EMA website on Permitted Daily Exposure (PDE) limits

Recommendation

4/5 October 2022
Heidelberg, Germany

Process Validation in the light of the revised Annex 15 and FDA Requirements

The issue of cross-contamination has been addressed by authorities since the publication of the first edition of the EU GMP Guidelines. The finalisation of the EMA "Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities" has started a new chapter on cross-contamination. Health-based exposure limits (HBEL) and Permitted Daily Exposure limits (PDE) have been in the focus ever since. Subsequently, chapter 5 of the EU GMP Guideline (Part I) and Annex 15 regarding cleaning validation have both been revised. A draft and now the final version of a Question and Answer document on "Shared and Dedicated Facilities" has been published, as well.

The EMA has compiled documents covering the issue on their website:

• Overview of comments received on 'Questions and answers on implementation of risk based prevention of cross contamination in production' and 'Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities' 
• Outcome of public consultation on 'Questions and Answers on implementation of risk-based prevention of cross contamination in production' and 'Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities'
• Questions and answers on implementation of risk based prevention of cross contamination in production and 'Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities
• Annexes to specifications for class 1 and class 2 residual solvents in active substances
• Volume 4 Good manufacturing practice (GMP) Guidelines
• ICH M7 Assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk
• ICH Q3C (R5) Residual solvents
• ICH Q3D Elemental impurities
• Workshop held by EMA on generation and use of Health Based Exposure Limits (HBEL)

The first and the last document are interesting, especially. On 96 pages, the first document lists the industry's comments on the Question and Answer (Q&A) draft document on the "shared facility" guideline. The last document includes several sets of lecture slides by authority and industry representatives on the issue of health-based exposure limits.

You may find the collection on the EMA's website.

If you are interested in HBEL and PDE, the webinar "EMA´s Q & A regarding PDE-values" on 17 October, 2019 might be interesting for you.