Chugai Pharmaceutical Bulk Antibody Production Plant, Utsunomiya, Japan

Chugai Pharmaceutical opened the first phase of their antibody production facility in Utsunomiya in Japan in the first quarter of 2004 following FDA approval along with validation and cGMP requirements being satisfied.

The second phase of the construction was started in May 2003. This is now completed and includes the addition of more bioreactor capacity than the original plan called for.

The company took a decision in late February 2005 to streamline their operations by integrating their existing five domestic plants into two at Utsunomiya and Fujeida. This will mean that the 21.9ha (54-acre) Utsunomiya plant will become their main facility for bulk production and the formulation of biopharmaceuticals (previously at Ukima). The final facility will, when the new phase three expansion is completed, be one of the largest biopharmaceutical production facilities in the world. Chugai now plans to spin off all of its production divisions into a separate subsidiary company by January 2006.

The total capital investment for phases one and two in the new facility amounted to some ¥14.96 billion: ¥5.6 billion for phase one and ¥9.36 billion for phase two. Phase three at Utsunomiya will also require additional investment but this has not yet been allocated; the company are concentrating on upgrading Fujeida first with an investment between 2005 and 2008 of over ¥20 billion.

The production capacity at Ukima will be gradually rationalised into the Utsunomiya plant from 2005-08 and any expansion of buildings will be carried out as required. Chugai will now produce biotechnology based medical products at the new Utsunomiya plant, including the recombinant erythropoietin Epogin and the recombinant human granulocyte-colony stimulating factor (rG-CSF) Neutrogin (Granocyte); this will include the formulation of the injectable versions of these products as well.

CONTRACTOR AND TIMELINES: PHASE ONE

Hitachi Ltd started construction of phase one of the antibody production facility in February 2001; building work was completed in January 2002 and the plant was fully equipped and outfitted by March 2003. The phase one facility commenced operations in January 2004 following final commissioning and validation. Hitachi provided the engineering, procurement, construction and validation services complying with cGMP.

The phase one facility had 8,600m² of floor space and was outfitted with two 10,000L bioreactors for experimental scale production of monoclonal antibody therapies. The first phase also has extensive preparation facilities, inoculation suite, media preparation, culture preparation tanks, downstream processing and separation suites.

The company's clinical trial / pre-commercial facilities included the two new 10,000L bioreactors and two 2,500L bioreactors at the Ukima plant in Tokyo.

CONTRACTOR AND TIMELINES: PHASE TWO

The phase two facility was constructed as a major commercial pharmaceutical production facility. Hitachi Ltd began construction in May 2003 and this was completed by January 2004. Amersham Biosciences supplied an integrated processing system including BioProcess systems, Chromaflow columns, affinity media (Protein A Sepharose) and ultrafilitration modules and also carried out some validation work.

The equipping and outfitting of the antibody production plant was complete by the second quarter of 2005 and operations will now start in the second quarter of 2006 following commissioning and validation.

The floor space of the phase two facility is 4,020m². The facility has six 10,000L bioreactors installed along with associated media, culture and inoculation preparation facilities. Phase two shares some of the infrastructure of the phase one facility.

Chugai upgraded its plans for the phase two facility in October 2003 by increasing the number of bioreactors intended from four to six.

TIMELINES: PHASE THREE

Following the completion of phase two the plant had a capacity of 80,000L, making it one of the largest facilities of its kind. Latest reports about phase three (late 2005) indicate that the capacity will be increased to over 90,000L.

This additional capacity will allow Chugai to conduct simultaneous development of several antibodies while producing bulk antibodies for the commercial market. This has become much more important because the company will no longer have the Ukima Plant. The Utsunomiya plant third phase (absorption of Ukima facilities and function) will be complete by 2008.

PRODUCTS AND PARTNERS

The Utsunomiya plant now produces several products including Epogin pre-filled syringes, Neutrogin, Granocyte, Epoetin Beta (recombinant erythropoietin) and Lenograstim.

The new phase two antibody facilities will initially be producing MRA, a humanised anti-IL-6 receptor monoclonal antibody (Atlizumab), which is expected to be a very effective treatment for Rheumatoid Arthritis (RA). Other indications, such as Castleman's disease, juvenile idiopathic arthritis, Crohn's diseases and multiple myeloma, are in clinical stages.

MRA is still in phase three clinical trials for RA in Japan, USA and Europe. Chugai have a strategic alliance with Hoffmann-La Roche (agreed in 2002) for the development of this treatment. The Utsunomiya plant will be crucial in establishing them as one of the largest potential commercial suppliers of these treatments.