Pharma builds recognised for excellence

In the 2015 Facility of the Year Awards (FOYA), three of the winning projects involved new GMP facilities with cleanrooms for producing modern medicines safely and more cost-effectively. Cleanroom Technology reviews these winning projects

IDT Biologika won the 2015 FOYA Award for Facility Integration at its biologics and vaccines production facility in Dessau, Germany

First established in 2004, the International Society for Pharmaceutical Engineering (ISPE) FOYA programme recognises state-of-the-art pharmaceutical manufacturing projects that utilise innovative technologies to enhance the delivery of a superior project, as well as reduce the cost of producing high-quality medicines. Projects selected for these prestigious awards set the standard for pharmaceutical facilities of the future by demonstrating excellence in: Project Execution, Facility Integration, Equipment Innovation, Sustainability, Process Innovation and Operational Excellence. A global judging panel of executive leaders assesses and designates winners in each of these six categories, when merited.

Project execution

AstraZeneca (AZ) China won the FOYA Project Execution category for its market supply solid dose facility located in Taizhou, China. AZ’s ‘in-country’ team used a broad range of global engineering, operations and safety practices to complete this 533,000ft2 (50,000m2) facility in a record time of 20 months. With a total investment cost of €148m the project ran from January 2011 to 2013 and the facility came in 18% under the sanctioned budget while maintaining an exemplary safety record.

This project represents Phase I of a planned three-phase, greenfield site development in Jiangsu Province, China, on the China Broad Market manufacturing site, in the medical city, Taizhou. The project comprises sterile dry powder filling for injectable cephalosporin products, and oral solid dosage (OSD) products.

This facility is capable of formulation, tableting, labelling, packing and distribution operations and it represents AZ’s largest ever investment in a single manufacturing facility globally.

A very significant characteristic of this project has been the effort to keep things simple and not ‘over-engineered'

The contractor providing procurement and construction management services for the plant was Cockram. The scope of its contract included offering construction services with a 40-member professional construction crew for two years.

NNE Pharmaplan, meanwhile, handled every aspect of the project from conceptual design to commissioning and qualification, with the exception of construction management. It says the facility was built with the mantra ‘fit for purpose’ in mind. ‘A very significant characteristic of this project has been the effort to keep things simple and not ‘over-engineered,’ said NNE Pharmaplan Project Director, Kenneth Borch Larsen.

‘AstraZeneca wants to ensure that this project reflects new ways of thinking in OSD plant design with focus on cost-efficient solutions,’ he added and explained that this was reflected, for example, in the agreed sourcing strategy, which meant that very little process equipment was imported for the project.

AstraZeneca China won the FOYA Project Execution category for its market supply solid dose facility located in Taizhou, China

Programmes including a fully integrated project execution team (One Team/One Goal) incorporating all key internal and external stakeholders, and a Plan-to-Do Review (PDR) process helped drive this project to success. Hiring and training focused on developing locally available employees as part of AZ’s ‘Farmers to Pharmaceuticals’ aspiration for this project. Some 89% of final staff were hired and trained locally. Training included the use of early mock-up training areas and temporary assignments to other AZ facilities. As a result, attrition rates were a lot lower: 6% versus much higher rates routinely experienced in China.

To achieve cost targets while maintaining global operating quality standards, AZ focused significant effort on local sourcing. It says 32 of some 37 major equipment packages and numerous key building components, such as the cleanroom wall systems, were successfully sourced locally in China. Quality was maintained through an aggressive programme of vendor support, including in-factory engineering monitoring and training.

Facility integration

IDT Biologika, a member of the Klocke Group and a contract manufacturer of biopharmaceuticals and vaccines, was the recipient of the Award for Facility Integration for its biologics and vaccines production facility in Dessau, Germany. The highly automated manufacturing facility for filling and freeze-drying is designed to be modular, efficient and expandable. The site’s layout was devised to guarantee the shortest supply and disposal routes. Design of the integrated equipment suite has resulted in efficient product changeover and increased efficiency.

IDT Biologika is involved in animal health, vaccines and pharmaceuticals fill-and-finish. Vaccines and all final drug products are produced using the highest biotechnological standards of the international markets. The facility has been designed and commissioned for employing a range of advanced biomedical technologies in medium-to-large clinical stage and commercial stage volumes. Included is a sterile liquid filling line engineered to handle up to 24,000 vials/hour within a 1,600m2 cleanroom area. This facility is certified to biosafety levels (BSL) 1 and 2 for live vaccines. Inspected for GMP certification in July 2014, qualified (for IQ, QQ and PQ) in September 2014 and authorised for manufacturing in October 2014, the facility is now fully operational.

The concept behind the multipurpose facility consists of strict horizontal division of the service areas

The concept behind the multipurpose facility consists of strict horizontal division of the service areas. The production area is located at the building’s centre with a maintenance level and air conditioning systems located above and the media supply for the production area below. The layout was devised to guarantee the shortest supply and disposal routes. Design of the integrated equipment suite represents significant contributions in operational excellence, including three isolator segments for high flexibility and fast product changes, resulting in efficient product changeover and increased efficiency.

Key to the efficiency of the new facility is a fully automated loading and unloading freeze dryer at shelf capacity of 40m2 each, equal to a maximum 178,000 vials/batch that is fully integrated into the isolator.

‘Designed to be modular, fast and expandable, the IDT Biologika facility is now one of the most flexible biologics operations in the world certified to biosafety levels (BSL) 1 and 2 for live vaccines,’ said Dr Andreas Neubert, Head of IDT’s Business Unit Vaccines. ‘Creating a “future-proof” and flexible production structure has given IDT the leeway it needed to move a number of projects quickly from the incubator, to fill-and-finish, freeze-dry, storage or market with state-of-the-art quality, better economics and operational efficiency.’

Particle and microbiological tests, repeated camera inspections, 100% fill volume controls, vial coding and washing of capped vials assure the highest quality filled vaccines

IDT Biologika expanded its vaccine production facility from two to three buildings, extending its capacity for large scale commercial production of new human vaccines. With expansion and integration complete, the company is now equipped to manufacture up to 100 million vials a year of freeze-dried and liquid presentations.

Particle and microbiological tests, repeated camera inspections, 100% fill volume controls, vial coding and washing of capped vials assure the highest quality filled vaccines. The new isolator filling line can be expanded with two additional 40m2 freeze-dryers for scaled-up commercial supply. Furthermore, the building concept allows the implementation of an additional filling line effectively to double manufacturing capacity upon request.

Honourable mention

Pharmalucence Pharmaceuticals received an honourable mention for the execution and entrepreneurial spirit demonstrated in the construction of its new 70,000ft2 aseptic filling facility in Billerica, MA, US. Through good planning and prioritisation, the company met the challenge of balancing investment, appropriate compliance, efficient operations and business viability.

Pharmalucence is a New England-based manufacturer of human injectable pharmaceuticals. It has chosen to implement what it believes is the most advanced approach to aseptic processes, with an eye towards the highest levels of regulatory compliance.

The company recognised that a significant change was needed to ensure the long term availability of its product supply and viability of the business

The company aseptically fills and finishes a portfolio of legacy and generic radio-pharmaceutical products, many of which are in market shortage. The existing operations, housed in four separate rental facilities, were in need of modernisation. The company recognised that a significant change was needed to ensure the long term availability of its product supply and viability of the business. Given limited financial resources, the challenge was to plan, prioritise and implement effectively the upgrades needed for full regulatory compliance and product supply integrity, all within a competitive business model.

The company took the bold decision to consolidate the four existing operations into a single modern facility. An existing facility large enough for these objectives and near enough to retain existing staff was identified. Using QbD principles, the facility was designed with the project deliverables well defined to minimise costly delays and changes. RABS and isolators were fully compared and for these particular aseptic processing needs, isolators proved the most cost-effective solution.

The project implementation plan took into account the existing lease obligations, product supply obligations and construction timelines. New areas were prepared and equipment transferred to correspond with the expiration of leases for economic efficiency. The completed facility is fitted with high quality finishes and an installed equipment base consistent with industry best practices. The use of risked-based commissioning, qualification, validation (CQV) helped to ensure a quick and effective operational start-up.

Its new commercial vial filling line features full integration; automated and isolated aseptic filling; piston and peristaltic pump technology; 100% fill check by weight on all vials; low oxygen filling for oxygen-sensitive products; and 2ml to 100ml vial sizes. The facility is designed to produce both aseptic and terminally sterilised (liquid and lyophilised) small volume parenteral products.

In addition, Pharmalucence currently manufactures its own line of diagnostic commercial products (non-radioactive radio-pharmaceuticals) and a number of products on a contract basis for pre-clinical, clinical and commercial needs.

Pharmalucence Pharmaceuticals received an honourable mention for the execution and the construction of its aseptic filling facility in Billerica, MA, US

The manufacturing scale at the new Billerica site is up to 34,000 10cc vials per batch for lyophilised products and 14,000 10cc vials for terminally sterilised products. The filling line, manufactured by Bosch, is fully isolated. The IMA/Life lyophiliser includes an auto load/unload system. The line is designed to handle vial sizes from 2cc to 100cc and incorporates 100% fill check by weight. The filler has the capability to dispense product solution by peristaltic or piston pumps.

The Pharmalucence QC group maintains a full range of analytical test equipment and has extensive experience with the transfer and validation of methods. Pharmalucence services include access to a cGMP warehouse with refrigerated and freezer storage for incoming material, intermediates and/or drug product. Full ICH (International Conference on Harmonisation) stability storage is also utilised.

Product classes currently manufactured in the facility are all non-potent, non-cytotoxic. All product manufacture is supported with specific cleaning validation. Pharmalucence has extensive manufacturing expertise with small volume parenterals, including fill volumes ranging from 0.5ml to 5ml. All products undergo 100% visual inspection. The company maintains a full complement of labelling and packaging operations.

The contract for the facility’s architectural design, engineering and construction was awarded to Integrated Project Services (IPS), a Pennsylvania based full-service engineering company, in June 2011. The facility features state-of-the-art automation and employs barrier isolation and equipment from Robert Bosch Packaging. Pilgrim Software is providing information technology to allow Pharmalucence to advance from a manual to a fully automated compliance system.

The facility is modular and designed to accommodate two automated suites featuring barrier isolation. The first suite can automatically feed two 180ft2 lyophilisers. The plans involved a second suite equipped to handle highly potent compounds. This suite mirrors the design of the first, but shares no infrastructure that would compromise the full separation of the high potency operation. The second suite also feeds two similarly sized lyophilisers.

The 2015 FOYA Overall Winner will be announced during the plenary session at the 2015 ISPE Annual Meeting on 8–11 November in Philadelphia, Pennsylvania.

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