Final EMEA Guideline on Excipients Excludes Products in Development

The European Medicines Agency’s (EMEA) final guideline on data submission requirements for excipients in marketing authorization applications does not apply to drug products currently in the clinical research stages of development.

Excipients are components of a drug compound other than the active ingredient. Examples include fillers, disintegrants, lubricants, antioxidants, preservatives, stabilizers and permeation enhancers.
 
The exemption was not included in the draft guideline released last year, although the EMEA recommends that firms consider the principles in the guideline during the development stages of drug candidates.
 
In addition to the exemption for drugs in the clinical research stages of development, the EMEA removed the following recommendation from the final guideline: “For biological excipients of animal or human origin, the risk of transmitting adventitious agents should be considered and appropriate documentation submitted (e.g., method of preparation and control of tissues and body fluids used as starting materials).”

The section of the guideline concerning the use of antioxidants and antimicrobial preservatives was slightly modified from the draft version with the added recommendation that the concentration of such preservatives in pharmaceuticals should be at the lowest feasible level, the EMEA says.

In explaining that both antioxidants (used to improve the stability of medicines) and antimicrobial preservatives (used to prevent microbial proliferation) are usually harmful to living cells, the EMEA says that use of such agents should be avoided whenever possible, particularly in pediatric formulations.

“Where antioxidants are used during the manufacture of the medicinal product, the release limits should be justified by batch data or a sound justification has to be provided, if the proposed specifications do not include an identification test and a content determination test for the antioxidant. If needed, the adequacy of the specified limits should be justified on the basis of controlled conditions and (in-use) stability testing, to ensure that sufficient antioxidant remains,” the EMEA says.

The guideline can be accessed at www.emea.europa.eu/pdfs/human/qwp/39695106enfin.pdf.