The growth in outsourced commercial and development biopharmaceutical programs drives the demand for contract manufacturing services. The biopharmaceutical contract manufacturing market experienced double-digit growth over the past three years as new biopharmaceuticals reached the market or entered the pipeline. High demand plus low capacity expansion rates caused high industry utilization rates last year. In response, biopharmaceutical contract manufacturing organizations (CMOs) are aggressively adding capacity and investing in productivity improving technologies. 

The information presented in this article draws from HighTech Business Decisions’ latest report, “Biopharmaceutical Contract Manufacturing 2017: Growing Markets, Capacities, and Innovations.” This report uses primary research from senior-level executives and scientists at pharmaceutical and biotechnology companies plus executives at contract manufacturing organizations. For purposes of our article, HighTech Business Decisions defines biopharmaceuticals as complex molecules created through the genetic manipulation of living cells or organisms used for therapeutics or vaccines. 

Demand and utilization rates
Over the past three years, the biopharmaceutical contract manufacturing market grew at a compound annual rate of 13%, higher than the previously projected growth rates of 8% to 10%. Both higher volumes and higher prices drove this growth. The growth in volumes occurred for both clinical and commercial products. Last year, the biopharmaceutical contract manufacturing markets reached $3.8 billion. This year, the biopharmaceutical contract manufacturing market will grow 8% and surpass $4 billion.

During the first half of this decade, capacity utilization rates at most CMOs were below ideal levels. The industry had excess capacity. Capacity was readily available. With large fixed costs to cover, the CMOs experienced an intensely competitive marketplace causing downward price pressure and less favorable contract terms. Thus, most CMOs limited their capacity expansion plans. With low capacity investments, capacity increased at a slower rate than demand. This led to very high capacity utilization rates with little or no excess capacity available by 2016 (see Figure A). Furthermore, with the acceptance of single-use bioreactors, CMOs could economically add production capacity in smaller increments. As a result, contract mammalian cell culture capacity grew at a compound annual rate of 4% from 2011 through 2014. 

Bookings
To confirm higher utilization rates, we investigated CMOs booking levels in 2016. From our study, a large majority of the CMOs reported their capacity either fully or nearly-fully booked in 2016. Furthermore, the larger CMOs were more likely to be fully booked compared to smaller CMOs. In addition, mammalian cell culture production was more fully booked compared to microbial fermentation production. In response to high capacity utilization rates, pharmaceutical and biotechnology companies booked manufacturing slots in advance and locked in capacity for longer periods to ensure availability. On average, CMO facilities were booked 16 months into the future in 2016.

Below are selected comments from CMOs regarding their production lead times:

• “One plant is fully booked until the middle of 2018 and the other until the middle of 2017. The lead time is 9 to 16 months.” —CMO Respondent
• “Booking manufacturing slots are always in flux. We have existing customers that have booked slots for the next two years and new projects that will take two years. Right now, we are booking into 2018.” —CMO Respondent
• “I expect we’ll be fully booked for drug substance this year in the U.S. and into 2018 in Europe.”  —CMO Respondent
• “Some of our products are booked out for several years. Clients could get a spot in about nine months.” —CMO Respondent
• “Slots would be available for large-scale mammalian products in 2020, large-scale microbial products in 2018, small-scale mammalian products in 2018, and small-scale microbial products in 2018.” —CMO Respondent
• “Our next opening is about nine months out. We have got capacity booked out for 18 months based on forecast predictions.” —CMO Respondent

Higher prices
The lack of excess capacity also affects prices paid for biopharmaceutical contract manufacturing services. Overall, 79% of the pharmaceutical and biotechnology executives in our study have observed higher prices for biopharmaceutical contract manufacturing services (Figure B). The lack of excess capacity is the main reason for the price increase. The pharmaceutical and biotechnology executives also observed that the lack of excess capacity is more prominent at the top-tier CMOs. This observation by the biopharmaceutical respondents is consistent with the analysis that 80% of the large contractors reported their manufacturing plants were fully booked in 2016. The respondents also saw higher prices for analytical testing, support activities, and raw materials. From the respondents’ inputs, prices have increased from 5% to 50%, with an average observed price increase of 18%. For the few respondents who saw stable prices, they attributed long-term supply agreements and strategic alliances, with set prices, as the reasons they have not experienced higher prices.

Below are selected comments from our study’s respondents regarding their observation of biopharmaceutical contract manufacturing prices:

• “We have been seeing a steady increase in the unit-per-effort pricing.  It’s a supply and demand situation. A few years ago, the CMOs were eager to develop a relationship early on to get you in the door and were willing to offer lower costs with the understanding that once they had built a relationship with you, they were more likely to get your business down the line.” —Pharma/Biotechnology Respondent
• “It was easier to find capacity five years ago. Now there are so many mAbs in later stages that there’s a capacity crunch. We don’t get access to all the scales of production that we want. The base price for runs might be the same, but prices for support activities are increasing, e.g., regulatory, analytical. Nowadays, things are good for CMOs.” —Pharma/Biotechnology Respondent
• “We are seeing higher prices from CMOs for biopharmaceutical services. There is some waning of capacity. Batch prices have gone up about 10%, and analytical testing about 5%.”—Pharma/Biotechnology Respondent
• “For the gene therapy space, batch prices seem to be going up as the demand goes up. We are struggling to find CMOs for cell banking, process development, and analytical testing.” —Pharma/Biotechnology Respondent
• “Many CMOs’ prices are very similar. There is not that much difference at 1,000 L to 2,000 L scale. The prices are 10% higher than five years ago.” —Pharma/Biotechnology Respondent
• “Each time we go back to a CMO the prices are higher. Over the last three years, prices for manufacturing, purification, vialing and testing have all increased. The first manufacturing run we did one-and-a-half years ago costs $0.8 million, now it costs $1.2 million. That’s a 40% increase. Another area where with large increases is analytical development and validation; charges are up 30% to 40%. We are also seeing a 10% to 20% increase for analytical testing.” —Pharma/Biotechnology Respondent
• “Prices are higher. Five years ago there was more capacity. We recently received a quote that was 50% higher than the one we’d had received previously, although to be fair, we haven’t negotiated it down yet.” —Pharma/Biotechnology Respondent

CMOs add capacity
In response to the high capacity utilization rates, CMOs are tightly managing schedules to meet critical production requirements. As indicated by the higher utilization rates, CMOs are also hiring more personnel and adding more shifts. Although not expanding overall industry capacity, CMO consolidations provide more financially sound and capable alternatives for some clients. In addition, smaller CMOs are working with each other as a network to meet their clients’ needs. Besides these and other short-term actions, CMOs are investing in new capacity. These investments include expanding existing facilities, building new sites, and installing single-use technologies for more flexible capacity. Consequently, mammalian cell culture capacity will grow at a compound annual rate of 12% from the period of 2014 through 2019—a rate greater than overall demand.

From our study, three-quarters of the CMOs are adding new capacity over the next few years. The result from these additions will double total industry capacity this decade. For mammalian cell culture capacity, nearly one-fifth of the capacity increase will be single-use bioreactors. These capacity increases will support both clinical- and commercial-phase projects. The respondents also noted their adding or adding to other production-related capabilities including a) continuous manufacturing/perfusion, b) analytical capability, c) cell-line development, d) high-titer processes, and e) process development capability.

Comments from CMO respondents regarding new capacity investments are shown below:

• “We are in negotiation for a commercial project. We expect to increase capacity with two trains of 2,000 L which will enhance our capabilities and increase compliance.” —CMO Respondent
• “Mostly, we are investing in more manufacturing capacity. We have a 5,000 L mammalian facility approved, and we are working on a 5,000 L microbial facility. It has not been approved yet. We are adding process characterization and cell development capability.” —CMO Respondent
• “We’re mainly adding capacity (e.g., more incubators, more disposable bioreactors) to produce material for preclinical and Phase I. We will also be doing more process development for serum-free production.” —CMO Respondent
• “We have invested in disposables for both up- and downstream processing. Also, more analytical capabilities, such as digital PCR and UPLC.” —CMO Respondent
• “We will be adding microbial expression systems and looking for novel technology, such as disposable technology, that can be used to reduce overall time for first-to-patient.” —CMO Respondent
• “We will continue to work on microbial technology and invest in soluble expression and in vitro refolding. Our biggest challenge right now is to increase capacity to satisfy increasing demands, since our customer base in late phase is growing.” —CMO Respondent
• “We will continue investment in drug development and product development capability. We want to be able to offer our clients a broader range of services so we can build our pipeline of projects coming into the bioreactors. We want to have a pipeline of future partnerships with clients who will stay with us once we develop their process. We are considering investing in mammalian culture capability. Clients want cell culture.”—CMO Respondent
• “In the future, we will invest in complex processes (also legacy), continuous manufacturing, high-titer processes and second generation processes.” —CMO Respondent
• “Our current emphasis is on expanding our commercial capabilities. We are expanding manufacturing on the mammalian side supporting late-stage projects. Previously, we focused on early-stage only. We are looking at new perfusion technology with complementary downstream capacity. In the biosimilar space, some clients see perfusion manufacturing as the most effective way to exert a finer degree of control on the manufacturing process and to minimize the cost of goods. In fed-batch processes where the bioreactor is occupied for an extended period of time, molecules made early will sit in the growth media for longer and are more likely to undergo modifications that affect the character of the product. We are investing in 300 L single-use fermenters to provide additional smaller scale capacity, mostly for early-stage projects, although we are engaged on a couple of inquiries for the small-scale capacity for late-stage or commercial fermenter projects.” —CMO Respondent
• “In the next five years, in addition to our upcoming expansions we will be investing in an in-line dilution system.” —CMO Respondent

Closing
Last year, capacity utilization rates were at very high levels. As a result, the industry has experienced more favorable pricing and contract terms. In response to the higher demand, CMOs are adding new capacity and investing in process improvements. From our analysis, we expect the market to continue to grow and exceed $4 billion in 2017. 

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William Downey is the president of HighTech Business Decisions, a market research and consulting company that has been publishing reports on the biopharmaceutical contract manufacturing market since 1997. For more information, visit www.hightechdecisions.com or call (408) 978-1035.