Innovative drug research and development is a very complicated and risky process from discovery to marketing, which includes preclinical research, clinical trial application, clinical trial (also divided into clinical phases I, II, and III), marketing application, post-marketing commercialization (phase IV clinical), and other stages. During the pre-market R&D, with the continuous in-depth exploration of pharmacological and toxicological effects of compounds, drug efficacy, and other aspects, the developers will constantly evaluate the medicinal prospects of the target compounds, that is, whether it is worth continuing development.
Chemistry, manufacturing, and control, referred to as CMC, including studies on the drug production process, impurity, quality, stability, process validation, and other aspects, is a vital section of drug research and development. It provides technical and material support to non-clinical and clinical research trials throughout the full life cycle of drug development and manufacturing.
Characteristics of CMC in drug development
The research and development of novel drugs is a process of gradual cognition. The CMC research likewise has the same characteristics, which are embodied in the following aspects:
1. CMC proceeds along with the pace of clinical research. In the preclinical and early stages of clinical studies, CMC provides high-quality research samples, then determines stable, reproducible, industrial-scale manufacturing processes, and builds sound drug quality control systems.
2. Combined with the needs of clinical research, scale-up production, and a deepening understanding of drugs, CMC researchers aim to adjust and optimize the dosage form, specifications, prescription technologies, analytical methods, quality standards, etc. During the drug discovery process, pharmaceutic-related changes are almost inevitable, especially in the early stages where changes occur more frequently. For example, phase I clinical studies often consider the simplest dosage form, such as solution or drug powder filled directly into capsules. The dosage form should later be optimized based on clinical needs and production feasibility.
In general, CMC research should be adapted to the exact drug development stage since superfluous pharmaceutical research may delay the development process, resulting in a waste of R&D resources. On the other hand, to ensure the safety of subjects, sufficient research and development data must be obtained for risk assessment and control. The regulatory requirements for CMC research are based on the following factors: the stage of the clinical study, the number of subjects and study period, the novelty of the drug structure and mechanism of action, the dosage form and route of administration, and the exposed and potential risks.
To enable CMC research to support drug development without a waste of time and money, its focus should vary according to drug development stages. Take the chemical synthetic drug development as an example:
Preclinical research phase
A drug molecule enters preclinical research after early target study, molecular design, and preliminary evaluation to obtain candidate compounds. This process includes pharmacological, pharmacodynamic, toxicological, pharmacokinetic, and other evaluations of drug properties. CMC is mainly to provide exact test samples, complete the process, and control the quality.
Confirmatory clinical trial phase
It includes phase I and II clinical studies, which investigate drug safety and preliminary effectiveness. At this stage, there are fewer subjects and the period is short. CMC studies are mainly concerned with drug quality controllability and consistency.
The critical clinical research phase
That is the phase III clinical research stage, through expanding the size of the subjects, to conduct a comprehensive study on the safety and efficacy of drugs. A detailed study of CMC can prepare relevant information for the listing approval application stage.
In addition, drug development should undergo three other crucial stages: management of changes at the clinical research stage, marketing application, and post-marketing.
At BOC Sciences, our team of CMC experts with decades of global regulatory and quality experience enables us to assess CMC changes in major markets and help determine global CMC strategies. We support all development stages of small molecule APIs and biologics products, including product, process, and analytical development, stability testing, and field validation. Our goal is to expedite your novel drugs to the market while saving time, money, and human resources.