How do you know when to stop optimising your analytical method? This question was asked during one of the training sessions I was giving. Although I knew the answer, it still surprised me. Because it’s not obvious at all.
I bet everyone has spent entire days ‘“tightening up” the parameters of an analytical method. You change the gradient, column temperature, buffer pH, striving for the perfect peak shape or even better resolution, even though the method is already ‘pretty good’.
This is a classic trap of perfectionism in R&D.
In the world of pharmaceutical and biotechnology analytics, time is money and resources are limited. So how do you know where to draw the line between a ‘good enough’ method and one that needs further work? The answer is the Analytical Target Profile (ATP), which was introduced in the ICH Q14 guideline.
In this post, I will explain how ATP helps you set your destination before you even get started.
What is an ATP (Analytical Target Profile)?
Imagine you are building a house. Do you start by buying bricks or by designing the architectural plans? ATP (Analytical Target Profile) is precisely that architectural plan for your analytical method.
According to ICH Q14 guidance, an ATP is a prospective summary of quality requirements for analytical measurement. In simpler terms:
ATP defines what the method must measure and with what requirements, before you even decide which technique to use.
In the traditional approach, we often start with: “Let’s do it on HPLC.” In quality by design (QbD), we start with: “We need to measure impurity X at 0.1% with a precision of +/- 10%.”
To put it simply, that is what ATP is.
What should ATP contain?
A well-structured ATP is a concise set of specific requirements. It should combine the expectations of regulatory bodies, quality control needs and product specifics.
According to ICH Q14 guideline, ATP should contain:
- Analyte (What are we measuring?): Determination of active substances, impurities, degradation products, excipients, or biological or microbiological properties.
- Matrix (What do we measure?): Tablet, injection solution, culture broth, plasma, etc.
- Measuring range: Expected concentrations at which the method must work correctly.
- Acceptance criteria for performance characteristics:
- Precision
- Accuracy
- LOD/LOQ
- Specifity
Personally, I believe that it is also worth adding the method used, as this may result in other requirements. For example, an analytical method will be used to test the API content in a product and to test release. In this case, the concentration range of the method will be determined by the second objective.
How to use ATP in development, validation and transfer?
An ATP is not a document that we write ‘for the drawer’. It is a living tool that guides the method throughout its entire lifecycle (Lifecycle Management). A well-prepared ATP allows you to quickly assess the scope of work and facilitates work in subsequent stages of the method’s lifecycle.
In the development of the method
Here, ATP acts as a finish line. When your method meets the criteria defined in ATP (e.g., you have achieved the required recovery and precision), you can officially stop optimising. This protects the team from over-engineering the method. Instead of looking for the “perfect peak,” you are looking for a “result consistent with ATP.” And here lies the answer to the question posed at the beginning of this post. In short: we optimise the method until the criteria set out in ATP are met.
In validation
The ATP criteria become the direct basis for establishing the acceptance criteria for the validation protocol. This means that validation is merely a formal confirmation of what you already know – that the method meets its intended purpose.
In transfer and changes (Change Control)
This is a powerful advantage. If you need to change columns in the future or transfer the method to another laboratory (transfer), ATP is the benchmark. If the new procedure (e.g., with a new column) meets ATP requirements, the change is easier to justify from a regulatory standpoint.
Good advice for creating ATP
Creating an ATP may seem difficult at the beginning. Here are some practical tips to make the process easier:
- The tabular form will be transparent. You do not need to write an elaboration and justify everything in full sentences.
- Be a realist, not an idealist.
Do not include requirements in the ATP that are impossible to meet or unnecessary. If the specification limit for contamination is 1.0%, you do not need a method with a LOQ of 0.0001%. Tailor the ATP to your business needs and quality requirements (CQA – Critical Quality Attributes).
- Separate “WHAT” from “HOW”. Try not to enter a specific technique (e.g. “Column C18 brand X”) into the ATP unless absolutely necessary. The ATP defines the measurement objective. How it is achieved should be determined by the stage of method development. This gives you flexibility in the future.
- Involve your team. Do not write the ATP yourself. Other specialists, such as production technologists, will help you determine many parameters. They know what is in the sample and what the expected concentration is. Involve someone from quality control, especially if the method is to be transferred to that department later. There may be various barriers that can be addressed now. These may include, for example, equipment availability or differences in the design of the devices.
- Look to the future.
Remember that the method will be used for years. The ATP should take into account that the method must be robust. The method may also be performed by other laboratories, and you need to be prepared for this as well.
The method itself is not everything. Various requirements can be included in the ATP. They do not have to relate only to the quality parameters of the method. You can include operational or business requirements, e.g. method duration, throughput, cost, use of available equipment, etc.
Summary
I started using ATP in my work some time before the introduction of ICH Q14. As I have never been good with paperwork, at first it seemed to me to be “just another pointless document”. However, I quickly realised that it is a really powerful tool and a huge help. It is a compass that tells you: “This is where we are, and this is where we want to go”. Thanks to it, you know exactly when to stop optimising, saving your team time and nerves. Implementing an ICH Q14-compliant approach is a step towards modern, conscious analytics.
Would you like to know how to define ATP for your specific product?
Contact us – we will be happy to help you map your analytical needs!
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