From natural health products to life-saving medicines, all pharmaceutical products must undergo an analytical method development process. Through analytical method development, validation, and transfer, drug development and manufacturing are kept safe, efficient, and compliant with the law.
What is analytical method development?
Analytical method development is the creation of a set of experimental conditions to perform analytical procedures in chemical samples. Developed analytical methods can be used to identify, separate, quantify, and learn more about the chemical components in drug products intended for commercial manufacturing.
Pre-clinical candidates must undergo a process that includes pre-formulation, formulation, clinical and commercial manufacturing, and manufacturers must understand the nature of the medicines they are producing for these procedures to be successful.
What is an example of the analytical method?
An in vitro analytical method can be used to identify the amount of cobalt within a person’s organism and assess the risk of cobalt poisoning. This method consists in taking samples from different bodily fluids to analyze and contrast their cobalt content.
Having a certain amount of cobalt in one’s organism is normal. Nonetheless, exposure to industrial environments or wear and tear from certain prosthetics can increase the amount of cobalt in the body to unhealthy levels. The difference between a body’s normal cobalt content and unusual increases can be gauged by using fecal and urine samples.
A fecal sample can be used to assess the amount of organic cobalt that is being eliminated or not being absorbed by the gut. On the other hand, urine can be used to determine the amount of inorganic cobalt in the body. Furthermore, tissue, blood, or bone can be used to estimate the amount of cobalt in an entire body region, although this method is used on a more limited basis (source).
What is the importance of the analytical method?
The analytical method and validation procedures are essential for the pharmaceutical product development process. Every biotechnical company involved in drug product development must make analytical testing one of its major priorities.
A pharmaceutical development company’s main goal is to produce a high-quality product. Analytical development techniques are indispensable to understanding the minute details of a chemical compound’s composition, making the analytic method crucial to the development of new drugs.
Skilled method development scientists can help devise novel, innovative treatments using information gathered by using the analytical method. Therefore, it is in the best interest of pharmaceutical companies to attain the best analytical service.
Regulatory authorities at a global scale require appropriate analytical method validation before a drug can be used for clinical trial applications. Likewise, a drug can’t be legally advertised until product quality and safety have been properly analyzed.
For instance, European drug agencies will be very hesitant to approve any clinical trials for a drug with a poorly documented chemistry, manufacturing, and controls (CMC) section in its Investigation Medicinal Products Dossier (IMPD). Analytical development can drastically simplify regulatory compliance, as the authorities will possess clear information about the chemical compounds they are legislating over.
Ensure patient safety
Patient safety must be a primary concern from the early stages of the product development process. After all, human patients will be the recipients of a drug during Phase I studies. Analytical methods guarantee the safest compounds are used in drug product development. Keeping the safety of patients in mind will allow for the improved efficacy of all current and future treatments.
How do you develop an analysis method?
1. Understand the sample
Method development begins with the physical characterization of the analyte. Beyond assessing its physical and chemical properties, researchers must also quantify the number of analyte compounds in the sample and their concentration rate. Furthermore, other compounds in the sample should be recognized. It is important to consider how the different properties of the chemicals in the sample will affect the analysis.
2. Define the goals of the study
Researchers must have a clear idea of why they are analyzing the sample, as it will define the purpose of the method. Common method goals include:
- Detect: Recognize if the analyte is present in the sample.
- Quantitate: Assess how much of the compound is present.
- Identify: Discover the chemical composition of an unrecognized compound.
- Characterize: Study the properties of a compound.
- Purify/Isolate: Collect a compound for later use.
3. Identify analysis requirements
The variables associated with the method goals must be determined. Consequently, researchers must identify what they need to know to reach the method’s goals. In addition, the number of samples needed for the experiments and the required level of precision for the success of the study must also be determined.
If an analysis is meant to detect an analyte, then researchers must consider what the right detection techniques are. Depending on the compound, it may be ionized, UV absorbing, observable under certain temperatures, or possess other properties that can be used to identify it.
4. Look at previous research
It’s important to determine if similar research has been already conducted. Previous research can provide valuable insights and stand as a starting point for method development.
Sources of information available to researchers include:
- Professional and technical journals
- Corporate application notes
- FDA requirements
- EPA requirements
- USDA methods
- United States Pharmacopoeia (USP)
- The Internet
5. Choose an analysis technique
The information gathered by the previous steps must then be used to decide what analysis technique is the most appropriate.
Here are some examples of analysis techniques:
- Mass spectrometry (MS): The measurement of the mass-to-charge ratio of charged particles.
- Liquid chromatography (LC): The physical separation of a sample in a solution based on properties such as its ionic strength, polarity, and molecular size.
- Liquid chromatography-mass spectrometry (LC-MS): This approach uses a combination of the two previous analysis techniques.
- Thermal analysis: The analysis of materials by subjecting them to different temperatures and observing how they change.
6. Determine initial conditions
The initial conditions are dependent on the analysis technique that will be used. For instance, an LC would require the selection of a detector, column, and mobile phase.
7. Preparing the sample
Same as with the initial conditions, the analysis technique in use will define how the sample must be prepared.
8. Develop a method
Once everything is in place, the method development process can commence. While developing the method, one of these two approaches may be used:
- A one-factor-at-a-time, incremental approach. This procedure can be based on the results of previous experiments.
- A systematic screening protocol, where several factors such as stationary phases, solvents, pH levels, and column chemistry are evaluated. This approach can be used to fine-tune selectivity and retention, thereby improving resolution.
9. Choose a standardization technique
If required, a standardization technique must also be selected. Both internal and external standards should be taken into consideration during this step. A PDA detector can be useful to investigate the linearity of active pharmaceutical ingredients (APIs) and related substances, for example.
10. Monitor performance
The overall performance of the analysis technique must be evaluated. Variables that may be present during performance assessment include:
- Limits of detection
- Limits of quantitation
11. Method verification
By using an experimental design approach, the method’s optimization and robustness must be verified.
The following factors can have a drastic impact on the method:
- HPLC conditions
- MS conditions
- Sample preparation
12. Analytical method validation
The goal of analytical method validation is to provide a solid base upon which the method can be repeated in the future. Validated methods can be successfully reproduced without being impacted by slight changes in the method conditions.
Analytical method development services
If you need analytical method development services for an upcoming pharmaceutical product or if you want to start to develop a new drug from scratch, Altus is your best ally. Thanks to a fully-integrated drug development strategy, Altus provides analytical services for all types of drug products. Our team of experts has created quality-driven processes to facilitate analytical method transfers, making the sharing of information between laboratories easier than ever.
By offering a complete drug development strategy, Altus offers much more than analytical method development services. Companies partnered with Altus can also expect to receive state-of-the-art drug formulation development services, cost-effective active pharmaceutical ingredients (APIs) supply, first in human (FiH) trial management, and much more.