PIC/S publishes Aide-Memoire for the Inspection of Health Based Exposure Limit

Recommendation

15/16 February 2024

Process Understanding - Live Online Training
Statistical Process Control (SPC) as a tool to get there

In June, the Pharmaceutical Inspection Convention/Cooperation Scheme (PIC/S) issued the new document PI 052-1. What is in it?
The PI 052-1 document is entitled "INSPECTION OF HEALTH BASED EXPOSURE LIMIT (HBEL) ASSESSMENTS AND USE IN QUALITY RISK MANAGEMENT". The document is divided into seven chapters:

• Document History
• Introduction
• Purpose
• Scope
• Aide Memoire
• References
• Revision history

and comprises 10 pages.

It is intended to help a GMP inspector who does not have specialized toxicology knowledge to evaluate Health Based Exposure Limits (HBEL). In the introduction it is pointed out that HBELs may well differ for the same substance if they have been calculated by different experts. Variations with a factor of 3 are considered normal, variations with a factor > 10 are intended to prompt the inspector to conduct further "investigations"... The introduction also points out that Permitted Daily Exposure (PDE) and similarly Acceptable Daily Exposure (ADE) also refer to health based limits. Finally, the introduction contains a note on the classification of inspection deficiencies with regard to their significance and influence on patient safety. For example, deficiencies should only be classified as critical if they have a direct impact on patient safety.  

The actual Aide memoire part (Chapter 5) is divided into three columns in a table: a column with questions ("prompt"), a column with expectations and a reference column regarding GMP regulations and further information. The table is then split into 2 sections by rows. One section deals with the evaluation of health based limits. The other section deals with the quality risk management studies derived from the health based limits, which then lead to organisational and technical measures. For example, Section 1 contains questions or instructions such as

• Is there a summary report?
• Review the CV for the person(s) who completed the health based limit value information (the expectations column explicitly states that self-taught health experiences in HBEL may not be adequate without other relevant qualifications and experience). 
• Review the contract if the assessment of health based thresholds has been outsourced
• Is a literature search well documented and broad enough?
• Is the search strategy for a literature search documented?

etc.

The following questions or instructions are listed in section 2:

• Examine the procedures for cross-contamination controls in relation to the use of health based limits in the context of a risk-based approach.
• Review the QRM study with regard to the level of health based limits (e.g. in the expectations column it is noted that QRM studies are usually supported by risk analysis tools such as HACCP or FMEA or FMECA. However, other tools are also accepted).
• Consider the structure and general content of the QRM assessment report on health-based limit values (here, for example, the expectations column points out that a 100-page document without structure should in itself be a deficiency).
• Question individual aspects of the QRM assessment with regard to health-based limit values.

The document concludes with references and the revision history.

The topic of cross-contamination from the point of view of cleaning validation will be dealt with during the ECA Live Online Training Cleaning Validation on 3/4 September 2020.

You can find the document on the PIC/S website, see PI 052-1.