Biomedical Engineering Reference
In-Depth Information
involve nanotechnology. FDA will offer technical advice and guidance to manufacturers, as needed, so
that they can improve pre-market product development and safety assessments. *
In the absence of binding regulations, the agency is putting great stock in the invitation to con-
sult. No one knows how successful that effort will be.
On many of the web pages of the several FDA centers, there are detailed guidances, and even
references to regulations, to assist in the generation of data and the preparation and submission of
a marketing application for products containing macro materials. A good example is the wealth of
material on the Center for Food Safety and Applied Nutrition (CFSAN) site addressing food ingre-
dients and packaging. That degree of specificity is not available for products that employ delib-
erately manipulated nanoscale material. There are, however, a number of documents that provide
insight into how the FDA would like to regulate products using deliberately manipulated nanoma-
terials. It is useful to consider those documents, center by center.
The Center for Drug Evaluation and Research (CDER) has posted on its website nanomaterial-
related information in its Manual of Policies and Procedures (MAPP), effective June 3, 2010. The
Manual provides chemistry, manufacturing, and controls (CMC) reviewers in CDER with “the
framework by which relevant information about nanomaterial-containing drugs will now be cap-
tured in CMC reviews of CDER drug application submissions.” CDER states that this is important,
because to this point, “much of the information that was necessary to populate the fields of the data-
base were not being captured consistently.” § The information to be entered by the reviewer includes
whether any nanoscale materials are included, and if so, what material, and its source. Next, the
reviewer is to indicate whether the material is a reformulation of a previously approved product.
That is followed by a description of the nanomaterial functionality (i.e., carrier, API, excipient,
packaging, or other) and whether the material is soluble or insoluble in an aqueous environment.
Then the reviewer is to note whether the particle size was reported in the application and, if so,
the size reported. If the particle size was not included, the reviewer is to put down the reason for
that, and then go on to discuss other disclosed properties, and the methods used to characterize the
nanomaterial. Collection of this sort of information will assist in addressing the need to develop an
inventory in order for the regulator not to be “blind,” as discussed earlier.
A product review flow chart is included to make it easier to envision the steps of the review, and
then there is a list of the common techniques used as the basis to characterize nanomaterials, such
as morphology, surface, and chemical composition. More than 25 techniques are listed. A manu-
facturer can expect that its application will be considered incomplete if it does not address all of
the points in the reporting format, or if the manufacturer does not use the listed techniques for
characterization. It will make the review go more smoothly if the manufacturer explains why all the
points were not addressed, if that is the case. The characterization is particularly relevant, since the
reporting format states that reviewers can use their scientific judgment to determine the adequacy
of the techniques used by the sponsor. The procedure can take the place of “hard” regulation at this
juncture in the development of a regulatory scheme.
The Center for Veterinary Medicine (CVM) has a procedure similar to the CDER CMC
policy described above. In the section on the purpose of the procedure, CVM writes that the
procedure is intended to identify “points to consider for technical sections for products containing
* Id., Questions and answers about the draft guidance.
U.S. Food and Drug Administration. 2013. Ingredients, packaging, labeling. http://www.fda.gov/Food/
IngredientsPackagingLabeling/default.htm.
U.S. Food and Drug Administration. 2010. CDER Manual of Policies & Procedures , Chapter 5015.9, Reporting
format for nanotechnology-related information in CMC review. http://www.fda.gov/AboutFDA/CentersOffices/
OfficeofMedicalProductsandTobacco/CDER/ManualofPoliciesProcedures/default.htm.
§ Id.
U.S. Food and Drug Administration. 2011. Center for Veterinary Medicine, Program and Policy Procedure Manual
1234.2600, Review of ONADE regulated products that contain nanomaterials or otherwise involve the use of nanotechnology.
http://www.fda.gov/…/AnimalVeterinary/GuidanceComplianceEnforcement/PoliciesProceduresManual/ucm270271.pdf.
Search WWH ::




Custom Search