Buffers are used widely in molecular biology, biochemistry, and biopharmaceutical manufacturing. For the latter, buffers play a pivotal role in modulating the characteristics of biologics, influencing their interactions with other molecules and surfaces as well as the structure and stability of the biologics themselves
(
1
). Biopharmaceuticals invariably are formulated with buffers, which serve to stabilize them and affect their physiological transport and function. Buffers are used extensively in biopharmaceutical processes, particularly chromatography steps in downstream processing (
2
). A buffer’s pH level can affect significantly the state of a chromatographic resin and protein of interest, determining the effectiveness of binding and elution of both products and impurities
(
3
).
To design buffers effectively, we must understand basics of their chemistry and reactions, including how those relate to solution pH and ionic concentrations. Once buffers are designed, we can analyze them for compound...
Biopharmaceutical companies must take a holistic approach to automate material delivery and warehouse activities in their facilities for biopharmaceutical production.
This two-part review provides high-level analytical development considerations for ex vivo, genome-modified hematopoietic stem and progenitor cell (GM-HSPC) products derived from primary donor cells.
Part 1 in BPI’s May 2024 issue
addresses analytical controls for in-process drug substances and drug products. Here in Part 2, we take a step back to examine concerns for HSPC source materials. Look to other recently published reviews for a broader discussion of chemistry, manufacturing, and controls (CMC) for GM-HSPCs (
19, 20
) and for development considerations with gene-edited pluripotent stem cells (PSCs) (
21
). Note that we use the term
genome modified
in a generic sense herein to include products that are manufactured by means of viral-vector transduction (typically by lentiviral vectors (LVVs)) and those subject to genome editing by such means as a system based on clustered regularly interspaced palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9).
Analytical Controls for Starting ...
Demand has surged for good manufacturing practice (GMP)–grade plasmid DNA (pDNA) used in late-phase clinical trials and commercial manufacturing due to the starting material’s critical role in producing nextgeneration therapies. The same is true for minicircle DNA (mcDNA) — supercoiled-DNA vectors that can be obtained from plasmids through cutting-edge in vivo recombination techniques. Because mcDNA lacks plasmid backbone sequences and contains primarily active genes, it can provide enhanced transgene expression with greater persistence than conventional plasmids can. Considering the biopharmaceutical industry’s great need for both pDNA and mcDNA, tools supporting fast-growing, high-yielding microbial cultures are becoming increasingly important.
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