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RSSImplementing Single-Use Technology In Biopharmaceutical Manufacturing
March 31, 2009
•Article: Implementing Single-Use Technology In Biopharmaceutical Manufacturing
By Weibing Ding and Jerold Martin
In biopharmaceutical manufacturing, single-use components and systems can offer distinct advantages over reusable, cleanable systems. Deciding whether to move to a single-use approach, however, depends on many factors. In a recent review of biomanufacturers and CMOs, the risk of leachable materials entering drug products was highest on a list of end-user concerns. That's not surprising in view of the high organic polymer content of disposable components, a general inexperience with such polymeric materials in process contact, and the need to ensure that safety and regulatory requirements are satisfied.
For example, the US FDA's GMP requirements for finished pharmaceuticals 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" . The task of assessing leachable materials in process fluids may appear to be very difficult and demanding, especially for multicomponent polymeric systems containing flexible containers, tubing, filter capsules, connectors, and so on. Furthermore, individual components may be supplied by different vendors and also may have diverse materials of construction.
Detailed information on extractable or leachable compounds, however, can be discovered through the use of sophisticated analytical equipment. In addition, recent industry recommendations have been issued on disposable manufacturing systems to facilitate validation. For example, the Bio-Process Systems Alliance (BPSA) offered detailed recommendations to assist end-users in risk assessment of specific products and process systems as well as testing programs .
Those recommendations define clearly the distinction between extractables testing and leachables testing. Extractables are compounds that can migrate from a material into a model solvent under exaggerated test conditions. Leachables are compounds that are shown to migrate into a drug product in final-dosage containers under normal process conditions. Their quantities are typically a relatively small proportion of total extractables. Extractables studies can show the potential for a material to release leachables into a drug product or process fluid. Such data provide an important platform on which decisions can be made regarding the need for or extent of leachable substances testing in process fluids or final drug formulations and dosage containers. Furthermore, because extractables data are usually generic and involve model solvents, they can be made available by suppliers to end users for incorporation into users' own test program assessments and regulatory submissions.
This first installment of a series on components and single-use systems describes supplier-generated extractables testing of two individual components typically used in integrated single-use systems. The significance of these studies is discussed here with regard to risk analysis and links between extractables and potential leachables in final formulation containers.
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