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Episode 6 – “Current State and Trends Impacting Fill-Finish from Formulation through Commercialization”

Participants

  • Guest: Parrish Galliher, Independent Bioprocess Consultant
  • Hosted by: Rizwan Chaudhrey

Rizwan Chaudhrey: Hi everybody, this is RIzwan Chaudhrey and you are listening to the Fill-Finish Podcast sponsored by ApiJect. The show that shares expertise on all aspects of injectables, vaccines, and aseptic fill-finish.  Season One is offering 10 episodes focused on topics including facility design, regulatory, quality, supply chain management and AR/VR to name a few. And so I’m delighted to be joined by Parrish Galliher, an independent bioprocess consultant and we are going to be talking about the current state and trends impacting Fill-Finish from formulation through to commercialization. So Parrish, first of all it’s lovely to meet you. How are you?

Parrish Galliher: Very well, thank you.

Rizwan Chaudhrey: Well, Parrish, before we start talking about the impact of fill-finish and the trends, would you mind giving the listeners a quick overview of your role and your business?

Parrish Galliher: So, I’ve been in bioprocessing for over 40 years in four different drug companies, I helped bring two drugs to market, built a number of stainless-steel facilities and single-use facilities, and I started my own company 20 years ago in single use manufacturing and sold that to GE Healthcare couple of years ago. Right now, I’m an independent bioprocess consultant.

Rizwan Chaudhrey: Fantastic. So, my first question for you is what are the different types of fill-finish technologies available right now?

Parrish Galliher: So, there are a number of them. The traditional fill-finish technology is an open vial process where vials are filled in the open in a class 100 clean rooms suite with operators standing in that suite servicing the production line as it operates. Another approach is to put all of that production line in an isolator and use robotic machines to do the filling and the maintenance and the stoppering and capping of the vials after they are filled. So, those are the two main filling approaches today.

Rizwan Chaudhrey: Right, what are the capital costs of those different technologies? Is it very different?

Parrish Galliher: Yeah, it is very different. The open vial filling is the highest capital cost process because of the expense of the cleanroom facility and the operational expense to maintain that clean air. And the machinery that does the filling and the processing of the conveyors and processing the vials is very capital intensive. By comparison, the robotic approach to the closed cleanroom with robots is quite a bit less expensive and it does not require being placed in a very cleanroom space, so that reduces the capital costs of the facility in which it sits.

Rizwan Chaudhrey: Right. So, what are the main strengths and weaknesses of the different technologies?

Parrish Galliher: I’m sorry, which technology?

Rizwan Chaudhrey: Of the two technologies. What are the strengths and weaknesses of each of them?

Parrish Galliher: So, the open filling technologies weaknesses are that the vial is exposed to the environment. So that can jeopardize the quality of the product if it’s infected with a dust particle containing bacteria or fungi. That’s the main objection against open vial filling. The other weakness, of course, is the validation is is very expensive on top of the capital costs because you got to validate a very clean environment and demonstrate that it does not contaminate the vials that are being processed.

Rizwan Chaudhrey: Okay, what are the strengths, for it, though?

Parrish Galliher: Well, the strengths are that you can do very large-scale fills with open vial filling. So, open vial filling facilities can do 10s of thousands to 100,000 vials a day because of the high throughput machinery, and that of course is very good for reducing cost of goods and supplying big markets.

Rizwan Chaudhrey: And with regards to the robotic use of technology, what are the strengths and weaknesses to that?

 Parrish Galliher: So, the weaknesses are it’s not as large-scale, so the robots cannot work as quickly as you can operate an open vial filling line. Robots move methodically within the within the chamber and do the vial placements and the vial filling in the vial stoppering and capping. So, those machines are limited in their speed. The other weakness, of course, is that you need to clean-in-place the entire chamber. That’s an expensive and time-consuming step. The strength of the closed chambers approach is that you have a much cleaner environment because there are no humans standing in the environment, and so the chances of contaminating a vial are nearly eliminated. And that’s, of course, increases the assurance of safety in doing the filling process.

Rizwan Chaudhrey: Now, you touched on it a bit earlier in your previous answer, but how do the cost of goods compare across the different technologies?

Parrish Galliher: Well, the cost of goods are lowest for open vial filling because you can do such large fills. You’re amortizing all of the overhead costs over many more vials of drug. Despite the fact that you have a high capital cost, which of course turns into a high depreciation cost, usually open vial filling gets lower operational costs. Compared to closed chamber filling, which is a smaller system as fewer vials per fill therefore the overhead costs are amortized over fewer vials which drives up the cost per vial.

Rizwan Chaudhrey: OK. Now let’s talk about validation and how do the validation burdens compare across different technologies?

Parrish Galliher: So, the validation of the open vial filling focuses on the validation of the clean air system that’s maintaining the environment over the production line since that’s critical to ensuring that the vials do not get contaminated. So that validation has to be done in both static and dynamic conditions to demonstrate the robustness of the HVAC filtration system in the production room. Validation of the closed chamber system includes environmental monitoring to show that the clean-in-place and sterilization in place of the chamber itself is effective and thorough and will ensure a clean environment for the filling operation of the vials. So, the focus there is on cleaning and sterilization validation compared to the open vial filling line.

Rizwan Chaudhrey: So, in terms of the facilities themselves, what are the actual differences in regards the facilities across the different technologies?

Parrish Galliher: So, in the open filling line process the facility is dominated by HVAC systems to provide all the clean air. You’re providing class 100 air over a large area and you’re fighting the contamination brought in by humans into that space. So, the facility systems and utility systems and open filling vial facility are more extensive and more expensive, as a result and cost more to maintain. The facility in the clothed chamber process is much simpler. It does not have to be any cleaner than class D, because the chamber itself is operating at a class one level of purity. That reduces the capital cost very significantly and it allows you to put a second or third or fifth or 10th chamber in that same facility. And that way you can amortize the cost of operations over many more filling chambers. That reduces the capital cost of the facility amortized over many more filling operations right.

 Rizwan Chaudhrey: So, Parrish. That’s fantastic. So, what do you see as the future fill-finish?

Parrish Galliher: The really exciting future is the ability to fill the vial when it’s closed. In other words, the vials are already stoppered, they’re sterilized, and they’re filled by injecting the drug through the stopper, backfilling the vial, and then withdrawing the needle and sealing the hole in the stopper. This is being commercialized by a company called Aseptic Technologies located in Belgium. Another company that’s taken that technology to the next step is Intact Technologies, they’re located in Connecticut. And with regard to them the FDA has reviewed their technology and has supported it very strongly and believes it is the future of vial filling. So, they’ve licensed them to do vial filling and also to do compounding of solutions in bags using this same stopper that’s by the filling needle and backfilled. That future looks very strong and very interesting and, of course, by having a closed stopper, you relieved a lot of the validation around maintaining clean air over the open vial process. There’s a great savings there.

Rizwan Chaudhrey: Brilliant. Well, thank you very much for talking to me today, Parrish. Now, if you want to know more about what you do and your solutions, how can we get hold of you?

Parrish Galliher: So, my email address is xlrxone@aol.com

Rizwan Chaudhrey: Brilliant. There you go. If you’d like to know more than you can get in touch with Parrish use that email address. And if you’d like to listen to more podcasts around fill-finish and related topics, please check out the Fill-Finish Podcast website, which is www.fillfinishpodcast.com, where you can hear other podcasts as well as put any topics that you’d like to hear more about as well and, hopefully, you can see that in future editions of the series. So, let me say thank you, Parrish, for your time today. Thank you, listeners. It’s been great to have you here, and until next time, goodbye.


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