Stress Factors in Primary Packaging, Transportation and Handling of Protein Drug Products and Their Impact on Product Quality.

Protein-based biologic drugs encounter a variety of stress factors during drug substance (DS) and drug product (DP) manufacturing, and the subsequent steps that result in clinical administration by the end user. This article is the third in a series of commentaries on these stress factors and their effects on biotherapeutics. It focuses on assessing the potential negative impact from primary packaging, transportation, and handling on the quality of the DP.

Emerging Challenges and Innovations in Surfactant-mediated Stabilization of Biologic Formulations.

Biologics may be subjected to various destabilizing conditions during manufacturing, transportation, storage, and use. Therefore, biologics must be appropriately formulated to meet their desired quality target product profiles. In the formulations of protein-based biologics, one critical component is surfactant.

Stress Factors in Protein Drug Product Manufacturing and Their Impact on Product Quality.

Injectable protein-based medicinal products (drug products, or DPs) must be produced by using sterile manufacturing processes to ensure product safety. In DP manufacturing the protein drug substance, in a suitable final formulation, is combined with the desired primary packaging (e.g.

Re-Envisioning Pharmaceutical Manufacturing: Increasing Agility for Global Patient Access.

The traditional paradigm for pharmaceutical manufacturing is focused primarily upon centralized facilities that enable mass production and distribution. While this system reliably maintains high product quality and reproducibility, its rigidity imposes limitations upon new manufacturing innovations that could improve efficiency and support supply chain resiliency. Agile manufacturing methodologies, which leverage flexibility through portability and decentralization, allow manufacturers to respond to patient needs on demand and present a potential solution to enable timely access to critical medicines.

An Industry Perspective on the Challenges of Using Closed System Transfer Devices with Biologics and Communication Guidance to Healthcare Professionals.

Closed system transfer devices (CSTDs) have been used with hazardous drugs for several decades. The goal of this whitepaper is to increase awareness among healthcare professionals, device manufacturers, regulators, and pharmaceutical/biotech companies on the potential issues around the use of CSTDs with biologic drug products to allow their informed use in clinics. Specifically, we discuss the key topics related to the use of CSTDs with biologics products, including components and materials of construction, a breakdown of regulatory, technical, clinical site-related risks and challenges associated with the use of CSTDs with biological products, gathered from stakeholder discussion at the IQ CSTD workshop, and considerations on current testing requirements and communication strategies to drive further dialog on the appropriate use of CSTDs.

The Confluence of Innovation in Therapeutics and Regulation: Recent CMC Considerations.

The field of human therapeutics has expanded tremendously from small molecules to complex biological modalities, and this trend has accelerated in the last two decades with a greater diversity in the types and applications of novel modalities, accompanied by increasing sophistication in drug delivery technology. These innovations have led to a corresponding increase in the number of therapies seeking regulatory approval, and as the industry continues to evolve regulations will need to adapt to the ever-changing landscape. The growth in this field thus represents a challenge for regulatory authorities as well as for sponsors.

Challenges of Using Closed System Transfer Devices With Biological Drug Products: An Industry Perspective.

Hazardous drug is a common term used by the National Institute of Occupational Health and Safety (NIOSH) to classify medications that may induce adverse mutagenic and reproductive responses in health care personnel. NIOSH publishes a list of drugs it defines as hazardous where it may be appropriate for health care workers to take protective measures to reduce the potential for occupational exposure. Recent updates and proposed updates to this list have included large molecule biological products with oncology indications.

Characterization of Subvisible Particles in Biotherapeutic Prefilled Syringes: The Role of Polysorbate and Protein on the Formation of Silicone Oil and Protein Subvisible Particles After Drop Shock.

Subvisible particles (SbVPs) are a critical quality attribute for biotherapeutics. Particle content in prefilled syringes (PFSs) of a biotherapeutic can include protein particles and silicone oil particles (SiOP). Here, a real-world protein therapeutic PFS shows that although polysorbate is effective in preventing protein particle formation, it also leads to the formation of SiOP.

Silicone Oil Particles in Prefilled Syringes With Human Monoclonal Antibody, Representative of Real-World Drug Products, Did Not Increase Immunogenicity in In Vivo and In Vitro Model Systems.

Silicone oil is a lubricant for prefilled syringes (PFS), a common primary container for biotherapeutics. Silicone oil particles (SiOP) shed from PFS are a concern for patients due to their potential for increased immunogenicity and therefore also of regulatory concern. To address the safety concern in a context of manufacturing and distribution of drug product (DP), SiOP was increased (up to ∼25,000 particles/mL) in PFS filled with mAb1, a fully human antibody drug, by simulated handling of DP mimicked by drop shock.