Downstream Validation

Use of Blast Freezers in Vaccine Manufacture

    Vaccines are powerful and cost effective prophylactic tools for protecting public health. The Global Alliance for Vaccines and Immunizations (GAVI) estimates that ~5.4 million lives are saved each year by the administration of vaccines for hepatitis B, measles, haemophilus influenza type B (hib), pertussis (whooping cough), yellow fever, and polio (1). According to the World Health Organization, seasonal influenza alone claims 250,000–500,000 lives every year globally, many of which could be prevented by more widespread vaccination with the…

Implementation of the ASTM Standard for Manufacturing Systems Verification

In 2007, ASTM International (ASTM), formerly known as the American Society for Testing and Materials, published its “E2500-07” international industry consensus standard for conducting a risk-based design and qualification of good manufacturing practice (GMP) manufacturing systems (1). This guide incorporates risk- and science-based practices to focus on critical aspects affecting equipment systems throughout their design–qualification–operation lifecycle. Presentations at recent PDA and ISPE annual meetings indicate that the bioprocess industry is embracing E2500 to improve system designs and reduce costly validations.…

Localized Surface Plasmon Resonance for Bioprocess Development, Monitoring, and Validation

    Academic laboratories have embraced localized surface plasmon resonance (LSPR) as the “new wave” of label-free technology (1). This technique is based on the ability of colloidal metal nanoparticles or nanostructured metallic films to absorb light in a narrow wavelength range. Metal nanostructures “sense” changes occurring at their surfaces by shifting the frequency of the light they absorb or reflect. As a consequence, a basic LSPR system requires only optical fibers, a source of white light, and a detector…

Top 10 Changes in FDA’s Process Validation Guidance

Two years after drafting a comprehensive revision of the 1987 process validation guidance, the FDA finalized the document this year. The revision elaborates on modern quality by design (QbD) techniques for developing a process, analyzing risks, and monitoring for control. The initial draft update remains largely intact, with some important adjustments focused on clarifying the FDA’s intent for how the industry is expected to validate its processes. 1 — Minor Changes: The guidance includes more references to the Code of…

Distinctions Between Analytical and Bioanalytical Test Methods

Analytical methods used for characterization, release, and stability testing of biotechnological/biological products are often automatically referred to as “bioanalytical” methods by some in the field. Many times the term is used to distinguish between test methods applied to small-molecule chemical products and those for macromolecular, biologically based products. It seems sensible enough: We use analytical methods to test chemical pharmaceutical products, so aren’t test methods used for biopharmaceutical products therefore bioanalytical methods? Any way, who cares whether the term is…

Understanding Virus Preparations Using Nanoscale Particle Characterization

As regulators become increasingly stringent in demanding a fuller understanding of whole virus preparations, researchers and manufacturers are looking beyond well-known characterization methodologies. Existing technologies for quantifying and characterizing viral preparations such as infectivity assays, quantitative polymerase chain reaction (qPCR), and protein assays provide crucial information but tell only half the story. We evaluated a unique technology developed by NanoSight Ltd. (www.nanosight.com) for visualizing viruses in liquid suspensions, measuring their approximate concentration, and characterizing their state of aggregation. Information generated…

Microanalytical Techniques for Identifying Nonprotein Contaminants in Biologics

Proteins can aggregate at any point during pharmaceutical manufacturing. Regulatory agencies pay special attention to aggregates that can enhance immune responses and cause adverse clinical effects and those that can compromise the safety and efficacy of a drug product. Biopharmaceutical companies have stringent quality control (QC) procedures in place to ensure that their final products are free of contaminants and defects, including protein aggregates. Trained QC inspectors, however, can typically see product defects or particulate material only as small as…

A Modular Approach to Facility Validation

Biopharmaceutical manufacturers are striving to maintain productivity and profits while controlling increasing costs. Historically, validation has been seen as an expensive, non–value-added necessity to gaining regulatory approval to manufacture. Less often is it seen as a key element of an overall quality management system (QMS) that supports the safety, quality, and efficacy of end products for patients while also providing invaluable knowledge and experience for enhanced process control and management. When fully integrated with a QMS, a modular validation platform…

New Validation Guidance Causes a Stir

In November 2008 the US FDA finally issued a new draft guidance on process validation (1). The original guidance on this topic was published in May 1987, and the FDA explained that “since then, we have obtained additional experience through our regulatory oversight that allows us to update our recommendations to industry on this topic.” The new guidance is intended to reflect some goals of the FDA’s Pharmaceutical GMPs for the 21st Century, an initiative that was finalized in 2004.…

The Reoccurrence of Mycoplasma Contamination: Prevention Strategies

    The contamination of microbiological media by mycoplasmas such as Acholeplasma laidlawii is not a recent phenomenon. It has been a major problem with animal-derived sera since the 1980s and has been a concern in the management of cell cultures for decades. The main culprit of serum contamination was the inadequate blood collection methodology and was eliminated with the introduction of hollow collection needles. In addition to the introduction of an improved collection method, serum was filtered with 0.1…