Health and wellbeing

When the factory was constructed in 1945, it began manufacturing fermented healthcare products, specifically penicillin. Following the purchase of the site by Lilly in 1963, the plant began to expand its product range, and in the late 1970’s was principally focused on the manufacture of protein-based products. Today, products developed for human use have been largely related to biosynthetic protein production, but the plant continues to produce several animal products which are derived from natural product fermentations.

Animal health
The Lilly corporation, based in the US, has a dedicated animal health business, Elanco, which has a global turnover of approximately $1.2bn.

Lilly Speke Operations manufactures animal healthcare products on behalf of Elanco, supplying approximately onethird of the division’s total products — with responsibility for around 400 end sale items.

With the UK site making such a considerable contribution to the Elanco global business, the company exports a great deal of its products. “We sell across most of the world, with only a relatively small proportion consumed in the UK,” says Alan Spreadbury, manufacturing leader for animal health. “The major Western European countries are the biggest market for this site, but we supply to countries throughout the world including North and South America, Asia and Australasia. Exports constitute up to 95% of what is produced on site.” The bulk of the animal health care products are used for the treatment of livestock such as cattle, swine and poultry. Elanco is, however, beginning to diversify into other areas, including treatments for companion animals as well as the growing animal vaccine market.

Human health
In addition to the animal market, Lilly Speke Operations produces two primary products for the human healthcare market: a biosynthetic hormone product and a treatment for multi-drug resistant tuberculosis.

Commercial team leader, Jon Westcott, says they supply the former into a relatively mature and stable market where it is used to treat hormone deficiency.

The treatment for multi-drug resistant tuberculosis is a product that Lilly Speke Operations has been making for nigh on 40 years. According to Communications and PR associate, Julie Stanley, in the last few years the product has become much more important due to the growing incidence of Multi-Drug Resistant Tuberculosis (MDR-TB) worldwide.

In 2003, Eli Lilly created the Lilly MDR-TB Partnership to help contain and ultimately conquer multi-drug resistant tuberculosis (MDR-TB), a disease so daunting that no single organisation can fight it alone. The Partnership, a publicprivate initiative, mobilises 22 partners on five continents in the battle to stop the spread of MDR-TB and save lives. Lilly has committed $120 million in cash, medicines and technology to increase access to treatment and focus global resources on prevention, diagnosis and treatment of patients with MDRTB.

“The WHO estimates that there are around 500,000 new cases every year of multi-drug resistant tuberculosis, of whom up to 150,000 may die” says Stanley. “Last year we supplied 1.1m vials of the medicine that we make on site to the World Health Organisation’s programmes. Even that quantity only treats a small proportion of the patients.

In 2008 we made more of this product than ever before, and last year we made even more again.” Interestingly, the Lilly MDR-TB partnership is both a public and private initiative that provides access to medicines, trains healthcare workers, raises awareness and promotes research and prevention, while providing support for communities and advocating on behalf of patients. In addition, Lilly scientists and engineers are working with partner companies in countries most affected by MDRTB to allow them to produce the drug themselves. “We have not just been supplying the product,” says Stanley, “we’ve been going countries that need it the most and working to dramatically increase the quantity of medicine available. These include India, China, South Africa and Russia, which are the four MDR-TB hotspots. Where necessary we have then also assisted in the development of manufacturing plants and other associated systems.”

Important improvements
Lilly Speke has invested a considerable amount of effort to ensure its business and manufacturing processes are operating as efficiently as possible. The site, in line with the global corporation, has adopted a formal six sigma program with a number of black belt-accredited key staff working fulltime on productivity initiatives within various teams. The site has also introduced what they term a green belt structure, where people train and deliver a project in an area in which they have a specific knowledge and day to day responsibility.

“We have seen a whole raft of different improvements within business process efficiencies, the supply chain and our asset and capital base,” says manufacturing information and Control Systems team leader and six sigma champion, Tracy Critchley.

“We’ve achieved some spectacular improvements in areas such as throughput in particular plants, where we’ve set up particular projects to work on where demand has been exceeding supply. One of the earliest successes was in one of our plants where we reduced the turnaround time by about 50% from one campaign product to another which gave us, together with another project, about 25% more days of extra capacity which translated directly into having more product available.

“Quite a significant number of our employees have been involved in various teams,” says Critchley. “We also have a whole communication strategy. We have a video bulletin board onsite and we typically post updates on every project running.

We really try and ensure that everybody understands how important productivity is to the organisation. We are also starting a yellow belt program this year to look at delivering the six sigma tools down to grass roots level.” Jon Westcott says another area of specific improvement has been the decrease in manufacturing deviations as well as a decrease in product rejection rates. “We’ve been able to demonstrate some significant reductions in those over a number of years, which have been the result of a range of different contributing factors including equipment improvements.” Each year, the site invests close to £7m into facility infrastructure, of which a considerable proportion is spent on equipment. “We have made investments around development and new technology, and have also been investing relatively steadily across existing equipment lines to replace, where appropriate, equipment,” says Westcott.

Impending changes
“The general environment that we are in is changing from an external perspective,” says Alan Spreadbury, referring to the increasing regulatory requirements within Europe for veterinary products which become part of the food chain — as well as greater competitiveness within the animal healthcare market. He says this has coincided with increasing demand for Elanco’s products in developing markets such as Latin America and China.

“We’ve seen an unprecedented rate of change, driven largely by the external market and the economics within the animal health industry,” says Spreadbury. “The impact on us as a site is really quite profound in terms of accelerating the changes that we need to make.” These changes have included a reduction in one of the site’s traditionally biggest product line.

Whilst there are other new types of technologies and new product lines which the company are pursuing, Spreadbury says the transition requires focussed management.

“We are having to deal with a lot of change where we are reducing in some areas and potentially increasing in others,” he says. “That change is something that is occupying a lot of attention. This involves a huge amount of in-house training. We are trying to manage some of the changes with our flexible temporary workforce, but permanent staff are also adapting as we move people from one area to another.” Continued focus on high levels of productivity whilst undergoing considerable internal adjustments will certainly test the capacity of Lilly Speke’s managerial team. However, with a firm grounding in operational best practice and the backing of a multi-national organisational structure, the site at Liverpool will undoubtedly rise to meet the challenge and continue to contribute significantly to the company’s overall success.

Eli Lilly and tuberculosis – a continuing battle
Tuberculosis (TB) is among the oldest of all historically identifiable diseases. Under different names, confused with other conditions, and often misdiagnosed, tuberculosis can be traced throughout history and in many diverse civilisations.

Pulmonary tuberculosis was known to the Greeks as phthisis, the word meaning “wasting away.” Hippocrates used the word to denote the inexorable, progressive, debilitating condition that seemed to affect primarily young people. Pale, emaciated, with difficulty breathing and racked by fits of coughing that sometimes produced flecks of blood, they died in the flower of youth.

For a certain period, it was believed that the bacillus that causes tuberculosis in humans was originally transmitted to man by animals, particularly cows.

But recently researchers reached the conclusion TB probably originated from an ancestral progenitor bacillus that infected the pre-hominids (apes) millions of years ago.

In Europe and North America the spread of tuberculosis reached epidemic proportions in the nineteenth century. The slums of teeming cities became cauldrons for the incubation of TB, and, as they boiled over, the disease spread to the upper classes and into rural communities.

TB is now a disease that is frequent and widespread and is especially prevalent in developing countries. It is estimated that over 90% of cases and deaths occur in such countries.

Industrialised countries are not spared and TB is still present, causing thousands of cases in Europe and the US as well.

In the developing world, TB incidence rates are highest in Africa, although about 60% of all cases of the world originate in Asia. Twenty-two countries are responsible for 80% of the global burden. These high-burden countries are India, China, Indonesia, Nigeria, Bangladesh, Pakistan, South Africa, Ethiopia, Philippines, Kenya, DR Congo, Russian Federation, Vietnam, UR Tanzania, Brazil, Uganda, Thailand, Mozambique, Myanmar, Zimbabwe, Cambodia, and Afghanistan.

Iain Richardson, senior director, global supply chain and logistics at Eli Lilly says that “by the middle of the 20th century, the common perception was that TB was vanquished with antibiotics so it disappeared from most peoples’ consciousness. Little known to us was that TB was still active and was still being treated. However it wasn’t being treated appropriately and so resistance to treatments has developed. Multi-drug resistant TB (MDR-TB) has developed and by definition it is resistant to some of the first line drugs that are used to treat regular TB.” In 2002 pharmaceutical company Eli Lilly, who produce two MDR-TB treatments raised concerns about the growing demand for its MDR-TB drugs.

In the same period, the World Health Organisation (WHO) also noticed a growth in instances of drug resistant TB. Discussions took place and an idea was developed for Lilly to partner with the WHO to help contain and ultimately conquer multidrug-resistant tuberculosis (MDR-TB), a disease so daunting that no single organisation can fight it alone. The result was the launch of the Lilly MDR-TB Partnership in Geneva in June 2003.

In addition to the supply of medicine, Lilly has undertaken the transfer of its manufacturing technology and information to other companies so as to keep up with demand. At the time of the Partnership launch, Lilly produced two MDR-TB drug treatments: cycloserine, which is an oral drug; and capreomycin, which is injected. “We have successfully transferred our technology to a number of partners,” says Richardson. “Lilly’s goal was to find partners in the areas most affected by MDR-TB which are China, India, Russia and the entire continent of Africa. We have partners in South Africa, Russia, China and India and then we have additional manufacturing partners in Greece and the US.” According to Richardson, a decade ago Lilly supplied approximately 100,000 vials of the drug capreomycin. Last year the company shipped over 1,200,000 vials. “So demand has grown ten times in ten years,” says Richardson. “We don’t market this treatment. It is a forty year old drug. There is no commercial interest on our side in terms of trying to sell more of this. It is purely demand driven. We primarily supply to the WHO, with less than 20% going to commercial markets.” The WHO estimates 500,000 patients develop MDR-TB every year. On average it may take 180 vials of capreomycin to treat one patient, one vial every day, as part of a lengthy regimen that may last up to two years. There are three injection drugs recommended in the WHO MDR-TB treatment regimen of which capreomycin is only one in the range. As Richardson says, the number of drug doses required to treat all cases is well beyond the production capabilities of any one single company. As a result of this realisation, Lilly decided that other partners would be needed to ensure adequate supply.

“We believe that based on current demand, when these partners are all approved, the capacity for production will exceed the demand,” says Richardson. “However the number of patients that the WHO hopes to treat is so high that these partners should all have a very healthy level of activity for some time.” The current focus of the Transfer of Technology program is to obtain regulatory approvals for Lilly’s partners. Several of the partners hope to become approved by their local regulatory agencies this year and, as a result, a number of them will automatically become WHO approved. Those that don’t qualify automatically have to undertake another regulatory approval process with the WHO called the pre-qualification process. Lilly anticipates that either this year or next year, all of the partners will receive the necessary approvals and the project will launch in to full scale operation.