Source : IN VIVO
No noise and no drama. It is a precept that has been keenly respected by the staff and management of BTG Specialty Pharma over the past few years, much to the pride of its president, Anthony Higham.
In November 2018, Boston Scientific Corporation announced the $4.2bn purchase of UK group BTG plc, which had built a strong position in interventional medicine with a series of astute M&A moves. It closed the deal in August 2019. ()
Anthony Higham ran technical operations at GSK before joining BTG
Predating that was BTG’s accumulation of expertise in niche pharma and antidotes, which began with the purchase of Protherics in 2008. Boston sold BTG’s licensing business royalties in late 2019. Specialty Pharma was also not a good fit, so Boston, the 11th leading medtech by sales globally, set about finding a new owner, carefully keeping the process out of the public view.
The arrival of COVID-19 in 2020 complicated matters, and Brexit was looming, which forced all health care product manufacturers, in the UK especially, to scrutinize supply chain stability and the continuity of their manufacturing operations.
While BTG SP needed to find a future away from Boston, the pressure was on to ensure that the business and its 280 staff quietly and efficiently continued operations as usual. It was crucial to avoid any ripples that would prompt questions about Boston’s purchase of BTG. Higham stressed that Boston handled the transaction with care, and was eager to ensure the suitability of the new owners.
The collective efforts paid off when BTG SP and Belgian-based SERB Specialty Pharmaceuticals SA on 1 December 2020 announced a definitive merger agreement, ending a remarkable period of self-control and discipline at the UK company. The purchase of BTG SP for $800m closed on 2 March 2021. ()
Meanwhile, the pandemic was making life very hard for pharma and health care product manufacturers. However, BTG SP was able fall back on contingency plans for the products in its portfolio, including its leading product, CroFab, which is the antidote to envenomation by rattlesnakes and other crotilinae in North America.
CroFab made sales of $132.4m in 2018-19, 49% of the speciality pharma division’s sales. The product was not itemized in Boston’s FY2020 10k, but BTG SP’s overall revenues were reported as $219m. With a relatively COVID-resistant portfolio, BTG SP exceeded budgeted sales by 5% in 2020. Because the pandemic impacted elective procedures where most Boston Scientific devices are used, no other Boston group division was able to hit target, Higham told In Vivo.
Even under BTG, specialty pharma latterly received less attention after the strategy turned towards interventional medicine. But BTG SP communications director Chris Sampson said it was always a highly profitable business and provided much of the cash used to build the interventional business through acquisition.
The need to keep CroFab’s manufacturing and supply chain intact during the pandemic was paramount. The market in North America is growing, and BTG SP recently gained a Mexico-based market competitor.
CroFab has a uniquely complex production pathway spanning three continents and five global logistics stages. In spite of that, BTG SP had an advantage over many pharmas during COVID. “We’ve tried over the years to introduce a degree of robustness and resilience into the supply chain, and that benefited us in 2020 in terms of having a pretty fault free supply for the 2020 bite season (April to September),” said Higham.
BTG SP’s snake colony is kept in a facility in Utah. Extracted venom is sent to a sheep facility in the Barossa Valley, Australia, a country with a WHO disease-free classification, stringent quarantine and high levels of biosecurity and animal welfare. Minute quantities of venom are injected into the specially reared sheep to produce antibodies.
The sheep’s blood is sent to an antivenom manufacturing facility in Wales, where BTG uses purification equipment and makes its own chromatography columns using the snake venom. It uses two viral filtrations steps, which is an expensive part of the process. “The purification of our product is close to 100%,” said Higham, adding that the rival (Anavip, from Instituto Bioclón) cannot compare.
The product is then sent back to the US for freeze drying and packaging to complete what many observers believe to be the most complex and global supply chain in the industry. Higham would agree. “After 30 years in industry, I’ve not come across anything as complex as the ovine polyclonal network,” he said.
Higham is sometimes questioned about why the entire process for North American snakes cannot be done in one country. His reply is that that the added expense of BTG SP’s manufacturing process is worthwhile, given the value of Australia’s certified disease-sheep into the quality of the product.
There are two options for supply chain: made to order; and made to forecast. Higham indicated that given the lead times to produce its products, BTG SP needs to estimate what will be sold in two to three years’ times.
So BTG is not a “just in time” manufacturer, and as it transpired when COVID hit, strategic stocks were the logical answer to any likely supply issues. A policy of building inventory at various locations ̶ buffer stocks of serum are held in Australia and the UK ̶ allowed the continued manufacturing of CroFab and the digoxicin toxicity treatment, DigiFab, without delay, disruption or compromised quality.
Higham has a background in manufacturing. Before joining BTG some 10 years ago as head of operations, he ran technical operations for GlaxoSmithKline plc at 30 sites, including CMC (chemistry, manufacturing and controls), engineering, new product introductions and portfolio management. In 2015, he was made BTG head of the specialty pharma business, in addition to running all BTG manufacturing.
Higham is likely to have responsibilities across the combined BTG/SERB group, and tasked with creating a common identity for the merged company.
Moreover, his manufacturing experience has given him expertise in risk minimization and risk management, key factors for business continuity, and vital should an unexpected disaster striking the operation. In the Barossa valley, for instance, there is a major risk of bush fires, as seen on a devasting level in 2020.
Some 5,000-8,000 snake bites occur in North America in a typical year. Higham targets having products on the shelf as of 1 April to meet that demand. Sometimes stock must be increased for spikes in demand, for instance after flooding events that drive snakes out of their habitats and into contact with people.
“Over the past five years, we’ve developed the supply chain so that we are buffered for some very short-term increases in demand. We’ve always had sufficient stock across the supply chain,” said Higham, adding that the company has not failed to fill an order in 15 years. It has also increased the shelf life of CroFab from three to five years, which gives the supply chain more resilience, he added.
BTG SP holds two years’ worth of stock of ingredients, the serum and drug substance, and knows it can if necessary get more production up and running within that timeframe.
The inbuilt resilience has been helped by having an understanding board that is aware of both the stock holding costs and of the need to keep sheep on the farm that are not productive until they have reached 18 months of age.
Before COVID hit, the company’s operational contingency planning was directed at the disruption that the UK’s EU exit would cause it. “We were focused on Brexit and life after that,” said Higham. The company was focusing attention on how to get its Voraxaze (glucarpidase) antidote product and DigiFab antidote product into the EU.
Voraxaze is a carboxypeptidase indicated to reduce toxic plasma methotrexate concentration in adult and pediatric patients with delayed methotrexate clearance due to impaired renal function. DigiFab is a treatment for patients with life-threatening or potentially life-threatening digoxin toxicity or overdose. It clears digoxin from the body.
“Decisions on moving products were an extension of our preparation for Brexit,” said Higham. “When COVID hit, after Christmas 2020, we decided to clear the whole of the drug substance out of Wales and get it into the US, as we weren’t sure what COVID would do.”
This policy paid off during the pandemic. “In hindsight there is nothing we would have differently, and that’s a pretty big tick in the box,” said Higham. “We had logistics all in place. We lost no sales and were able to provide product for every patient.” Not everyone had such a positive experience during 2020, he observed.
Manufacturing is not straightforward, he added. “As a manufacturing person at heart, I know you’ll always get issues at a plant, but you’ve just got to make it work as a business. I’m proud of that ethos.” It might be a cliché, but for BTG SP, in the most unstable of periods, “no noise, no drama,” seems to have worked out well.
By Ashley Yeo