A comprehensive approach for Comparability of biological product

Ensuring comparability of biological products is challenging but essential in a product life-cycle

Comparability of biological products refers to the process of demonstrating that changes in manufacturing, formulation, or production site do not negatively impact the safety, efficacy, or quality of the final product. Due to the inherent complexity and variability of biological products, ensuring comparability is challenging but essential for maintaining consistent therapeutic outcomes. It has become an integral part of the product development life cycle. In fact, manufacturing changes between clinical trial phases, such as from Phase 1-2 to Phase 2-3 or beyond, are almost inevitable.

As the field has matured, regulatory agencies have provided increasing guidance on this topic. One of the most recent examples is the FDA's draft guidance on "Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products," issued in July 2023. Regulatory bodies are now scrutinizing product comparability more closely, with clearer expectations about the evidence required to demonstrate that changes in production do not compromise the product’s integrity.

To address these regulatory requirements, Inits developed a comprehensive approach to analytical product comparability. Demonstrating comparability is a multidisciplinary process, where changes in both the production process and analytical methods are closely interconnected and must be thoroughly evaluated. The first step in establishing comparability is through an analytical comparison of the product. However, this alone may not always suffice. In some cases, further non-clinical or clinical studies may be required to definitively prove comparability.

The focus of Inits' approach to analytical comparability is structured into three distinct phases: a) preparing a protocol, b) conducting the study, and c) analyzing the data and formalizing conclusions in a report. Before drafting the comparability protocol, certain prerequisites must be met, such as defining the product’s quality target profile and identifying critical quality attributes. Additionally, products from the pre-change manufacturing process must be secured for inclusion in the comparability study.

Inits developed a detailed comparability protocol consisting of five key steps:

**Identification and Evaluation of Process Changes**: This begins with a risk assessment to identify the potential impact of the changes.
**Selection of Analytical Methods**: Methods must be selected to assess the quality attributes critical to product comparability. In some cases, head-to-head testing may be conducted to directly compare pre- and post-change products.
**Batch Selection**: It is essential to select appropriate batches for comparison, including both pre-change and post-change products.
**Determination of Acceptance Criteria**: The criteria for assessing comparability must be clearly defined, often using statistical tools to ensure objectivity.
**Implementation of a Stability Program**: This program supports the comparability study by monitoring the stability of the product over time.

It is crucial to engage regulatory agencies early in the comparability process and present them with a well-defined comparability plan. Inits' comparability protocol is a valuable tool for facilitating these interactions with regulatory bodies, as it takes their requirements into account.

In conclusion, ensuring the comparability of biological products is a complex but crucial part of the product life cycle.

Inits offers pharmaceutical and biotech companies a comprehensive, structured approach to navigating this challenging but essential work, ensuring that regulatory expectations are met and product integrity is maintained throughout development.

By Laura GIERSCH, CMC Consultant at INITS

Our poster is available in PDF format upon request! Contact us at hello@inits.fr

Ensuring comparability of biological products is challenging but essential in a product life-cycle

Comparability of biological products refers to the process of demonstrating that changes in manufacturing, formulation, or production site do not negatively impact the safety, efficacy, or quality of the final product. Due to the inherent complexity and variability of biological products, ensuring comparability is challenging but essential for maintaining consistent therapeutic outcomes. It has become an integral part of the product development life cycle. In fact, manufacturing changes between clinical trial phases, such as from Phase 1-2 to Phase 2-3 or beyond, are almost inevitable.

As the field has matured, regulatory agencies have provided increasing guidance on this topic. One of the most recent examples is the FDA's draft guidance on "Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products," issued in July 2023. Regulatory bodies are now scrutinizing product comparability more closely, with clearer expectations about the evidence required to demonstrate that changes in production do not compromise the product’s integrity.

To address these regulatory requirements, Inits developed a comprehensive approach to analytical product comparability. Demonstrating comparability is a multidisciplinary process, where changes in both the production process and analytical methods are closely interconnected and must be thoroughly evaluated. The first step in establishing comparability is through an analytical comparison of the product. However, this alone may not always suffice. In some cases, further non-clinical or clinical studies may be required to definitively prove comparability.

The focus of Inits' approach to analytical comparability is structured into three distinct phases: a) preparing a protocol, b) conducting the study, and c) analyzing the data and formalizing conclusions in a report. Before drafting the comparability protocol, certain prerequisites must be met, such as defining the product’s quality target profile and identifying critical quality attributes. Additionally, products from the pre-change manufacturing process must be secured for inclusion in the comparability study.

Inits developed a detailed comparability protocol consisting of five key steps:

**Identification and Evaluation of Process Changes**: This begins with a risk assessment to identify the potential impact of the changes.
**Selection of Analytical Methods**: Methods must be selected to assess the quality attributes critical to product comparability. In some cases, head-to-head testing may be conducted to directly compare pre- and post-change products.
**Batch Selection**: It is essential to select appropriate batches for comparison, including both pre-change and post-change products.
**Determination of Acceptance Criteria**: The criteria for assessing comparability must be clearly defined, often using statistical tools to ensure objectivity.
**Implementation of a Stability Program**: This program supports the comparability study by monitoring the stability of the product over time.

It is crucial to engage regulatory agencies early in the comparability process and present them with a well-defined comparability plan. Inits' comparability protocol is a valuable tool for facilitating these interactions with regulatory bodies, as it takes their requirements into account.

In conclusion, ensuring the comparability of biological products is a complex but crucial part of the product life cycle.

Inits offers pharmaceutical and biotech companies a comprehensive, structured approach to navigating this challenging but essential work, ensuring that regulatory expectations are met and product integrity is maintained throughout development.

By Laura GIERSCH, CMC Consultant at INITS

Our poster is available in PDF format upon request! Contact us at hello@inits.fr

Ensuring comparability of biological products is challenging but essential in a product life-cycle

Comparability of biological products refers to the process of demonstrating that changes in manufacturing, formulation, or production site do not negatively impact the safety, efficacy, or quality of the final product. Due to the inherent complexity and variability of biological products, ensuring comparability is challenging but essential for maintaining consistent therapeutic outcomes. It has become an integral part of the product development life cycle. In fact, manufacturing changes between clinical trial phases, such as from Phase 1-2 to Phase 2-3 or beyond, are almost inevitable.

As the field has matured, regulatory agencies have provided increasing guidance on this topic. One of the most recent examples is the FDA's draft guidance on "Manufacturing Changes and Comparability for Human Cellular and Gene Therapy Products," issued in July 2023. Regulatory bodies are now scrutinizing product comparability more closely, with clearer expectations about the evidence required to demonstrate that changes in production do not compromise the product’s integrity.

To address these regulatory requirements, Inits developed a comprehensive approach to analytical product comparability. Demonstrating comparability is a multidisciplinary process, where changes in both the production process and analytical methods are closely interconnected and must be thoroughly evaluated. The first step in establishing comparability is through an analytical comparison of the product. However, this alone may not always suffice. In some cases, further non-clinical or clinical studies may be required to definitively prove comparability.

The focus of Inits' approach to analytical comparability is structured into three distinct phases: a) preparing a protocol, b) conducting the study, and c) analyzing the data and formalizing conclusions in a report. Before drafting the comparability protocol, certain prerequisites must be met, such as defining the product’s quality target profile and identifying critical quality attributes. Additionally, products from the pre-change manufacturing process must be secured for inclusion in the comparability study.

Inits developed a detailed comparability protocol consisting of five key steps:

**Identification and Evaluation of Process Changes**: This begins with a risk assessment to identify the potential impact of the changes.
**Selection of Analytical Methods**: Methods must be selected to assess the quality attributes critical to product comparability. In some cases, head-to-head testing may be conducted to directly compare pre- and post-change products.
**Batch Selection**: It is essential to select appropriate batches for comparison, including both pre-change and post-change products.
**Determination of Acceptance Criteria**: The criteria for assessing comparability must be clearly defined, often using statistical tools to ensure objectivity.
**Implementation of a Stability Program**: This program supports the comparability study by monitoring the stability of the product over time.

It is crucial to engage regulatory agencies early in the comparability process and present them with a well-defined comparability plan. Inits' comparability protocol is a valuable tool for facilitating these interactions with regulatory bodies, as it takes their requirements into account.

In conclusion, ensuring the comparability of biological products is a complex but crucial part of the product life cycle.

Inits offers pharmaceutical and biotech companies a comprehensive, structured approach to navigating this challenging but essential work, ensuring that regulatory expectations are met and product integrity is maintained throughout development.

By Laura GIERSCH, CMC Consultant at INITS

Our poster is available in PDF format upon request! Contact us at hello@inits.fr