The Biopharm Industry

As the world’s populations grow and age, developing countries expectations rise and new research brings new health solutions to the world, the biopharmaceutical (biopharm) industry flourishes. Like all chemical processing, biopharm has its own set of standards, special processing needs and challenges in materials and design.

THE CHEMICAL INDUSTRY

At its most general level, one can define the chemical industry as the aggregate of entities engaged in processing raw materials using chemical reactions (often aided by pressure and/or forms of energy such as heat) to convert those materials into products. That general level has numerous subgroups, such as biopharmaceutical, organic/inorganic chemicals, industrial gases, petrochemicals, agrochemicals, polymers and paints. These subgroups are categorized further by the end-product goods and commodities such as dyes, acids, alcohols, fertilizers, hydrogen, nitrogen, herbicides, ammonia, soaps, detergents, hair sprays, enamels, varnishes and many more.

Commonly, the processes required to manufacture these products use constituents or conversion enablers that are toxic, or they result in products and byproducts that may be toxic themselves. The inputs and outputs to those processes can present additional challenges because of physical and chemical properties that can make media extremely corrosive or abrasive. Also, the media can be difficult to propagate and control throughout the process flow in situations where physical/chemical properties result in media that is semi-solid.

In each segment of the industry and in every subcategory of these segments, valves play a critical role. A variety of valves are appropriate for various applications and deployed for handling different types of media. Covering the entire industry is too great a task for one article. Therefore, the information that follows highlights where and how valves are used in chemical processing for the biopharm market.

THE MARKET

The biopharm industry can be divided into two segments: Pharmaceutical, which uses chemical processes to manufacture therapeutic and health-related products; and biotechnology (biotech), which uses living organisms and biological processes to create products used in many fields such as pharmacology, medicine, agriculture and many others. A primary example is therapeutic protein used for medical and therapeutic applications. Most biotech applications involve cell cultures of genetically modified organisms including yeasts, insect cells, bacteria cells or mammalian cells.

A full range of pumps, valves and instrumentation comparable to other processing systems can be used in the biopharm industry. However, stringent requirements regarding cleanability and materials of construction mean that some products that perform ordinary and useful flow control functions in other applications must either be used with great caution or not used at all. An example is check valves. Check valves are installed tentatively because even sanitary check valves allow formation of “dead areas,” despite the fact they are functioning according to specifications. Such areas potentially harbor contaminants or toxic agents.

FLOW CONTROL CHALLENGES

Flow control devices in the biopharm industry, especially in the biotech sector, need to be constructed from materials that will not result in an end product deleterious to a patient (or to others handling the product) and that will not damage or adulterate the drug product in any way. This requirement applies to materials of construction, which are typically metallic, and any other components of the processing system, such as polymers or elastomers used for seals. Material selection in many cases is controlled by the need to comply with regulatory requirements written into the Code of Federal Regulations, authored by the Federal Drug Administration or the United States Pharmacopeia, or included in the bioprocessing equipment standards of the American Society of Mechancial Engineers, as well as standards set by other regulatory agencies.

The design of flow control components and systems also must allow cleaning and sanitization between batches or maintenance intervals. Most processes are batch type though water for injection (WFI) is generated and stored in re-circulating loops that run continually. Proper cleaning (clean in place—CIP) and proper heat sanitization (steam in place—SIP) depend on full drainability of systems and components.

Additionally, components must be designed to reduce the amount of wetted area and to reduce stagnant zones, also called “dead legs.” These stagnant areas can foster microbial growth and prove difficult to clean and sanitize.

RELEVANT VALVES AND EQUIPMENT

The centrifugal pump is the most commonly used pump type, especially with critical utilities such as purified water, WFI, buffers and certain other media. Protein solutions can be shear sensitive so these applications typically use rotary lobe and other positive displacement-type pumps. Air-operated diaphragm pumps often are used to move product between process modules and to pack chromatography skids.

Weir-type diaphragm valves are the mainstay for critical utilities and process applications (Figure 1). This valve offers crevice and entrapment-free valve bore, self-drains in both vertical and horizontal orientations, has a top entry design, provides positive closure against both pressure and vacuum and has an isolating diaphragm that separates “top works” from process media (Figure 2). Over the past 15 years, the aseptic diaphragm valve has evolved from the once-standard, two-way type to encompass multiple valve clusters machined from a single block of stainless steel (Figures 3 and 4). These custom designs greatly reduce wetted area and dead legs and have become a key element in the design of biotech process systems.

Radial-type weir diaphragm valves frequently are used as tank outlet valves because of their contour—the radial diaphragm valve contour often closely matches the contour of the vessel.

Ball valves typically are used for clean steam distribution and supply lines. These valves also are used in chemical and general purpose applications that do not require high levels of sterility or cleanability.

Double seat, mix-proof valves are often used on CIP systems. This valve type is incorporated into a matrix that allows simultaneous cleaning and processing with minimal risk of cross contamination.

Comparatively few control valves are used in biotech systems because most applications are batch type. WFI loops will have a back-pressure control valve or regulator, which is used to maintain minimum flow conditions. This is because flow rates must be maintained to sustain turbulent flow conditions, and turbulent flow is required to avoid stagnant areas in the pipe works. Control valves and regulators used in biopharm applications must use designs and materials of construction allowing CIP and SIP, and must be trim compliant with materials regulations.

The industry employs a full range of instrumentation that controls and/or monitors temperature, pressure, flow and conductivity. Most of these instruments are specialized adaptations compatible with the unique process requirements of the industry. Increasingly, valves are equipped with position feedback, which includes point-to-point and networking. Valve switchboxes, along with other instrumentation, must be suitable for wash-down and wipe-down environments.

HSE REQUIREMENTS

Health, safety and environment requirements are similar to other process industries. Some cell culture processes involve microbes that can present risk and require special care needs to minimize possible exposure. Most processing plants use a “kill system,” which destroys any living cells or microbes and chemically neutralizes wastewater prior to disposal.

FAVORABLE MARKET TRENDS

Both the short-term and long-term demand for biopharm products looks favorable because of several factors, which means corresponding growth in demand for relevant processing equipment such as valves. The favorable factors include (and this list is not exhaustive) the following global developments:

An aging population in developed countries
Greater amounts of disposable income and expectations for quality of life in developing countries
Medical breakthroughs and new treatments that call for new or greater volumes of biopharm products
The world’s general population growth
Societal structural changes where medical care will be provided or paid for by the government in countries with less-than-universal health care.

Biopharm companies also are spending new resources on drug discovery and biotech research, which opens up new avenues for treatments, dovetailing with efforts of the medical establishment.

Valve manufacturers with proven track records of providing safe and effective solutions to the manufacturing world that are capable of handling the challenging processing requirements of the biopharm industry stand ready to fulfill the rising demand. As in other processing fields, the valve industry will also introduce its own contributions to the biopharm industry with pioneering concepts in valve design.

CARL TAYLOR is application sales specialist, CRANE ChemPharma, Saunders (www.cranechempharma.com). Reach him at ctaylor@cranechempharma.com.