Bioproduction capacity building, part 2 Construction option


By Matthew Pillar, Editor, BioProcess Online

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In conference event programming, in the trade press, and in conversations about water coolers, we make too many generalizations, which in turn create misperceptions, about the so-called manufacturing “capacity” crisis. biopharmaceutical.

It is often inferred that by “capacity” we mean “manufacturing space”, as in “we have to wait 18 months to start production because the outsourcing industry has no capacity”. But in reality, this capacity issue probably has a lot more to do with inflation, consumable/API/raw material sourcing, manufacturing inefficiencies, and short cash runs than it does with foot access. squares and large liter bioreactors.

Let me put it to you this way. I have, by the standards of a middle-aged man, a larger than average skull. It could give me a lot of thought manufacturing spaceBut that certainly doesn’t explain my lack of thought. ability. It is the raw materials – the genetics, the lipids, the building blocks of gray matter – that are missing. Supplementing these with new supplies of oily fish and green leafy vegetables becomes quite expensive to do. This is before going into everything detrimental influences on my thought-making ability (I’m approaching half a century, and who needs another Yuengling?).

Point is, ability is more complete than Physical infrastructure.

Sole sourcing is a bad idea

Last week’s coverage of a discussion about BioProcess International’s manufacturing capacity and supply chain between sponsors and CDMOs underscored the point. This column stopped at the hard-realized evils of sole-vendoring, and that’s where we’ll pick up here. One of the participants in the discussion, Brian Taylor, executive vice president of biopharmaceutical solutions at SmartLabs, summed up the observation that biopharmaceutical sponsors need to create options – from suppliers of raw materials, consumables and equipment to sources of manufacturing capacity. He says this is especially true for companies exploring new modalities, where precedents for supply and capacity have yet to be set.

Larry Lockwood, Vice President of Sales at Aldevron Company, likens sole-sourcing to no insurance policy – ​​it’s not that bad as long as you don’t, jokes. he. Aldevron is a CDMO, and Lockwood says the company tries to avoid a lack of assurance by understanding customer needs as early in the process as possible, translating those needs into sourcing, and gaining a full understanding of the materials required. . He says Aldevron also more effectively gauges how long it takes to close deals with customers by predicting how much material it needs in a specific time frame. He says it’s important because once you realize you’re a sole-source, you’re in bad shape and it’s probably too late to make a difference.

Kumar Dhanasekharan, senior vice president of technical operations at Renovacor, recognizes the importance of moving away from single sourcing, but he doesn’t see multiple sourcing as a panacea. Manufacturing efficiencies, he says, are the most powerful antidote to capacity issues. When you reduce manufacturing risk by developing closed, continuous systems, you conserve raw materials, preserve clinical supply, and therefore relieve pressure on capacity. Of course, we are far from “lights out” manufacturing in the field of biological products, and more specifically of ATMPs. But Dhanasekharan suggests pursuing opportunities to integrate process intensification practices into process design wherever possible. Look for areas to design “closed” processes, he says, and reduce some of the waste in the manufacturing process. Vertex Sr. Dir. From MSAT-Commercial Manufacturing & Supply Chain, Ken Green agrees, stressing the importance of adopting technologies that improve yield from step to step.

The Impact of Inflation on Biologics Manufacturers

It was at this point in the conversation that moderator and founder and CEO of Darkhorse Consulting Anthony Davies, Ph.D. brought up the 8.3% 12-month inflation figure in the United States and asked the panel his view on the impact. Once inflation at this level begins to worsen year on year, he surmised, it will impact manufacturing, capacity and the ability of the biopharma industry to meet demand. .

Again, Green agreed, focusing on the rising cost of raw materials. Long delivery times and increasingly expensive materials combine to create considerable supply challenges, which will become even more acute as more ATMPs move from the clinic to commercial markets – and with price tags of several million dollars to start.

Kelly O’Hare, senior vice president of operations at CDMO Lykan Bioscience, suggests that the combination of inflation and conservatism in capital markets could ultimately – and perhaps ironically – have a favorable impact on innovative companies. She hopes the challenging environment will make sponsors think more about their long-term process development and avoid rushing into clinical trials before their process development is optimized. Going back to Dhanasekharan’s earlier point, O’Hare suggests partnering with development experts and only starting production when you’re really ready.

But Taylor, whose company works almost exclusively with early-stage biopharmaceutical innovators, sees firsthand how the combination of tight capital markets and inflation makes life difficult for small biotechs. With no revenue, tight capital positions, and inflated cost of goods, they struggle to reach the point of development optimization that O’Hare refers to. These challenging factors, he says, only exacerbate the need to relentlessly pursue optionality, in the name of conserving money and efficiency.

Optimistically, Dhanasekharan speculates that a rapidly expanding outsourced manufacturing footprint could, at least partially, offset the rate of inflation. While he doesn’t expect ATMP’s manufacturing infrastructure to sit idle, he notes that several CDMOs have doubled and tripled their facilities in recent years and several dozen are capable of full-scale manufacturing. Dr. Davies notes that many of these footprint extensions came at the hands of CDMOs that salvaged facilities built by companies whose Phase 3 programs failed. It’s telling, he says, that the people with the clearest sights on future demand for manufacturing capacity are eager to grab manufacturing facilities as soon as they come to market.

Will underfunded innovation dampen manufacturing demand?

While Dhanasekharan hopes the expansion of facilities will result in sufficient availability of supply to at least somewhat measure the cost of rent, Green warned that gloomy economic factors were reducing the volume of programming from corporate sponsors. pre-recipes. These companies, he says, are increasingly only funding their most promising candidates, at least for now. This is yet another wrinkle in the capacity crisis that has yet to be resolved – will a shortage of innovation dampen the demand that contributes to the challenges of outsourced manufacturing capacity?

Dr. Davies doesn’t think so. It predicts that if early-stage programs come under increased pressure due to reduced funding and deal flow, late-stage programs and pre-commercial programs moving toward commercialization will bear a percentage even higher for active programs in the field. He says the past five years have seen startup programs swell — some of which, perhaps, shouldn’t have been in the clinic — but the next few could see a glut of consumer capacity from commercial and near-commercial activities.

Dr. Davies concludes that at this stage and under these conditions, it is difficult to discern whether the current availability of manufacturing facilities is positive, negative or neutral. On the one hand, however, the panelists agree that we are in the long term “capacity shortage”. When asked if the conversation at BioProcess International would be different 12 months from now when the conference resumes in Boston, responses ranged from “no” to “not much.” The mitigating controls you have of the situation, agree, are proactive multiplication of raw material sources (and corresponding QA work required) and active investment in process intensification and optimization technologies .

As for me, I guess I’ll go to Wegman’s when I get home. It’s kale, salmon and a glass of water tonight.

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