Can I Use Non-Pharmaceutical grade chemicals or compounds in my study?
Please to the text provided below for an explanation o= f the OLAW and USDA guidelines for the use of non-pharmaceutical grade chemicals = or compounds
1.
May investigators use non-pharmaceutica=
l-grade
compounds in animals?
OLAW and USDA agree that pharmaceutical-grade1
chemicals and other substances, when available, must be used to avoid toxic=
ity
or side effects that may threaten the health and welfare of vertebrate anim=
als
and / or interfere with the interpretation of research results. However, it=
is
frequently necessary to use investigational compounds, veterinarian- or
pharmacy-compounded2 drugs, and / or Schedule I3
controlled substances to meet scientific and research goals.
The IACUC is responsible for evaluating the potential adverse
consequences of such agents when used for research. In making its evaluatio=
n,
the IACUC may consider factors including, for example:
o gr=
ade,
o pu=
rity,
o st=
erility,
o ac=
id-base
balance,
o pyrogenicity,
o osmolality,
o st=
ability,
o si=
te and
route of administration,
o co=
mpatibility
of components,
o si=
de
effects and adverse reactions,
o st=
orage,
and
o pharmacokinetics.
The IACUC may use a variety of administrative methods to review
and approve the use of such non-pharmaceutical-grade agents. For example, t=
he
IACUC may establish acceptable scientific criter=
ia for
use of these agents within the institution, rather than on a case-by-case
basis. Investigators and IACUCs should consider relevant animal welfare and
scientific issues including safety, efficacy, availability of
pharmaceutical-grade compounds, and the inadvertent introduction of new
variables. Cost savings alone are not an adequate justification for the use=
of
non-pharmaceutical-grade or compounded drugs in animals.
Although the potential animal welfare consequences of
complications are less evident in non-survival studies, the scientific issu=
es
remain the same. The principles and need for professional judgment outlined
above apply to non-survival studies.
Procedures that may cause more than momentary or slight pain or
distress to animals must be relieved by sedation, analgesia, or anesthesia
using veterinary or human pharmaceutical-grade compounds, unless the use of=
an
investigational chemical or formulation is scientifically necessary,
appropriately justified, and approved by the IACUC. The use of a
non-pharmaceutical-grade euthanasia agent must meet the same criteria.
1 A pharmaceutical grade
compound is a drug, biologic, or reagent that is approved by the Food and D=
rug
Administration (FDA) or for which a chemical purity standard has been
established by the United Stat=
es
Pharmacopeia-National Formulary (USP-NF),
or British Pharmacopeia (BP).
2 Veterinary compounding is =
the
customized manipulation of an approved drug by a veterinarian, or by a
pharmacist upon the prescription of a veterinarian, to meet the needs of a
research study. IACUCs considering the use of veterinary compounding for
research purposes are advised to consult: http://www.avma.org/issues/drugs/compounding/veterinary_comp=
ounding_brochure.asp
for more information about federal regulations.
3 United States Department of Justice Drug Enforcement Agency controlled substances Schedule I and II-IV drugs may be used in biomedical research according to the standards of the Code = of Federal Regulations 1301.13.
http://gra= nts.nih.gov/grants/olaw/faqs.htm#useandmgmt_4 .
This information is also contained in the document ent= itled IACUC 119 Non-Pharmaceutical Grade Chemicals.
IACUC 119
Approved by the IACUC on August 18, 2010
IACUC POLICIES, PROCEDURES, and GUIDELINES
The Use of Non-Pharmaceutical-Grade
Chemicals/Compounds
in Laboratory Animals
119.1 OBJECTIVE
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>To remain compliant with the guidance provided by the Of=
fice
of Laboratory Animal
Welfare (OLAW) and the United States Department of Agriculture
– Animal Plant Health
Inspection Service (USDA-APHIS), this document details what is
required in regards to
=
the use of
non-pharmaceutical-grade chemicals or compounds in laboratory animals at
=
the University =
of
Kentucky. Non- parenteral drugs used in agricul=
tural
animals are
=
excluded
from this policy.
119.2 DEFINITIONS
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>1. USP/NF: United States Pharmacopeia/National Formulary=
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>2. BP: British Pharmacopeia
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>3. Pharmaceutical grade chemical: ~97% purity; a chemical
that states it meets the
=
USP/NF or BP standard on the label. A certificate of analysis is usually available o=
n request.
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>4. Analytical Standards: “Certificate of
Analysis” a document that goes with each
=
product
run. This certificate lists the formula for the ingredients as well as the
amount of
=
each raw
material/ingredient. The product name and lot number are listed to avoid
=
confusion
with other batches. The Certificate of Analysis also may contain results of=
=
tests for
contaminants.
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>5. Analytical Grade: ~99% purity; Certificate of Analysi=
s usually
available; appropriate preparation is imperative.
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>6. Reagent ACS: This designates the highest quality
commercial chemical. The “ACS”
=
means the American
Chemical Society. A Certificate of Analysis is available upon request.
<=
i>7. Reagent Grad=
e:
The highest quality commercial chemical; However, ACS has not set specifica=
tions
for materials. A Certificate of Analysis is usually not available=
119.3 DESCRIPTION OF USE
IACUC 119
Approved by the IACUC on August 18, 2010
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>The use of pharmaceutical-grade chemicals/compounds in
laboratory animals ensures that the chemicals/compounds administered meet t=
he
established documentable
=
standards=
of
purity (~97%) and composition established by the United States
=
Pharmacopeia National Formulary (USP/NF) or the British
Pharmacopoeia (BP). The
=
indiscriminant=
use
of lower grade chemicals/compounds with higher levels of impurities
=
or poorly
formulated non-commercial preparations can introduce unwanted
=
experimental
variables or even toxic effects. Although pharmaceutical grade
=
chemicals/compounds should be used in experimental animals whenever possible, the=
= use of non-pharmaceutical-grade chemicals/compounds in experimental animals is an<= o:p>
=
acceptable
practice under certain circumstances. OLAW and USDA both have
=
determined
that the use of non-pharmaceutical-grade products should be based on:
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>(1) scientific necessity,
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>(2) non-availability of an
acceptable veterinary or human pharmaceutical-grade
=
compound,
and
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>(3) specific review and appro=
val by
the IACUC.
Cost savings alone is not considered an adequate
justification for the use of nonpharmaceutical-=
grade
reagents in laboratory animals. =
(See
USDA Policy 3).
119.4 WHAT SHOULD BE CONSIDERED?
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>Consideration should be given to the grade/purity of the
chemical/compound being
=
proposed=
, as
well as the formulation of the final product. Issues such as sterility,
pyrogenicity
= physiological compatibility, and quality control should be considered when proposing the<= o:p>
= use of a non-pharmaceutical-grade agent. The IACUC will expect these considerations<= o:p>
=
to be included=
as
justification in IACUC animal care and use protocols. When
=
developing=
and
reviewing a proposal to use non-pharmaceutical-grade agents the
=
investigator=
and
the IACUC will also consider animal welfare and scientific issues
=
related=
to
the use of the agent, including potential for contamination, safety, effica=
cy,
=
and the inadver=
tent
introduction of confounding research variables. Whereas, many of
=
the above issues
have been addressed in the commercial manufacturing and
=
formulation=
of
pharmaceutical-grade products, the same cannot be said for noncommercial
=
formulations
using non-pharmaceutical-grade reagents or those
=
manufactured=
in
the laboratory.
119.5 WHAT ABOUT USE IN NON-SURVIVAL PROCEDURES?
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>Although the possible implications of the use of
non-pharmaceutical-grade
=
chemicals/compounds in non-survival studies appears less evident, OLAW has stated=
=
that the scienti=
fic
issues remain the same and professional judgment, as outlined above,
=
must still apply.
The IACUC will expect a justification for non-survival use applications
=
and will determ=
ine
approval on a case-by-case basis. Remember, cost savings alone is
=
not considered
adequate justification.
IACUC 119
Page 3 of 3
Approved by the IACUC on August 18, 2010
119.6 WHAT SPECIFICALLY NEEDS TO BE INCLUDED IN THE
PROTOCOL?
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>The use of non-pharmaceutical-grade agents in laboratory
animals should be clearly
=
delineated=
and
justified in the IACUC Animal Care and Use Protocol. Where possible
=
the description
should include the chemical grade of the agent(s) being used (See
=
definitions
above), source of the reagents, as well as a description of the
=
appropriateness=
of
the agent, its formulation and vehicle. Formulations and vehicles
=
may need to be
adjusted depending on the route and site of administration, as well as
=
the species und=
er
consideration.
119.7 WHAT DOES THE GUIDE FOR THE CARE AND USE OF LABORA=
TORY
ANIMALS SAY?
<=
span
style=3D'font-size:10.0pt;font-family:"Verdana","sans-serif";mso-bidi-font-=
family:
Arial;color:black'>“The use of pharmaceutical grade chemicals and oth=
er
substances ensures that toxic or unwanted side effects are not introduced i=
nto
studies conducted with experimental
=
animals.
Pharmaceutical grade chemicals should be used, when available, for all
=
animal-related
procedures (NIH 2008; USDA 1997b). There may be circumstances
=
when the use of a
non-pharmaceutical grade chemical or substance is necessary to
=
meet the scienti=
fic
goals of a project or when a veterinary or human pharmaceutical
=
grade product is =
unavailable.
The use of non-pharmaceutical grade chemicals or
=
substances
should be described and justified in the animal use protocol and be
= approved= by the IACUC (Wolff et al. 2003). Consideration should be given to the grade,<= o:p>
=
purity,
sterility, pH, pyrogenicity, osmolality,
stability, site and route of administration,
=
formulation,
compatibility, and pharmacokinetics of the chemical or substance to be
=
administered=
, as
well as animal welfare and scientific issues relating to its use (NIH
2008).”
Approved and Adopted by the
Institutional Animal Care and Use Committee
August 18, 2=
010