High on High-Potency

The announcement of Carbogen Amcis’ opening of a high containment facility in India raised the question of whether Indian CMOs could repeat their mastery in production architecture in the making of ultra-sensitive high-potency APIs.

Carbogen Amcis, which became a subsidiary of Dishman Pharmaceuticals & Chemicals Ltd. after the Indian CMO acquired the Swiss firm in 2007, started the high containment factory at Bavla, in the western Indian state of Gujarat, a couple of months ago.

The class IV facility is claimed to be the first of its kind in India. Class IV categorization, top-most in the four-tier rating scale of containment manufacturing, means the facility can handle even the most potent APIs with the least exposure to the handlers or with minimal impact to the environment.

High potency drugs – which comprise small molecules, complex biologics and combinations of both – are growing at a faster pace than the industry average globally, thanks to targeted therapy approaches. Currently valued around $100 billion, the market is forecast to grow at a CAGR of more than 8% through 2015 worldwide, driven by oncology drugs including cytotoxic compounds, the fastest growing HPAPI segment.

Explosive growth in demand for high-potency drugs in the therapeutics marketplace due to their widening usage across therapies could result in greater opportunities for CMOs that offer high potency APIs in coming years.

HPAPIs manufacturing, however, requires specialized handling. Unlike conventional ingredients, HPAPIs can be pharmacologically active in very low doses. Their high selectivity has the potential to cause cancer, mutations, developmental effects, and/or reproductive toxicity. Because of significant exposure risks to employees and the environment, HPAPIs are usually handled in specialized factories. Such high containment facilities can cost several times than that of normal drug manufacturing factories.

Know-How Via Acquisition

The Asia-Pacific region is also coming up fast in HPAPI production, although most of the HPAPI producers are presently centered on North America and Europe. Sensing the opportunity, Indian CMOs have already started drawing up plans to try out HPAPI production. These aspirants, though few in number, expect to take advantage of their process skills and cost arbitrage.

“Indian facilities can produce high potency APIs for less than half of their cost of production in Europe or U.S.,” claimed JR Vyas, managing director, Dishman Pharmaceticals.

Dishman, which has accomplished the task of setting up the class IV factory utilizing the technical support from Carbogen Amcis, expects to see returns from the huge investments reflected in its bottom line in the coming quarters.

The Bavla facility will produce HPAPIs including cytotoxic, cytostatic and narcotic substances to Carbogen Amcis on an exclusive basis. The Swiss CMO subsidiary will supply them to its clientele in Europe.

Dishman has plans to diversify production and expand the Bavla plant’s capacity at least four-fold from the current 20 cubic meters in next two or three years so that it can cater to more markets, including the U.S., Mr. Vyas added.

Piramal Healthcare also resorted to an overseas acquisition route to acquire expertise in HPAPIs. Pharma Solutions, the contract services division of the Indian generic firm, carries out the synthesis and manufacturing of prostaglandins, cytotoxics and antibody drug conjugates at its Grangemouth site in Scotland, UK, acquired from Avecia in 2005.

Other HPAPI players operating in India include Dr. Reddy’s, Ranbaxy, Cipla, Strides Arcolab, and Fresenius Kabi Oncology. Most restrict their activities to small molecules and are yet to explore the terrain of more complex biologics in a big way.

Expertise: A Vexing Issue?

Smaller companies like Hikal Ltd. of Mumbai or Neuland Labs of Hyderabad, among others, would also like to expand their franchise in HPAPIs in spite of the huge investment constraints. Even as the growing demand stirs up investment, some Indian CMOs that wish to build HPAPI capacities are facing with a hurdle. It is not about funding, but the challenge of acquiring the expertise. Experts well-versed in handling HPAPIs are far and few and know-how in the field is hard to come by, according to industry analysts.

“Expertise is a crucial issue. There is presently a big gap [in demands and production capabilities of HPAPIs],” commented Dr. Yasir Rowjee, senior vice-president, API division Matrix Laboratories, Hyderabad, southern India.

A subsidiary of U.S.-based Mylan Labs, Matrix’s HPAPI division focuses on tinibs or tyrosine kinase inhibitors such as lapatinib, dasatinib, erlotinib and nilotinib, which represent a new class of therapies that selectively target cancer cells.

While acquiring the know-how in niche segments to get into more complex HPAPIs continues a challenge for some, other CMOs find dearth of expertise in handling them hamper the rapid upgrade plans, at the moment. But these issues are only temporary, asserted Dr. Rowjee. Considering the steadfastness of Indian API makers, it won’t be that far they come through the learning curve.

S. Harachand is a pharmaceutical journalist based in Mumbai. He can be reached at harachand@gmail.com.