The rebukes of Hazzard

Operating in the pre-launch and launch pharmaceutical arenas, Shasun Pharma Solutions manufacture advanced intermediates and APIs for products that have (i) already been approved by the FDA or relevant regulatory authority and (ii) are still navigating the labyrinth of requirements necessary for commercial launch.

Regarding the latter, pharmaceutical agents journey through a host of developmental stages prior to launch: from pre-clinical to phase one, two and three of clinical trials — a process which can take up to a decade. So, says Shasun’s President Kevin Cook, “A customer will come to us with a molecule for pre-clinical work, looking to us and our capabilities to develop a commercially viable process to get their product to market.” While initial production may peak at hundreds of grams, more often than not Shasun will be required to develop a manufacturing process that can deliver multiple tones of any given product. “Taking a molecule; designing a route of manufacturing; providing hazard evaluation capabilities, chemistry expertise and analytical techniques; offering the legislative and quality support so as to navigate the regulatory roadmap and allow safe and rapid scale up and, ultimately, commercialisation of the product — we do it all,” he says.

The Dudley-based business is a wholly-owned subsidiary of Shasun Chemicals and Drugs Limited, a manufacturer of active pharmaceutical ingredients, their intermediates and enteric coating excipients, trading out of Chennai, India. Beginning life in 1976 to produce Ibuprofen, Shasun’s parent company has grown to become one of the largest global suppliers of the anti-inflammatory drug — with an output exceeding 6,000 tonnes annually.

Not wanting to paint itself into a corner, during the last decade the organisation sought to diversify into adjacent products and markets, establishing a formulation and research facility in Chennai with a view to moving into the contract research and manufacturing services business.

Formed by the acquisition of Rhodia Pharma Solutions in 2006, Shasun’s UK arm was instituted to offer a vertically-integrated chemistry partner to its parent organisation and the wider pharmaceutical industry.

“Our business in the UK is purely for contract research and manufacturing, with approximately 40% of revenue generated through sales to big pharma and 60% from partnerships with Emerging and Biotech companies,” says Cook.

Safe passage
Priding itself on a world-class service provision regardless of customer, it is when dealing with emerging and Biotech companies that Shasun really comes into its own as a drug substance development one-stop shop. Although such entities are highly knowledgeable with regard to the biochemistry, mode of action and design of molecules, they often have little experience of scaling the process for full commercial delivery.

Explains Cook, “One of our core offerings relates to hazard evaluation capabilities, which allows Shasun to take on very challenging chemistries. With this appreciation of the raw components involved in manufacture, we understand which safety parameters need to be controlled for a given reaction and the envelope within which we need to operate in order to provide a safe and robust process.

We can therefore take on a range of processes which the majority of our competition may not be comfortable with.” “If the process is ‘stack it high, sell it cheap’ then it’s probably not going to be for us, and more than likely to be secured in China, for instance. However, if you require a extensive degree of customer involvement and high-service interaction, together with increasing complexity within the production process, we are ideally placed to bring value to the table — through our dedicated and passionate people, and drawing on over 40 years of experience within the industry,” he says.

Chiral technologies
Shasun operate from a state-of-the-art, fully equipped development centre at Dudley, Northumberland which, when coupled with its portfolio of proprietary technology, acts as an umbrella for the company’s research undertakings. Described by Cook as “little R; big D,” the application of such technology has enabled Shasun to develop and commercialise key intermediates for industryleading medicines in a cost-effective fashion: chirally pure drugs, for example.

For those unfamiliar with the term, a vast majority of pharmaceuticals exist as a right and left ‘hand,’ he explains. “Just as your hands can’t be super-imposed, while the chemical structure of the molecules is the same, the reactions they have within the body are very different.

So, if you consume what is known as a racemic mix one of the molecules is often inactive and lacks any medical benefit, whereas we can produce the single, chirally-pure, active molecule.” “This is a unique offering,” says Cook, “in terms of the technology we use to enable these advances. Moreover, we have a number of exciting technologies that the company is further developing — we are also looking at customers’ pipelines to understand how we can best apply our technologies and bring value to their supply chains.” The relationships Shasun enjoys with its customers vary greatly according to individual needs. Some, for example, simply require a number of kilos on at set date, while others wish to be on-site and play an integral role in the development and scale-up work that the company undertakes. Emerging Pharma and Biotech companies, being closer to the integrated mode and given that they have little or no manufacturing capability, are naturally keener to adopt the latter approach.

Lean, by any other name
Shasun is continually looking at its processes and the ways in which the company can both drive out fixedcost by collapsing cycle time and using any appropriate methodology to remove ‘waste’ and operations which don’t add value — having used Lean principles for the better part of two decades, and with two Six Sigma Black Belts currently on site.

“We have a particularly robust review process, undertaken at the monthly senior management meeting and falling under the banner of business improvement.

Indeed, everything we do is based around a project structure,” says Cook. Having identified a recent opportunity to capitalise on one of the company’s pharmaceutical intermediate products due to increased demand, the first option for many manufactures is to simply throw capital spend at the increase. “While it would be foolish to deny that certain projects require an increased capital outlay, Shasun equally looks at how to get the best out of our facilities, the result being that we regularly double productivity without major capital investment.”

Really right first time
A critical part of the company’s balance scorecard remains its quality indicators: process ‘right first time,’ for example.

With a development project target of 98% — which Shasun routinely achieves — Cook nonetheless highlights that a two per cent failure leaves questions still to be answered; undesirable for a company dedicated to the elixir of process research.

Accordingly, over the past six years Shasun has implemented ‘really right first time,’ incorporating documentation and process deviation indicators.

“Documentation right first time is perhaps the hardest thing to achieve, as you might have hundreds of pages of analytic and batch documentation, with fifty entries per page,” says Cook. Designed with involvement from the company’s operational team, a format which is both easier to complete but also fully compliant means that the document recycle is vastly reduced — with operational quality heightened throughout the organisation.

In addition to quality compliance, environmental compliance and sustainable chemistry are equally high on Shasun’s agenda. “The company is looking at what we call our ‘E-number’, which is related to investigating how many kilos of waste are produced per kilo of product,” he says. Once a process has been approved on the market, it is notoriously difficult to change it, given that the regulatory framework will have been established.

Resultantly, the company’s chemists are hard at work to develop evergreener methods of production, reducing the amount raw materials used and producing both less waste or wastes streams that are engineered to be easier to dispose of.

A key component of Shasun’s strength in this area is the on-site Biological Treatment Capability, established as a leading technology in 1993 and which remains one of the largest facilities in the UK. Says Cook, “In 2009 we took steps to exploit under-utilised capability within the facility and successfully commercialised the operation, having partnered with The William Tracey Group, a leading resource and recycling management company.” With Shasun’s capacity to treat aqueous waste with a high chemical oxygen demand, what was previously a cost centre has been transformed into a profit-making entity — providing a green waste option for the wider industry, to boot.

Splitting the difference
“Given our reputation for working with complex and hazardous molecules which require particularly careful handling, a number of customers have asked us to consider new projects involving highly potent materials,” says Cook. “We recently created a capability at our site to enable the research, development and supply of these substances, and we are seeing pleasing occupancy of the facility. The degree to which the products increase in scale will determine the next level of investment for this particular aspect of manufacture.” “We differentiate through our people and the way in which we do business, bringing world-class project management capability and 40 years of process and analytical development and scale-up experience,” he concludes. “With a comprehensive asset base to support the industry, a customer-focussed and service-orientated work force and our ability to handle the most problematic chemistries being requested by our clients, Shasun’s capacity to take those molecules which others in the industry may shy away from and develop them from discovery to commercial manufacture is one which our customers see as being especially beneficial.”