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Sec. 635.100 Large Volume Parenterals (LVP's) for Animal Use (CPG 7125.31)
BACKGROUND:
Large volume parenterals or LVPs (sometimes called large volume injections) are aqueous
solutions usually supplied in volumes of at least 100 ml with sizes of 250 ml, 500 ml, and
1000 ml most common. Directions usually recommend that large quantities be administered.
The usual route of administration is intravenous (IV) but other routes, such as
intraperitoneal (IP) or subcutaneous (SQ or SC), are sometimes recommended. Examples of
LVPs include:
All parenterals for animal use including LVPs must be sterile.*
Preservatives (antimicrobial agents) are not permitted in LVPs in the absence of an
approved NADA that specifically establishes the safety of the preservative, in a
particular product. If a preservative were to be added to an LVP in a concentration
adequate to prevent the multiplication of microorganisms, an animal could receive a toxic
dose of the preservative because of the large amount of solution administered. Based on
limited animal toxicity and epidemiological data it appears that at least one preservative
commonly used in small volume parenterals, benzyl alcohol, can be toxic, even fatal, to
animals when used in LVPs.
Antimicrobial agents are permitted in multiple dose containers where the preservatives
are added to protect the products from inadvertent microbial contamination during multiple
entry and subsequent storage. Only a small amount of such a product is injected into any
particular animal.
LVPs should be supplied in container sizes appropriate for their intended use or uses
so that the majority of the contents would ordinarily be used promptly following initial
entry. Too large a container size relative to intended use would encourage retention of
unused contents which could result in microbial contamination of a product containing no
preservatives. Labeling of LVPs should clearly indicate the lack of preservatives and
should promote use of contents promptly following initial entry and disposal of unused
contents. The concentration of individual ingredients should be clearly expressed. If the
product is not a compendial item or the physiologic parameters are not otherwise clearly
defined, the label should bear an indication of the pH and osmolarity (tonicity) of the
solution.
Labeling should in all other respects bear adequate directions for use and not be false
or misleading in any particular.
POLICY:
Large volume parenterals must be:
1. Sterile.
2. Free of preservatives.
3. Supplied in sizes appropriate to label claims facilitating use of the contents promptly
following initial entry.
4. Labeled to indicate that: a) they contain no preservatives, b) they are intended for
use promptly following initial entry, and (c) any portions not used promptly should be
discarded.
5. Labeled to clearly indicate concentration of individual ingredients and physiological
parameters of the solution.
LVPs that contain preservatives are considered new animal drugs and, in the absence of
an approved NADA, are deemed unsafe under section 512 of the Federal Food, Drug, and
Cosmetic Act and adulterated under section 501(a)(5) of the Act. LVPs may also be
considered new animal drugs for reasons other than the presence of preservatives (e.g.,
due to other constituents of the formulation or the claims made for the product). LVPs
which are not sterile (or which are produced under unvalidated procedures) would violate
501(a)(2)(B), 501(b), or 501(c). Failure to bear adequate labeling would result in
violations of 502(a), 502(f)(1) or (2), among others.
The *Center* will review labeling and batch records to determine compliance with this
policy. Initial action will ordinarily be a *Warning letter* or, if warranted by the
circumstances, seizure.
*Material between asterisks is new or revised*
Issued: 12/1/82
Revised: 3/95