Top 10 deficiencies in new application for Certification of suitability

The following table presents a detailed analysis of the top ten deficiencies commonly encountered during the Certification of Suitability application process within pharmaceutical manufacturing (Source: EDQM). It meticulously addresses complex challenges, from insufficient product specifications to potential contamination risks and the intricacies of risk assessment.

For each identified issue, the table describes the implications on the final product and suggests recommended actions, including consultations with experts and specific assessments. It serves as a critical quality control tool to ensure the safety and efficacy of pharmaceutical products.

#DeficiencyCheck points for CoS and DMF (What is expected)How Veeprho can help you (Solution offered)Link to EDQM guidline
1Poor description of the manufacturing processAppropriate synthetic flow diagram representing all isolated non-isolated intermediates as well as starting materials including recovered material along with clear process descriptionExpert support to draft the comprehensive flow diagram and inclusive process detailsView EDQM Guideline
2Poorly justified specifications for intermediates and starting materialsDefine suitable acceptance criteria for impurities in starting material and intermediates. Identification of major impurities and their carry over.Identification and characterization of major impurities in SM and intermediates.
Computation purge assessment for carryover studies
View EDQM Guideline
3Absence of discussion about potential mutagenic impurities in the APIMutagenicity assessment of all actual and potential impurities of final API as well as associated with staring material and intermediate followed by classification to justify the limits as per ICH M7. Control strategy for genotoxic impurities as per option 3 and 4 in ICH M7Our computational (Q)SAR based toxicology for prediction of a Mutagenicity & Carcinogenicity of impurities followed by classification as per recommendation of ICH M7. We also support for recommendation of limits of impurities.
Purge assessment to support Option 3 & 4.
View EDQM Guideline
4Same as 2Same as 2Same as 2View EDQM Guideline
5Inadequate acceptance criteria for raw materials (incl. recovered materials)Accurately designed specification of raw material including recovered raw material.Report on risk assessment for nitrosamine as per EMA and FDA requirements followed by support on confirmatory test.
Identification of degradation products and risk assessment
Acceptable Intake determination by computational read across based on surrogate as per EMA & FDA
View EDQM Guideline
6Reprocessing and recovery of raw materials are inadequately addressedDetailed description of reprocessing and recovery.Support for risk assessment of impurities due to reprocessingView EDQM Guideline
7Deficient risk assessment related to NitrosaminesRisk assessment of Nitrosamine formation with respect to manufacturing process and raw material, reagents used in synthesis.
Also due to degradation products and carry over of amine impurities in drug product (including NDSRI)
Report on risk assessment for nitrosamine as per EMA and FDA requirement followed by support on confirmatory test.
Identification of degradation products and risk assessment
Acceptable Intake determination by computational read across based on surrogate as per EMA & FDA
View EDQM Guideline
8Failure to adequately address the origin, fate, and carryover of impuritiesDiscussion for carry over of impurities and precursor of toxic impurities to final API and formulation product for non pharmacopeial impurities (specific to process and materials used) and degradation productSupport on complete assessment of identification of process specific impurities and degradation products followed by risk assessment and purge/carry over studiesView EDQM Guideline
9Deficient discussion on residual solventsProvide appropriate LoD/LOQ for solvents which are not detected. Discussion of solvents as byproduct. Risk assessment of Class 1 solventsRisk assessment report for residual solvents including class 1 solvents.View EDQM Guideline
10Failure to suitably identify starting materialsCarry over of toxic precursors and reagents to final APIOur expert will guide you to define appropriate starting material and their risk assessmentView EDQM Guideline

Source: TOP TEN DEFICIENCIES in New Applications for Certificates of Suitability for chemical purity (EDQM)

Recognizing the importance of proactive measures, we advocate for strategic consultations with industry experts and the implementation of specialized assessments.

Designed as an essential tool for quality assurance, this table aims to reinforce the commitment to excellence and safety in pharmaceutical products.

By sharing our insights, we strive to foster a culture of continuous improvement and collaboration across the pharmaceutical industry.

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