The inherent cleanliness and properties of stainless steel enhanced by preparation processes make it the material of choice for critical applications
By Ken Sullivan, PB Power
Stainless steel has historically been the material of choice for the pharmaceutical industry due to its unique metallurgical composition, which is inherently hygienic and chemically resistant. The objective of this article will be to review pharmaceutical quality requirements and examine some of stainless steel’s intrinsic properties and the benefits that make this material well suited for pharmaceutical water systems. The focus will be on 304, 316, and 316L AISI stainless-steel pipes as they apply to high-purity (HP) water systems used for critical applications.
Pharmaceutical water is one of the most important of all pharmaceutical utilities and is an essential component in most pharmaceutical processes, used in preparations, products, processing, and cleaning.
There are two basic grades of pharmaceutical water commonly used: purified water (USP) and water for injection (WFI), which is the most purified water. USP water is used in the preparation of non-sterile products and as feed water in the preparation of WFI and pharmaceutical-grade pure steam; it cannot be used for preparations intended for injections. It is also used for rinsing purposes (cleaning of containers) and for preparing cleaning solutions. WFI is used to dissolve or dilute other drugs, which may be delivered intravenously. The primary difference between these grades is the absence of bacterial endotoxin requirements for USP water, degree of system control, and final purification techniques for bacterial removal. Water quality standards for USP water have been established by a number of professional organizations. The standards that the pharmaceutical industry must comply with are the United States Pharmacopeia (USP), the official public standards-setting authority for all prescription and over-the-counter medicines, dietary supplements, and other health-care products manufactured and sold in the United States.
All in the family
In metallurgy, stainless steel is defined as an iron-carbon alloy with a minimum of 10 percent chromium by weight.1 It is the addition of chromium that gives stainless steel excellent resistance to corrosion and good strength at high temperature and pressure. The three main classes of stainless steels, designated in accordance with their metallurgical structure, include martensitic, ferritic, and austenitic; however, all are not suitable for pharmaceutical-grade water systems.
The austenitic family of stainless-steel alloys includes more than 70 percent of the total stainless-steel production. It generally has much greater toughness than the ferritic type, such as the 400 series, which cannot be hardened by heat treatment. While martensitic types are not as corrosion resistant as the other two grades, they are extremely durable as well as highly machinable and can be hardened by heat treatment. Because austenitic stainless-steel pipes are excellent in terms of mechanical strength and abrasion and heat resistance, they are the preferred choice for pharmaceutical water systems.
The 300 series of austenitic stainless steels is an iron-based, low-carbon alloy that is non-magnetic and owes its very high corrosion resistance to its chromium content. Nickel is required to stabilize the austenite, which forms at elevated temperatures so that it can be retained when cooled to room temperature. The basic composition of the 300 series is 18 percent chromium, 8 percent nickel alloy, and 0.10 percent carbon (commonly known as 18/8 stainless). The nickel and chromium content can be increased to improve corrosion resistance; in addition manganese, nitrogen, and molybdenum can also be added to further enhance the corrosion resistance properties. A lower carbon content reduces carbide precipitation during welding.
These steels cannot be hardened by heat treatment although cold work will cause an increase in both hardness and strength. After cold working, the material is annealed to preserve the structural integrity. Also, if any carbon precipitate occurs while slow cooling (sensitization) from a high temperature, they may be reheated and quenched to re-dissolve the carbon and keep it in solution. These steels exhibit excellent structural integrity and thermal stability.
The 300 Series consists of the following types of austenitic chromium-nickel alloys:
- Type 304 is also known as “surgical stainless steel.” The most common grade is the classic 18/8 stainless steel with excellent strength, formability, fabricability, and ductility. 304 stainless steel is typically used in brewery, dairy, food, and pharmaceutical production equipment applications. 304 costs less than 316 stainless steel.
- Type 304L is similar to 304 grade but specially modified for welding and fabricability.
- Type 316 contains molybdenum and a higher nickel content (10 percent) than 304. Molybdenum, in conjunction with chromium, provides superior resistance to attack by most chemicals and an increased resistance to chloride corrosion compared to type 304. The additional nickel content aids in repassivation of the passive layer in case of damage.
- Type 316L is the most common material used in the pharmaceutical industry. The corrosion resistance of 316L is the same as standard 316. However, low-carbon “L” grade is used to avoid possible sensitization corrosion in welding.
The phenomenon of passivity
Historically, pharmaceutical companies have chosen high-polished stainless-steel for pure water piping systems because of its inherent hygienic properties that render it non-reactive, non-additive, non-absorptive and non-corrosive (see Fig. 1). Their goal is to choose a material that will not release contaminants and thus lower the water purity. The way stainless steel achieves this is the chromium content of the steel combines with oxygen in the atmosphere to form a thin, invisible film of chrome-containing oxide, called the passive layer. The sizes of the chromium atoms and their oxides are similar, so they pack tightly together on the surface of the metal, forming a stable layer only a few atoms thick.
The protective layer is too thin to be visible, meaning the surface appears glossy. If the metal is cut or scratched and the passive film is disrupted, more oxide will quickly form and recover the exposed surface, protecting it from oxidation corrosion. This phenomenon is called passivation by materials scientists and is similar to the oxide layer on aluminum. However, high steam velocities, vibration, and thermal shock all can have adverse effects on the film’s continuity.
Corrosion is a primary concern for HP water systems because its presence contaminates the water quality. That is why stainless steel is used more often in place of other available materials. Because pharmaceutical water is so pure, deionized or “ion hungry,” a concentration gradient is established between the de-mineralized water and the stainless steel with only the passive layer preventing the diffusion or leaching of minerals (free iron) from the pipe into the water. This contamination could be potentially dangerous to the process or the final product. The types of corrosion that can occur include general, concentration cell (crevice), pitting, intergranular, stress, de-alloying, erosion, and microbial-induced corrosion.
Stainless steels perform best under fully aerated or oxidizing conditions, which enhance the passive layer. The lower alloyed grades of stainless steel resist corrosion in atmospheric and pure water environments, while high-alloyed grades can resist corrosion in most acids, alkaline solutions, and chlorine-bearing environments, properties which are utilized in the process industries. Fortunately, the corrosion-resistant properties of stainless steel can be further enhanced to meet the requirements of the pharmaceutical industry by increasing the chromium content and the addition of other elements such as molybdenum, nickel, and nitrogen.
Stainless-steel piping is susceptible to “rouging,” an extremely fine rust that produces a red/brown discoloration on the internal, wetted surfaces of the pipe, which results from the aggressive action of hot (typically above 65°C) pure water on the ferrite content of the stainless steel, breaking it down. This condition is typical for hot/purified/WFI/clean-in-place systems where less dissolved air is carried by the water. For rouging to occur, it may be assumed that either the protective chromium oxide layer has either not been established or that it may have been disrupted. Water systems that operate at ambient temperatures do not typically exhibit any rouge formation in their lifetime.
The easy cleaning ability of stainless steel makes it the first choice for strict hygiene conditions. Keeping the alloy surface clean and free from contamination helps eliminate concentration cells that might cause pitting.
Organisms exist in water systems either as free floating or attached to the walls of the pipe where they can grow in the rough pipe surfaces or crevices. When they attach themselves to the pipe walls they are known as biofilm. The pipe surface finish is often cited as one of the critical factors in the proliferation of bacteria colonies; the smoother the finish is, the more difficult it is for biofilm to attach to the pipe’s internal surface. Hygienic design factors such as maintaining a constant turbulent (3 to 5 ft/s) flow, smooth pipe-joining methods, and minimizing deadlegs and air pockets will all reduce the risk associated with bacterial growth and contamination.
The presence of biofilm on the pipe surface leads to microbially induced corrosion (MIC) and occurs when microbes create colonies and remove pipe material, forming deep pits with small pinhole openings on the interior of the pipe. Microbial contamination can result in the loss of millions of dollars in pharmaceutical products.
The corrosion resistance of the stainless steel is affected by the roughness of the pipe surface. Roughness average (Ra) indicates the average distance between the microscopic peaks and valleys on the surface of the stainless steel: the lower the value, the smoother the finish.
There are two surface finish conditions used for these systems: mechanical polishing and electropolishing. Mechanically polished surfaces retain the basic alloy composition with only slight depletion of the other alloy elements, whereas electropolished surfaces contain essentially only chromium and iron.
In a mechanical polishing process, the internal diameter of the tube is polished by a number of progressively finer abrasives passed through the tube via a pneumatic bellows. For the initial pass a coarse grit is used to remove surface imperfections such as weld splatter and slag formations. Finer grits are used for the final passes to enhance the finish.
The surface irregularities of stainless steel can be improved by electropolishing, which is an electrochemical method of polishing stainless steel in which surface iron is removed by anodic dissolution, a chemical reaction that removes surface metal, more simply electroplating in reverse. By removing these peaks and surface contaminates, electropolishing will improve and smooth the surface finish and restore the passive layer.
Electropolishing is required for the pharmaceutical industry because surface smoothness, with fewer sites for trapping impurities, means a purer product without the danger of bacteria growing in surface defects. Oxygen is a critical component in creating the special properties of electropolished surfaces, both to increase the depth of the passive layer and to produce a true passive layer (see Fig. 2).
The rougher the pipe surface, the easier it is for bacteria to adhere to it and resist flushing; a smoother finish allows for easier sanitization. A smooth internal surface finish would be a 20-Ra average and 25-Ra maximum. Similarly, the outside diameter of the pipe is polished to meet cleanroom standards.
Following electropolishing, the tubes are water-rinsed then further passivated in hot nitric acid. This additional passivation is necessary to remove any residual nickel sulfite and to improve the surface ratio of chromium to iron. Following passivation, tubes are rinsed with process water, placed in hot deionized water, dried, and packaged. If cleanroom packaging is required, the tubes are further rinsed in deionized water until a specified conductivity is met then dried with hot nitrogen gas before packaging.
There are two types of fitting joints commonly used in hygienic piping systems: fusion-welded butt joints and sanitary tri-clamp connections. Prior to the advent of CIP systems, manual cleaning of piping systems and equipment required disassembly of the piping system and reassembly after internal cleaning. Potential issues have arisen associated with gasket extrusion’s effect on drainability and flow turbulence. Hygienic design requires that pipe joints should not trap impurities that might allow microbial growth and contaminate the process, such as threaded joints or even sanitary clamps; therefore, the preferred pipe-joining method is fusion butt-welding.
The 300 series stainless steels have a high degree of weldability; with a higher expansion rate and a lower thermal conductivity than plain carbon steel, the heat is not dissipated as fast from the weld region, which reduces the required welding current. The austenitic stainless steels are susceptible to intergranular corrosion at welding temperatures between 800° and 1,600°F because of carbide precipitation in the grain boundaries. This phenomenon is known as sensitization and occurs from the absence of chromium at a region immediately adjacent to the grain boundaries. Chromium and carbon, originally distributed through the austenitic structure, combine to form chromium carbide. These chromium carbides are not as corrosion resistant as the base austenitic structure. The sensitization can rapidly occur at temperatures of about 1,200°F; at higher temperatures the process is reversed and the precipitate is re-dissolved and kept in solution. The time when precipitation can occur is dependent on the amount of carbon present; low-carbon, 316L-grade stainless steel increases resistance to sensitization and is the material of choice for welded pipe systems.
Pharmaceutical process piping is orbitally/autogenously welded in place, a fusion-welding process using heat without the addition of filler metal to join two pieces of the same metal (see Fig. 3). This welding is fast and avoids the crevices and potential for corrosion common with mechanical couplings where bacteria can grow and contaminate the system.
After welding, the “sensitized” steel should be annealed to re-dissolve the carbide and rapidly cooled through the sensitizing range. The heating causes the carbides to go back into solid solution and the quenching stabilizes the structure. Water quenching is important in order to pass through the sensitization temperature range (1,800° to 8,000°F) as rapidly as possible.
Orbital welding results in an area within which the alloy chemistry is not balanced for optimum corrosion resistance. Passivation is necessary to remove the manganese and to boost the chromium/iron ratio. Unless this is done, there will be an area where accelerated corrosion can occur, and in those environments containing electrolytes galvanic corrosion may also take place.
The final operation after fabrication or heat treatment is cleaning to remove surface contamination and restore corrosion resistance of the exposed surfaces. Degreasing to remove cutting oils, grease, crayon markings, fingerprints, dirt, grime, and other organic residues is the first step. When degreasing, only non-chlorinated solvents should be used in order to avoid leaving residues of chloride ions in crevices and other locations where they can initiate crevice attack, pitting, and/or stress corrosion later on when the system is placed in service. And only deionized water at 1,800°F should be used as a final flushing and sanitizing rinse.
Pharmaceutical piping systems deliver high-purity water to their processes and this requires high-quality materials that ensure a source of water that is free of bacteria, rust, or other contaminants. Stainless steel’s inherent hygienic properties and the ability to enhance these features with electropolishing and passivation have made it the leading material for pharmaceutical water systems. The main advantages of stainless-steel systems are mechanical strength within a wide temperature range and a low coefficient of thermal expansion. This simplifies equipment and piping design and allows for sanitization of the piping system. Potential disadvantages for consideration are the high cost of sanitary stainless-steel components, susceptibility to rouging, and the need for periodic chemical passivation to restore the oxide film that provides stainless steel with its corrosion resistance.
Ken Sullivan is a senior engineer with PB Power (www.pbworld.com), a division of Parsons Brinckerhoff NYC. He has 30 years of industry experience in design and construction of mechanical systems for research and industrial facilities including laboratories, cleanrooms, and pharmaceutical facilities, and has managed capital projects with an international cosmetics manufacturer. He is a graduate of Farmingdale State University and Dowling College, and is currently teaching at the Institute of Design & Construction in Brooklyn, NY.
- Steel Glossary, American Iron and Steel Institute (AISI).