Why do OEL Fastrac monographs not contain the "PDE Determination Strategy" summary sheet contained in the Annex? Does this make the monograph non-compliant?
No. OEL Fastrac TM monographs with ADEs are compliant with the EMA, PIC/s and ANVISA requirements. As indicated by the “should” in the excerpt from the EMA Guideline (shown below), the use of the template shown in the Annex is not mandatory.
It is also important to understand the regulatory definition of "should." As indicated in numerous FDA guidance documents, the word "should" indicates that something is suggested, but not required.
In past situations where an auditor would inquire about the absence of the "summary sheet" in our monographs, we have "pushed back" for the following reasons and in all cases they were satisfied with our response.
The Use of the Summary Sheet Creates Conflicts with Other Regulatory Requirements.
In addition to the above statements, the use of the Annex creates problems because of the checkboxes for “genotoxicant,” “reproductive developmental toxicant”, “carcinogen”, and “highly sensitizing potential.” Toxicology is a weight-of-the-evidence science; therefore, the answer to these questions is rarely a simple yes/no/unknown answer. A more sophisticated response would be required to appropriately address these questions.
Finally, the FDA labeling requirements ( 21 CFR Part 201) detail the required, relevant information on toxicological studies. This regulatory requirements means that you only present the facts associated with the results of the study. As is the practice at Affygility, the long-term studies performed are described, including in what species, and the obtained results. The Annex checkboxes do not capture this important information.
The Company Name and Address are at the bottom of each page. The Expert Name, Signature, and Assessment Review Date are on the signature page at the end of each monograph. The Chemical Name, Hazard Identified, and Basis for the PDE are on the first page. The References are provided in each monograph. Our search strategy is provided in our OEL Fastrac Guidance Document, which is provided to every client. A link to our CVs is below the signature line on each monograph.
It is the widespread belief by expert toxicologists in the pharmaceutical industry that the use of the PDE Determination Strategy summary sheet is unnecessary and creates numerous problems as indicated above.