Ph. Eur. 2.4.20. Determination of elemental impurities

Recommendation

5-7 November 2024
Hamburg, Germany

GMP meets Development
GMP and FDA Compliance in Pharmaceutical Development and IMP Manufacturing

A revised version of Ph. Eur. chapter 2.4.20. Determination of elemental impurities has been published in Pharmeuropa, Issue 31.4. The deadline for comments is 31 December 2019. The draft proposes a complete revision, for example regarding the SAMPLE PREPARATION.

The draft corresponds to the stage 2 version 4 text (as per the revised Pharmacopoeial Discussion Group (PDG) working procedure; previously stage 4) in the pharmacopoeial harmonization process (Ph. Eur., JP, USP). The coordinating pharmacopoeia is the USP. The original text submitted to the PDG is published in the Pharmacopoeial harmonization section. However, the general approach for the determination of elemental impurities is mostly preserved compared to the current general chapter published in Ph. Eur.´s 10th Edition. It is emphasized that procedures 1 and 2 are provided as examples only. According to the draft, the user is free to use any method provided it satisfies the corresponding validation requirements for Detectability, Specificity, Precision (Repeatability), Accuracy, Specificity, Range and Linearity and Limit of Quantification (LOQ) detailed in the chapter.

In addition, a Glossary has been introduced at the end of the chapter providing definitions for:

• Target elements: Elements which must be evaluated according to the requirements defined in other Ph. Eur. chapters,
  
• Target limit or target concentration: The acceptance value for the elemental impurity being evaluated. Exceeding the target limit indicates that a material under test exceeds the acceptable value. (Target limits can be approximated by dividing the permitted daily exposures (PDEs) by the maximum daily dose of the medicinal product),
  
• Appropriate reference materials: Where appropriate reference materials are specified in the general chapter. Certified reference materials (CRM) from a national metrology institute (NMI), or reference materials that are traceable to the CRM of an NMI should be used.

The draft states that the chemical composition of the considered substances and the specification limits for the target element(s) may vary considerably. Thus, it is difficult to describe all suitable sample preparation and measurement methods. Furthermore, in August 2019, a new Ph. Eur. Chapter with the title: 2.4.35 Extractable elements in plastic materials for pharmaceutical use has been announced to be elaborated (in the "Update to the work programme of the European Pharmacopoeia").

Following your registration to Pharmeuropa online you will have access to the full Ph. Eur. draft for 2.4.20. Determination of elemental impurities.