Blog articles

Inferring accuracy from linearity – 2. Approach: Recovery

Written by Dr. Janet Thode on . Posted in Method validation

In our last blog post we had a look on the first approach to infer accuracy from linearity in method validations by applying normalization. This can be used to determine accuracy in case no alternative methods or impurities for spiking are available. Apart from normalization, another possibility to solve this problem exists, which will be highlighted today.

We stick to our example of the last time: a SE-HPLC method is used for purity determination. The impurities are given as the sum of minor peaks, while the main peak is our desired product. The approach to infer accuracy from linearity is allowed by the ICH Q2(1) validation guideline, when specificity (we suppose this again) and precision is given.

Inferring accuracy from linearity – 1. Approach: Normalization

Written by Dr. Janet Thode on . Posted in Method validation

In today's blog, we’d like to address a quite common problem during method validations and by using a practical example showing possibilities to solve it.

A SE-HPLC method used as a purity test of a drug shall be validated. It's known that impurities (e.g. aggregates and / or fragments of the product) may arise in low concentrations. In the chromatogram, you’ll see the main peak corresponding to the intact product and a few minor peaks corresponding to impurities, which will be reported as sum.

Let's have a look at the validation parameter "accuracy". Unfortunately, neither impurities are separately available for spiking experiments nor independent alternative methods are existing. In this case, the validation guideline ICH Q2(R1) offers the following possibility for the evaluation of accuracy: "Accuracy may be inferred once precision, linearity and specificity have been established" (4.1.1 c / 4.1.2 c).

Journal Club: RP-UHPLC-MS versus peptide mapping for antibody characterization

Written by Dr. Janet Thode on . Posted in Method validation

Introduction and background

Monoclonal antibodies (mABs) are immunoglobulin molecules that bind to the same epitope and have a variety of applications in medicine and healthcare. Although therapeutic mABs are extremely favourable due to their specificity, they are heterogenous due to their manufacturing process and hence provide a challenge for characterization. During expression, purification and storage, enzymatic and chemical modifications such as e.g. oxidation or glycosylation occur. Changes in these modifications can interfere with their safety and efficacy. In case these modifications are classified as critical quality attributes (CQAs), they are been mandated by the regulatory guidelines to be fully characterized. For their evaluation, stress studies can be applied.

Stability-indicating methods and their role in drug’s quality control

Written by Dr. Janet Thode on . Posted in Think out of the box

Have you ever thought about expiry dates on drug packages and wondered how these dates are determined? In today’s blog article we will discuss the very same topic from an analytical perspective.

Every drug product has a shelf life after which it starts to degrade. This shelf life is determined by the evaluation of storage conditions during the product’s development. Performing formal stability studies (including long term studies --> 12 months and accelerated stability studies --> 6 months) is required before submission of the drug’s dossier to regulatory authorities. The duration of these stability studies makes the situation untenable when aiming to develop stability-indicating analytical methods. These are methods which are used to quantitate the decrease of the active pharmaceutical ingredient (API) over time due to degradation and the subsequent increase of degradants. Thus, to save time, an analyst is faced with the necessity to artificially generate degraded samples and API is forced degraded. Therefore, it is stressed by different means such as subjecting it to acid, base, oxidants, heat, humidity and light and then analysing the degradants. There are two basic aspects of the drug that are considered afterwards:

Bioanalytical method validation

Written by Dr. Janet Thode on . Posted in Method validation

In today’s small blog article, we will learn about bioanalytical method validation and its recent advancements. Bioanalytical method validation refers to validation of analytical methods that deal with analysis of an analyte in biological matrices (like urine, saliva, blood etc.). Validation of such methods for the quantitative determination of analytes (e.g. drugs under development or their metabolites) and biomarkers in a given bio-matrix are critical for the successful conduct of nonclinical and clinical pharmacology studies. Validated methods provide critical information to support the safety and potency of drugs. Validating the analytical method provides us with results that can be trusted. Validation of bioanalytical methods answers 4 major questions:

What are system suitability tests (SST) of analytical methods?

Written by Dr. Janet Thode on . Posted in Method validation

In today’s blog article we will learn about the System Suitability Testing of an analytical method, its importance in quality control (QC) and how it differs from the Analytical Instrument Qualification.

The System Suitability Testing (SST) is used to verify that an analytical method was suitable for its intended purpose the day the analysis was done. It is an essential parameter to ensure the quality of the method for correct measurements. An SST is run each time an analysis is performed and each SST is specific to an individual method with pre-defined acceptance criteria for certain parameters e.g. absorbance values being between 0.2 and 1.0 for a photometric content determination method or some resolution factors for chromatographic methods.

Analytical versus bioanalytical method validation

Written by Dr. Janet Thode on . Posted in Method validation

Methods that are used in a quality control (QC) lab for characterization, release, and stability testing of pharmaceutical products (biologicals or small molecules) are called analytical methods in the official guidelines. Analytical methods are not synonymous to bioanalytical methods as referred by many. In today’s blog article we will learn about the distinct differences between the two and their respective validation procedures. Although it seems logical to use the term “bioanalytical” when dealing with biotechnological products but that is definitely not the case and care must be taken while using it.

As per the FDA guideline, a bioanalytical method is used for “quantitative determination of drugs and / or metabolites in biological matrices such as blood, serum, plasma, or urine… tissue and skin samples.” Such methods are primarily applied in pharmacological, pharmacokinetic, and toxicological studies and are mainly performed in humans and animals during clinical and pre-clinical trials. Bioanalytical methods also include immunogenicity tests since their target analytes are usually antibodies in biological fluids such as serum and plasma – the corresponding methods are called ligand binding assays. Bioanalytical methods are specifically directed towards determining the quantity of a drug or biomolecules in biological samples.

Staff change

Written by Dr. Janet Thode on . Posted in General

At the end of last week, the Loesungsfabrik had to take leave of Mr. Anindya Ghosh Roy. We thank you for the good cooperation, especially for the excellent contact with clients. His contributions to our blog will continue to be published under his name. We wish him all the best for his professional and private future.


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