Issue 3 Volume 14 (2025)

Pharmacogenomics has generated clinically relevant gene–drug associations, increasingly standardized variant interpretations, prescribing recommendations, and implementation infrastructures. Nevertheless, a persistent translational discontinuity remains between identifying an association and making a defensible therapeutic decision for an individual patient. This discontinuity arises because association credibility, variant and haplotype resolution, functional interpretation, genotype-to-phenoty

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Pharmacogenomics can improve medicine selection and dose individualization, but greater biological precision does not automatically produce equitable care. Exclusion may arise when evidence is derived from narrowly represented populations, genomic associations are transferred without adequate validation, ancestry is replaced by racial or geographic proxies, uncertain variants are treated as definitive, testing is inaccessible, or recommended alternatives cannot be obtained. This article proposes

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Pharmaceutical biotechnology is increasingly described through the language of platforms: reusable biological parts, programmable cells, automated design cycles, intensified bioprocesses, and adaptable manufacturing systems. This framing captures genuine advances but can also obscure differences between technical reuse, process repeatability, product transferability, and pharmaceutical readiness. This conceptual review examines how platform claims are constructed across synthetic biology, cellul

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Biopharmaceuticals have transformed treatment across oncology, immunology, and other therapeutic fields, but their molecular heterogeneity, manufacturing dependence, immunogenic potential, and cost complicate development and access. Biosimilars seek to expand competition without reproducing an originator’s proprietary manufacturing process or exact molecular microheterogeneity. This integrative review examines how evidence from manufacturing knowledge, analytical and functional comparability, co

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Analytical similarity is foundational to biosimilar development, yet modern comparability programs generate heterogeneous evidence that cannot be represented adequately by one composite score. This article proposes an original hierarchical evidence model that preserves attribute identity across structural, physicochemical, functional, clinical-consequence, residual-uncertainty, and decision-response layers. The model rejects context-free compensation because extensive agreement among low-critica

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Pharmacogenomics is increasingly used to guide medication selection and dose individualization, yet routine implementation produces inconsistent clinical and patient outcomes. This realist review examines how pharmacogenomic programmes operate, for whom, and under which conditions they generate therapeutic benefit, limited uptake, or unintended consequences. The initial programme theory proposed that benefit becomes more likely when a clinically consequential drug–gene relationship is translated

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Biopharmaceuticals are heterogeneous products whose molecular distributions may vary across batches, manufacturing sites, process states, storage periods, analytical platforms, and delivery configurations. Lifecycle assurance should therefore focus less on preserving historical manufacturing sameness and more on determining whether product evolution remains compatible with clinically relevant quality, safety, efficacy, exposure, and immunogenicity expectations. This article proposes a non-empiri

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Indication extrapolation allows a biosimilar to be used in approved reference-product indications that were not independently tested in comparative efficacy trials. Its scientific justification, however, cannot rest on analytical similarity, shared target identity, pharmacokinetic equivalence, or clinical similarity in one sensitive population alone. This original framework article proposes a mechanism-based evidence pathway integrating reference-product knowledge, comparative analytical and fun

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Sequence design can optimize biologics for target engagement, specificity, format, and predicted structure, but sequence-level promise does not establish efficient expression, productive folding, consistent modification, robust purification, formulation, or stability. This non-empirical article proposes a sequence-to-product translation framework for recombinant therapeutic proteins, particularly antibodies and antibody-derived formats. Manufacturability is treated as a conditional interaction a

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Therapeutic-protein manufacturing is often optimized through productivity-centered objectives, although increased product formation can alter metabolic allocation, folding demand, molecular heterogeneity, biological activity, cellular stability, and process sensitivity. This article proposes the Therapeutic Cell-Factory Reconciliation Architecture, an original non-empirical framework that organizes these interdependencies without reducing performance to titer or a single composite score. The arc

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Observed exposure–response associations are often interpreted as evidence that changing dose or exposure will alter clinical outcome. Such interpretation may fail when prescribed dose differs from administered dose, adherence changes over time, disease severity modifies pharmacokinetic disposition, prior response influences subsequent treatment, concomitant medicines alter exposure or pharmacodynamic state, or measurement and sampling processes determine which observations enter the analysis. Th

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