Chao Center for Industrial Pharmacy and Contract Manufacturing, West Lafayette, IN, USA

The Chao Center for Industrial Pharmacy and Contract Manufacturing is based in Purdue Research Park, West Lafayette, Indiana and linked to the Purdue University department of Industrial and Physical Pharmacy and Pharmaceutical Sciences. The facility is one of only five university-affiliated pharmaceutical manufacturing centres in the US.

The centre required an estimated investment of $8m to construct. Allen Chao, a Californian Purdue University alumnus, donated the bulk of the investment. Dr Chao, chairman, president and chief executive officer of Watson Pharmaceuticals Inc, and his wife, Lee-Hwa Chao donated a $5m gift in 2001 towards the construction and outfitting of the12,000ft² pharmaceutical manufacturing and development facility.

Chao earned his PhD in industrial and physical pharmacy from Purdue in 1973. His wife, Lee Hwa-Chao, earned her BSc in pharmacy from Purdue that same year. Chao founded Watson Pharmaceuticals in 1983. The company develops manufactures and markets branded and off-patent niche or generic pharmaceutical products. The Chao Center is a joint project involving Purdue University and Elli Lilly and will also work with the Purdue College of Pharmacy, Nursing and Health Sciences, which is a centre partner.

The construction of the facility, which began in 2003, was completed in early 2005 and was opened officially on 13 October 2005.

Legacy drugs and the fight with tuberculosis

The cGMP-compliant facility will assist with the development and production of legacy drugs, which are drugs for diseases and conditions that affect the underprivileged, especially in third-world countries, as well as less profitable drugs that are made in small volumes for the treatment of specific diseases.

The first drugs to come off the production line are expected to be antibiotics that are effective for treating multiple-drug resistant tuberculosis (MDR-TB) or extreme drug-resistant TB (XDR-TB). The combination of drugs needed to eliminate the TB bacteria from a patient’s system are often not available – or when they are available, are not administered in the necessary quantities or for a sufficient period of time for them to be totally effective.

The TB bacillus can then become resistant to standard treatment, and two specialist antibiotics – capreomycin and cycloserine (seromycin) – are needed to fight it.

More than 450,000 new cases of this form of TB were reported in 100 countries in 2004. Out of nine million cases of TB in the world, around 180,000 are of the new extreme drug-resistant strain, which is almost untreatable.

The centre's mission includes pharmaceutical education, development and manufacturing for students of Purdue pharmacy and pharmaceutical science. It also calls for its participation in the development of the next generation of pharmaceutical manufacturing professionals.

Eli Lilly generously offered to assist several developing countries fight TB by transferring the specific technology necessary to produce these two drugs and assist in their start-up efforts. Under a partnership with Eli Lilly, the Chao Center agreed to produce the drugs, which Lilly was to distribute, and the centre to then assist with training programmes to allow developing countries to manufacture these drugs and others using well-founded general manufacturing principles and quality standards through good manufacturing processes.

In May 2007 Eli Lilly awarded the Chao Center exclusive rights to manufacture, distribute and sell the multidrug-resistant tuberculosis drug cycloserine (Seromycin). The drug is expected to be available to consumers in the US, Canada, Puerto Rico, Guam and the US Virgin Islands.

Martin C Jischke, Purdue president, commented: "This agreement places the Chao Center among the first university-affiliated contract manufacturing organisations to receive rights to a commercially available pharmaceutical drug product... It enables Purdue's Chao Center to join Lilly in its initiative with the World Health Organization to fight multidrug-resistant tuberculosis."

Prior to selling seromycin, the Chao Center was required to have its manufacturing process validated by the US Food and Drug Administration (FDA) and secure regulatory approval. This process was completed in July 2008 when the FDA approved the centre to manufacture seromycin under its own brand name using the process transferred by Eli Lilly. Prior to this, in March 2008, the Canada government permitted the Chao Center to sell seromycin directly to physicians in Canada under the Health Canada Special Access Programme.

With the FDA approval, the Chao Center became the first university-affiliated prescription drug manufacturer in the US. During the period prior to approval, Eli Lilly manufactured seromycin and supplied the centre with the drug for sale and distribution.

Design and construction

The Allen Chao Center for Industrial Pharmacy and Contract Manufacturing was coordinated and designed by Purdue Architects and Lockwood Greene / CH2MHill. The Engineering, Procurement and Construction (EPC) contract was also awarded to Lockwood Greene/CH2MHill.

The construction was completed in two phases with phase one encompassing conceptual, preliminary and detailed design work. This was followed by phase two EPC and validation. The manufacturing centre design included 2,000ft² of office space including two conference rooms, 10,000ft² of good manufacturing process space that included a multi-use analytical and drug-development lab, five multi-use rooms, a drug packaging room, areas for handling materials and for cleaning equipment, a warehouse facility and a viewing corridor that allows pharmacy students to see the manufacturing process in action.

Under federal regulations, the cGMP areas were required to be completely secure, operate under differential air pressure and be manned by highly trained individuals. Air handlers exchange old air for new 20 times an hour within the manufacturing area, which has nonporous floors that are easily cleanable.

In addition to the new building, the centre also makes use of 6,500ft² of space for pharmaceutical, analytical and formulation development within the Purdue Technology Park.

Staffing and structure

Student interns supported the efforts of half-a-dozen initial employees. There were 18 employees by the end of 2005 and the centre eventually employed 19 full-time staff, including three adjunct faculty members. Most of these positions required a college degree, with the exception of a few technician positions.

In the long-term it is expected that the centre will support approximately 50 high-skills, high-wage careers. Purdue Research Foundation and Elli Lilly Corporation are administering the centre as the largest shareholders in the Chao Center's Limited Liability Corporate (LLC) structure. The staff include some well-known Purdue names: Craig Davis, PhD is the Center Director; Joseph Stowell, PhD is the Director of Quality Assurance and Associate Director of Education and Gerald Thomas is the Business Development/Project Manager.

The centre is not only working with legacy drugs and multi-resistant TB but also on several other projects, including: formulating a dosing procedure for a powder-based product, manufacturing placebo tablets for use in a human clinical trial, and formulating and manufacturing a new oral spray drug-delivery technology.

Services and equipment

Specific services provided to clients include preformulation, formulation and analytical development; the preparation of regulatory submissions; and the manufacturing of non-sterile solid and liquid pharmaceutical products (tablets, capsules, semi-solids, syrups, suspensions and over-encapsulation) for clinical trials and commercial sale.

Centre services include:

• cGMP manufacturing
• Dosage form preparation and blinding
• Open and blinded clinical packaging and labelling
• Semi-automated over-encapsulation; granulation, tableting, encapsulation and coating
• Schedule II–IV control drug manufacturing
• Analytical services
• Dissolution testing
• Stability testing
• Purity testing
• Impurity identification
• Particle-size determination
• Compatibility testing
• Solubility screening
• Hygroscopicity studies
• Method development and validation
• Chromatography
• Controlled drug substances testing
• Cytotoxic drug substance testing

The centre's drug manufacturing equipment includes:

Tablet press: Manesty Betapress, fully instrumented for ejection and compression monitoring and producing 750 to 1,500 tablets per minute.

Capsule filler: Zanazi 40E, vacuum-assisted powder fill producing 40,000 capsules per hour.

Granulator / coater: Diosna high-shear granulator Model P10-60, bottom drive impeller, side mounted chopper / intensifier with 10L, 25L, and 60L capacities. Fluid Air Model 20 fluid bed processor with a Wurster coater, top and bottom spray and a 45L / 5kg capacity. AccelaCota Compu-Lab with interchangeable fully perforated 12in, 15in, 19in, 24in pans and a 25kg capacity.

Blending: Kinetics Tote System blender with a 1.5ft³ bin.