Behind every drug lies a long history of measurements. Before a drug becomes clinically usable, it needs to be proven that it is indeed the intended drug , what is its purity level, concentration and ability to remain stable for a certain period of time. All the proofs are provided by the analytical testing in drug development. The questions that such tests should answer may vary depending on the lifecycle stage of a molecule. Understanding the evolution of testing methods explains why some development programs proceed successfully and others stumble due to the data that could be generated many years ago.
Questions evolve when the molecule grows up
At the early research stage, scientists have different demands for the testing methods. They must be fast, flexible and capable of adjusting to the new challenges arising with each step taken by the development team. During the discovery stage, the medicinal chemist wants to be sure that the synthesis went well and what kind of impurities were generated. Biologics team will focus on the aggregation, charge variants and glycosylation of a molecule to decide whether it is worthy of further research. The type of the method – either chromatography, mass spectrometry or electrophoretic separation – determines the following steps in development of the testing method.
These initial assays usually do not need validation, but they must be scientifically credible and fit for purpose. Poor initial data can easily turn into serious problems that cost a lot of money during the next phase of the program development. That’s how the reputation of the analytical testing in drug development as a decision making tool is formed.
From flexible methods to validated ones
As a candidate moves towards the clinic, there is no room left for flexibility and the methods that were just sufficient for research should gain credibility. This process consists of three stages: the method development, qualification and validation according to the ICH Q2 criteria: specificity, accuracy, precision, linearity, and the detection and quantitation limit, dependent on the quality attribute that is assessed.
The same applies to the method of transfer. The assay that works well in the hands of its developer needs to give the same result in another laboratory, using different instruments operated by other analysts. Correct method transfer can become the key to the successful registration of a drug avoiding numerous deviations and delays.
Transition to GMP
This transition is more about changing the expectations regarding the existing procedures than implementing anything new. According to Good Manufacturing Practice (GMP), the result depends on the whole system producing it, so the instruments are qualified, reference standards characterised, analysts GMP trained , and everything is documented properly. Data integrity, i.e. the data that is attributable, legible, contemporaneous, original and accurate (ALCOA) is the key of the whole process.
GMP analytical testing is also used to release the batch for human use. The drug substance or drug product batch is tested according to the specified parameters, the results reviewed and approved. System suitability checks ensure the proper operation of the instrument and the method before the results can be considered valid. An out-of-specification result leads to the official investigation of the issue, which is what the regulators expect to see.
Stability, release and life in commercial production
Stability testing accompanies all the above processes. Long-term, intermediate and accelerated studies according to ICH requirements define the behaviour of the product over time and provide justification of the shelf life and storage conditions. Forced degradation testing shows the mechanisms of a molecule breakdown and the ability of the methods to detect the changes. For sensitive modalities, stability data obtained in advance influence the packaging and handling procedures.
Analytical work does not stop once the product is registered. Every batch goes through the release test and ongoing stability program ensures its stability. Any changes to the process and the supply chain require comparability data. GMP analytical testing makes the supply possible, ensuring that the drug received by the patient is the same as the one initially approved.
One continuous line of evidence
Seen from bird’s eye view, analytical testing can appear as a sequence of hurdles. In fact, it is just one line of evidence starting with the research question and finishing with the released commercial batch. The programs that treat the analytical testing in drug development as a continuous lifecycle, with the initial data guiding the further development of methods, and the method knowledge being preserved throughout the development, reach the approval faster and face fewer surprises during the filing defense. The experienced analytical partner working throughout the whole arc from the non-GMP research batch to GMP release will keep this thread.
FAQs:
Q1. What is analytical testing in drug development?
It is the set of laboratory measurements proving the identity, purity, potency and stability of a drug from its discovery through commercial manufacturing. The generated data supports the decision-making process for the developers and regulators about the safety, efficacy and consistency of the drug candidate.
Q2. Why is GMP analytical testing important?
GMP analytical testing provides evidence that the batch meets its specification prior to release and distribution. Due to the use of validated procedures, qualified instruments and adherence to the data integrity principles, the results of GMP analytical testing withstand any regulatory inspection and provide assurance about the safety and consistency of every batch.
Q3. How does analytical testing support the drug lifecycle?
It covers from discovery to commercialization. Early on, flexible methods support the candidate selection. Further, the methods are developed, qualified, and transferred; under GMP, the testing releases the clinical and commercial batches; the stability studies proves the quality and safety over time.
