March 29, 2016
There’s a slightly hollow feeling about the faded business park which was once home to Pfizer’s bustling R&D community and supported thousands of jobs in the nearby Kent town of Sandwich. Vacant buildings and a distinct lack of people in this vast 297-acre campus are hard to ignore. Outdoor patios with tables and chairs, which presumably would have once been buzzing with scientists snacking on their lunches and drinking their lattes, stand eerily empty.
Five years ago little Sandwich suffered a major blow when pharmaceuticals giant shuttered its research and development facility on the outskirts of the town – the site of Viagra’s discovery- with the loss of more than 1,500 jobs.
“They announced it on a Tuesday and on the Thursday you would not believe the number of for sale signs on houses,” a local cabbie said. “Not much goes on around here. It has gone very quiet since Pfizer left, but actually it is starting to pick up now”.
Indeed, the business park, now officially designated an enterprise zone and re-named Discovery Park, is showing renewed signs of life and has attracted a growing number of small businesses. There are now 123 companies there, employing 2,300 staff, although it’s still only 61pc full.
And Pfizer hasn’t completely abandoned the site either. Although the closure of the R&D facility made the headlines, the US-listed drugs company still retains some 700 full-time staff and 200 temporary workers at Sandwich. They play a pivotal role in Pfizer’s global operations, manufacturing potentially life-saving medications for clinical trials – think pills, syringes and liquids. It’s the only site within Pfizer’s R&D network able to perform every step in the complex process of producing new treatments, from molecule right the way through to medicine.
“Discovery and R&D is done at various places around the world where scientists find molecules that can cure diseases. That doesn’t happen here,” explains Tommy Dolan, the site head at Sandwich.
Instead, when a researcher discovers a breakthrough molecule, Sandwich takes that molecule and turns it into medication exclusively for clinical trials.
“It could be a treatment for any disease, but we only deal in small molecules,” explains Tommy. “They are discovered all over the world and come to Sandwich.
“We make oral products, such as tablets and capsules, as well as intravenous products, all for trials. We find ways to build the molecule that are fast, safe and robust.”
The site is also home to a big regulatory division, which helps medications get approved. In 2015, Sandwich managed over 10,700 regulatory submissions for more than 100 countries, representing 43pc of Pfizer’s global portfolio.
To a layman, the process of converting a molecule into a medication might sound relatively straightforward. Extract the active ingredient, mix it with some inert powder, mould it into a pill, et voila, a medication is born.
Not quite so simple. In fact, the process is phenomenally complicated.
When researchers discover a potentially life-saving molecule, its structure, also known as a crystal, can be unstable. Pfizer’s chemists at Sandwich are therefore charged with engineering it into a safe and sturdy design with all the right attributes, such as shape, strength and solubility.
Once the molecule is turned into a stable entity, it’s up to Jay McCauley, head of active pharmaceutical ingredient manufacturing, and his team to produce the active ingredient on a much larger scale.
Vast rooms with huge reactors mix the raw materials together to create the drug. Chemists wearing bright yellow protective body suits oversee the process and programme the reactors to manipulate certain factors, such as heat and saturation. Probes monitor in real time how the chemical make-up changes and watch the growth of the crystals.
Jay’s facility opened in 2002 and is Pfizer’s only fully automated pilot plant that manufactures small molecule active pharmaceutical ingredients for clinical trials. His team works two shifts over a five-day schedule, producing up to 240 batches a year. Last year they made 1,000kg of active ingredient. That’s a lot considering that a tiny amount goes into each pill, syringe or liquid drug.
And despite having been in the same job for many years, Jay says he still gets excited when one of his batches eventually makes it onto the market.
“Every now and then you hear stories about what we do. It makes you proud that you have worked on a treatment that is out in clinical trials and helping people,” he says.
“You see a kid with a life ending illness like cancer and you hear a mother talk about having hope. When my guys hear those stories you should see their faces when they walk out of here.”
That said, there are an awful lot of drugs that never make it past clinical trials. Millions of pounds and thousands of hours are spent every year producing treatments that fail to satisfy regulators.
“For every one you make a lot don’t make it into the market. You work on it for five years and it doesn’t get past trials,” Jay says. “The first time it happens it is like air being let out of your sails, but it just takes one to make a meaningful impact on someone’s life.”
The molecule’s journey ends with the actual process of putting it into the right format for the patient, be it a pill, liquid or intravenous medication. In the case of pills, the Sandwich facility can make up to 120,000 tablets an hour, and the process is highly complex.
Scientists have to consider who the medication is meant for and how it should be administered. Pills, for instance, may contain several layers of different ingredients, each with a specific function which might regulate dosage, solubility and absorption.
Tablets can also have microscopic holes in them, cut by lasers at Pfizer’s labs through which the active ingredient gets squeezed at a specified rate.
Kate Barclay, director of drug product supply, says one of the toughest aspects of her job is manufacturing so many different types of products in one facility, and with medications which are relatively untested. Paediatric formulas are also a big challenge.
“Increasingly, regulators want drugs companies to conduct paediatric trials and make formulas specially for children,” she says.
“And it’s not just a matter of halving the dosage. Children’s metabolism rates differ to adults and with kids, you have to think about delivery and how the child is going to take the meds. They might need to be chewable, or dissolvable on the tongue.
“We also make micro-beads that can be sprinkled on food. In that case, they might need a special layer to prevent them from dissolving too quickly. Most drugs taste awful, so this needs to be masked. Getting your two-year old to take a drug that makes you sick and gag is not easy.”
The pills are scanned under powerful microscopes at various stages of design, so scientists can make sure each layer is intact, in the right shape and performs the correct function. Chemists also need to be certain that the active and inert ingredients are distributed evenly. The room where this analysis is carried out looks more like an artist’s studio than a scientist’s laboratory. Bright 3D images of magnified molecules and colourful compounds line the walls, resembling works of modern art, rather than the product of scientific discovery.
“We do this because if you put it together you have to be sure that what you think you made you actually made. It might have changed, the crystal might have changed. And in the manufacturing process, if the crystal is a different size, it could block the hoppers,” one scientist explains.
When a pill reaches late stage clinical trials, such as phase III, Pfizer’s marketing team usually determines what the branded product will actually look like in terms of shape and colour, to make sure it stands out from other products on the market.
And of course, the Pfizer logo eventually has to be imprinted.
“I wish someone had thought of the ‘F’ in Pfizer, by which I mean the curly bit at the top,” says Kate. “It is tricky to stamp.”
Asked which type of pill is her favourite, she replies: “I like the micro beads that are coming through, this is relatively new technology. I also like some of the funky formulations, like extended release. That said, sometimes you can’t beat your standard round white tablet.”
Tommy Dolan, who heads up the Sandwich site, says Pfizer is committed to investing in manufacturing in the UK. He says manufacturing is an area of the pharmaceuticals industry which is growing increasingly important because of the advent of precision medicine.
Deeper scientific understanding of the underlying and often genetic causes of disease, such as cancer, means treatments are becoming much more patient specific and the days of big blockbuster drugs are coming to an end. For Pfizer, it means that the ability to manufacture drugs in small volume batches, cost effectively and in the right formats, is vital.
“The whole industry is going through a renaissance in manufacturing,” says Tommy.
“The world is changing and we need to work very differently. A quantum leap is needed.”
Author: Julia Bradshaw, The Telegraph
Link: http://www.telegraph.co.uk/business/2016/03/24/inside-pfizer-from-molecule-to-medicine/