Corrosion equipment and material compatibility

The incentives to use more corrosion resistant material is to ensure compliance to federal regulations. Title 21 CFF1 parts 210 and 211, “Current good manufacturing practice in manufacturing, processing, packaging or holding of drugs; general and current good manufacturing practice for finished pharmaceuticals,” Subpart D-211.65 states:

Equipment shall be constructed so that surfaces that “contact components , in-process materials, or drug products shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements(2).”

This regulation clearly implies corrosion of equipment or product contamination of any kind is not acceptable.

Fabrication of vessels

Vessels made of austenitic stainless steels and the higher corrosion resistant materials such as super austenitic and nickel alloys are generally used in more critical applications with regard to corrosion resistance, some of those being final product or "payload" vessels where the value of the product in these vessels are much higher than any other.

The vessels made of these higher alloys are expected to be at a minimum equivalent in surface-finish characteristics to austenitic stainless steels. By meeting this requirement, the cleaning and sterilization will be equivalent to known practices and the higher corrosion resistance will be automatic.

Overall, the surface-finish quality and corrosion resistance must be at a premium. If there are any problems encountered during manufacturing of the vessels that do not allow this premium quality to be achieved, it hampers fabrication schedules, which can in turn affect a company's schedule of getting a drug to market.Raw materials are received into the fabrication shop normally in the mill hot-rolled, annealed, and descaled condition, but on occasion are in a cold-rolled 2B type finish. The material is thoroughly inspected. Raw-material markings are checked, and material certifications are received and reviewed for compliance. Positive material identification is performed to verify the correct material chemistry. After inspection, components such as vessel heads, liners, heat-transfer coils, and heat-transfer jackets are cold-formed and prepared for welding.

Welding is performed in compliance with the applicable code and customer specifications; typically for the American Society of Mechanical Engineers' (ASME) Section VIII, Division I code vessels, ASME Section IX is required (3, 4). Then parts of the equipment are joined by welding them together. After this, welding and surface finish inspections are carried out to check compliance with customer needs and ASME bioprocessing equipment standard.

High performance corrosion resistant materials

Stainless steel 316L has traditionally been the workhorse of the biopharmaceutical industry because of the unforeseen decrease in the quality due to chemistry changes and heat-treatment practices.Over the past 10 years, increased use of high-performance corrosion-resistant alloys has involved super-austenitic stainless steels, commonly referred to as 6% moly alloys and nickel base alloys in the family of nickel–chromium–molybdenum alloys. The most common alloys in these groups are AL6XN (UNS N08367) and Alloy 22 (UNS N06022). The melting and processing method for each alloy can vary, which can ultimately affect the metallurgical and corrosion performance of the alloy.

The melting and processing method for each alloy can vary, which can ultimately affect the metallurgical and corrosion performance of the alloy. The alloying elements in the super-austenitic stainless steels must be in solid solution to maintain optimum corrosion resistance and fabricability of these alloys. Precipitation of intermetallic compounds, particularly sigma, but also chi and Laves phases, in the super-austenitic alloys can result in depletion of chromium and molybdenum in adjacent areas. These areas can serve as sites for pitting and, in some cases, inter-granular corrosion. For high-purity applications, these alloys must undergo electro-slag re-melting to avoid the segregation effects.

Almost all nickel–chromium–molybdenum alloys are poured from the AOD furnace into ingots and subsequently electro-slag remelted. These alloys are expected to have good microstructure. Because of thermomechanical-processing problems, however, these materials have shown tendencies to form intermetallic phases that are deleterious to corrosion resistance and electropolish quality.

Stainless steels gain their corrosion resistance by forming a protective oxide surface layer. This layer, composed primarily of chromium oxides, is readily formed in presence of oxygen. This protective layer is susceptible to damage from halogens, but if oxygen is present in the environment, repair of the film is often rapid enough to prevent any significant damage. In the absence of a source to replenish oxygen, such as in a tight crevice, corrosion can accelerate as the available oxygen is consumed and the pH drops as a result of the corrosion process.Another location where depleted oxygen can lead to corrosion of stainless steel is at low points of piping systems without adequate drains.

A pitting index, called the pitting resistance equivalent number (PREN), has been developed to predict resistance of an alloy based on its composition. The PREN is defined as %Cr +3.3 × %Mo + 30 × %N.

Pitting Resistance Equivalent Number (PREN)

Need for electro polishing

The 300-series type stainless steels are often electro polished and passivated primarily to improve their corrosion resistance and clean ability.

300 Series stainless steels are classified as austenitic, and are hardenable only by cold working methods. These grades of stainless have chromium (approx. 18 to 30%) and nickel (approx. 6 to 20%) as their major alloying additions.

300 Series Stainless steel alloys resist corrosion, maintain their strength at high temperatures and are easy to maintain.

Rouging Rouging is a phenomenon of particular interest to the pharmaceutical industry. It is the presence of a surface layer of oxide on stainless steel equipment or piping typically handling high-purity water at temperatures above ambient. This include stills, steam systems, purified water, and water for injection. The oxides can vary in composition, colour, texture and adherence.

The rouge itself is typically composed primarily of iron oxides or iron hydroxides, but because these are developing on stainless surfaces, they may also contain oxides of chromium, nickel, and molybdenum.

Material of construction for pharmaceutical processing• Equipment made with wetted surfaces of fluoropolymers especially

Teflon PFA HP represents the most functional 21st century material of construction for pharmaceutical manufacturing.• Stainless steel corrodes over time as minor ingredients are lost and as

electrochemical potential arise which promotes the oxidation of iron. In stainless steel weldments for example iron is made more readily accessible to oxidation in even the mildest of chemical condition i.e., hot steam, and the resulting rust rouging contaminates and compromises the quality of the products being produced in such equipment.

• Stainless steel can further be chemically treated to be made less reactive i.e., passivated.• Passivated or not, stainless steel is reactive to many harsh chemicals

particularly chlorides and other halides, preventing their beneficial use in pharmaceutical application. • Surface physical chemistry of stainless steel is another significant

negative for its pharmaceutical use. It is wettable by aqueous solution, a characteristic which enhances not only chemical corrosion, but also biofilm adhesion and biofilm resistance to detachment

GLASS

• It is chemically resistant to most organic chemicals and many but not all inorganic chemicals. It can be formed in to many unsupported components and can be further supported by attachment to steel for larger processing components .• Glass is reactive to many harsh chemicals , preventing their beneficial

use in pharmaceuticals.

Fluoropolymers

• Because of its outstanding friction reduction , material release, chemical resistance, and thermal stability, fluoropolymers especially Teflon have found increasing applications as material of construction in pharmaceutical industries. These adoptions showcase its anticorrosive and non wetting surface characteristics, enhanced by its reduce surface friction• Fully fluorinated fluoropolymers , such as Teflon PFA and Teflon PTFE

are electrochemically, bio-chemically, enzymatically and chemically virtually inert.• Fully fluorinated fluoropolymers can sustain high temperature service,

up to 260°C for PFA and PTFE.