Criticality Management of a Drug Product and its Manufacturing Process - Pharmaceutical Technology

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Criticality Management of a Drug Product and its Manufacturing Process
Criticality management combines pharmaceutical product, process, and material knowledge and risk management in one approach, which is reflected in a single document.

Pharmaceutical Technology
Volume 9, Issue 32, pp. 6680

Criticality management: an integrated approach

The literature describes the criticality management of the API-synthesis process (6). This article describes the criticality management of the drug product and its manufacturing process using a direct-compression tablet as an example (see Figure 1).

Drug-product criticality management

The drug-product criticality-management process translates the target product profile into a list of potentially critical quality attributes of the drug product. The formulation is designed and selected based upon these quality criteria and further optimized by studying and managing the criticality of the composition and material properties, the packaging design, shipping, stability, and the in-use procedure.

Table I: Quality attributes of a drug product (tablet).
Translating the target product profile into critical quality attributes (CQAs) is the initial step. It is important that the right attributes be defined with proper measurement methods. These quality attributes are initially chosen based upon the requirements of the target product profile, prior knowledge of this type of product, the manufacturing process, and the sensitivities of the API. The attributes are further refined during development, based upon the characterization of the product, relationship with in vivo behavior (when possible), or new findings. Table I defines the quality attributes, which tests are used to check the fulfillment of these quality attributes, and whether a quality attribute is critical for the safety, efficacy, and usability for the patient. The last column defines whether the CQAs are controlled by the process, by the materials, or by GMP systems. If the control relies on GMP systems, criticality management of the attribute is not pursued.

The next steps—criticality in product, materials, and package—are similar to those in the manufacturing-process criticality management, which is described below.

Materials play a role both in the drug product and in the manufacturing process. Therefore, they can be part of either the drug-product criticality management or the manufacturing-process criticality management.

Manufacturing-process criticality management

Figure 2 outlines the steps in the manufacturing-process criticality management. The list of end-product CQAs and a detailed process map are the starting points.

Table II: Potentially influential steps and process parameters or material attributes for a direct-compression tablet.
In the first step, a team of experts identifies factors that might influence these CQAs and which process steps, process parameters, material attributes, and attributes of the pharmaceutical intermediate or in-process product are worthwhile to investigate further. This evaluation is based on prior knowledge and thus is a science-based risk assessment. This assessment is represented in a tabular format that provides a clear overview of the parameters and attributes that will be investigated further (see Table II).


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