Formulation

Formulation Development of Microbiome Therapeutics Localized in the Intestines

Scientists have discovered that microorganisms associated with the body play a critical role in human health (1). The intestinal microbiome is the collection of all combined genetic material of microorganisms in the intestines. An intestinal microbiota, a term frequently used interchangeably with microbiome, is the collection of such microorganisms in the intestine. With the volume of research into the human microbiome expanding, so too is the number of examples of its benefits to our health (1). Like diseases of the…

Introduction: Drug Product Discussions

Quality by design (QbD), risk management, and new technologies are shaping biologics formulation work in the 21st century. We saw much evidence of this at the BioProcess International Conference and Exhibition in Boston last fall, where a wide range of talks filled the Drug Product, Fill–Finish, and Formulations track during the week after Labor Day. Dingjiang Liu (Regeneron) offered a high-level discussion from the BioPhorum Development Group (BPDG) on “An Intercompany Perspective on Biopharmaceutical Product Robustness Studies.” Such studies ensure…

Analytical Strategies for Fixed-Dose Coformulated Protein Therapeutics

Coformulation of two or more proteins in a single formulation is an emerging approach to delivering multiple biotherapeutics that previously have been administered in sequence. This approach brings multiple benefits to all stakeholders. Foremost for patients, the primary benefits are combined therapeutic effects and improved convenience (e.g., fewer administration events). Healthcare providers see logistical benefits and decreased risk of medical errors. Additionally, coformulations also simplify manufacturing logistics, reduce costs of packaging and distribution, and provide new opportunities for product portfolio…

Early Stage Development of Advanced Formulations in the Drug Development Process Provides Competitive Advantages: Survey Predicts That Drug Product Formulation Recognition and Budgets Will Increase Significantly

New antibody formats and aggregate-prone, subcutaneously administered protein therapeutics present biopharmaceutical companies with major challenges regarding protein stability and aggregation. At the same time, protein stability often is not given enough attention in early stages of development. Protein aggregation reduces drug activity so that increasing doses are needed to achieve the same desired effect. Even worse, protein aggregates can induce immunogenecity that endangers patients and compromises product approval. A market study presented for the first time at the Bio-Europe 2018…

Apparent Matrix Effects in an Iduronate 2-Sulfatase Specific Activity Assay

The recombinant fusion protein SHP631 consists of a chimeric monoclonal antibody binding to human insulin receptor and iduronate-2-sulfatase (I2S). This product is being developed as an enzyme replacement therapy to treat cognitive symptoms of Hunter’s syndrome. Because the current therapy (idursulfase, brand name Elaprase from Shire) cannot cross the blood–brain barrier (BBB), SHP631 is being developed to do so, enabling the presence of I2S in the brain. The enzymatic activity of this molecule is measured using the substrate 4-methyl umbelliferyl-α-L-idopyranosiduronic…

Rational Selection of Sugars for Biotherapeutic Stabilization: A Practitioner’s Perspective

Biotherapeutics from recombinant DNA technology include diverse modalities such as peptides; enzymes, antibodies, and other proteins; nucleic acids; and cellular therapies. Such products present physical, chemical, and biophysical challenges. Excipients used in stabilization of these biotherapeutics can be broadly classified into the following classes (subgroups) that have been reviewed carefully elsewhere (1–4) : Buffers (e.g., phosphate, acetate, and histidine) Tonicity agents/stabilizers (sugars such as sucrose, polyols such as sorbitol) Bulking agents (lyoprotectants such as mannitol) Surfactants (e.g., polysorbates) Antioxidants (e.g.,…

Development of a Freeze-Dried Ebola-Expressing Adenoviral Vector: Unexpected Findings and Problems Solved

In December 2013, a two-year-old child in Guinea became the first person to be killed by Ebola in the most recent outbreak. In March of the following year, that outbreak was declared in West Africa. By mid-2014, the World Health Organization (WHO) had declared it to be a public health emergency of international concern and urged pharmaceutical companies to accelerate their development of candidate vaccines. At the peak of the outbreak in 2014, more than 1,200 new cases of Ebola…

Rational Design of Liquid Protein Formulations: Application of Biophysical Stability Predictors and Descriptors to Reformulate Biotherapeutics

Successful development of liquid biopharmaceutical formulations requires careful assessment of the biophysical properties of the protein in solution, primarily focused on achieving optimal conformational and colloidal stability of the drug-substance molecule (1–11). It also involves extensive stability studies under stressed conditions. Using state-of-the-art biophysical tools for characterization of developed products, those studies are based on key biophysical descriptors and extended particulate characterization methods (subvisible particles in micro- and nano-size range) to deliver a stable product for market with a shelf…

eBook: Alternative Delivery of Biologics — Underdogs Pursue Roads Less Traveled

A number of failures in development of noninjectable delivery methods for therapeutic proteins have caused numerous development programs to crash and burn along with investors’ hopes, dreams, and cash. Most everyone reading BioProcess International is familiar with the issues and challenges: Needles hurt and involve risks to both caregivers and patients. Injections often require administration by trained personnel in specialized settings. But alternative delivery methods are fraught with greater challenges related to dosing, bioavailability (particularly for oral dosing), and inherent…

Conference Report: The Drug Product Track at 2017’s BioProcess International Conference and Exhibition in Boston, MA

At the Hynes Convention Center in Boston, MA, during Knect365’s “Biotech Week Boston” in late September of 2017, one track of the BioProcess International Conference focused on drug products, fill–finish, and formulations. Presenters represented a number of major biopharmaceutical companies — AbbVie, Amgen, Biogen, Eli Lilly, Genentech (Roche), GlaxoSmithKline, Johnson & Johnson, Lonza, Pfizer, and Sanofi — as well as suppliers Bosch, Merck (MilliporeSigma), ReForm, and Single-Use Support. They focused on predictive modeling, quality by design (QbD) and process analytics,…