Small molecules and antibodies have dominated the pharmaceutical landscape for decades. However, limitations associated with therapeutic targets deemed "undruggable" and progress in biology and chemistry have led to the blossoming of drug modalities and therapeutic approaches. In 2023, a high number of 9 oligonucleotide and peptide products were approved by the Food and Drug Administration (FDA), accounting for 16% of all drugs approved. Additionally, for the first time, a clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 gene therapy product was approved for the treatment of sickle cell disease. New drug modalities possess a wide range of physicochemical properties and structures, which complicates their analytical characterization. Impurities are formed at each step of the oligonucleotide and peptide solid phase synthesis and during shelf life. Longer chain lengths lead to a higher number of closely related impurities that become increasingly more difficult to separate from the full-length product. Chemical modifications such as phosphorothioates (PS) result in the presence of diastereomers, which often require orthogonal methods for their profiling and strategies to prevent their interference with the separation of achiral impurities. In-vitro produced mRNA and plasmid DNA also present a variety of quality attributes that need to be determined, such as the polyA tail length or capping efficiency. Analytical challenges arise from the variety of drug modality physiochemical properties and attributes, fast turnaround times, and heightened level of characterization needed to enable data-driven decisions early in the drug development process. This perspective provides the author's views on the lessons learned and strategies employed in recent years.