I need to calculate PDE value for a drug which is being manufactured as oral and intravenous formulation. Whether the PDE calculated will differ for the formulation with the different route of administration? Kindly throw me light on this and it will be useful to me and my colleagues.
We assume you need to calculate the PDE for manufacturing purposes - Occupational Health, right? So the intravenous route is not applicable for exposure of workers. Exposure is probably by inhalation (or dermal). But you do not have inhalation tox studies with a NOEL/NOAEL. So you take the oral route tox studies and assume 100% absorption unless you have the pharmacokinetics available. From the the oral tox NOEL/NOAEL you calculate the PDE. Okay? Good luck.
Hi Morkonda,
I will add to what Gian has already said. Since you are asking about PDEs for Oral and IV routes it sounds to me like you need them for GMP purposes and not worker exposure (OELs).
As Gian mentioned the bioavailability may be different for the Oral vs. the IV route and this should be taken into consideration when calculating the PDEs for these routes - if it is known.
FYI, there is a new ASTM (American Society for Testing an Materials) Standard Guide coming out soon that gives much more detail on the "Derivation of Health Based Exposure Limits (HBELs)". As you may know, the EMA guidance on HBELs is only 4 pages long; in the ISPE's Risk-MaPP Guideline it is only 8 pages long while the upcoming ASTM Standard will be at least 84 pages long. So there will be much more substantial guidance soon.
The ASTM Standard will also describe who is a "Qualified Expert" for doing these derivations, and looking at you background I think you would fit this definition.
In the mean time, you may want to join the LinkedIn Discussion group "ASTM Standard E3106: Science-Based and Risk-Based Cleaning Process Development and Validation" where almost all of the authors of the HBEL Standard are members and can answer questions concerning HBELs and the Standard. You may also be interested in the group since all the authors of ASTM E3106 are also members and can answer questions concerning the application of HBELs to cleaning :
https://www.linkedin.com/groups/12100534/
Best regards,
Andy
Dear Gian and Andrew, thanks a lot for your answers and it is helpful in clearing my doubt.
Dear Andrew, I have sent a request to join the ASTM linkedin group. kindly approve the same to join this group.
Thanks and Regards
Srinivasan