East Meets West in Contract Biologics Manufacturing

The contract manufacturing organization (CMO) Kemwell (Bangalore, Karnataka, India) and Boehringer Ingelheim (BI, Ingelheim, Germany) plan to jointly build a biopharmaceutical manufacturing plant in Bangalore, India. The joint facility provides BI with low-cost production in Asia for its contract biologics manufacturing business and adds contract biologics manufacturing to Kemwell's toolbox.

A biologics marriage

The 15,000-m² facility will be designed for process development, fermentation, purification, and formulation of biologics for early-phase preclinical and clinical studies. The facility will have drug-substance manufacturing under current good manufacturing practices, sterile fill–finish, and process development to support production of therapeutic proteins from mammalian-cell culture or microbial fermentation. Kemwell will provide in-house expertise in toxicology and clinical development and partner with Indian contract research organizations (CROs) to manage toxicology and clinical studies in India.

Building the toolbox

Kemwell's contract-service capabilities are largely centered on formulation development and secondary manufacturing. Its Bangalore site manufactures tablets, semisolids, and liquids and provides pharmaceutical development services. It also performs contract manufacturing of small-molecule active pharmaceutical ingredients (APIs) at its facility in Uppsala, Sweden. The Uppsala facility also produces and packages tablets and suppositories and has annual capacity of one billion tablets. Kemwell acquired the Uppsala facility from Pfizer (New York) in 2006.

Kemwell's pact with BI is its third alliance with a Western CMO or Big Pharma company during the past 12 months. In November 2008, Kemwell set up a research and development (R&D) facility in Bangalore in partnership with GlaxoSmithKline (London) for developing oral healthcare products. In April 2009, Kemwell formed a strategic pact with the CMO Patheon (Toronto) for client referral and marketing services. The latter deal provides Kemwell with aseptic and high-potency manufacturing and gives Patheon low-cost manufacturing for solids, semisolids, and liquids and related development services in India.

The Kemwell–BI facility provides BI a low-cost manufacturing base in Asia. BI produces biologics captively for its own products and its contract-manufacturing business. BI's contract business produces biological drug substances, finished-drug products, and pharmaceutical chemicals. Under the pact, BI is contributing access to its BI-HEX cell-line development process, large-scale commercial production at its European facilities, and client referrals.

BI's European biopharmaceutical facilities are in Biberach, Germany, and Vienna, Austria. The Biberach facility focuses on mammalian-cell-culture technologies, which include the BI-HEX expression system, for producing high-volume protein therapeutics, primarily monoclonal antibodies. BI's Vienna facility uses microbial and yeast-based fermentation to produce therapeutic proteins, protein subunit vaccines, protein scaffolds, antibody fragments, and plasmid DNA for gene therapy, according to BI's 2008 annual report.

Deepening the relationship

The Kemwell–BI joint facility represents two important turns to pharmaceutical outsourcing in Asia: the entry of an Indian CMO in contract biologics manufacturing and a joint facility by Indian and Western CMOs. Unlike the established market for contract small-molecule manufacturing, contract biologics manufacturing in India and China is emerging. Indian and Chinese CMOs compete with Western CMOs in contract small-molecule manufacturing, particularly in early-stage intermediates and generic APIs, and to a larger degree Indian CMOs compete in advanced intermediates and custom APIs. Pure-play CMOs for biologics manufacturing in India are less common and largely serve the domestic market (1).

Recent deals between Western CMOs and pharmaceutical companies with Indian CMOs have involved outright acquisitions of companies or production facilities as well as strategic alliances. These moves have strengthened Indian CMOs' positions in North America and Western Europe and given Western companies access to lower-cost production.

Some notable deals include Piramal's Pharma Solution's (Mumbai) acquisition of Pfizer's former primary and secondary manufacturing facility in Morpeth, United Kingdom (UK), in 2006, and of Avecia's custom-manufacturing business and related manufacturing facilities in the UK and Canada in 2005. In 2008, Dr. Reddy's Laboratories (Hyderabad, India), bought Dow Chemical's (Midland, MI) small-molecules business associated with its UK sites, as well as BASF's (Ludwigshafen, Germany) manufacturing facility in Shreveport, Louisiana, and related contract-manufacturing business for finished pharmaceuticals. Dr. Reddy's started building its custom manufacturing business in 2005 with the acquisition of a former Roche API manufacturing facility in Cuernavaca, Mexico.

Dishman Pharmaceutical & Chemicals (Ahmedabad, Gujarat, India) bought the Swiss-based CMO Carbogen Amcis and I03S, a company specializing in ozone chemistry, in 2006, and the UK-based contract-research company Synprotec in 2005. In 2007, Dishman acquired Solvay Pharmaceuticals' (Brussels) fine-chemicals and vitamin businesses, which included facilities in The Netherlands, and the intellectual property rights for fine chemicals, vitamin D, and vitamin D analogues (4). Jubilant Organosys (Noida, Uttar Pradesh, India), made two key acquisitions in contract secondary manufacturing: Hollister-Stier Spokane, WA) in 2007and Draxis (Montreal) in 2008. And in 2006, Degussa (now Evonik, Essen Germany) formed a long-term, nonexclusive agreement with the Indian CMO Hikal (Mumbai), India) for Hikal to supply advanced intermediates and APIs (3).

Joint facility development and ownership are far less common, although there are some examples. The CRO/CMO Syngene (Bangalore), a subsidiary of the biotechnology company Biocon (Bangalore), opened a dedicated R&D facility for Bristol-Myers Squibb (New York) earlier this year. The CROs Covance (Princeton, NJ) and WuXi Apptec (Shanghai) had announced plans for a joint preclinical facility in 2008, but Covance later announced that it would build the facility alone.

Patricia Van Arnum is a senior editor at Pharmaceutical Technology and guest contributor for Jim Miller while on vacation, tel. 732.346.3072, pvanarnum@advanstar.com

Reference

1. P.Van Arnum, "Assessing Market Opportunities in Contract Biologics Manufacturing," Pharm. Technol. 33 (5), 56–60 (2009).