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26 BioPharm International eBook June 2018 www.biopharminternational.com Single-Use Systems Quality biopharmaceutical drug products. The targeted implementation date will be around 2020. Qualification of single-use systems is a science- driven and risk-based approach to develop a comprehensive under- standing of the risks associated with the use of polymeric manufactur- ing components utilizing process knowledge and experience of using single-use systems. Currently, the regulatory expectations are similar between the US and Europe. BPSA: Because current regulatory guidelines for single-use pharma- ceutical manufacturing systems only offer general direction, drug manufacturers may not be cer- tain of how best to approach the qualification process. In fact, vari- ous industry groups are attempting to develop more detailed standard qualification requirements for sin- gle-use pharmaceutical manufactur- ing systems based upon current, relatively general regulations. The qualification of single-use suppliers, materials, components, and completed assemblies require attention to several factors. It is important to use a scientific risk- based approach to qualif y both materials and completed assemblies for single-use systems in pharma- ceutical development and manufac- ture. The assessment of risk must be based on the complexity of the system and its intended use (e.g., product contact versus non-prod- uct contact, upstream versus down- stream use, shor t-term contact versus long-term storage). In addi- tion, scientific principles must be applied to: • Identify and monitor extractable materials from films and other components • Investigate potential interactions with product critical qualit y attributes (CQAs) or significant process pa ra meter s l i ke cel l culture media • Assess the effects of assembly pro c e s s e s s uc h a s we ld i n g , fusing, mechanical stress, and s t e r i l i z a t i o n (e . g . , g a m m a irradiation) on the materials d u r i n g m a n u f a c t u r i n g . I n assessing the suitability of the single-use system with respect to potential leachables in the f i n a l p r o d u c t , e x t r a c t a ble s may be considered potential leachables. Finally, the design and functional integrity of the completed single-use system must be verified and maintained by appropriately trained end u se r s v ia su it able pro cesses for const r uc t ion, packag ing, shipping, and deployment. The supplier of the single-use system must prov ide suff icient data to qualify the materials and components used to assemble the final single-use system. In this regard, the end user may use the documents from the supplier to meet most of the verification cri- teria required to make sure that the single-use system is fit for the intended application and purpose. This requires a thorough qualifi- cation of the supplier by the end user to ascertain an acceptable sup- plier quality system, documenta- tion, and an appropriate level of technical capability that extends all the way to the original sources of materials to the supplier. Since understanding the qualit y and variability of raw materials is criti- cal, this information for single-use systems is best obtained via a for- mal partnership between end user and supplier. Industry associations and groups, suc h as BP SA a nd BioPhor u m Operations Group (BPOG), have been more advanced in setting best practices in the US than in Europe. This also includes standard-set- ting organizations, such as ASTM, American Society of Mechanical E n g i n e e r s : B i o p r o c e s s i n g Equipment (ASME-BPE), and USP. As these standards are defined, it makes sense that Europe regulators will reference and align with these developments. Bulpin (MilliporeSigma): The regu- latory expectations for the quali- fication of single-use systems are very high level with no specific guidance for drug manufacturers. The GMP guidelines indicate that manufacturing systems should not be additive, reactive, or absorptive to an extent that it affects the qual- ity of the product and, therefore, patient safety. These guidelines have been applied to ensure that single-use systems are sterile and integral, so as not to expose the product to the external environ- ment or introduce any adventitious agents. Single-use systems should not introduce any chemical impuri- ties to the process, or the product. The use of well-characterized mate- rials of construction (USP <661> [6] or European Pharmacopoeia 3.1.X series [7]), testing for extractables and subsequent leachables evalua- tion qualifies that. Testing for par- ticulate matter ensures extraneous particulate matter is controlled. The basic principles and requirements in the European Union and US are similar at a high level, but some of the standard methods for evalua- tion and specifications differ. The EU requires extractables and bio- compatibility data but do not have any standards prescribed. Pora (Pall Biotech): It is important to remember that there is not yet any specific regulations pertaining to single-use technologies, yet they need to be used in compliance to current good manufacturing prac- tice (cGMP) standards. In Europe, the EMEA Annex (8) regulation is still in draft form. And in the US, we see progress with the USP <665>. Overall, the regulatory