Thermo Fisher Scientific Inc. (TMO) Earnings Call Transcript & Summary

Hello, everyone, and thank you for joining us for today's webinar, a Quality Roundtable: Optimizing Biologics Manufacturing Processes with Raw Materials. Now I'm Miles Szkoda, I'm your host from Bioprocess Online and Life Science Connect, but it's going to be an easy one for me today. So basically, with that, I'm going to hand it over to our moderator for today, to introduce herself and the subject better experts that we have with us today.

Thank you, Miles. Hi, everyone. We appreciate you taking time out of your day to join us for this critical topic. I'm Dion Aviki, the General Manager of Production Chemicals and Services for BioProduction at Thermo Fisher Scientific. Joining us today are several subject matter experts from Thermo Fisher Scientific. Kasey Kime, is the Director of Regulatory Affairs for Cell, Gene and Advanced Therapies; Mike Brewer is the Director and Global Principal Consultant for BioProduction; and we have Dr. Jai Murthy, the Director of Product Management for cGMP Chemical Sourcing for BioProduction. They will be answering questions live that you've sent in with your webinar registration as well as those questions you are able to send through the chat feature of this webinar, that are focused on optimizing biologics manufacturing processes with raw materials. [Operator Instructions] Finally, the webinar will be available for on-demand viewing. You'll receive a link via e-mail as soon as it's available. Okay. I think we're ready to get started. The first question to our experts is, how early in your commercial process development, you start thinking about the raw materials and critical reagents that are going to be used in your manufacturing process? Let's start this off with Kasey.

Hi, Sam, I don't think it's ever too early to start thinking about your critical raw materials. So my advice is to review supplier documentation as early on as possible. That's going to help you identify, if there's any potential CMC gap with your raw materials. And that's going to help you when you're planning your filing. So you're going to be thinking about those CMC factors early on. Remember to consider the grade of material and also the manufacturing conditions. So while we know that research use only materials can be used in early phase, eventually, the regulators will want you to move to a higher quality grade material made under GMP manufacturing conditions. So if you can start with the highest quality grade materials as early as possible, this will help you avoid the need for change. And naturally, you want to sidestep initiating any kind of comparability studies based on raw material changes alone, particularly when you can avoid this way strategic planning.

Thank you, Kasey. Very insightful. Mike, what are your thoughts on this?

Yes, I always tell people to try to identify instead of critical on potential critical quality attributes early in the process, you're developing your scale-up for your cell culture. Things like tighter in glycan profile aggregates, et cetera, for mAbs or recombinant proteins and potency, viable cell titer as an example for cell-based products. Make sure the attributes you select correlate with your product candidates' performance as a pharmaceutical pharmacokinetics, pharmacodynamics, potency potentially for cell therapy. But what this will allow is it will enable meaningful comparisons when you're screening raw materials, bring optimization of your cell culture process and also in selection of secondary materials or suppliers where when that's appropriate. Early optimization and understanding of critical variables that could impact CQA, or critical process parameters, helps you reduce the risk of having to make change later. And the further you go in clinical development, the more rigorous the change process becomes. So early is always good.

Thank you, Mike. The earlier, the better. All right. With that, let's move to the next question, and Mike will stay with you on this one first. What are some key considerations for raw material selection?

Yes. And I'm going to I'm going to cover a couple, and I'm going to let Jay address a couple -- a few of them as well. But I look at things like you're using supplements, feeds or peptones in your cell culture process, especially around peptones tend to be more variable from vendor-to-vendor. So you should try to select the appropriate peptone for your process early. Talk to your supplier around, if you need a custom formulation, and your [ media ] and your supplier provide that for you, they have experienced some custom formulations, not just their catalog or stock formulations. Working with your supplier and form a close relationship around supply chain. Supply chain forecasting partnerships are critical. It's even more important as product demand increases and processes are scaled up or scaled out. Regulatory support from your supplier can be critical, both on the internal manufacturing compliance side as well as implementation and validation, support of regulatory filings from my side. Thick redundant manufacturing sites are something that you should inquire about. There's no substitute for being prepared, if an issue comes up at the primary site. Auditability, that is your supplier's open and willing to be audited. Most of them in this space should be able to answer that in the affirmative, and their experience and success, supporting successful audits from regulators or from customers, is something that you should look for. And then I'll kick this over to Jai, and he -- there's a couple more topics for him to cover.

Yes. Yes. I think that thematically, you really want to look for suppliers and raw materials, which can help you reduce your risk as you go from -- going to scale up. So for example, you want to make sure that the suppliers you're dealing with have the ability to produce the volumes that you need for your commercial scale manufacturing. Additionally, if there is a supply disruption for one type of material, you want that material to have, at least, a secondary source, if not more. So you need to consider a backup supplier. And of course, when it comes to derisking your supply chain, you want to make sure that you have cGMP facilities, cGMP-compliant warehousing and any type of business continuity considerations that you have to make sure that one site goes down, another side is able to provide you with the raw materials that you need to manufacture.

All right. Thank you, Jai. That shares of supplies, definitely important manufacturing. We move on to the next question. And Kasey, I think this is right for you to answer. What are some of the key quality and regulatory documentation that is needed to support raw materials in clinical manufacturing?

In terms of the key quality document that I'd recommend, it would be a lot specific Certificate of Analysis. So you need a CFA for every single raw material used in your manufacturing process, as part of your preparation for your filing. And for regulatory, we want to consider things like whether your supplier offers master files because these can be a very efficient pathway for both the drug developer and the supplier. But we know that not all regions have the ability to lodge raw material master files. But just consider discussing with your supplier if they have that ability. If they don't have master files, but discuss with them how they plan to support you for your clinical manufacturing. It could be things like access to regulatory support files under a CDA. But the earlier you can have these discussions with your supplier, the better.

Thank you, Kasey. All right. This next question, I'm going to come back to you on this one, Kasey. This is a really good question. This comes up, but we all know changes are inevitable. What are some of the tips that you have for managing change?

Okay. I can think of 2 tips here that I would recommend. So my first step is to really understand the criticality of your raw material in your process and the risk to product quality. So not every raw material will carry the same risk weight in your process. The raw materials that are capable of influencing CQA, or CPPs or those that are part of your established conditions, are going to hold more significance than those with minimal impacts. So that criticality of the raw material is linked to the process of change management in the regulatory filing. So that leads me to Tip 2. So when possible, try and aim for maximum regulatory flexibility when registering your non-compendial raw materials in your filing. By this, I mean instead of registering a raw material by its brand name or its part number, you can opt to register it based on its functionality and its critical material attributes. So this approach will give you more room to maneuver, if you found multiple raw materials that can meet your required material attributes, because it's about strategically positioning yourself for that maximum reg flexibility. But at the same time, simplifying your raw material change management where possible.

Thank you, Kasey. That added flexibility can be extremely helpful. Great tips. The next question coming in is very -- it's along these same lines, but -- and Kasey, I'll stay with you on this one, and then I'll move to Dr. Murthy. What are some of the tools one can use to select raw materials?

Okay. So the best tools that I'm aware of are one is based on quality risk management. And I can think of 2. The first is the bio form risk assessment guideline. And what I like about this guideline is it gives a very holistic overview of raw material risks. So it includes things like the functionality of the raw material and the level of characterization. It gets you to consider we're about in the process your raw materials used, for example, upstream versus downstream? And then it delves into overall supply chain considerations like whether you're material single-sourced or multisourced whether it has a long lead time and whether your supplier is experienced in supporting pharmaceutical manufacturing or not. And so I really like that one. It's very holistic. It's a very good tool. The second tool that I'm aware of is found within the USP General Chapter 143, which is a chapter specifically around ancillary materials used in Celgene and tissue-based products. And within that general chapter, it has a section on risk and it breaks the risks of different raw materials into tier groups. And it gives you really good advice of how to move from 1 tier group to the next with Tier Group 1 being the least risk and Tier Group 4 being the highest risk. So it gives you very good advice of how to move something from a Tier Group 3 into a 2 or 2 into 1. So they are 2 really good tools that I'm aware of that I use in my job.

Thank you, Kasey. Jai, what are your thoughts?

Yes. So in terms of looking for a successful partnership and a supplier of raw material supply chain, you really want to look for a proven track record of success with the supplier. We want to make sure that your suppliers have contingency planning in case of supply challenges. We noticed this during the pandemic, of course, that there are a lot of supply challenges. And the most successful suppliers were the ones that had contingency planning in place, the ability to pivot and to provide their customers with raw material supply. Additionally, technical resources like technical field specialists and application scientists to work specifically with your unique processes in order to make sure that you have the right products and the right supply chain organized to meet your manufacturing needs. And lastly, making sure that you have cGMP compliance storage and sampling support to provide flexibility to you as a manufacturer.

All right. This next question, I think is very applicable to all 3 of our panel members today. So I will ask for all of you, and this will start with Jai. What are some of the key things to look for when selecting a manufacturer or supplier of raw material?

Well, I already mentioned a lot of the points already in my previous response. I think that you really want to make sure that the supplier can grow with you, that they have the ability to manage our regulatory requirements, like if you have a need for regulatory support for an audit. Some of these themes have already come out today in today's discussion. And you want to make sure they can do the change management. So any kind of change management, change notification capability. That's very, very important as you deal with the regulatory agencies.

Thank you, Jai. Mike, what are your thoughts?

Yes. I think building out of Jai's comments, technical support capabilities, especially experienced technical support capabilities can be so important. From technical sales specialists work with you on procurement, but also partnering with you on your supply chain, on your forecast, experienced field application scientists to help you develop your process and regulatory support. And it's not just in developing the processes and support during a regulatory review, but also in the future potentially for change control and potential comparability study design.

Thank you, Mike. Kasey, what's your perspective?

I guess I'd like to really highlight scale. So the ability to scale to meet commercial demand for drug developers, particularly in the field of advanced therapies because we know a lot of these therapies are eligible for expedited drug development, meaning they move very quickly through the clinical trial phases. So it's really important to consider whether your supplier can scale to meet your commercial demand and your commercial time lines that planned expedited approval date. So I know with Thermo Fisher, we've seen requests to scale up 5x in as little as 3 years for some cell culture media products that are used specifically in advanced therapy manufacturing. But I also want to touch on that change management piece that both Jai and Mike have already mentioned because robust change management is a requirement to manage your post-approval CMC obligations. So occasionally at Thermo, we'll observe instances where late-phase customers have not subscribed to change notifications. And that can be quite detrimental because I'll face an unnecessary challenge of, say, an unexpected comparability study because a change has been made to a raw material, and they weren't prenotified of that change. So change notification and that ability to understand all of that is really important.