Drug products potency assessment

The FDA s dehnition of comparability protocol is a well-defined, written plan for assessing the effect of specific CMC changes in the identity, strength, purity, and potency of a specific drug product as these factors relate to the safety and effectiveness of the product. A comparability protocol describes changes that are covered under the protocol and specifies the tests and studies that will be performed, including analytical procedures that will be used, and acceptance criteria that will be achieved to demonstrate that specified CMC changes do not adversely affect the product. ... 

It is widely understood within the industry that risk is defined as the combination of the probability of harm and the severity of that harm. Within the pharmaceutical industry whenever risk is considered the equipment or product being assessed must be viewed in the context of the protection of the patient. From our perspective, analytical instruments may impact on the validity of data that determines the safety and efficacy of drug products, or on the quality of the drug product. They may also impact on the identity or potency of the drug product and therefore it is important to ensure that risk management is performed throughout the complete life cycle of the instrument. 

Concern about the quality of botanical products poses another regulatory challenge. Most botanical products are complex and variable mixtures of constituents too numerous to characterize individually. For many preparations, active ingredients have not been identified and it is thus difficult to quantify strength or potency of the botanical product. Because of the biological nature of botanical products, the assessment of their impurity and stability is often more problematic than that of nonbotanical pure drugs. 

A comparability protocol is a well-defined, detailed, written plan for assessing the effect of specific CMC changes in the identity, strength, quality, purity, and potency of a specific drug product as these factors relate to the safety and effectiveness of the product. 

Whether it is a drug substance or a drug product, the final product will need to be analyzed to assess its potency or strength. The potency of a drug substance is typically reported as a percentage value (e.g., 98.0%), whereas a drug product is reported in terms of its intended concentration or label claim. 

Based on a large number of batches, the mean content in active material in the final drug product, or its bioactivity, should be found consistent with the claimed content or potency. The extent of the losses throughout manufacturing should be assessed statistically. 

The most important assessment during stability studies is analysis of the protein by an activity assay. Degradation of a protein that results in compromised activity is of great concern because this affects the potency of the drug product. Expiration dating of the drug product is made to minimize the loss of potency. 

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