Picture this: It’s the 1940s. A pharmaceutical factory is producing penicillin. One round of production is just over and the workers are in the process of dismantling every pipe, piece of machinery, and process vessel that was used in the manufacturing process. Each of these will be manually cleaned and sterilised to adequate standards, to be put back together painstakingly before the production of the next batch of penicillin. Only for the facility’s workers to repeat the entire dismantling, cleaning, sterilising, and reassembly process all over again after this production run.
Aren’t you glad we have SIP systems now?
The decade after our imaginary scenario brought with it the SIP system, or sterilization in place – a game changer for the food and beverage and pharmaceutical industries which required frequent cleaning to adhere to stringent sanitary standards.
The manual method of going about sterilisation was just too cumbersome, labour intensive and time consuming. Not only did it introduce the possibility of contamination during reassembly, but it also took away from what could otherwise have been productive time for the equipment – be it a heat exchanger, compounding vessel, bio kill system, or bioreactor.
What is sterilisation in place?
Before we address the question of what SIP systems are, let us first understand what sterilisation is.
A device, product or piece of equipment is considered sterile when it has absolutely no trace of active microorganisms in it. The complete absence of bacteria, viruses, yeasts and other microbes is achieved via chemical, thermal, radiation or filtration methods – with the method selected depending on the physical properties of the material in question, like its heat stability and tolerance to chemicals. Regulatory acceptance criteria assess sterility based on calculated contamination probability.
Now, sterilisation in place refers to the in situ sterilisation of manufacturing equipment (and all allied elements in the system) without its disassembly. It is a critical aspect of meeting current Good Manufacturing Practice, or cGMP, requirements, and is particularly important in areas where germ reduction transforms the safety or efficacy of the final pharmaceutical preparation. Often carried out by means of superheated steam in the pharma, biotech and F&B industries, SIP systems permit the whole processing system to be treated as a single entity, minimising the need for aseptic connections and post-sterilisation handling.
An SIP system goes hand-in-hand with a CIP, or clean in place, system. SIP is ordinarily an extension of the CIP process, and ensures than any microorganisms still left behind in the system after CIP are eliminated with hot water, saturated pure steam at a temperature greater than 120°C, or whatever other mechanism is employed.
What does the sterilization in place process involve?
As we mentioned earlier, the specifics of the sterilization in place process vary depending on the mechanical properties of the equipment, the nature of the pharmaceutical preparation being produced, and the level of sterility demanded by the process.
In pharma and biotech, thermal sterilisation is fairly common. Industries may also rely on radiation sterilization via X-rays, electron beams, or gamma rays. Sterile filtration may rid the system of larger particulate and microbial contaminants. And when none of these methods is practical, those in sterile industries may rely on chemical sterilisation.
We’re sure you want to know more about the specifics of different methods, so let’s take a tiny glimpse into the mechanisms SIP systems may employ:
- Steam (moist heat): thermal sterilisation is of more than one kind. Of these, steam is the most commonly used as an SIP system for large scale processes. Usually, bioreactors, holding vessels, sterile bulk production lines, and sterile delivery lines all use this form of SIP system. In all these cases, steam sterilisation is followed up with air removal, condensate discharge and steam removal – all usually automated, at least to some extent – to prevent post-SIP contamination.
- Superheated water: Water heated above its boiling point and pressurised in a way which maintains its liquid state is often used for sterilisation of purified water systems and water for injection. The superheated water is circulated through all the equipment, piping, vessels, filters and process components to rid them of any residual contaminants.
- Dry heat: Dry heat, meanwhile, is provided via HEPA filters for the sterilisation in place of pharmaceutical spray dryers.
- Gas: Equipment which cannot take high temperature-pressure sterilisation – these could be certain process vessels of freeze dryers – are subjected to gas-phase sterilisation using gases like ethylene oxide.
- Chemical liquids: Liquid chemical sterilisation in place is used only in those situations in which liquid sterilant toxicity is not a problem. It is employed only in systems in which internal surfaces can come in complete contact with the liquid sterilising chemical.
- Chemical vapours: Vapours of hydrogen peroxide or peracetic acid may be used in the same way as sterilising gases. When used, it is critical that off-gassing is also carried about appropriately so that toxic sterilising substances don’t contaminate the pharma equipment or product.
How to choose the best SIP system for pharma?
Understanding the sterilization in place process, as you have done so far in this blog post, is the first step towards making an informed SIP system procurement decision. But here are some more things to look out for, some insider strategies, that will help you make sure your SIP systems will, in fact, serve your facility’s purposes well and for a long time to come.
- Combo CIP + SIP system
CIP and SIP systems go together. SIP is just a natural extension of the clean in place process, so always go for cleaning systems which integrate the two and minimise your and your staff’s work in the long run. Combos are the way to go!
- Comprehensive sterilisation
Cleaning and sterilisation are holistic processes. You can’t sterilise your compounding vesselswithout also sterilising the holding vessels, process piping, valves, filters, hoses, skid components, and any other surface that your pharma preparation may come in contact with. This means that sterilisation may have to be carried out in sections, with adjacent sterilisation processes overlapping, so that not a single spot is missed. Comprehensive sterilisation will keep your product safe from cross-contamination from prior batch residue, cleaning agents, and cell debris.
- Design considerations
You want to ensure that the SIP systems you invest in are intelligently designed. There are tiny design considerations that reveal a manufacturer’s attention to detail. These include static or dynamic spray balls which work together with desired temperatures, spray concentrations, and time duration. Also, the system should ideally include mechanisms for complete displacement of entrapped air and elimination of condensate build up. Customisations which include single or multiple tank and pump design also allow you to tailor the system to perfectly suit your needs.
- Complete qualification and validation package
It’s not important that your equipment manufacturer only claims that they have what it takes to meet your SIP system needs. Make sure you go for a manufacturer who provides you with complete validation documentation, facilities for cleanroom FAT, as well as the life-cycle benefits of Annual Maintenance Contracts, or AMCs, and the provision of spares as and when needed. Your purchase of an SIP system should not be the end of your journey with your supplier; in fact, it can be the beginning of a long, fruitful partnership to maintain the sterile integrity of your facility and products. TSA provides best-in-class CIP and SIP systems for all your pharma, biotech and other sterile manufacturing needs. We love a good process or high purity challenge, and we would love to wrack our brains about yours. Reach out to us today.