Plasma Product Biotechnology Meeting 2019

May 13-17, 2019

Giardini Naxos, Sicily

The Plasma Product Biotechnology Conference Series provides a valuable opportunity to discuss topics relevant to the plasma fractionation industry including manufacturing, quality, regulatory, pathogen safety, clinical development and technical innovations.

The following MilliporeSigma data will be presented at the forum:

From Concept to Reality: Successful use of single-pass TFF to reach high protein concentration during commercial production of Plasma derived products

Torsten Bisschop, Merck KGaA, Darmstadt, Germany
Gert Verheyden, Takeda, Belgium

The concept of Single Pass Tangential Flow Filtration (SPTFF) technology requires only one pass through the filter assembly to achieve the desired concentration with no recirculation of product. This could, compared to the conventional Tangential Flow Filtration, offer several advantages in downstream processing, such as optimized processing of high shear-sensitive products, reduction of foam formation and increased product recovery. Although the SPTFF technique is already known for several years and despite the expected advantages, there are only limited examples of applications at commercial scale.

This case study describes how Takeda, in collaboration with MilliporeSigma, developed a specific SPTFF system as an alternative to traditional TFF for concentration a plasma-derived IgG solution from 10% to 20% at commercial production scale.

Related Resource:
Pellicon Single-pass TFF white paper

Protein Purification using novel chromatographic affinity ligands

Achim Schwammle, Merck KGaA, Darmstadt, Germany

Within the EU-funded Horizon 2020 project, a novel class of affinity ligands based on a unique family of small, thermostable proteins (Nanofitins™) has been evaluated and applied to the purification of vaccine-related proteins. Immobilized on suitable chromatographic supports, the affinity ligands showed a very high binding specificity to the respective target proteins, which could be isolated in high purity and yields directly from crude bacterial lysates in a single chromatographic step. Due to the high operational stability of the affinity columns which allows the re-use over many cycles including sodium hydroxide cleaning, the concept is not only feasible in a technical sense but also economically beneficial. The applicability of Nanofitins™ based affinity chromatography to the purification of therapeutic proteins from other biological sources, such as human plasma, will be evaluated soon.

A Simple Static Cleaning Procedure for SPTFF

Manuel Brantner, Merck KGaA, Darmstadt, Germany

One of the key technologies that can help to realize a continuous production flow is Single Pass Tangential Flow Filtration (SPTFF); a continuous TFF operation with a simple, straight forward flow path, typically without a recirculation loop. SPTFF is used to directly link different unit operations, i.e., by altering inline buffer composition and product concentration or for increasing the final concentration at high yield. However, there are also limitations in the available options and flow rate for cleaning. Yet, the high value of TFF devices makes the assessment of reuse by cleaning economically interesting. This poster presentation highlights a case study in which a static cleaning methodology for SPTFF was applied. To maintain the simplicity of the straight forward path, a cleaning procedure was assessed using a combination of flush to drain and static hold steps without recirculation. The cleaning procedure efficacy and its effect on process performance over multiple cycles will also be discussed.

Related Resource:

Efficacy of a simple static cleaning procedure for SPTFF, Biopharm International, Jan 2019

Evaluation of chromatographic methods on IgG purification

Josephine Cheng, Merck KGaA, Darmstadt, Germany

This poster demonstrates two real case studies addressing the use of ion exchange chromatography resins in IgG process optimization. In the first case study, we demonstrate a systematic approach integrating chromatography in IgG purification strategies by evaluating the quality of IgG and confirming the robustness of the purification method. Results show that with just one ion exchange chromatography step, efficient and reliable purity improvement can be achieved with no changes in the IgG attributes. In the second case study, we evaluated three different starting fraction pools to check the improvement of IgG product quality using chromatography in comparison to the original purification scheme. The pros and cons are discussed with quality testing data according to regulatory guidelines and with consideration of industrial practical aspects.

Related Resources:

• Webinar: Addressing Immunoglobulin (Ig) purification challenges with chromatographic technologies
• Webinar: Chromatographic strategies for IVIG purification

Addressing handling challenges of chemicals by granulation

Balu Guduri, Merck KGaA, Darmstadt, Germany

Buffers, salts and stabilizing chemicals are used in multi-ton quantities during fractionation of blood plasma. The handling of such quantities in a pharmaceutical production environment can be challenging. Very find powders can show high dust formation thereby leading to lengthy cleaning procedures and higher safety measures for employees. Furthermore, appropriate handling can be impeded due to poor flowability and caking of the bulk material. Strong mechanical forces are needed to break up the caked material posing a safety risk for employees. Remaining lumps can damage vessels and other processing equipment. In many cases, these limitations can be overcome by granulation of the bulk chemicals. In this study, stability and particle size of granules were analyzed. Flowability, bulk and tapped densities, dissolution kinetics and degree of caking were compared between bulk and granules. Results demonstrate how granulation can address challenges and greatly improve the handling of chemical raw materials.