Analytical Target Profile

The analytical target profile (ATP) concept was first introduced in the ICH Q14¹ Guideline in 2022. This guideline, which compliments the ICH Q2² Guideline, describes science and risk-based approaches for developing and maintaining analytical procedures suitable for the evaluation of the quality of drug substances and drug products. The ATP approach can be utilized for analytical procedures used for release and stability testing of commercial drug substances and products and can be introduced during development in a phase-appropriate manner.

The ICH Q14 Guideline describes two suitable approaches (minimal and enhanced) to develop analytical procedures. While the minimal approach is more traditional, the enhanced approach is a more systematic way to develop an analytical procedure. The enhanced approach includes the ATP along with prior knowledge, risk assessment, uni- or multi-variate experiments and/or modeling, control strategy, proven acceptable ranges and/or method operable design regions.

The Analytical Target Profile Compared to the Quality Target Product Profile

The ICH Q8³ Guideline defines the quality target product profile (QTPP) as a prospective summary of the quality characteristics of a drug product that ideally will be achieved to ensure the desired quality of the drug product while taking safety and efficacy into account. It is a very useful tool for drug product development. The product and process understanding are important to identify the critical quality attributes (CQAs) that are part of the QTPP and for which analytical tools need to be developed.

Similar to the QTPP for drug product development, the ATP captures the prospective summary of the quality characteristics of an analytical procedure. It describes the measuring needs for the CQAs, the analytical procedure performance characteristics (system suitability, accuracy, linearity, precision, specificity, range, and robustness), established conditions, and a procedure for change assessments. An example of an ATP is presented below.

Integrating ATP into Development

The Analytical Target Profile (ATP) is a key concept in the ICH Q14 guideline and describes the requirements that the analytical method needs to meet for the proper measurement of a product quality attribute. Such requirements are necessary so that decision makers can establish high confidence in the results guiding their decisions. It is expected that an analytical procedure evolves with product development stages. As such, it is very important that an analytical procedure control strategy be in place and followed throughout the analytical lifecycle.

Implementing the use of an ATP early in the analytical procedure development can greatly facilitate monitoring and help with the continual improvement of an analytical procedure. The ATP is the foundation for the analytical procedure attributes, performance criteria, and is thus the foundation for the analytical procedure’s validation per the ICH Q2(R2) Guideline.

During the analytical procedure lifecycle, the analytical procedure will inevitably undergo changes which will need to be evaluated. As part of a strong quality risk management system, the ATP will help guide the evaluation or impact of such change. As part of the evaluation, the analytical procedure may need to be revalidated. The ATP as described in the ICH Q14 guideline along with its complement ICH Q2 guideline, will guide decision makers to determine which part or parts of the method validation will be required to be reassessed (system suitability, specificity, linearity, range, accuracy, precision, robustness) after a change.

The established conditions can be identified using the tools within the ATP such as risk assessment, prior knowledge, and results obtained from uni- or multi-variates experimentation.

Part 2 of this blog series includes a more in-depth discussion on analytical procedure control strategy, and the benefits of the enhanced approach in the lifecycle management and post-approval changes of analytical procedures.

The ICH Q14 guideline describes principles to support change management of analytical procedures based on risk management, comprehensive understanding of the analytical procedure, and adherence to predefined criteria for performance characteristics. This is done by using the tools such as the established conditions and the pharmaceutical quality system and others as described in the ICH Q12⁴ Guideline, Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management.

The use of an ATP during the analytical procedure development and related lifecycle will help interaction with regulatory authorities. The interaction is streamlined since the ATP defines the development activities and how any changes to the analytical procedures will be assessed to ensure it continues to be fit for its intended purpose (to measure an attribute or attributes of the analyzed material with the needed specificity/selectivity, accuracy, and/or precision over the reportable range).

Example of ATP

There are various acceptable ways to use and to present an ATP to regulatory authorities. The following example, as shown in Table 1, is only one example for illustrative purposes. It can be adjusted to meet the needs for various analytical methods and various project types. In addition to the ATP as described in Table 1, a description of the analytical procedure development, the analytical procedure methodology, the analytical procedure validation status, along with the proposed and justified established conditions should be part of the ATP. It should be noted that the proposed established conditions should be part of the submission and should be evaluated as part of the quality risk management as defined in the ICH Q12 Guideline, Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management.

Table 1: Analytical Target Profile
Intended Purpose
Description of what the analytical procedure should be measuring (Quantitation of the active ingredient, biological activity, impurity level, etc.).
Technology Selection
Description of which technology was selected (HPLC, SDS-PAGE, cell-based assay, ELISA, etc.) and a rationale for selecting it (could be based on development studies, prior knowledge, literature, etc.).
Link to Critical Quality Attributes (CQAs)
Summary on how the analytical procedure should be able to provide reliable results about the CQA being assessed. For example, the quantitation of impurity levels or the measure of a biological potency which could be linked to the drug’s mechanism of action.
Characteristics of the Reportable Result
Performance Characteristics	Acceptance Criteria	Rationale
Accuracy	Acceptable accuracy level	Based on linearity experiment, compendial guidance, considering the intended purpose and performance characteristics.
Precision	Needed precision across the reportable range.
Specificity
	No significant interference from the matrix to the characteristics of the dose response curve.
	Ability to quantitate impurity levels in presence of other process or substance related impurities with a bias of not more than 0.03%.	Potential interference by other components (impurities or matrix) with the quantitation.
	Analytical procedure is capable to detect a change in the potency to ensure the product remain within specifications throughout its shelf life.
Reportable Range	Reportable range that meets the accuracy and precision.	Reporting threshold of x% of the specification limits.

Conclusion

The ATP is an important tool to document the analytical procedure lifecycle and help communication with regulatory agencies. It can be introduced during development in a phase-appropriate manner for analytical procedures used for release and stability testing for drug substances and drug products.

Premier Consulting has deep technical and regulatory CMC expertise and has successfully supported multiple projects at all stages of development. Contact us today to find out how we can support your program.

Author: Eric Leblanc, RAC, Associate Director, CMC Services

Reviewed by:  Marianthi Karakatsani, PhD, RAC, Director, Regulatory Affairs, CMC

References:

¹ International Council for Harmonisation Of Technical Requirements for Pharmaceuticals for Human Use. ICH Harmonised Guideline. Analytical Procedure Development Q14. Available at: https://database.ich.org/sites/default/files/ICH_Q14_Guideline_2023_1116.pdf

² International Council for Harmonisation Of Technical Requirements for Pharmaceuticals for Human Use. ICH Harmonised Guideline. Validation of Analytical Procedures Q2(R2). Available at: https://database.ich.org/sites/default/files/ICH_Q2%28R2%29_Guideline_2023_1130.pdf

³ International Council for Harmonisation Of Technical Requirements for Pharmaceuticals for Human Use. ICH Harmonised Guideline. Pharmaceutical Development Q8(R2). Available at: https://database.ich.org/sites/default/files/Q8%28R2%29%20Guideline.pdf

⁴ International Council for Harmonisation Of Technical Requirements for Pharmaceuticals for Human Use. ICH Harmonised Guideline. Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management Q12. Available at: https://database.ich.org/sites/default/files/Q12_Guideline_Step4_2019_1119.pdf