Contract Manufacturing, Biopharmaceutical Production

Discovery Laboratories (Warrington, PA) could see the end of its struggle to launch its Surfaxin (lucinactant) drug on the US market soon, as the manufacturing issues it has faced have been resolved.

There wasn't much of a contract services industry when BioPharm International began publishing 20 years ago. Today's big names in biomanufacturing, including Lonza, Boehringer-Ingelheim, and Avecia, had not yet entered the business.

From the earliest days of the biotechnology industry, companies have grappled with the complexities of making innovative biopharmaceuticals on a large scale. Success in manufacturing begins with process science, since biotech production requires perfection in maintaining living organisms in a sterile environment under controlled physiological conditions. But unless companies can solve the challenge of planning for and managing manufacturing capacity, they will not be able to achieve the full potential of promising biotech products.

The US Food and Drug Administration (FDA, Rockville, MD, www.fda.gov) issued a revised draft guidance on July 20 to help ensure that the safety, purity, and potency of biologics products is not compromised as a result of innovative, flexible manufacturing arrangements.

Eden Biodesign (Liverpool, UK, www.edenbiodesign.com), SAFC (St. Louis, MO, www.sigmaaldrich.com/SAFC/Pharma), Midatech Group (Oxfordshire, OX, www.midatechgroup.com), Cellexus Systems (Cambridgeshire, UK, www.cellexusbiosystems.com), and BioConvergence LLC (Bloomington, IN, www.bioc.us) are sprucing up their product development and services with the construction of new manufacturing facilities.

Partnering with a surging number of CROs, CMOs, CSOs, and other niche providers, biopharm companies in 2007 will have an estimated spend of more than $7 billion on international clinical trial outsourcing alone.

The contract manufacturer must have sufficient capacity so it can absorb possible surge in demand, and back-up capability in case of a power failure or other event.

The three largest players have accumulated, or are in the process of accumulating, nearly a million liters of capacity between them.

The changes in biologics manufacturing regulations contained in the 1997 FDA Modernization Act significantly bolstered the growth of CMOs.

China is home to more than 400 biogeneric manufacturers, which develop generic biopharmaceuticals for the domestic population.

Many CMO relationships are established while a product is early in clinical or preclinical development.

Disposables require less space than conventional equipment, and they can be assembled offsite into complete process trains.

Moving aggressively to implement its Vision 2010 strategy, which debuted in October 2005, DSM N.V. (Heerlen, Netherlands) announced in December 2005 that it would shut down its Montreal biomanufacturing facility in early 2006. The move doesn't signal an exit from manufacturing, however, but a change in focus; DSM will simultaneously expand its expression-technology relationship with Crucell (Leiden, the Netherlands). Both moves reflect changing circumstances in the biomanufacturing sector.

Avariety of forces are combining to fundamentally change the financial dynamics of the biopharmaceutical industry. The initial public offering (IPO) appears to be giving way to licensing arrangements with, and acquisitions by, major pharmaceutical companies.

Your company's job is to make biopharmaceutical products. Managing facilities is a function supporting the main task. General manufacturing companies discovered this long ago, but pharmaceutical producers have been lagging. Once you consider the outsouring of non-core activities like facility management (FM), office services, space planning, and utilities management, you can focus on core business functions that make profits.

During the past several years in the pharmaceutical and biopharmaceutical industries, conflicts and misunderstandings have arisen between companies and their contractors. Too often, productive working relationships have crumbled, resulting in expensive production delays with companies and contractors squabbling over their roles and responsibilities. Such conflicts may have their roots in the lack of a sound quality agreement (QAG). QAGs that clearly delineate good manufacturing practice (GMP) responsibilities between a sponsor and a contractor can help companies and their contractors avoid certain conflicts.

Speed of response, small-scale manufacturing and process flexibility will become increasingly important.

The bulk of a biopharmaceutical processing unit can be assembled with off-the-shelf components. However, special fabrications — especially fluid components — enable fabricators and manufacturers to meet critical construction deadlines and move projects forward with minimal or no delays.

Outsourcing Report