Pharma Digests
Worst-Case Product in Cleaning Validation
Product grouping is a way to reduce validation activities in sites with multiple products and processes. Products may be grouped together if they are cleaned by the same process. If a product in that group requires a more aggressive cleaning process, that product becomes the worst-case product in that group. ... Read More
Impact of Genomic Variation on Drug Response
The impact of genomic variation on drug response may require investigation in clinical studies. For genomic variation that may affect the PK of a medicinal product, clinical studies should be designed in accordance with the Guideline on the use of pharmacogenetic methodologies in the pharmacokinetic evaluation of medicinal products. Genetic ... Read More
DNA Analytics for Genomic Study
A variety of protocols are available for the extraction of gDNA from different sources. It is important to employ a validated method leading to an isolation of gDNA of highest quality, suitable for the nucleotide variation analysis (single or array-based qPCR or end-point PCR), and for sequencing (Sanger, NGS). It ... Read More
Sample Acquisition and Handling During Genomic Study
Identification of genetic variants demands high quality genomic DNA (gDNA). Pre-analytical variations in (i) sample collection, (ii) stability, (iii) sample labelling, (iv) transport to the site of analysis, (v) tissue/sample processing and (vi) storage, should be minimized throughout the workflow to guarantee the highest possible sample quality (see guideline ICH ... Read More
Specific Issues for HLA Alleles
Idiosyncratic adverse drug reactions (ADRs) include examples of strong associations between genotypes and drug responses. These reactions: It is therefore recommended to collect DNA for later HLA typing in a drug developmental program to identify possible useful predictive HLA biomarkers. A comprehensive database listing ADRs associated with the HLA alleles ... Read More
Phenotype and Genotype Correlations
Genetic variants may influence the function of a gene: The PK-phenotype can also be determined by multiple variations in different alleles, e.g. for medicinal products metabolized by multiple pathways. The detection of specific genetic variants in clinical routine helps to improve efficacy and safety of specific medicinal products in use, ... Read More
Common and Rare Genetic Variants
A genetic variant is defined as an allele carrying variation(s) as compared to the gene reference sequence. The term variant is preferably being used instead of the term mutation, which is reserved for rare variants (<1% frequency). Furthermore, the term polymorphism defined as variations having >1 % frequency in the ... Read More
pH Sensitivity in Liquid Oral Dosage Forms
When developing liquid oral dosage forms, one critical consideration is pH sensitivity—the impact of pH on the stability, solubility, and bioavailability of active pharmaceutical ingredients (APIs). This factor can make or break the formulation process and ultimately determine the drug’s efficacy and safety for patients. During preformulation, it’s essential to: ... Read More
Temperature Sensitivity in Liquid Dosage Form Development
In the development of liquid oral dosage forms, temperature sensitivity is a critical factor that impacts solubility, stability, and overall performance. Preformulation studies help us understand how temperature fluctuations can affect the formulation, ensuring that the drug maintains efficacy and safety under various conditions. Key considerations include:Solubility & Dissolution: Temperature ... Read More
Excipient Compatibility in Liquid Oral Dosage Form
In the development of liquid oral dosage forms, “excipient compatibility” is essential to ensure the stability, efficacy, and safety of the final product. The choice of excipients plays a pivotal role in determining how well the active pharmaceutical ingredient (API) performs, and how it interacts with other components within the ... Read More
Exploring Preformulation Studies in Liquid Oral Dosage Forms
When developing liquid oral dosage forms, preformulation studies are key to ensuring the product’s stability, efficacy, and patient compliance. These studies help identify the ideal formulation parameters, including: Solubility & Stability: Assessing the drug’s solubility in different solvents and conditions to predict shelf-life and storage needs. pH Sensitivity: Understanding the ... Read More