STEP 1: BASELINE INFORMATION

One of the major challenges in the implementation of ICH Q3D is communication with suppliers.

At this stage it is necessary to collect all available information on those elements that could contribute to the presence of elemental impurities in the final product.

Facilitating the information collection work means a reduction in time and costs.

STEP 2 : DEFINITION OF STRATEGY TO FOLLOW

There are four options for the evaluation of elemental impurities :

Option 1, 2A and 2B represent the "component-based approach" for the risk assessment, whereas Option 3 represents the "finished-product-based approach"

Option 1: Considers that all the components could be used in any proportion and that the product intake is not more than 10 g/day. For each elemental impurity, the concentration limit (CL) is calculated by dividing the PDE by 10 g/day. Acceptance criteria: None of the components exceeds the calculated CL.

Option 2A: Considers that all the components could be used in any proportion and calculates the real maximum daily product intake (MDI). For each elemental impurity, the concentration limit (CL) is calculated by dividing the PDE by the MDI in grams. Acceptance criteria: None of the components exceeds the calculated CL.

Option 2B: Considers the real quantitative composition of the product and the real maximum daily product intake. Calculate, for each component, the level of all elemental impurities. Then, for each elemental impurity, calculate the total level (aggregated from all the components). Acceptance criteria: The total level does not exceed the PDE. 

Option 3: Consists in the finished product analysis. The levels of the elemental impurities should be individually determined by appropriate techniques (ICP-MS) by analyzing 3 representative batches (industrial scale) or 6 representative batches (pilot scale). The total exposition to the elemental impurities is calculated with the maximum daily intake of the product. Acceptance criteria: The total exposition does not exceed the PDE.

STEP 3 : ANALYTICAL PLAN

The analytical procedures will be based on some of these methods:

• Procedure 1: ICP-AES/OES
• Procedure 2: ICP-MS
• Alternative procedure: e.g. Flame - AA, Graphite - AA, Cold Vapor Atomic Absorption Spectroscopy (CVAAS) - Hg, may be used provided that they are validated.

The analytical plan allows to define what elements we have to analyse, how many samples we need and which volume of it, what analytical technique is the most appropriate etc …

When testing, the ICH Q3D requires that the screening is performed in at least 3 representative batches produced in an industrial scale or at least 6 representative batches produced in a pilot scale.

Costs can be reduced through an appropriate selection of the elemental impurities to be tested as well as the analytical methodology to apply.

We offer the best service with our partner Kymos Laboratories, which is a GMP, EU and FDA certified analytical lab with a vast experience in this topic.

STEP 4 : CONTROL STRATEGY

In the case of the presence of any elemental impurity, its significance is considered on the basis of its determined or predicted value and compared with its PDE value. ICH Q3D establishes a control limit of 30% of the PDE value for each elemental impurity.

STEP 5: LIFE CYCLE MANAGEMENT

The implementation of ICH Q3D is a living process. In the case of changes to the product and/or components which are potential sources of elemental impurities, it must be re-evaluated. These changes may be (but not limited to): changes to synthesis route, changes of manufacturers, changes in the processes, changes to the packaging materials, facilities. All of these changes will be subject to change controls and, if necessary, regulatory variation.

HOW TO FULLFILL ICH Q3D REQUIREMENTS ?

We develop Elemental Impurities Implementation of Risk Assessment Reports, for both API manufacturers and drug product manufacturers. You can contact us regarding a QUOTATION REQUEST for an ICH Q3D report development.