Pushing the boundaries

26-Apr-2011

Setting up manufacturing operations in the rapidly developing Asian region is not without risks. Hans Ole Klingenberg, product director at Novozymes, discusses the reasons and benefits behind the opening of the company’s new hyaluronic acid facility in China

Setting up manufacturing operations in the rapidly developing Asian region is not without risks. Hans Ole Klingenberg, product director at Novozymes, discusses the reasons and benefits behind the opening of the company’s new hyaluronic acid facility in China

Recent years have seen double-digit growth in China’s biotechnology industry, transforming the country into one of the fastest growing in terms of biotech innovation. With the Chinese government recently publicising measures to boost its domestic biological industry through increased tax incentives and funding, China now offers a promising location for biotech companies looking to expand.

Novozymes was one of the first Western biotech companies to enter China and has more than 20 years’ experience in running and operating facilities in the country. With this experience in hand, the company is now looking to push the boundaries further and plans to be the first western biotech company to establish a wholly-owned GMP facility for manufacturing a biological API. Due to start production later this year, the new site will be a dedicated facility for the production of hyaluronic acid (HA) for biomedical and pharmaceutical applications. The site will operate under Novozymes’ global biopharma operations group, spanning facilities in China, the UK and Sweden.

Novozymes now offers a consistent source of high grade Bacillus-derived hyaluronic acid from its new production facility in China

Novozymes now offers a consistent source of high grade Bacillus-derived hyaluronic acid from its new production facility in China

HA is a naturally occurring polysaccharide that gives structure to tissues and contributes to optimal functioning of a number of biological systems in the human body. Due to its intrinsic biocompatibility, biodegradability, and diverse biological functions, HA is widely used in medical devices and pharmaceutical applications.

Novozymes’ Bacillus-derived HA is produced using the fermentation of the safe bacterial strain, Bacillus subtilis, a non-pathogenic host, the products from which are Generally Recognised As Safe (GRAS) by the US Food and Drug Administration. To achieve a high degree of purity, the process uses minimal media, no animal-derived raw materials and a proprietary water-based technology that eliminates the use of organic solvents and offers increased safety, batch-to-batch consistency and stability in large scale.

The new HA facility shares its location with Novozymes’ current operations in China. With more than 1,000 employees, Novozymes China now accounts for about 20% of its global staff and China is the company’s second largest market by region.

NNE Pharmaplan designed the hyaluronic acid plant located on Novozymes’ current site in China

NNE Pharmaplan designed the hyaluronic acid plant located on Novozymes’ current site in China

The new HA facility is run in full compliance with the ICH Q7 and cGMP (current good manufacturing practices) guidelines for API manufacturing and will enable all regulatory requirements for using HA in drug products to be met. This expansion also reflects the company’s philosophy of being a global business but dedicated to utilising local resources.

critical parameters

The company conducted an extensive selection process regarding the location prior to the design and development of the site and three critical parameters – current presence, resourcing and room for growth – were instrumental in the final decision.

The company was keen to take advantage of the team and processes already working at its existing operations in China and leverage this activity to function on a larger scale. By taking the logical next step of building on already existing operations, potential complications associated with developing a completely new site, such as reduced ownership and quality control, were avoided.

In line with the associated benefits of an established presence, a further consideration was access to resources. With more than 55 million trained scientists now living and working in China, there is a wealth of locally sourced engineers, operators and biotech-trained production individuals providing a significant resource for recruitment.

Future growth within the Chinese domestic biotech market was also a critical factor in the location of the facility. Recent business intelligence reports predict that the Chinese biotech market is expected to grow at a CAGR of 23% from 2007–2012.1 A local presence will enable the company to capitalise on this expanding market.

quality control

Strict measures are carried out at all the company’s facilities to ensure that, regardless of where the manufacturing site is located, the product quality is to the same global standard. To avoid quality control issues, it is essential for companies to be fully invested in every aspect of a site, with full transparency and ownership assured. The Novozymes facility has been designed to enable rigorous control of all activity within the site, alongside full compliance with cGMP regulations.

Novozymes hyaluronic acid is produced using an innovative manufacturing process that raises the current standards of purity, safety and consistency

Novozymes hyaluronic acid is produced using an innovative manufacturing process that raises the current standards of purity, safety and consistency

The facility was designed and built by engineering and consulting company NNE Pharmaplan, headquartered in Denmark, which has a reputation for delivering state-of-the-art facilities for drug manufacturing. In addition, Novozymes runs its own QC labs on site, testing and monitoring all incoming and outgoing materials. The new site also sources compendial grade (USP grade) raw materials and selects internationally recognised vendors, using a risk-based approach.

Overseeing all this activity is a team with extensive experience of running cGMP facilities in large international companies.

safety and delivery

The decision to implement cGMP operations in China is about breaking new ground and looking at new ways of manufacturing high quality ingredients. Along with the move to China, the technology utilised at the facility is a significant departure from traditional methods, which require the use of ethanol for recovery.

In contrast the Bacillus-derived HA technology uses water-based techniques in the recovery process and replaces traditional solvent-based techniques. Novozymes’ spray-drying method produces a very fine powder composed of microparticles that delivers performance benefits to customers.

Bacillus-derived HA is characterised by properties that include well-controlled and reproducible molecular weight, low poly-dispersity and long shelf-life. It is easy to dissolve and filter during manufacturing, and its exceptional heat stability permits autoclaving as a sterilisation option. Because of its novel source, the product is free of animal-derived raw materials and organic solvent remains. It can be used in a wide range of pharma applications, including improved drug delivery, as well as in medical device applications such as dermatology, osteoarthritis, ophthalmology, dermal fillers, adhesion prevention, coating, and wound healing.

Working with raw materials that are already Q7 compliant helps speed up processes and can greatly reduce testing time

Working with raw materials that are already Q7 compliant helps speed up processes and can greatly reduce testing time

Having assessed the main criteria (current presence, resourcing, future growth) and investment cost, China was determined as the ideal location for the new Novozymes’ HA facility and overall strategic expansion.

The risk of quality control in this location was carefully assessed by the company and dealt with through the implementation of significant control measures to ensure that standardised quality levels prevail. The company’s focus has been to deliver to its clients a more consistent source of HA, offering a high degree of purity while decreasing regulatory burden.

reference:

1. China Biotechnology Market, Report Buyer, http://www.reportbuyer.com/press/chinas-biotechnology-market-will-show-23-annual-growth-from-2007-2012/?doing_wp_cron

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