Good day, ladies and gentlemen, and welcome to Repligen Corporation's fourth quarter of 2021 earnings conference call. My name is Chad, and I will be your coordinator. All participants will be in a listen only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. Please note that there will be a Q&A session following the company's formal remarks. To ask a question, you may do so by pressing star then one on your telephone keypad. In order to accommodate all individuals who wish to ask questions, there will be a limit to two questions at a time. Please also note today's event is being recorded. I would now like to turn the call over to your host for today's call, Sondra Newman, Head of Investor Relations for Repligen. Please go ahead.
Thank you, Chad. Welcome to everyone listening in today. On this call, we'll cover business highlights and financial performance for the three and 12-month periods ended December 31st, 2021. We'll also provide financial guidance for the current year, 2022. Repligen's President and CEO, Tony Hunt, and our CFO, Jon Snodgres, will deliver our report and then address questions. As a reminder, the forward-looking statements that we make during this call, including those regarding our business goals and expectations for the financial performance of the company, are subject to risks and uncertainties that may cause actual events or results to differ. Additional information concerning risks related to our business is included in our annual report on Form 10-K, which we filed today, and other filings that we make with the SEC.
Today's comments reflect management's current views, which could change as a result of new information, future events, or otherwise. The company does not obligate or commit itself to update forward-looking statements except as required by law. During this call, we are providing non-GAAP results and guidance. Reconciliations of GAAP to non-GAAP financial measures are included in the press release that we issued this morning, which is posted to Repligen's website and on sec.gov. Non-GAAP figures in today's report include the following. Revenue growth at constant currency, gross profit and gross margin, operating expenses, including R&D and SG&A, operating income and operating margin, contingent consideration, income tax expense, net income and earnings per share, as well as EBITDA and adjusted EBITDA.
These adjusted financial measures should not be viewed as an alternative to GAAP measures, but are intended to better enable investors to benchmark Repligen's current results against historical performance and the performance of peers when evaluating investment opportunities. Now I'll turn the call over to Tony Hunt.
Great. Thanks, Sandra. Good morning, everybody, and welcome to our 2021 year-end update. We are delighted with the way we finished off the year with 69% organic growth in the fourth quarter, 71% organic growth for the full year, and overall 2021 growth for the company coming in at 83%. Our base business continues to deliver above market growth with 42% growth in the quarter and 38% for the year, reflecting accelerated demand for our products on top of COVID tailwinds. Overall, 2021 was an outstanding year for the company as we continue to execute on our core business strategy of enabling our bioprocess customers with highly differentiated technologies. Let's cover some of the key highlights.
On the M&A front, we strengthened our market position in Filtration with the Polymem deal, in Proteins with the Avitide acquisition, and in fluid management with the BioFlex Solutions deal. We are well positioned as we enter 2022 to take additional market share with strong brand recognition, a reputation in our industry as the innovation leader in bioprocessing, and a growing portfolio of new products, mainly targeting gene therapy. Operationally, we increased our capacity between three and nine-fold across all our major product lines. This allowed us to support, in a very meaningful way, the ongoing fight against the pandemic with the company delivering approximately $190 million in product to the leading COVID vaccine manufacturers. The increased capacity also supported our base business growth, which was exceptional, with adoption by gene therapy customers being a key driver of this growth.
Our total addressable market increased significantly from $3.7 billion in 2020 to over $8 billion in 2021, driven by COVID market expansion, base business acceleration, and M&As that have allowed us to expand our markets. Finally, 2021 was all about increased commitment in the area of safety, sustainability and DEI. We published our first sustainability report in Q4. Some highlights in the report include a reduction in carbon emissions of 12% versus our baseline year in 2019, the conversion to 100% renewable energy at four key sites, and the launch of our diversity and inclusion initiative. In 2022, we will focus our efforts on DEI initiatives, moving to 100% renewable energy at additional sites, packaging, and single-use recycling programs.
Before jumping into our business highlights for Q4 and full year, I want to spend a few minutes on the strategic initiatives that we have highlighted at the beginning of the year. Number one was around building out our capacity to support our business unit growth. Number two was around increasing our market traction in gene therapy. Three was around launching disruptive technologies from our R&D pipeline, and four was around integrating EMT, NMS, and ARTeSYN into Repligen. Let's start with our progress on capacity. Our goal, like many of our peers, was to rapidly expand capacity across our product lines. The progress we made was significant, especially in the area of Filtration, where the combination of Polymem acquisition and the expansion programs at our Rancho site increased our hollow fiber capacity over nine-fold.
We also brought our European OPUS manufacturing facility online, and by the end of 2021, 90% of our European customers had qualified in Breda for production of pre-packed columns. Much of what we accomplished last year came from a combination of increased efficiency and expansion of our workforce. In 2022, we expect to spend an additional $60 million-$70 million to complete the majority of our site and capacity expansion plans. This includes adding more Filtration space in Rancho and Marlborough and opening up our first assembly center for fluid management in Hopkinton, Mass. In cell and gene therapy, we increased our market presence with overall growth close to 40% for the year, driven by our Filtration and Process Analytics portfolios and increased traction in Asia. We successfully focused our efforts on acquiring new customers, adding about 50 new accounts during the year.
We finished 2021 with approximately 100 significant accounts, up from 70 in 2020. With our gene therapy application center up and running and a focus in the industry on scale-up, we expect growth to be north of 30% here in 2022. New products continue to be a core pillar in our overall strategy. In 2021, our R&D team delivered on three key programs. The first was around launching the FlowVPX platform, which is a GMP compliant inline analytics system, which has been quickly adopted by our customer base on the manufacturing floor. Second was working with Navigo and Purolite Life Sciences to launch the industry's first Protein A resin to effectively purify pH sensitive monoclonal antibodies, overcoming aggregation challenges. The third was around optimizing our ARTeSYN custom systems to deliver on a portfolio of standardized Chromatography systems.
We expect 2022 to be another strong year for R&D as we focus on launching a family of AAV resins, which we announced earlier this week, and expanding our ARTeSYN family of filtration systems, reinforcing our position in bioprocessing as the innovation leader. Finally, on the integration front, we successfully completed the integration of EMT, NMS, and ARTeSYN into Repligen. The combined business performance came in as expected, up approximately 26% on a pro forma basis, while contributing in a very meaningful way to the manufacturing of internal Repligen products. The integration of EMT and ARTeSYN was a key focus for us in 2021, with the build-out of both our Clifton Park, New York and Waterford, Ireland sites to address the growing need for single-use flow paths in our industry.
With the addition of BioFlex Solutions in late 2021, we now have a broad portfolio of fluid management products, and we plan to move these products into a new franchise for the company here in 2022. Moving now to Q4 and full year business performance. As reported today, we had a record quarter with nearly $187 million in sales and overall growth of 72%, with all four franchises delivering exceptional performance in the quarter. Within our base business growth, gene therapy revenues were up 85% in the quarter and approximately 40% for the year, reinforcing our market position and demonstrating accelerated traction for our products, especially in the second half of last year. COVID related revenues also increased in the quarter, driven by increased demand from COVID vaccine customers and increased production output coming from our Polymem facility.
COVID demand accounted for 33% of our revenue or 34 points of total revenue growth in the quarter. For the year, COVID revenues increased to $190 million, representing 28% of our overall revenue. We continue to see strong demand from our COVID customer base and expect that COVID accounts will contribute $200 million-$220 million in revenues for the company this year. On the orders front, we finished the year up approximately 80% year-on-year, with base business orders growing at 40%. In the quarter, base business orders were up over 20% off a tough comp in Q4 of 2020. Sequentially, COVID orders were down following a stellar Q3 when the majority of COVID orders for 2022 were placed.
Our COVID order book for 2022 is now over $180 million and very much in line with our expectations for the year. Moving to franchise level performance, whereas of this report, we are placing revenue from Avitide and Affinity Resins, which to date have been in Chromatography into our Proteins franchise to better align with our affinity ligands business. Our Chromatography franchise will now consist of OPUS prepacked columns, ARTeSYN chromatography systems, and ELISA kits. Our Chromatography business had a solid quarter and was up 29% for the year, excluding the contribution from Avitide and Affinity Resins, and up approximately 40% if these products were included. Within Chromatography, our OPUS revenues for full year 2021 increased by 22%.
In the quarter and throughout the year, we have seen strong demand for our largest OPUS 80 columns as more customers put OPUS into late stage in commercial processes, including COVID vaccines. The main challenge we are dealing with continues to be the extended lead times on resin availability from the top suppliers. We expect that the resin supply issue will improve as we move through 2022, which will accelerate growth for OPUS in the second half of this year. We expect our Chromatography franchise to grow in the range of 25%-30% for 2022. Our Proteins franchise had another strong quarter and finished the year up 48% with the Avitide and Affinity Resins included and approximately 40% excluded. 2021 was a pivotal year for us as we executed strategically on many fronts. First, we signed a new supply agreement with Cytiva.
Second, we developed a new ligand and launched our NGL high pH resin with Purolite. Third, we acquired Avitide, increasing our affinity content. In 2022, we expect that demand from Cytiva will decrease and will be mostly offset by Avitide revenue and continued traction in the marketplace for our NGL ligands. Overall, we expect Proteins to be down approximately 5% in 2022. Our Filtration franchise was the big growth driver for Repligen in 2021, up more than 100% in the quarter and over 130% for the year. The story of the quarter and the year was the continued momentum in the marketplace for our flat sheet cassette, hollow fiber, and systems products.
Key highlights in the quarter included the launch of our new KrosFlo FS system for flat sheet cassettes, the speccing in of XCell ATF into multiple next-generation commercial drugs, and the acceleration in gene therapy demand. For the year, we saw significant growth in COVID vaccine revenues, which comprised about 40% of our overall franchise revenue. With strong momentum in the marketplace, we expect the Filtration franchise will grow in the range of 25%-35% in 2022. Finally, our Process Analytics franchise had an outstanding quarter and year in 2021. Revenue growth was over 50% for the quarter and 44% for the year. The expanded commercial team has focused on new account development, which represented approximately 60% of Q4 revenues and driving our VPE technology into new application areas, especially in cell and gene therapy.
We continue to be encouraged by the adoption of FlowVPX, and we expect 2022 to be another strong year for Analytics, with growth of approximately 25%. Overall, we expect the company to grow at 19%-24% in 2022, including strong base business growth of 20%-22% and organic growth in the range of 18%-22%. As we move through the year, our strategic priorities will center on the following. Number one will be around building out our capacity to support accelerating growth in our businesses. Number two will be around successfully integrating Polymem, Avitide, and BioFlex Solutions. Number three will be around launching new products, including AAV resins and ARTeSYN TFF systems. Finally, number four will be on continued traction at cell and gene therapy accounts.
We believe we are well positioned to gain further market share in bioprocessing over the next three-five years, and we are confident about hitting our goal of $1 billion by 2024. Before concluding, I wish to recognize our 1,800+ employees around the globe, including our new colleagues at Polymem, Avitide, and BioFlex Solutions, for their commitment and leadership last year. I also want to thank our loyal shareholders and customers for their part in Repligen's success as we look forward to delivering another strong year here in 2022. Now, I'd like to turn the call over to Jon for a report on our financial performance.
Thank you, Tony, and good day, everyone. Today, we are reporting our financial results for the fourth quarter 2021, as well as providing our financial guidance for the year 2022. Unless otherwise mentioned, all financial measures discussed reflect adjusted non-GAAP measures. As emphasized in our press release this morning, we've again delivered record revenue of $186.5 million in the quarter and $670.5 million for the full year, as well as reporting strong earnings growth. Our base business strength was a highlight, up 42% in the quarter and 38% for the year. We also continued to support COVID vaccine and therapeutic programs with our technologies, with COVID programs accounting for 33% of our total revenue in the quarter and 28% of the total revenue for the year.
In addition to delivering outstanding revenue growth of 83% year-over-year, it has been an incredibly fulfilling year at Repligen as we've executed on our numerous capacity expansion initiatives. In 2021, we spent approximately $71 million in CapEx, of which about 80% was investment in capacity. We also brought several new innovative products to the market through our internal product development initiatives. We continue to spend approximately 5% of our growing revenue base on R&D, and 25% of our revenue in 2021 came from major product launches over the last seven years. In addition, we continued to expand our relationships with gene and cell therapy customers, who in 2021 represented 11% of our total revenue.
Finally, we've continued with our significant progress in acquiring and integrating new businesses and technologies. We are also pleased to have closed on our acquisition of BioFlex Solutions on December 16th, expanding our portfolio of fluid management products and bringing a previous supplier in-house. The BioFlex acquisition adds to an already impressive year in M&A with our strategic acquisitions of hollow fiber specialist, Polymem, and affinity ligand developer, Avitide, deals which were completed earlier in the year. In addition, here in 2022, we've completed our phase IV SAP implementation, going live with our Korea and India selling offices and our Auburn and Hopkinton, Massachusetts, locations in early February. Now transitioning to our fourth quarter and full year of 2021 revenue commentary.
For fourth quarter, we had revenue of $186.5 million, representing 72% reported and 69% organic growth, with inorganic acquisition revenue accounting for 5 points of growth and foreign exchange driving a 2-point headwind. To add further context to our fourth quarter growth, our base business contributed 33 points and COVID programs contributed 34 points. In 2021, our full year revenue of $670.5 million represents reported growth of 83% and organic growth of 71%, with 10 points of inorganic acquisition revenue and approximately 2 points of foreign exchange tailwind. Looking deeper into the components of our full year reported growth, our base business accounted for 34 points and COVID revenues contributed 39 points.
From a product franchise viewpoint, effective in this report and in our 10-K expected to be filed this week, we are shifting our Affinity Resins into our Proteins franchise from their historical positioning in Chromatography. This shift will better align our franchise reporting streams with total available market reporting streams that we reference. With this change in effect, we're reporting full year 2021 franchise revenue growth for Filtration at 131%, Chromatography at 29%, Process Analytics at 44%, and 48% for our Proteins business. As it relates to full year 2021 regional revenue growth for our total business, we continue to see positive traction in each of our three global regions. Revenues from Asia rest of world increased 136%, Europe grew 94%, and North America grew at 58%.
Concerning our total business regional revenue distribution for the full year of 2021, Asia represented 19%, Europe represented 40%, and North America represented 41% of our global business. Now moving down our income statement. Adjusted gross profit in the fourth quarter of 2021 grew to $105.2 million, an increase of $44.1 million or 72% compared to the same period in 2020. Adjusted gross margin of 56.4% for the fourth quarter was in line with the 56.3% level from the same period in 2020. Adjusted gross profit for full year 2021 finished at $394.9 million, an increase of $183.8 million or 87% compared to 2020.
Adjusted gross margin for full year 2021 was 58.9%, a 120 basis point improvement year- over- year. The improvement in gross margin was driven by strong volume leverage in our facilities, which outpaced capacity investments, most significantly in the first half of 2021. Now transitioning down the P&L to adjusted operating expenses. Adjusted research and development expenses for the fourth quarter and full year 2021 were 4.7% and 4.9% of total revenue, respectively. Our dollar level increases in R&D spend were critical to the launch of several innovative new products, including our XCell ATF lab scale controllers, FlowVPX, high pH affinity ligand, KrosFlo flat sheet filtration systems, and configurable ARTeSYN chromatography systems.
Adjusted SG&A expenses for both the fourth quarter and full year 2021 were approximately 22% of total revenue, compared to 25%-26% in the same 2020 periods. The year-over-year dollar increases were related to the timing of our 2020 and 2021 acquisitions and continuing investments in personnel, facilities, and equipment expansion, supporting our long-term growth expectations. Now moving to adjusted earnings and EPS. Adjusted operating income for the fourth quarter 2021 was $55.9 million, an increase of $28.6 million or 105% compared to fourth quarter 2020. Adjusted operating margin for the fourth quarter 2021 was 30%, an improvement of 490 basis points compared to 25.1% in the fourth quarter of 2020.
Adjusted operating income for the full year of 2021 was $215.2 million, an increase of $117.1 million or 119% compared to 2020. Adjusted operating margin for full year 2021 finished at 32.1%, an increase of 530 basis points compared to 26.8% for 2020. Adjusted operating profit and margin increases are indicative of the impact of strong volume leverage on our overall business more than offsetting expansion investments. Adjusted net income for the fourth quarter of 2021 was $46.9 million, an increase of $18.3 million or 64% compared to the 2020 quarter.
Adjusted net income for full year 2021 was $175.3 million, an increase of $86.2 million or 97% compared to 2020. Adjusted EPS for the fourth quarter of 2021 increased by $0.81 per fully diluted share, an increase of $0.29 or 56% compared to $0.52 in the 2020 period. Adjusted fully diluted EPS for the full year 2021 finished at $3.06, an increase of $1.41 or 85% compared to $1.65 in the 2020 full year period. Our cash and cash equivalents, which are GAAP metrics, totaled $603.8 million at December 31st, 2021, including the impact on cash from our fourth quarter BioFlex Solutions acquisition and related deal expenses.
We'll now transition to our 2022 full year guidance. Our GAAP to non-GAAP reconciliations for our 2022 financial guidance are included in the reconciliation tables in today's earnings press release. As previously mentioned, unless otherwise noted, all 2022 financial guidance discussed will be non-GAAP. Please also keep in mind that our 2022 guidance may be impacted by fluctuations in foreign exchange rates beyond our current projection of a 2% headwind on full year sales, and does not include the potential impact of any future acquisitions that the company may pursue.
Based on the strength we are seeing in the bioprocessing market and the expanded capacity that we've created in our business, and inclusive of the impacts of Polymem, Avitide, and BioFlex Solutions acquisitions that we closed in 2021, we are setting our 2022 full year revenue guidance, a GAAP metric, at $800 million-$830 million, representing reported growth in the range of 19%-24% and organic growth of 18%-22%. This revenue guidance includes base business revenue of $578 million-$587 million, growing at 20%-22%, COVID revenue of $200 million-$220 million, growing at 5%-16%, and 2021 non-organic acquisition-related revenue of $22 million-$23 million. We are setting our 2022 adjusted gross margin guidance at 57%-58%.
We expect adjusted operating income to be in the range of $234 million-$240 million, with adjusted operating margins in the range of 28.5%-29.5% of revenue for the year. Adjusted other income and expense is expected to be $0 for the year. We expect 2022 adjusted income tax expense to be approximately 21% of adjusted pre-tax income for the year. We are setting adjusted net income guidance in the range of $185 million-$190 million, and adjusted EPS guidance in the range of $3.21-$3.30 per fully diluted share. Our adjusted EPS guidance reflects an estimated 57.6 million weighted average fully diluted shares outstanding at year-end 2022.
Adjusted EBITDA is expected in the range of $265 million-$271 million, with depreciation and intangible amortization expenses expected to be approximately $30.3 million and $26.3 million respectively. The company expects to invest $60 million-$70 million into capital expenditures in 2022. We expect year-end cash and cash equivalents, a GAAP metric, to be in the range of $660 million-$680 million, with our CapEx investments being fully funded by cash generation from our operations. This completes our financial report and guidance update, and I will now turn the call back to the operator to open the lines for questions.
Thank you. We will now begin the Q&A session. To ask a question, you may press star then one on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. Once again, we please ask that you limit yourself to two questions. At this time, we will pause momentarily to assemble our roster. The first question will come from Dan Arias with Stifel. Please go ahead.
Good morning, guys. Thanks for the questions. Tony, on Filtration, obviously that franchise is doing quite well. Can you just sort of put some color to your outlook for 25%-30%, just thinking about the, you know, the fact that obviously the comp is very difficult, but the market dynamics that got you to 100% growth are still looking pretty in place. Maybe just touch on some of the things that you think are the lynchpins that sort of determine where that business lands in terms of growth. Is Filtration one of the areas where you think you might be able to take some share? You made a comment about potential gains there.
Yeah. You know, the projected growth for Filtration, Dan, is 25%-35% in 2022. Outside the COVID component, when you look at the base Filtration business, I think we're seeing real traction with our flat sheet cassette business. We're seeing real traction with ATF. You know, as maybe noted, we got into a number of commercial wins in the last three-four months of the year, which is a very positive indication. I think when you think about our Filtration franchise, we've had, I would say over the last three or four years, a lot of clinical success, and now it's beginning to move into the commercial side. Yeah, look, we think 25%-35% is a good number.
As we move through the year, we'll probably be able to see if we revise that up in any way, shape, or form. I think it's, you know, to maybe reiterate, it's our ATF portfolio, it's our flat sheet cassette, and it's our systems. We're really happy with the way our systems business has filled out. You know, we talked a little bit, Dan, about the R&D element of last year, but we launched 11 products last year, so I think many of them into the Filtration portfolio. I think that just gives us a lot of, you know, additional fuel as we go through 2022.
Okay. Maybe just, you know, that probably leads into this question or this line of thinking here. Just on cell and gene therapy, you know, the growth you're seeing there is obviously coming from new customers and existing accounts. I suppose it's a hard question to answer, but are you able to sort of put some thought to those two buckets if you just think about the existing body of work and how that scales up from an earlier stage to a later stage, and then what you might see in terms of just acquiring new customers in 2022, because it does feel like your momentum there is pretty good.
Yes. Maybe start with the new customers. I mean, our expectation is we'll continue to add at a similar pace in 2022 as we did in 2021. I mean, our portfolio of products has expanded, so there's no reason why we can't move at a similar pace. I think what the industry needs. There's two things happening in the industry that we see. One is there's a lot more scale-up going on, which is really encouraging, but we also need to see, you know, more of the late-stage opportunities getting through to final approval. I think that's kind of the last litmus test, is to see more approvals, because I think with more approvals comes with more momentum in that clinical pipeline.
Yeah, we're, you know, we look at the first half of last year versus the second half. We saw a real uptick in our cell and gene therapy business in the second half of the year.
Just to finish the thought, Tony, we get a lot of questions about the, you know, the big picture things that are taking place in the cell and gene market, just in terms of companies working through safety and efficacy issues, et cetera. Has any of that showed up in your business when you look at your order book or in a way that, you know, we would be able to tell, or is it pretty smooth sailing at a high level because one company might be dealing with something, but overall, the industry is in good shape?
Yeah. I think overall, the industry is in good shape. I think the earlier comment about, you know, seeing more approvals is actually really important. We look at our order book really robust coming into 2022. We have seen no slowdown on the cell and gene therapy side.
Okay. Thanks a bunch.
Thank you. The next question will come from Jacob Johnson with Stephens. Please go ahead.
Hey, good morning, everybody. Tony, maybe just to follow up on something you mentioned during your prepared comments. You know, in your new investor deck, you know, your TAMs went from $3.7 billion to $8+ billion now, so more than double. Can you just expand on your comments on what drove that increase and maybe flesh out how much of that's COVID-based business, maybe things like cell and gene therapy?
Yeah. On the TAM, you know, clearly the impact of COVID has increased the TAM for our whole industry. Probably 80%, I would say. It didn't quite double our TAM, but probably added $3 billion onto the TAM. Everything else came from the businesses we've jumped into, the acquisitions that we've done, the expanded markets that we have now. You know, when you keep adding new products at the rate we've added them in, and again, I'll just kind of reiterate, 11 products launched last year, that just opens up additional parts of Filtration or Chromatography. Just this week, you know, launching now Affinity Resins into cell and gene therapy, that opens up, again, more of a market for us. So I would say, you know, $3 billion is probably COVID.
Everything else is, you know, M&A expanded markets.
Got it. That's super helpful. Then maybe as a follow-up, kind of sticking with high-level question. You know, I appreciate the $1 billion 2024 revenue target, and how you guys think about the long-term growth profile of the business. Something I've been asked recently is just on the margin side, how should investors think about the long-term margin opportunity at Repligen? You know, maybe if you get to $1 billion in revenues, what should your margin profile look like at that level?
Yeah. Jacob, this is Jon here. You know, we look at our margins this year, and it's interesting when we look across the industry, it's a very similar story to what a lot of our peers are saying right now. As we finish the year, our investments started to catch up to the revenue levels that we've had, and again, very consistent story across the board. Really pleased with the way we've been able to expand our gross and operating margins. As a matter of fact, you know, operating margins were up over you know up 530 basis points this year and I think about 1,180 basis points over the last three years. It's been a really great growth story.
We guided down a little bit for 2022 as we continue to invest in the business to make sure that we're well positioned long-term here to take advantage of the market opportunities that are out there. I think if you look at us, you know, at the billion-dollar level, we will continue to keep the targets out there that we have today, which will continue to be trying to get above 60% on the gross margin level. I think that's a good aspirational level for us. On the operating margins, you know, we'll obviously wanna continue to be above 30% on those as well. I think we have a good opportunity to get there.
Right now we're really in an investment phase, capacity expansion phase, as well as, you know, really continuing to build up our R&D team, our commercial teams, our administrative infrastructure, and everything else to support a billion-dollar business and above as we go forward.
Perfect. Thanks for that, Jon.
Mm-hmm.
The next question will come from Julia Qin with JP Morgan. Please go ahead.
Hi. Good morning. I'll start with a high level backdrop question. I mean, many investors are concerned about biotech funding environment in light of recent market volatilities, and some, like CRO companies, have called out a meaningful slowdown in orders earlier this week. I was just wondering if you're seeing any impact regarding your pipeline. Of course, we understand that Repligen sits more downstream, so the impact is probably more on early stage research than on development stage. If you could just talk about your customer quoting activities more recently and order funnel, that'd be great.
Yeah. I would agree with you, Julia, that the impact is more on the research side than it is on the bioprocessing side. You know, if we look at our orders in last year, if you take COVID aside and look at base business orders, they were sequentially up every quarter. You know, we look at our orders as we've gone through the initial first half of this quarter, again, been very solid. So we're not seeing, as of today, any impact from that. But you know, obviously, we'll go through the year and see what happens.
You know, our guidance is based on everything we see today, and I think there's definitely some confidence around our $800 million-$830 million.
The pipelines look exceptional, right? The clinical pipelines and new product development pipelines across gene therapy, across mAbs, most areas of our business.
That's great. In terms of inventory levels in the channel, your peer cut out about 5% tailwind from customer inventory building in each of the past two years, and they expect that to reverse this year. I'm just curious if this is in line with what you've seen, and is that what you've contemplated in your guidance as well?
Yeah. I think we're everyone in bioprocessing is witnessing similar trends, so I think that's it feels like a pretty reasonable amount of to assign to inventory build. And you know, we'll see as we go through the year, you know, what customers do from an inventory point of view. For sure, last year, there was a build up in inventory as people were worried about being able to get product. I don't think the concern about product availability has disappeared, so I think that, you know, inventory, say, slowing down on inventory build is probably for us. I don't think it's gonna happen really until the second half of this year.
Got it. Thank you.
Thank you. The next question will come from Paul Knight with KeyBanc. Please go ahead.
Tony, I think you mentioned the overall product lines in capacity expansions of 3x-9x. What's the overall capacity for the entire firm? Is it in between that, like 4x, or could you comment on that? The second question is on cell and gene therapy, is flat sheet your biggest, you know, driver and differentiator?
On the capacity, we probably haven't calculated exactly what the average capacity has been increase was last year because every product line was a little different. You know, I think your guesstimate is probably accurate. It's probably around 4x. For us though, you know, there were some key product lines that we really needed to build up capacity given the COVID demand. I think clearly hollow fibers was the one that we highlighted with the nine-fold increase. You know, what was interesting about last year is a lot of our capacity increases came from you know, addition of people and being more efficient and some you know, physical capacity space being added.
This year, you know, it's more about adding in that physical capacity space, which I think will set us up for the next three - five years, really drive our lead times down significantly versus what you might have seen in the past. I think that's really a positive sign for us, and it's no different than what our peers are doing as well. Everybody is on the same journey. On the cell and gene therapy side, I don't think I would call flat sheet out as the primary driver for us or differentiator. I would say, you know, when you look at our portfolio of products, you know, obviously Filtration, there's a large number of highly differentiated products in our Filtration portfolio.
I would say that the major driver of growth in cell and gene therapy is our combined Filtration portfolio, not any one individual product. What's nice about the rest of the portfolio is, you know, we've got some really nice traction with our OPUS pre-packed columns, and we've got some really nice traction with our FlowVPX and SoloVPE technologies in cell and gene therapy. Those franchises, because they just don't have the same number of products as filtration, will always naturally have a lower sort of percent impact on gene therapy than what you might get with Filtration.
Okay, thanks.
Thank you. The next question will come from Matt Hewitt with Craig-Hallum Capital Group. Please go ahead.
Good morning, and thank you for taking the questions. I realize it's very early days, but the recently launched new resin products for AAV manufacturing, what has been the initial response that you've heard from customers, and how quickly do you think you could start to see some of those hitting the order book?
Yeah, there's no, you know, there's no magic bullet, unfortunately, when it comes to Chromatography resins. It's a process that anyone in the industry that's launched products into this space know quite well. It takes, you know, this year, 2022, is all about seeding. The good news, Matt, is and your question, you know, the response has been very positive. There's lots and lots of customers that want to evaluate the resins. Yet they are differentiated versus the incumbents that are in the marketplace today, and we focused really on improved caustic stability, which allows customers to run the resins a lot more cycles. You hold on to that capacity on the Chromatography column a lot longer with the products that we've launched.
I'd expect this year it's a lot of seeding and then next year you start to see, you know, opportunities where we get into phase I, phase II, maybe even later stage, later phased programs as well. You know, we just wanna get off to the right start. I think it's incredibly encouraging for me as the leader of Repligen that, you know, five months after we did the Avitide acquisition that we have these three products launched. We said we would do it. We've executed on it. I think, you know, my comments about R&D, I just wanna make sure people really see it. We are really executing at a very high level within our R&D teams right now.
We're getting products launched, we're hitting our timelines, and that's just going to help us on our journey towards $1 billion in the next few years.
That's great. Maybe separately or in a different line. Cell and gene therapy, you've mentioned it a number of times, it's obviously going to be a key growth driver for you going forward. Where would you characterize those products today, the ones where you are actively involved? Are those still, you know, early clinical stage opportunities, or are you starting to see those shift into the commercial realm? And what will that mean from an increase in revenues for you as those do become more commercial based? Thank you.
Yeah, I would say that the majority of our opportunities today are in the clinical. Clearly the customers we've been working with for the last four years have some have scaled and moved it into the later stage clinical trials. As I said, when we were chatting with Dan earlier, we need to see more, you know, commercial wins. I think that's not just for us. I just think for the industry. I think the more we see approvals, the more momentum you have in that clinical pipeline. That's really what we all should be looking for is, you know, the increased number of approvals, and that will drive volume. It'll drive a lot of the clinical programs that are currently ongoing.
Hard to put a number on it, but obviously, if you're in a commercial process, it's very consistent revenue versus, you know, if you're in clinical, you may see revenue. If you're in one clinical application, you see revenue this year, but it could be, you know, 18 months before you see additional revenue.
Got it. All right, thank you.
The next question will be from Brandon Couillard with Jefferies. Please go ahead.
Hey, thanks. Good morning. Tony, if my math is right, it looks like your Asia Pac business more than doubled last year, and I would assume that most of the COVID vaccine contribution was mostly concentrated in the U.S. and Europe. Is that right? Is that a right assumption, first of all? Can you just elaborate kind of on the drivers of that, maybe the size of your commercial team in Asia?
Maybe start with the commercial team. You know, we've really increased our commercial organization over the last few years. I think we finished last year with almost 200 people between sales, field applications, field service. I think right now. By the time we finish up Q1, we're probably in that 225, 230. I don't have the exact number of sales people in Asia. I do know that in China it's around 40. We have probably 40 people on the team there. You know, I think the momentum in Asia has been just fantastic over the last few years. To your first question, the drivers of growth in Asia, I would say predominantly driven by our Filtration portfolio.
We have some, you know, bigger accounts that use our pre-packed columns, but a lot of times in, you know, countries where labor is not as expensive as in, say, the U.S., people tend to wanna pack their own columns. The big companies that we all know have definitely moved towards pre-packed columns. I would say Filtration is the main driver. Last year, there was a significant contribution, Brandon, from COVID. We have a number of accounts in China, in Korea, and in India that have implemented or used our technology in COVID vaccine manufacturing.
Remember, the way the COVID vaccine, sort of manufacturing, played out last year, you have some core companies, but there was a lot of CDMOs that ended up, you know, signing on and doing the manufacturing. Think about our impact. Some of it is through customers in Asia that are making their own vaccine and others are through CDMOs.
Gotcha, it's helpful. Just one for Jon. Any, you know, color direction you'd give us in terms of the phasing of margins and EPS in 2022? Should we expect the vaccine revenues to be ratable with kind of $50 million-$55 million a quarter?
Yeah. I can start with the first one in terms of the margin view and how that's gonna phase, and I'll hand off to Tony for the other question. Yeah, margins, as we come out of this year, you know, we're on a H2 run rate of about 57.3% on the gross margin level. Again, you know, this is because obviously our investments are now catching up to the revenue levels. That's a really good starting point coming into the year. Interestingly, though, you know, that's really right within the range of our full year. I'd say we expect to be fairly consistent throughout the year in that 57%-58% level.
And then o n operating margins, similar story. I mean, we finished the year at 30%. We've guided down a little bit because I'd say we got a faster jump in terms of capacity adds as opposed to maybe infrastructure and commercial adds with the catch-up on volumes and such. You know, I would say 30%, end of the year, we're expecting to come in at 28.5%-29.5% on operating margin. You know, I would say you're gonna start in at a fairly consistent level and then you'll finish. Should be reasonably consistent throughout the year.
Yeah, then Brandon, on the COVID vaccine revenues, we expect that, you know, I think Q4 was north of $60 million. We'd expect the first half of the year, you know, to be north of $60 million on a quarterly basis, and second half might be a little lighter. So I'd say like that 55%-45% type split is probably pretty reasonable assumption. First half, second half.
Super. Thank you.
Once again, if you have a question, please press star then one. The next question will come from Ram Selvaraju with H.C. Wainwright. Please go ahead.
Thanks very much for taking my questions. Firstly, I wanted to ask if your $1 billion + revenue guidance for 2024, achieving that threshold by 2024, does take into account the possibility of reduced vaccine demand, reduced vaccine production as the COVID-19 pandemic might shift to endemic status by that point. You know, if you could just maybe comment on the extent to which that number is essentially battle-proof, so to speak.
Yeah, great question, Ram. You know, when we look at our $1 billion target, you know, obviously, we talked about this back in November with a number of analysts. Our model is about a 25% reduction in 2023 and 2024, and we still are confident that we can hit $1 billion in 2024 even with that type of reduction. We think there's a long tailwind on COVID. We've modeled just from our perspective that type of drop. We're still very confident we can get to $1 billion+ .
It's 25% in 2023 and another 25% in 2024, just to be clear.
Great. Then, on the gene therapy side, I was wondering if, you know, in a more capital-constrained environment, this is kind of building on, you know, questions that were asked earlier, do you think that, for example, with the reusable resins, you would actually be able to take market share from your competitors from a bioprocessing perspective within gene therapy? Do you expect the bulk of the gene therapy demand to be driven by AAV products, particularly in the context of how your new resin products can be used?
Yeah. I mean, you know, when we launched, and obviously we just did it the other day, we launched three resins for AAV against, you know, the more dominant AAV types that are out there. So obviously, we have no market share, so we would hope to take some market share over the next couple of years. We think. You know, it was important for us when we launched the product that the products would be differentiated. They're clearly differentiated versus the competition. But it's gonna take time, Ram. It's not gonna happen overnight. So yeah, our expectation is we'll take market share. It'll take a couple of years to really build up our portfolio. Right now, AAV is the dominant, you know, gene therapy vector.
There are other vectors, and obviously we'll continue to look at that and decide what other affinity resins we'll bring to market over the next one-two years. Expect to see more Affinity Resins coming from Repligen in the next one-two years.
Thank you.
Thank you. Ladies and gentlemen, this concludes our Q&A session. I would like to turn the conference back over to Tony Hunt for any closing remarks.
Yeah. I'd just like to thank everybody for joining us this morning. Look forward to catching up with everybody again in May, which is not too far away. Thanks again, and we'll chat later.
Thank you, sir. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.