API sterilization is a very niche market. But when it’s needed, it must be done right. Sterilization a crucialis a crucial step in the manufacturing of certain drug products and is key to ensuring patient safety. 

Over the last few years, Teva API has been developing a state-of-the-art sterilization facility in Croatia that was built purely for this purpose. The site has recently started manufacturing two products with the potential for a much larger capacity. This facility is a unique and rare asset in the pharmaceutical market, complete with complex technologies that are not commonly seen. 

Background of the Facility: 

The project started from the ground up in 2016. Over a three-year period, the facility was designed and built, equipment was purchased, and the cleanroom and equipment installation was completed. From 2019 to 2022, the focus was on qualification activities, process simulation tests, and low volume manufacturing activities.  

In 2023, the site successfully received a manufacturing license, in line with all regulations including the recently updated Annex 1, allowing Teva API to begin to produce and distribute GMP material.  

The intention from the outset was to cover TEVAs own API’s as well as offering our services to third parties (CDMO).  

The Facility: 

The sterilization line is fully automated and operated in a completely closed environment where everything is controlled — from equipment to material. This is to ensure that no foreign particle or biological contaminant is introduced into the process and end material. 

Regulation is obviously one of our top concerns. The facility has an excellent regulatory record, with stringent quality and safety considerations incorporated throughout every aspect of the process, in close coordination with national and international health authorities.  

The construction material used in the facility is Hastelloy, rather than standard stainless steel. This allows for more flexibility in selecting the process, solvents, APIs and PH as Hastelloy is a much more endurable stainless steel.  

Another important element is that we have validated the plant to operate with OHC level 4. This means we can meet the requirements of the environment outside the isolator, which allows us to have maximum 1-10 micrograms of the API inside the cleanroom.  

The first out of two sterilizations line can deliver batches ranging in size from 5-35kg.   

The aseptic filtration process 

There are several different methods which can be used to sterilize APIs — such as dry heat, moist heat, and Gamma irradiation. At Teva api, we offer the noninvasive high-performance aseptic filtration. With this method, the API is not damaged, and no new impurities are formed. 

First, the API is dissolved. The solution is then filtered through a 0,22 micron membrane, which removes all biological contaminations. The API is then crystalized, dried, and micronized according to the particle size distribution (PSD) level requested by the customer. We can accommodate a wide range of PSD specs. 

Since the majority of sterile APIs we’ll be producing, will be used in their final form as suspensions, one of the key parameters is PSD, i.e. the size of the crystal. One of the first things we do with a potential customer is to evaluate the specification and see if we can fit the PSD request.  

Of course, we run a closed process. We use isolators throughout the entire process to ensure sterility and minimize the risk of contamination. It’s a grade A environment, of course, and the background of the isolators is a grade C.  

Packaging: 

Once the API is ready, there are two primary packaging solutions available for these sterilized products.  

The first is a multilayer 5-liter PE bag, and the second a 5-liter aluminum container that is stoppered and crimped. They both arrive to the site gamma irradiated and are then filled with the product and wrapped 4 times.  

To discuss our sterilization services further with a member of our team, please contact us. We’d love to hear what your needs are and see how best we can support you! 

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