Risk Management

eBook: Speed to IND — Practical Wisdom for Uncertain Times

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Even in “normal†times, companies need to balance time to filing an investigational new drug (IND) application against careful consideration of processes that can have far-reaching consequences on the quality of biologic products. But supply-chain interruptions still feature prominently in the news during the ongoing COVID-19 pandemic. From equipment to chemicals to plastic components, end users, their suppliers, and (critically) their suppliers’ suppliers all are feeling growing uncertainty about production timelines and availability of materials. In this eBook, BPI’s editor…

October 28, 2021

Risk Determination of Potential Mycotoxin Exposure to Patients: Testing Recombinant Human Factor VII from Transgenic Rabbits

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Sevenfact eptacog beta is a new recombinant human factor VIIa (rFVIIa) developed by LFB SA in Les Ulis, France, as a bypassing agent (BPA) for treatment and control of bleeding in people with hemophilia A and B and inhibitors (1, 2). The product was approved for use in adults and adolescents by the US Food and Drug Administration (FDA) in April 2020 (3). It is expressed in the milk of transgenic rabbits and purified through a multistep process using both…

October 28, 2021

Preparing for a Virtual Audit

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Audits are a vital quality-management tool of the biopharmaceutical industry. Whether the objective is to verify supplier or partner qualifications, contribute to corrective and preventative actions (CAPA), or fulfill regulatory compliance requirements, conducting proactive auditing is key to successful operations. Over the past year, virtual audits —also known as remote or distance audits — have enabled biopharmaceutical companies to meet compliance and quality assurance demands despite COVID-19–related travel restrictions and social-distancing protocols. Notwithstanding the challenges of virtual audits, the benefits…

September 30, 2021

No More Sleepwalking: New Mindsets for Manufacturing Cell and Gene Therapies at Commercial Scale

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Cell and gene therapies (CGTs) offer potential cures to some of the most challenging illnesses of our time. The number of such therapies approved for market is set to surge in the next 10 years (1). Yet current manufacturing approaches are not fit for purpose. Biomanufacturing must adapt to prevent the industry from unintentionally sleepwalking into causing harm to patients. Some urgently needed changes could come with learning about the mindset of the medical-devices industry. Background and Current State After…

September 30, 2021

Microbiome-Based Therapeutics: Negotiating Key Development Challenges

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Microbiome-based therapeutics have evolved significantly in recent years, with several promising candidates advancing through the clinical pipeline. That progress is the result of growing evidence showing that targeting and manipulating the microbiome could improve human health and treat more than 25 conditions by restoring healthy bacterial populations (1). The human microbiome comprises a diverse community of microorganisms, helpful and harmful. It differs by person based on factors such as genetics, environmental influences, diet, and immune function. Microorganisms play a role…

September 30, 2021

Risk Considerations for Aging Pharmaceutical Facility Cleanrooms

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Pharmaceutical facility cleanrooms are designed to reduce and control particle contamination and to minimize the ingress and retention of microorganisms. Such risks typically are easy to control in well-designed, modern facilities. But risk mitigation is more difficult in older facilities. There is no exact definition of what constitutes an aging facility (or what are sometimes euphemistically called legacy facilities). For example, a facility established 100 years ago to manufacture a simple tablet can continue to operate perfectly well with careful…

May 21, 2021

Emerging Strategies for Drug-Product Comparability and Process Validation: Part 2 — Validation, Legacy Products, and Lifecycle Management

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This two-day CASSS CMC Strategy Forum explored many technical, practical, and regulatory facets of biological drug-product (DP) analytics, process validation, and comparability. Part 1 of this report summarized the discussions on drug-product analytics and comparability in BPI’s March 2021 issue (1). Here we report on day two presentations and discussions on validation, legacy products, and lifecycle management. Session Three: Drug-Product Validation The morning session focused on principles of process validation with examples of challenges specific to drug products. New Risk-Based…

April 16, 2021

eBook: Buffers — Navigating New Demands on Downstream Raw Materials

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Bioreactor titers for monoclonal antibody (MAb) processes have increased significantly since the dawn of the biopharmaceutical industry, yet such gains have instigated bottlenecks for critical high-volume raw materials used in downstream processing, such as buffer solutions. As downstream purification is required for most, if not all, biopharmaceutical products, buffers and their preparation are topics that concern nearly every drug company. But those topics rarely receive direct attention. This BPI eBook explores what factors prompted the current buffer bottleneck and what…

March 31, 2021

Cold-Chain Validation: Emerging Vaccines for COVID-19 and Beyond Require More Extensive Evaluation

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In the wake of fast-track approvals for Pfizer’s and Moderna’s respective SARS-CoV-2 vaccines, now begins the largest immunization campaign in world history. Its success will depend not only on the products’ safety and efficacy, but also on several mass-distribution programs requiring significant cold-chain infrastructure. The public has become acutely aware of the Pfizer vaccine’s demanding cryostorage specifications, generating considerable anxiety about how mass distribution will happen. Behind the scenes, however, cold-chain engineering companies such as Modality Solutions have worked alongside…

February 5, 2021

Manufacturability Assessment: A Tool for Effective and Transparent Decision-Making and Efficient Process Development

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Design for manufacturing (DfM, also known as design for manufacturability) is a common approach in engineering industries when complex, multistep production processes are developed and installed to manufacture products. Adherence to DfM approaches has been prevalent for decades in the automotive, aerospace, and electronics industries, among others (1–3). Recently, a generalized manufacturability-assessment tool with strategies to weigh different aspects of manufacturing has been proposed with numerous similarities to that described herein specific to the field of bioprocess development (4). Although…

December 17, 2020