Pam Cheng is responsible for bringing the last of the major pharma companies to Ireland. Anglo-Swedish group AstraZeneca has had a marketing presence in the Irish market for years but, unlike all of its Big Pharma peers, never felt the need to invest in manufacturing here.
Until now.
The catalyst was the company’s 2020 purchase of a rival, Alexion. The US company, best known for producing one of the world’s most expensive medications – a drug called Soliris used for treating a number of blood disorders – established a presence in Ireland in 2013, before investing further over the following years.
By the time AstraZeneca moved to buy the business in a $39 billion deal (€39.5 billion), Alexion employed about 500 people in the State, having invested more than €600 million at sites in Dublin’s College Park in Blanchardstown and Athlone.
More importantly, it had space at its Dublin site.
That saw AstraZeneca announce plans last year for the construction of its first manufacturing plant in the State – a $360 million investment that Cheng says will give the business the sort of flexibility it requires in its supply chain for the future.
“As a result of Alexion joining AstraZeneca, Ireland is becoming really a strategic hub for AstraZeneca. So, I think we cannot ignore that’s a major piece of it [the decision to build here now],” Cheng says.
“But the other thing is really our robust pipeline. So, if you really think about the modalities and technology of the molecules coming through the pipeline, it really is calling for new technology, a different form of API [active pharmaceutical ingredient] than we’ve known before.”
Cheng, an American chemical engineer by training, is the woman charged with seeing the Irish project to fruition.
As executive vice-president, operations and IT, she is responsible for AstraZeneca’s manufacturing operations as well as supply chain, procurement and information technology globally.
“I have been in the industry for a long, long time, and for the first time there was an opportunity to build something quite unique and innovative,” she says of the Dublin project.
Ireland wasn’t entirely new ground to her as she had previously worked with rival MSD, which has had a significant presence in the State over many years, “so I am no stranger to Ireland. I understand the operating environment, and the talents and capabilities”.
When it was announced, the Irish investment was painted as a Brexit-inflicted blow to UK Inc. Cheng denies that it was a “direct factor” in the decision and it is true that AstraZeneca continues to invest in its British operations, but she concedes that supply chain and other issues had a bearing in the final call.
“As head of operations, when we look at making these decisions, it really is about end-to-end supply chain. Can I ensure supply? Do we have a friendly operating environment? Do we have the right capability and talent? And that we can make a return on our investment, if you will?
“So it [Brexit] was not a direct factor but certainly we have a multifaceted type of decision on these things.”
At the time it was announced, Bloomberg reported the decision as a blow to the UK government of Boris Johnson which had put together a package of incentives to persuade the FTSE-100 listed business to invest instead at its Macclesfield site. The decision was reported to be linked to a row between AstraZeneca and the ministers over Britain’s decision to go with Covid boosters from rival Pfizer.
Interestingly, while Alexion is very much a biologics operation with stand-alone status in the AstraZeneca group, the new plant that will share its Dublin site is what is known as a small-molecule API plant – a more traditional form of drug.
Cheng insists the new Dublin plant will be very different from those traditional operations.
“We are used to seeing what we call the traditional small-molecule API active ingredient measured in, I don’t know, tens of tonnes and sometimes hundreds of metric tonnes, right? But I think the landscape for the small molecule active ingredients are changing so much”, with newer sorts of small-molecule medicines, Cheng says. That includes new generation treatments for cancers.
“Sometimes now, we are measuring API in single-digit tonnes and even kilograms. So, these are more potent active ingredients, higher containment, much more complex.”
Cheng says this new project alongside further announced investment in Alexion’s Irish sites will bring the group’s spend in Ireland to more than €1.2 billion to date
Traditionally, she says, when a company such as AstraZeneca is creating a new medicine it starts in a small-scale, lab-heavy development facility before undergoing a tech transfer to a commercial-scale plant.
“This Dublin facility is actually development and commercialisation launch all in the one place,” says Cheng, adding that it allows the company to focus on speed of delivery for a new medicine to the patient.
The idea is that, over time, as a new medicine becomes more established commercially, it will be transferred to another site, with the Dublin space freed up for other pipeline products.
“The volumes are now much smaller, so a drug will be able to stay in this facility for a longer time,” Cheng says, adding that its modular design will allow the company to expand the number of production lines to facilitate additional drugs if necessary.
“This facility, no doubt, will focus on innovation. So, new science, new technologies and new innovation and new products. But to the extent that we can hold on to some growing products, we may be able to do that,” she says.
The AstraZeneca manufacturing sites boss was in Dublin last week to unveil the design of the new plant. It is still subject to planning approval but initially, she says, AstraZeneca plans to have the capacity on site for the development and early-stage commercialisation of three drugs simultaneously.
AstraZeneca may be late to Ireland but Cheng says this new project alongside further announced investment in Alexion’s Irish sites will bring the group’s spend in Ireland to more than €1.2 billion to date, which the woman running AstraZeneca’s 25 global manufacturing sites describes as “very substantial by any stretch of the imagination across our global footprint, no matter what country”.
It will also, she argues, put Ireland in the front seat of delivering breakthrough medicines globally.
Delivering a new pharmaceutical plant to “go live” stage generally takes between four and five years in a complex process that involves planning, construction and regulatory clearance before any medicines can be delivered from the site.
Cheng is confident of delivering the site for regulatory clearance and operations by early 2025, in part, she says, to the “incredibly supportive” IDA Ireland. “Of course, fingers crossed that we don’t get another global pandemic,” she says. “That was incredibly disruptive.”
Speaking of Covid, Cheng is amazed at the success of the medicines sector in working through the pandemic without serious supply chain disruption.
“We’ve had zero serious disruption of our medicine. I remember at the height of the pandemic sitting at home trying to figure out how to move materials across closed borders or with cancelled flights and everything. It’s quite amazing, looking back, that we’ve had zero disruptions,” she says, noting that the industry generally proved very resilient.
Conscious that it might sound like management speak but insisting it is anything but, she says the key factor was the self-motivation of staff.
“Covid-19 was the best motivator of all people of all times. I didn’t have to get out there and motivate our troops. People were working above and beyond,” she says. Of the 15,000 people working in AstraZeneca’s global operations division, more than 11,000 came into their plants throughout the pandemic “because we couldn’t make medicine from home”.
As the developer, with Oxford University, of the first Covid-19 vaccine to be approved, at least in Europe, AstraZeneca was at the coalface in the battle against coronavirus. Cheng says those years since 2020 have been the “most challenging, difficult and exhausting” for her, her team and their families.
“We’re super proud. We’ve made over three billion doses of our Covid-19 vaccine,” which was distributed across 183 countries. She references a report by data analytics group Airfinity suggesting that AstraZeneca’s vaccine was the most successful at saving lives in the first year of the crisis.
Taking a study conducted by London’s Imperial College which said vaccines saved 20 million lives worldwide in that period, Airfinity said the AstraZeneca vaccine was responsible for 6.3 million of those, ahead of Pfizer’s 5.9 million.
“It made everything worthwhile but going through it was not for the faint of heart,” Cheng says, noting that, alongside the Covid vaccine effort, the company also had to keep producing its other medicines.
Ireland’s reputation for excellence in manufacturing process engineering was one of the selling points when it came to choosing a site for the new ‘smart factory’
Not everything worked smoothly and AstraZeneca found itself in the middle of an unseemly row between authorities in the UK and the European Union over who had the right to certain vaccine supplies.
Cheng describes that period as complex. “It was daunting. From the governments to the companies to the people, we didn’t know what was going to happen. There was a lot of angst, a lot of anxiety. Looking back now, we can rationalise everything in terms of why certain things happened but I think, collectively, we can all say we’ve learned a lot through it, all of us.”
AstraZeneca has also run into problems with its efforts to follow up the success of that first generation of Covid vaccines. The company had high hopes for a nasal version of the vaccine that would have been very easy to apply in multiple settings but it recently failed to deliver the required immune response in an early-stage clinical trial.
AstraZeneca will continue to produce the more traditional form of injectable Covid-19 vaccine though, as Covid moves on from its pandemic phase, the company will be transitioning from the not-for-profit approach it adopted from the outset under the terms of its deal with Oxford. But the company’s single largest focus currently is in developing treatments for cancer.
Dublin will be central to that – though not to the exclusion of other areas – with many of its pipeline cancer drug candidates being small-molecule drugs.
“The short answer is that Dublin is going to go across all range,” says Cheng, before adding that “we are huge on oncology”.
“I mean we continue to challenge the way cancer care is provided globally. So, certainly, if you look at our oncology portfolio today, there are a fair number of medicines that are small molecule. And if you look in our pipeline that’s going to continue.”
But she also sees opportunity in the group’s respiratory and cardiovascular portfolios for drugs that will fit comfortably in the new Dublin site.
Ireland’s reputation for excellence in manufacturing process engineering was one of the selling points when it came to choosing a site for the new “smart factory”. It will feature the latest in digitally-enabled production, right down to using technology to predict when the equipment will need maintenance or modernisation.
Similarly, using a digital twin approach, the plant will be able to simulate in an hour more experiments than an engineer or scientist could have done in a month back when Cheng started out as a chemical engineer.
This, Cheng expects, will optimise the use of the facilities being built in Dublin and extend the life cycle of both the plant and equipment.
And what of the future now that AstraZeneca has invested in Ireland as a new era manufacturing base?
“Obviously, we never make significant investment decisions just for one time. Our intent is always to build on what we have invested in,” Cheng says. “The good news is that we have one of the most robust pipelines in the industry. That means we need a lot of capacity.”
Assessment of risk, supply continuity, site capability and talent will always be undertaken before any new investment, she cautions, “but the intent is that we build on our investment everywhere we go”.
