The materials used to fabricate single-use processing equipment for biopharmaceutical manufacturing are usually polymers, such as plastic or elastomers (rubber), rather than the traditional metal or glass. Polymers offer more versatility because they are light-weight, flexible, and much more durable than their traditional counterparts. Plastic and rubber are also disposable, so issues associated with cleaning and its validation can be avoided. Additives can also be incorporated into polymers to give them clarity rivaling that of glass or to add color that can be used to label or code various types of processing components.

Given all the positive attributes that polymers possess, there are also some negatives to consider when working with them in pharmaceutical applications. In the presence of heat, light, oxygen, and various external influences (such as sterilization), polymers can degrade over time if not properly stabilized. Degradation can manifest itself as cracking, discoloration, or surface blooming/exudation — and this can severely affect the mechanical properties of the polymers. Stabilizing additives are incorporated into many polymers to prevent this degradation. However, the resulting formulation is more complex than that of metal and glass, and it makes materials such as plastic and rubber much more prone to leaching unwanted chemicals into drug product formulations when they are used in applications such as manufacturing or packaging.

That does not mean such materials should not be used in bioprocess applications. In fact, their benefits greatly outweigh their risks. However, the risk must be managed.

Polymers and Additives

When a plastic resin is processed, it is often introduced into an extruder, where it is melted at high temperatures and mixed by a series of screws into a homogenous molten mixture. Additional heat and shear are encountered by the plastic when it is extruded and molded or shaped into a final product form, such as tubing or a bioprocessing bag. The degree of potential degradation depends on the nature of a polymer's chemical composition, the manner in which it is processed or molded, and the end use of the finished product.

For example, the inherent stability of a polymer substrate will be influenced by its molecular structure, polymerization process, presence of residual catalysts, and finishing steps used in production. Processing conditions during extrusion (e.g., temperature, shear, and residence time in the extruder) can dramatically affect polymer degradation. End-use conditions that expose a polymer to excessive heat or light (such as outdoor applications or sterilization techniques used in medical practices) can foster premature failure of polymer products as well, leading to a loss of flexibility or strength. If left unchecked the results often can be total failure of the plastic component.

Polymer degradation can be controlled by the use of additives in the plastic or elastomer system. These are specialty chemicals that provide a desired effect to a polymer. The effect can be stabilization that allows a polymer to maintain its strength and flexibility or performance improvement that adds color or some special characteristic such as antistatic or antimicrobial properties. There are typically three classes of stabilizers:

• melt processing aids such as phosphites and hindered phenols, antioxidants that protect a polymer during extrusion and molding

• long-term thermal stabilizers that provide defense against heat encountered in end-use applications (e.g., hindered phenols and hindered amines)

• light stabilizers that provide ultraviolet (UV) protection through mechanisms such as radical trapping, UV absorption, or excited state quenching.

One application in which an additive can improve or alter the performance of a polymer is a filler or modifier that affects its mechanical properties. Additives known as plasticizers can affect the stress–strain relationship of a polymer (1). Polyvinylchloride (PVC) is used for home water pipes and is a very rigid material. With the addition of plasticizers, however, it becomes very flexible and can be used to make intravenous (IV) bags and inflatable devices. Lubricants and processing aids are also used to reduce polymer manufacturing cycle times (e.g., mold-release agents) or facilitate the movement of plastic and elastomeric components that contact each other (e.g., rubber stoppers used in syringes).

Techniques used to analyze polymer additives vary depending on their chemical structures. For example, abietic acid is routinely analyzed with gas chromatography (GC), whereas high-performance liquid chromatography (HPLC) is the method of choice for an organic phosphite stabilizer such as Ciba's Irgafos 168 product. Figure 1 depicts the molecular structure of both compounds.