Emphasizing more on the risk assessment approaches for cross contamination (VICH GL 18, ICH Q3C) of one drug to another in shared manufacturing facilities, the European Medicines Agency (EMA) has released a new set of Good Manufacturing Practice (GMP) guidelines to calculate health-based exposure limits in Active Pharmaceutical Ingredients (APIs) and intend to cover safety for human and veterinary medicinal products. Using non-clinical study end points such as no-observed-adverse-effect level (NOAEL) / lowest observed adverse effect level (LOAEL) and the appropriate uncertainty factors (UFs), the health based exposure limit-Permissible Daily Exposure (PDE) value is calculated. With the EMA’s GMP guidelines already put into practice starting Nov 2015, manufacturers of drug products may face certain procedural complexities such as:

  • Establishment of PDE value and monitoring the levels of the cleaning validation for a huge set of medicinal products from various shared facilities
  • Access to the toxicological literature along with the expertise in risk assessment, which is required to derive a PDE value
  • High-level understanding of risk assessment for residual active pharmaceutical ingredients (APIs) / substances for streamlined data collection to be incorporated into PDE reporting requirements

With an industry-proven expertise in decoding and implementing various time-critical health authority mandates, Freyr’s health-based risk assessment team assists manufacturers of drug products to carry over cross contamination assessments and prepare audit-ready PDE reports. 


Freyr Capabilities

  • End-to-end health based risk assessment
  • Expertise in calculating and implementing PDE in cleaning validation processes
  • Access to professional databases and required tools for exhaustive literature search and prediction of toxicity based on (Q)SAR
  • On-time and compliant document deliverability 

Freyr Advantages

  • Qualified, trained and experienced data scientists and toxicologists
  • In case of scarce toxicological data / literature and absence of NOAEL value we use read-across data from surrogate compound or use (Q)SAR data as applicable to arrive at feasible PDE value
  • Well-maintained archival of the background information and literature, which helps in supporting regulatory queries, if any
  • Case-by-case consideration for medicinal products: manufacturing conditions, manufacturing requirements, route of administration in target patients, etc. to appropriately calculate the final PDE value
  • Audit-ready and highly professional dossier preparation

EMA Compliant Health Based Risk Assessment (PDE)

Freyr has performed toxicological gap analysis and streamlined 50 PDE value evaluations for established medicinal products Download


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    Terrific Job Freyr, GREAT TEAMWORK!!! 

    - Director of Regulatory Affairs-Operations,
    India based, Global 4+ Bn Pharmaceutical Company

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    An Independent regulatory and quality consulting company

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    Project Manager,
    A full-service Clinical Research Organization (CRO)
    Based in Florida

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    – VP and Head of Regulatory Operations of a Global Top 5 Pharma & Consumer Company

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    Program Manager, Global Top 5 Pharma and Consumer Health Company

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    Thanks to their commitment and discipline, we were able to deliver on all key objectives that had been outlined for us in 2014.

    - Head of Regulatory Operations, Top 5 Global Pharmaceutical Company

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    – Manager, Regulatory Operations, Global Top 20, $20+ Bn,
    Pharmaceutical Company

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    - Associate Director, Regulatory Technology and Ops,
    Global Top 20 Pharmaceutical Company