From Extractables to Exposure Data: Sensitivity Analysis of Extrapolation Algorithms with Focus on USP 〈665〉.

We evaluated algorithms designed to extrapolate extractables data for predicting process equipment-related leachables (PERLs) and assessing PERL exposure in single-use systems (SUSs) and their assemblies. The robustness and sensitivity of these algorithms were tested against variations in input data, including extrapolation algorithms for both short and long contact time extractables data obtained from the standardized extractables protocol provided in USP 〈665〉. Our findings demonstrate that extrapolated data for SUS and assemblies are suitable for safety assessments.

Parylene C Coating Efficacy Studies: Enhancing Biocompatibility of 3D Printed Polyurethane Parts for Biopharmaceutical and CGT Applications.

Additive manufacturing, particularly Vat photopolymerization, presents a promising technique for producing complex, tailor-made structures, making it an attractive option for generating single-use components used in biopharmaceutical manufacturing equipment or cell culture devices. However, the potential leaching of cytotoxic compounds from Vat photopolymer resins poses a significant concern, especially regarding cell growth and viability in cell culture applications. This study explores the potential of parylene C coating to enhance the inertness of a polyurethane-based photopolymer resin, aiming to prevent cytotoxicity and improve biocompatibility.

Assessing biologic/toxicologic effects of extractables from plastic contact materials for advanced therapy manufacturing using cell painting assay and cytotoxicity screening.

Plastic components are essential in the pharmaceutical industry, encompassing container closure systems, laboratory handling equipment, and single-use systems. As part of their material qualification process, studies on interactions between plastic contact materials and process solutions or drug products are conducted. The assessment of single-use systems includes their potential impact on patient safety, product quality, and process performance.

Dimethylsilanediol from silicone elastomers: Analysis, release from biopharmaceutical process equipment, and clearance studies.

Polysiloxanes are considered one of the most important commercial families of synthetic elastomers. They are frequently employed in biopharmaceutical manufacturing equipment as flexible single-use solutions due to superior material properties and compatibility with diverse sterilization methods. Extractables and leachables (E&L) testing is essential in qualifying such equipment, involving extraction studies to assess the potential release of compounds from plastic components for risk assessment.

Equivalence study of extractables from single-use biopharmaceutical manufacturing equipment after X-ray or gamma irradiation.

Single-use (SU) devices and assemblies used as manufacturing equipment in the biopharmaceutical industry require comprehensive qualifications. These qualifications include the assessment of compounds released from SU devices in contact with the process fluids, and how these leachable compounds potentially influence process performance, drug product quality, and patient safety. SU suppliers need to provide comprehensive qualification data for several parameters, for both new products and product changes, such as changes in the sterilization process applied to the SU device.

X-ray sterilization of biopharmaceutical manufacturing equipment-Extractables profile of a film material and copolyester Tritan™ compared to gamma irradiation.

The biopharmaceutical industry gains enormous flexibility in production processes by using sterilized preassembled single-use devices. Gamma irradiation is an established sterilization technology that may be restricted in the future by the availability of Co as irradiation source and irradiation capacities. X-ray technology is considered an alternative type of radiation for sterilizing SU equipment.

Rinsing Recommendations for Membrane Filters and Identification of Rinsables.

Filtration is universally used in biopharmaceutical processing. For example, in upstream processing for sterilizing-grade filtration of cell culture media or in various downstream operations, such as clarification, filtration of intermediates, and in critical final filling applications. It is well known that filtration devices can release a certain level of organic compounds within the first filtrate fractions, which can be measured as total organic carbon (TOC).

Using extractables data from single-use components for extrapolation to process equipment-related leachables: The toolbox and justifications.

Quantitative information on process equipment-related leachables (PERLs) is required for process qualification and within a safety assessment. Extractables data for single-use equipment are suitable and applicable if the extractables study conditions fit or are bracketing the expected conditions of use. It is necessary to extrapolate extractables data when the expected in-use conditions are not covered by the test conditions.

Identification and evaluation of cell- growth-inhibiting bDtBPP-analogue degradation products from phosphite antioxidants used in polyolefin bioprocessing materials.

The inhibiting effect of the secondary phosphite antioxidant degradation product bis(2,4-di-tert-butylphenyl)phosphate (bDtBPP) on cell growth is well-known. The present study describes structurally related compounds which are likely to be formed from similar widely used phosphite antioxidants used in materials for the manufacturing of single-use (SU) equipment. Two potential candidates of such compounds-3,3',5,5'-tetra-tert-butyl-2,2'-dihydroxybiphenylphosphate (TtBBP) and bis(p-nonylphenyl)phosphate (bNPP)-were identified by chromatography and mass spectrometry followed by synthesis and X-ray structure elucidation.

Using Extractables Data of Sterile Filter Components for Scaling Calculations.

Users of single-use (SU) components need extractables data to demonstrate material safety for regulatory bodies before incorporation in the biopharmaceutical process. In this context, the correct use of such extractables data is key to deriving realistic risk assessments for SU devices. In this paper, a standardized extractables approach was used that provides comprehensive extractables information including identity and quantity.

Filtration membranes - Scavengers for leachables?

This publication describes the development of an experimental set-up and testing protocol to test the hypothesis that filters used for sterile filtration can act as scavengers of leachables. The filter materials polyethersulfone (PESU) and cellulose acetate (CA) were tested. These membrane materials are used commonly in downstream operations during biopharmaceutical manufacturing.

Comparative Extractables Study of Autoclavable Polyethersulfone Filter Cartridges for Sterile Filtration.

Sterile filters are ubiquitous in biopharmaceutical manufacturing processes. Because such filters are in direct contact with the process fluid, profiling of the extractables is of utmost importance. The work presented here reveals the extractables profile from filter cartridges for sterilizing-grade filtration, which were obtained from six different vendors.

Analysis and evaluation of single-use bag extractables for validation in biopharmaceutical applications.

Unlabelled: This paper describes an approach of extractables determination and gives information on extractables profiles for gamma-sterilized single-use bags with polyethylene inner contact surfaces from five different suppliers. Four extraction solvents were chosen to capture a broad spectrum of extractables. An 80% ethanol extraction was used to extract compounds that represent the bag resin and the organic additives used to stabilize or process the polymer films which would not normally be water-soluble.

A risk analysis for production processes with disposable bioreactors.

: Quality management systems are, as a rule, tightly defined systems that conserve existing processes and therefore guarantee compliance with quality standards. But maintaining quality also includes introducing new enhanced production methods and making use of the latest findings of bioscience. The advances in biotechnology and single-use manufacturing methods for producing new drugs especially impose new challenges on quality management, as quality standards have not yet been set.

Study of protein adsorption effects on crossflow filtration using BSA and milk protein.

Three membrane materials were tested under similar conditions to determine the effects of membrane material on the performance and cleanability of the filters. The membrane materials investigated were stabilized cellulose (Hydrosart, Sartorius Corporation), cellulose triacetate, and polyethersulfone; all having a 10 kilodalton molecular weight cutoff. Stabilized cellulose is a cellulose-based membrane material, modified for low non-specific protein adsorption combined with high pH-resistance.