Issue link: https://www.e-digitaleditions.com/i/1248960
12 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2020 P h a r mTe c h . c o m Manufacturing Equipment for media fills Media fills are performed on equipment that is representative of the set-up used for the aseptic process (i.e., involving the same configuration of valves, hoses, gaskets, needles, and other equip- ment). In nearly all cases, an exact replica of the aseptic set up is impossible to attain. Manufactur- ers typically use new hoses and gaskets with each set-up to eliminate or reduce concerns regarding extractables, leachables, and potential product car- ryover on polymeric materials. Some firms, especially contract manufacturing organizations (CMOs), have chosen to dedicate their reusable parts to a single product. This prac- tice simplifies cleaning activities, reduces risk, and eliminates potential cross-contamination between different products. An additional set of identical change parts is dedicated to and used for media fills, supporting all of the products manufactured. The media fill parts can be used for operator train- ing and thus experience significant use. Regulators have cited some companies, object- ing to this common and risk-mitigating practice by insisting that product-dedicated parts be used for media fills. Their reasoning is f lawed because use of product-dedicated parts for media fills increases the potential for cross-contamination of product batches. In addition, because all of the parts are mechanically identical and require the same ma- nipulations, using production parts in media fills is pointless. Furthermore, the industry is increas- ingly using single-use components in aseptic pro- cessing and those can never be used twice. The sterilizing filtration of media rarely allows the use of a filter set-up that is identical to that utilized for product (e.g., aseptic powder media fills require the use of liquid fill equipment). The additional media fills required by this expectation, as well as the added cleaning and validation requirements, have the effect of reducing capacity and increasing costs, with no patient benefit. The filling equipment is perhaps the most constant component within the aseptic process. Because the reusable parts are pre- dominantly made of stainless steel, there is minimal loss in performance over time. The filling compo- nents subject to wear are elastomeric gaskets and seals, which are commonly replaced with each use. Personnel, containers, closures, product, and pro- cedures (e.g., set-up, intervention, sanitization, and others) all have greater variability from batch to batch than the reusable parts. Participation of personnel FDA's 2004 aseptic guidance requires that techni- cians and maintenance staff participate in a media fill at least once a year (18). The tasks that they perform during the media fill should parallel those that they carry out during routine production. But how can this be managed in a reasonable manner where there are numerous operators, operating lines, configurations, and interventions to be in- corporated into the process simulation? Consider a situation in which operators at one firm 'partici- pate' in the media fill program by performing an average of only nine interventions per year. Increase the number of operators and filling lines and the problem can become even more diffi- cult. At some large sites, media-fill execution could be described as an aseptic conga line, as operators queue up to 'participate' brief ly in the media fill before cycling out of the aseptic area. The more lines and operators a firm has, the less satisfactory this approach becomes. The problem of 'participation' can be resolved by