PDA Single-Use Systems Cross-Organizational Workshop-Meeting Summary, May 14, 2014-PDA Global Headquarters, Bethesda, MD.

UNLABELLED: The application of single-use systems, or disposables, has increased dramatically in the past 10 years. Although some elements of the pharmaceutical and biotech manufacturing process were single-use and therefore disposable and not reused, the majority of the process equipment and fluid path was cleaned and reused by end users. Today, much more of the manufacturing process is composed of single-use systems, and there are some biotech plants that use single-use systems exclusively. Because of this increasing reliance on suppliers, there is an urgent need for more formal standards specifically for single-use system technology. The objective of this PDA-sponsored workshop held on May 14, 2014 was twofold: (1) to promote a harmonized approach to supporting single-use system activities within the industry and in so doing to minimize duplication of efforts, and (2) to communicate ongoing single-use system initiatives among the group. Representatives of ASME, ASTM, BPOG, BPSA, ELSIE, PDA, PQRI, and USP, as well as representatives of CBER and CDER of FDA, attended. LAY ABSTRACT: Today, the majority of pharmaceutical and biotech drug manufacturing equipment is cleaned and reused. However, in the past 10 years, the use of disposable manufacturing systems has increased dramatically; there are even some biotech-derived drugs that are manufactured entirely using single-use technology. This movement toward disposables has placed increased reliance on disposable equipment suppliers, each of which manufactures its products independently to meet customer needs. This fact has led to non-uniformity in design for connectors and similar sub-processes, and has made the need for more formal industry standards. The objective of this PDA-sponsored workshop held on May 14, 2014 was twofold: (1) to promote a harmonized approach to supporting single-use system projects within the industry and in so doing to minimize duplication of efforts, and (2) to communicate ongoing single-use system initiatives among the group. Representatives of industry associations and standard-setting organizations, as well as representatives of the U.S. Food and Drug Administration, attended.

High-throughput screening of stabilizers for respiratory syncytial virus: identification of stabilizers and their effects on the conformational thermostability of viral particles.

Respiratory syncytial virus (RSV) is the leading cause of severe respiratory infection in children worldwide. Recombinant live attenuated viral preparations are one of the most promising strategies for vaccination but they typically possess poor thermostability. In this work, a library of compounds was screened and stabilizers were selected based on their ability to inhibit the aggregation of RSV perturbed at 56 degrees C. After screening and selection of excipients, the conformational stability of the RSV proteins was evaluated in the presence of potential stabilizers. The secondary and tertiary structures as well as aggregation/dissociation of RSV were monitored using circular dichroism and second derivative UV absorption spectroscopies and light scattering, respectively, as a function of temperature (10-90 degrees C). RSV membrane fluidity was also evaluated by generalized polarization of Laurdan fluorescence. Screening experiments showed that a variety of sugars, amino acids, polyols and polyanions inhibited the aggregation of viral particles. Conformational stability studies demonstrated that the addition of sugars and polyols stabilized RSV as indicated by a significant increase in the transition melting temperature (Tm) of both the secondary and tertiary structures as well as the gel to liquid crystalline membrane transition. These results should provide the basis for rational development of more physically stable formulations of live attenuated RSV vaccines.