Requirements from regulatory agencies have become increasingly rigorous with regards to the detection, identification, and quantitation of extractable and leachable compounds in pharmaceuticals, drug delivery systems, and biomedical devices. This heightened scrutiny is the result of several well‐documented incidents of contaminants leaching from containers and packaging, causing potential or real risk to humans. Therefore, regulatory agencies, such as the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA), have increased regulations on potential extractables and leachables in drug product container and closure systems.

An Alcami authored article will be featured in the upcoming September 2018 issue of Drug Development & Delivery titled High-Resolution Mass Spectrometry - A Map to Biologics.

INTRODUCTION
Biopharmaceutical products represent up to 20% of the total pharmaceutical market and are growing at a rate of nearly 8% annually. To keep up with this impressive growth rate, many CDMOs are making strategic investments in equipment and expertise to support analytical development and structural characterization of biopharmaceuticals in more economical and efficient ways.¹ Unlike small molecule active pharmaceutical ingredients that exist as a single chemical entity, biologics nearly always exist as a mixture of molecules. Different molecules can arise from numerous sources including N-terminal variants, post-translation modifications (PTMs), glycoforms, and degradation products. 

Durham, NC (USA) – March 15, 2018 – Alcami Corporation, a leading provider of fully-integrated custom end-to-end solutions for the pharmaceutical and biotechnology industries, and Triangle Residential Options for Substance Abusers, Inc. (TROSA), a Durham-based innovative, multi-year residential program that enables substance abusers to be productive, recovering individuals by providing comprehensive treatment, work-based vocational training, education, and continuing care, today announce Alcami’s donation of $10,000 to the nonprofit. Alcami’s gift will fund TROSA’s technology needs for its recently established Comprehensive Care Center.

Part One: Biologics and the Problem with Residual DNA 

Part Two: Cell-Based Bioassays 

Part Three: Micro-Flow Imaging

In this final post of our biologics blog series, bioassay scientists will construct a guide to the components of micro-flow imaging: imaging, counting and sorting, plus sample requirements.

Imaging
Micro-Flow Imaging™, or MFI, couples microfluidics with digital microscopic imaging to determine particle size and concentration in biologics and injectables. The concept of Micro-Flow Imaging is very simple. If a particle moves through the flow cell, the particle is imaged and counted. The principles of flow cytometry, microfluidics, microscopy and digital imaging are combined into one instrument.

Sub-visible particles can be unintentionally present in parenterals as a byproduct of drug formulation and manufacturing. This type of analysis allows for the visual assessment of the types of particles present in a solution. Particles that can be present in biopharmaceutical preparations are silicone oil, air bubbles, protein aggregates, rubber pieces from closures and glass shards.

Part Two: Cell-Based Bioassays

In part one of this biologics series, leading Alcami experts established the biologic challenges resulting from residual DNA. In this second part, we will build upon the fundamentals of bioassays.

Biological assays (bioassays) use biological substrates and entities to determine the critical quality attributes of a drug product. These applications are suitable to both small molecules and large molecules (i.e., biologics). While these assays typically exhibit more variability than chemical-based assays, bioassays provide vital tools in the assessment of product toxicity and potency.

Part One: Biologics and the Problem with Residual DNA

As opposed to traditional drug production, the production of biological products (biologics) requires the involvement of human, animal or microbial cells. Biologics are some of the most effective and cutting-edge therapeutics, such as vaccines and antibodies that are produced through recombinant protein technologies. Biologics produced in cell culture contain unique impurities, including host cell proteins and host cell DNA. Therefore, the World Health Organization (WHO), the European Pharmacopoeia, and the US Food and Drug Administration (FDA) have established strict regulatory guidelines to guarantee product quality in the drug substance.