3.4 Outside Contractor Control Program

This page will address various regulatory issues related to this section of the GMP Institute framework.  Click below to view the issues that are relevant to you.

Is there an acceptable substitute for DOP to integrity test HEPA filters?

Is there an acceptable substitute for DOP to integrity test HEPA filters?

Reference: 
21 CFR 211.46, Ventilation, air filtration, air heating and cooling, and
211.67 Equipment cleaning and maintenance.

Yes. Dioctyl phthalate aerosols also called Di (2-ethylexyl) phthalate, di-sec octyl phthalate, DOP, or DEHP, have long been used to test the integrity of high efficiency particulate air (HEPA) filters. Concern about the potential health effects to people working with DOP test aerosols has led to a search for a safer equivalent replacement.

The prime candidate from U.S. Army testing with assistance from various private companies was a Henkel Corporation (Emery Group) product called Emery 3004 PAO. This product is a polyalphaoefin (POA) in the 4 centistoke (4 cSt) viscosity grade, used primarily as a lubricant base stock for oils, lubricants, and electrical/hydraulic fluids.

As cited in the March 1994 Human Drug CGMP Notes, based on data submitted to FDA we have concluded that Emery 3004 (POA) can replace DOP in HEPA integrity testing.

The original manufacturing site which produced the Emery 3004 (POA) for the data submitted has changed since the study and Emery 3004 (POA) is now manufactured at a different site. Discussions with the Army and the companies involved in the original studies indicate the product remains the same from the new site of manufacturing. CDER has also compared the original specifications and the new site specifications along with data from the Material Safety Data Sheets and agrees that there is no significant difference in the product from either site.

The Chemical Abstracts Service (CAS) number which identifies this product also remained as 68649-12-7.

Other reported alternatives used in the industry include DOS ( Di (2-ethylhexyl) sebacate ) and Ondina Oil. However, no manufacturer has yet submitted all the necessary data to evaluate these alternatives.

As such, Emery 3004 POA with the CAS number 68649-12-7 still remains an acceptable replacement for DOP.

Contact for further information: Michael J. Verdi, HFD-322, 301-594-0095; e-mail: verdim@cder.fda.gov