Science and Technology

Summer 2008HighlightsProteins derived from natural plant- and animal-based sources are becoming increasingly important components in the manufacture of key biologic drugs. However, there are often concerns about the potential for cross-contamination. SAFC, the custom development and manufacturing services unit of Sigma-Aldrich, recently started up a facility at its St. Louis site that is among the first commercial-scale unit of its kind to have completely segregated operations for plant- and animal-based protein produc-

tion, completely eliminating the potential for cross-contamination.

A platform for growthThe $18-million facility, obtained by retrofitting and expanding a unit built in the early 1990s, contains some of the largest extraction and purification suites of their kind, capable of supporting products from pre-clinical development to full commercialization.

“A new, larger-capacity facility was just a logical extension of what we were already doing,” said Lance

Kunkel, director of production for Sigma-Aldrich Manufacturing.

“One of the company’s goals is to grow its contract manufactur-ing business in this area,” said Kunkel. “To do so, it needed a world-class facility that met the industry’s strict Current Good Manufacturing Practices (cGMP) to showcase the company’s unique expertise and capabilities in biolog-ics manufacturing.”

That meant SAFC also needed to address the concerns that prospec-tive customers might bring to the table, such as:

Customer Issue #1: Fears of cross-contamination

“One of the first things potential customers look for in such a facility

McCarthy Builds World-Class Biopharma Manufacturing CenterThe new facility enables SAFC to ensure protein purity for the Biopharma industry

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®

The $18-million facility,

obtained by retrofitting and

expanding a unit built in

the early 1990s, contains

some of the largest

extraction and purification

suites of their kind…

“

”

Buffer Prep Area

is the potential for cross contamina-tion between the animal and plant sides of the operation,” said Dick Kalin, Sigma-Aldrich’s project manager for design and construc-tion. With these products, there is potential for animal protein virus to migrate to another source.

“Customers don’t want to see workers —or anything else—moving from one area to another,” explained Kalin. “That’s why one doesn’t typically find adjoining facilities for both plant and animal sources.”

SAFC’s facility has been designed

and constructed to segregate the two sides into two totally indepen-dent operations. As a result, the animal and plant protein opera-tions share electrical power, drain-age systems, fire systems and an external façade—but not much else. Each maintains its own separate entrances, exits, locker rooms and HVAC systems.

Once inside, efforts to eliminate the potential of cross-contam-ination are visible everywhere. Equipment and raw materials enter and leave through separate entrances and exits on each side of the facility. The USP water dis-tribution systems are segregated by facility as well, as is the storage space for equipment, tools, raw materials and consumable supplies. To reduce the impact of cross-

contamination in the exhaust and intake systems, strobic fans have been installed on exhaust systems, preventing exhaust air from re-entering the building.

Workday duties are also restricted by facility. Employees of the plant-source facility wear green uni-forms when involved in the initial plant protein extraction process, and blue uniforms when working in the plant protein purification suites. Employees who work in animal protein processing areas wear maroon.

“We have done everything we can to eliminate possible causes for concern,” Kalin said.

Customer Issue #2: Can you meet MY needs?Potential customers appreciate hearing about a contract manufac-turing facility’s flexibility. But, what they really want to know is: can it handle their product? Given the sheer variety of products poten-tially processed there, the project team went to great pains to ensure that the answer to that question will almost always be, “Yes.”

Potential customers

appreciate hearing about

a contract manufacturing

facility’s flexibility.

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Clarification Area

“Typically, you design a process and then build the facility around it,” explained Eric Unrau, project man-ager for CRB Consulting Engineers, who served as engineer for the project. “But, in this case, SAFC will be working with many differ-

ent products from many different sources, and they’ll constantly be changing. So, they needed a facil-ity that would be flexible enough to accommodate custom projects of almost any scale, and also possess the ability to change over to new products quickly.”

Such criteria were central to the facility’s design. As a result, processing equipment in the facil-ity, which includes Class 100,000 (ISO 8) and Class 10,000 (ISO 7) cleanrooms and a Class 10,000 (ISO 7) lyophilization suite, can be set up in multiple configura-tions and arranged to minimize flow as well as ease operations between the extraction, separation and purification processes.

Equipment selection also takes into account the numerous potential product sources. The plant-source facility, for example, is equipped to process a variety of plant materials, ranging from milled grains, such as flour, to chopped leaves, such as tobacco. Isolated manufacturing suites make it possible for the com-pany to process up to four different products at once.

Customer Issue #3: Can you meet my budget?The stringent requirements for operational flexibility and cross-contamination control could have wreaked havoc with the project’s budget—and made it cost-pro-hibitive both for SAFC and its potential customers. “Capital costs were kept in check by renovating and repurposing an existing, aging Brownfield site and making judi-cious reuse of as much of the facil-ity’s existing equipment and sys-

tems as practical,” said Rich Corey, McCarthy project manager on the Sigma project.

“SAFC had identified a market need and a set amount of funds to invest in serving it,” said Corey. “The project team’s job was to find a way to enable them to achieve their goals,” he said.

“McCarthy drove much of the reuse activities,” said Unrau. “They found ways to re-use everything from the electrical and air handling systems, to HEPA filters and light fixtures and wiring,” he said.

However, not all items that could be reused were reused, due to concerns about cross contamina-tion. “In some cases,” said Corey,

“we were required to eliminate

McCarthy found ways

to re-use everything

from the electrical and

air handling systems, to

HEPA filters and light

fixtures and wiring.

“

”

CIP Room

some otherwise good systems and put in new ones.” This was accom-plished while working around existing operations and, one by one, addressing the myriad challenges associated with upgrading a cen-tury-old building to meet the FDA and EU standards needed for 21st century biopharma manufacturing.

Ultimately, the recycling, reuse and value engineering efforts not only enabled SAFC to meet its

budget targets, but also supported the company’s desire to minimize unnecessary waste and support sustainability efforts.

By the time the 16-month project was complete, SAFC had 2,500 m2 of world-class biopharma manu-facturing space, capable of produc-ing up to 1,000 kg of product per year for a total finished cost of $18 million—significantly more cost-effective per kg of output than more traditional therapeutic pro-tein facilities, according to Unrau.

Today, SAFC has achieved what it set out to do: demonstrate to its customers that it can handle multiple types of custom processes and support a full-range of cGMP biologics manufacturing for both plant and animal sources. And, it did it on a tight schedule with an even tighter budget.

“It took a world-class team to produce a world-class project,” said Kunkel. “We’ve received nothing but compliments from customers, which include both large and small pharma companies. The commit-ment to quality, as well as the equip-ment, support systems and fabrica-tion techniques, are all consistent with the highest level of protein extraction and purification facilities.”

Science and Technology Highlights is a publication of McCarthy Building Companies, Inc.

For more information contact: Jim Contrattojcontratto@mccarthy.com

1341 North Rock Hill Road St. Louis, MO 63124

(314) 919-2343www.mccarthy.com

It took a world-class team

to produce a world-class

project. We’ve received

nothing but compliments

from our customers…

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Extraction Area

Plant 100K Clean Room