temperature vs time chart for sterilization

Temperature and time of exposure should be validated by your QA and Microbiology staff. I do not have any chart with me to give it as refference. All you need to show the regulatory auditor that your exposure temperature and time regimes are good to attain desired level of sterility assurance in your terminally sterilized product. It also depends up on loading patterns, your sterilizer design, rate of heat loss from sterilizer, temperature and times of exposure etc.

I have super heated water spry sterilizer
our sterilization temperature is 108 , is there any reference or guidelines to determine the acceptable temperature variation during heat penetration study

Your sterilizer is adopted from Food Industry to sterilize Cans(Foods packed in Cans).
This is called a Retort. You need to look guidelines in food industry.
A company by name JBT is one of the leading masters in this technology.

Your cycle is typical cycle for termal labile product. You can refer to Decision trees for the selection of sterilization methods, Annex to note for guidance on development pharmaceutics, EMEA 2000, Validation of Moist Heat Sterilization Process: Cycle Design, Development, Qualification and Ongoing Control, Technical Report No. 1, 2007 Revision, Parenteral Drug Association, May/June 2007 and EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use, Annex 1 Manufacture of Sterile Medicinal Products.

Regulatory exects a Probability of a Non-Sterile Unit [pnsu] of not more than 1 in 10at6 units or for EMEA Decision trees for the selection of sterilization methods, minimum Fo is 8 minutes. Your cycle has Fo about 2,3 so you must prove that it is efficient enough to kill all bioburden and to has safety margin that provides Probability of a Non-Sterile Unit [pnsu] of not more than 1 in 10at6 units.
So, first, your bioburden must be under control, assume that production is aseptic. You must have low limit for bioburden. You must perform temperature mapping to find worst case location for minimum and maximum load and you can use in house BI to prove BIO log reduction. If you use comercial BI as b.subtilis you cycle will fail because your low Fo values are not enough for that BIs. Your cycle must be under control- for worst case location you must have criteria for temperature / time.
From my experience with regulatory, lowest expected Fo value is at least 4 and it is better to develope your cycle according to that parameter if you can (related to temperature / time). Fo 4 gives you at least 8 log red for D value 0.5, so with assuemed bioburden 10at6 you can calculate 6 log for B.subtilis . Be aware that we talking about Fo for 121oC and D for 121oC.

Dear joksavs

Thanks for reply, I am sharing some data and enclosed justification with you so you can understand my status and suggest the best practice accepted by regulatory auditors:

We have LVP products with LDPE primary packing with three stage 0.22 micron filtration system. Bio-burden before terminal sterilization is nil or 01-05 cfu. ( products & LDPE are heat sensitive.)

Cycle temperature 106°C for 60 minutes BI (Bacillus subtilis 5230) with D value 11.3 minute and Z value = 8.5°C

Akhilesh Kushwaha
Quality Assurance

low temperature spore news.pdf (230.5 KB)

Dear Akhilesh Kushwaha,

I dont have information for you lowest Fo or how your temperature in the coldest points is going. BI that you mention can have growth because D value is for 106oC arround 11minutes, so you have for 60 minutes about 5-6 log. I suppose that your temperatures are above 106oC and because of that you don’t have growth.
If you have met both requirements, then your process is under control, but be aware if your D value is higher (deviation up to 20% are listed) and temperature is lower (on the lower level) you can have growth.
Resistance Performance Data from Messa lab says that you need more then 64 minutes to kill this BI.
My suggestion is to prolong cycle if you want to use this BIs for validation.