With proliferating modalities entering and moving through the biopharmaceutical industry’s development pipeline, drug presentations are expanding and diversifying to accommodate. Even “traditional” biologics such as monoclonal antibodies (MAbs) have evolved in their formulation and packaging, with the emergence of highly concentrated drug products, prefilled syringes, and devices that enable patients to inject themselves at home. Patients, clinicians, and payers are demanding convenience and costeffectiveness as well as safety, quality, and efficacy from their medications — and compliance with treatment regimens improves with easier administration options. Contributors to this featured report include a consultant, an academic researcher, and a science executive with a commercial laboratory. They cover an array of topics under the formulation/fill–finish theme: Europe’s Annex 1 revision for drug products, applications of thin-film freeze-drying in producing powdered formulations inhaled delivery, and formulating cell therapies for cryopreservation and clinical use.

Introduction: Practicalities of Aseptic Processing for Modern Biological Drug Products
by Cheryl Scott
The work of biopharmaceutical formulators and fill–finish operators is changing, and changes often can introduce risk when it comes to regulatory compliance and quality systems. Discussions of such risks were prevalent throughout the final years of the Institute of Validation Technology’s (IVT’s) open-source Journal of Validation and Journal of GXP Compliance before they were discontinued in 2022. Here, BPI’s senior technical editor reviews a A number of recent IVT articles covering these risks and how to address them, now hosted on the BPI website. Topics include visual inspections, published warning letter results, container-closures and delivery devices, and combination products.

Focus on Aseptic Processing: A Report from the September 2022 PDA Annex 1 Event in Amsterdam
by Patrick Nieuwenhuizen (PharmaLex)
The PDA organized its third workshop from a series of four focused on the Annex 1 regulation revision in September 2022. Topics covered included implementation of the new regulation, quality risk management, contamination control strategies, preuse poststerilization integrity testing, container-closure integrity testing, and facilities and barrier systems for aseptic processing. Here, a European consultant reports on the meeting and its discussions of those topics. With the final text published in August 2022, time is flying by for organizations that need to comply with Annex 1 by 25 August 2023. Companies must ensure that they understand the requirements of the newly published version. A structured gap assessment and realistic remediation plan to address noncompliances as soon as possible will be important to satisfy regulatory inspections and future-proof a company’s compliance for the European market. All of this requires in-depth knowledge of drug-product manufacturing processes and identification of their associated risks, augmented with remediation actions based on correct adoption and successful implementation of QRM.

Advances Toward Dry-Powder Formulation of Monoclonal Antibodies
by Brian Gazaille, with Robert O. Williams
Historically, monoclonal antibody (MAb) products have been formulated as liquid suspensions for infusion or injection. However, branching off of successes among inhalable vaccine drug products, researchers are making significant progress in establishing equipment for dry-powder formulation of MAbs. Here, BPI’s managing editor speaks with a researcher whose team is leveraging thin-film freezing methods to create such formulations. Williams explains how liquid formulation and lyophilization can compromise biologic quality and why industry has yet to develop commercially viable processes for manufacturing inhalable MAb products. Then, he describes how thin-film freezing works, how it surpasses limitations associated with more-traditional lyophilization methods, and how his lab is leveraging machine learning to predict the aerosol properties of formulated drug products.

Cryopreserving Hematopoietic Stem Cells — Part 2: Methods, Materials, and Operations
by Brian Gazaille, with Erik Woods
The size and complexity of living cells raise distinctive hurdles during drug-product cryopreservation — even if such products are processed, frozen, and thawed in much smaller batch sizes than are drugs based on monoclonal antibodies and other proteins. Branching off of considerations published in BPI’s November 2022 eBook on cryopreservation, BPI’s managing editor herein speaks with Erik Woods, a presenter from the July 2022 Informa Connect Supply Chain & Cryopreservation of Advanced Therapies digital event, to explore cryopreservation requirements for hematopoietic stem cells. Whereas part 1 of the discussion featured considerations for recovering such cells from the bone marrow of deceased donors, this installment focuses on industry needs for effective cryoprotectants, freeze-thaw protocols, and operator training.