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It is possible to develop methods for developing medicinal compounds on the basis of analytical chemistry, which includes methodologies for identifying, separating, and quantifying the chemical components of medicinal compounds. An introduction to method development and validation in the context of early phase clinical trials is provided in this article as a practical introduction.
Definition of analytical method development
The development of analytical methods is intended to determine the identity, purity, physical characteristics, and potency of drugs, as well as the drug’s bioavailability and stability.
When it comes to analytical method development and validation, it can be defined as the process of demonstrating that analytical procedures are adequate for the purpose of evaluating drugs, and specifically the active pharmaceutical ingredient (API).
Analytical procedures are developed in order to compare specific characteristics of substances to predefined acceptance criteria for those characteristics, which are then used in the development of the procedures.
In order to determine the composition of a drug, analytical method development involves the evaluation and selection of the most precise assay procedures available to do so.
Importance of analytical method development
When it comes to drug development, analytical method development and validation are critical components of any successful programme.
There are at least three main reasons why analytical method development is critical for any biotechnology company developing new drug candidates, which we can summarise as follows:
First and foremost, the quality of a drug is unquestionably at the heart of the success prospects of a pharmaceutical development programme, and biotech companies developing novel compounds must take the development of analytical methods very seriously.
Second, analytical method validation is required by regulatory authorities around the world for both clinical trial applications and marketing authorizations, according to the FDA.
When a biotech company files an Investigational Medicinal Product Dossier (IMPD) for its drug and the chemistry, manufacturing, and controls (CMC) section is of poor quality, it will have a difficult time getting its clinical trials approved by European drug agencies. Then, in order to get clinical studies approved, method development is essential.
Patients will be the ones who will eventually receive an investigational medicinal product (IMP) in early phase clinical trials (first in human / Phase 1), so the development and manufacturing quality of a medicine is critical to ensuring patient safety while also demonstrating promising efficacy in new treatments, which is the ultimate goal.
A high-level overview of the analytical method development process is depicted in the figure below. It includes the method goals and analytic goals, as well as the validation requirements and documentation requirements at various stages of drug development.
Encountered types of analytical procedures
Some of the most common types of analytical procedures are identification tests, quantitative tests for impurity content, limit tests for impurity control, and quantitative tests for the active moiety in a pharmaceutical substance or a pharmaceutical product.
Validation parameters for compound testing include specificity, limit of detection, limit of quantitation, linearity, accuracy, range, precision (under laboratory repeatability conditions), and stability.
Aside from that, revalidation may be required if changes are introduced in the synthesis of the drug substance, changes are introduced in the composition of the drug product, or if changes are introduced in the analytical procedure.
During the course of writing a very useful article on pharmaceutical method development and validation, Dr. Joanna Greenhough made the following point about the lifecycle of an analytical method:
In the case of an analytical method, the lifecycle begins when a pharmaceutical company or a contract analytical testing laboratory recognises the need for a new analytical method.
Afterwards, they will either identify an existing or compendial procedure that is suitable for the specific need, or they will proceed to develop a completely new method from the ground up.
An evaluation (or verification) plan will be developed following the development stage, and method validation experiments will be carried out as a result of this plan.
The validation process should be guided by a validation protocol, which should clearly define the application purpose and scope of the method, performance characteristics with acceptance criteria, validation experiments, standards, and reagents, and other relevant information.
Analytical method transfer
According to Chapter 1224 of the United States Pharmacopeia (USP):
Specifically, “the transfer of analytical procedures (TAP), also known as method transfer, refers to the documented process that qualifies a laboratory (the receiving unit) to use an analytical test procedure that originated in another laboratory (the transferring unit), ensuring that the receiving unit possesses the procedural knowledge and capability to perform the transferred analytical procedure as intended.”
Transfer of analytical methods is typically managed through the use of a transfer protocol that specifies the parameters to be evaluated as well as the predetermined acceptance criteria that will be applied to the results.
Transfer studies typically involve two or more laboratories (the originating lab and the receiving labs) working together to execute a pre-approved transfer protocol in a controlled environment.
Guidelines to be taken into consideration
It is necessary to follow established international guidelines when developing and validating pharmaceutical methods, such as those published by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), the United States Food and Drug Administration (FDA), and the European Medicines Agency (EMA) (EMA).
The FDA and the United States Pharmacopoeia (USP) both refer to the International Conference on Harmonization (ICH) guidelines.
Of course, validation of analytical methods must be done in accordance with good manufacturing practise (GMP) and good laboratory practise (GLP) guidelines and regulations.
Conclusion
The development, validation, and transfer of analytical methods are critical components of the drug development process.
Method development is critical for a biotech company for a variety of reasons, including commercial, regulatory, and patient safety.
It is impossible to obtain approval for clinical trials or to obtain marketing authorizations unless high-quality method development and validation are carried out in advance.
Having the support of a capable contract development and manufacturing organisation (CDMO) ensures the success of a drug development programme, at least in terms of CMC aspects.
