The exemption attempts to avoid duplication of paperwork because
the Food and Drug Administration requires the transmittal of
detailed information from the manufacturer in the form of package
inserts and labels. Investigational drugs use clinical brochures as
a substitute for the package insert.

Clinical brochures should be available on the clinical drugs at your
institution for personnel handling and administering these antitumor
agents, please request them from:

    Pharmaceutical Management Branch
    Cancer Therapy Evaluation Program
    Division of Cancer Treatment
    National Cancer Institute
    Room 804, Executive Plaza North
    Bethesda, Maryland 20892

Proper Handling and Disposal of Anti-Cancer Drugs:

The potential risks to individuals working with antineoplastic drugs
have been the subject of much interest and concern in the health
care community. Procedures for proper handling and disposal of
anti-cancer drugs should be considered. Several guidelines on this
subject have been published to assist practitioners who prepare and
administer antineoplastic drugs in establishing a program of
procedures designed to minimize inadvertent exposure to these
agents (1-3). In addition, a videotape entitled "Safe Handling of
Cytotoxic and Hazardous Drugs", 1990 edition, is available from
the American Society of Hospital Pharmacists and may be used in
training staff members. Although the nature and extent of any
risks that might exist are uncertain, practitioners are encouraged
to implement a program that will minimize their level of exposure.

Material Safety Data Sheets:

There have been several recent changes in the Hazard
Communication Standard. The Hazard Communication Standard
final rule was published August 24, 1987 and required that
chemical manufacturers, importers, and distributors ensure that
Material Safety Data Sheets (MSDS's) are provided with the next
shipment of hazardous chemicals to non-manufacturing employers
or distributors after September 23, 1987 (Federal Register
52:31852-31886, 1987). This revised standard exempted "drugs
when they are solid, and in final form for direct administration to
the patient (i.e., pills or tablets)".

Subsequently the final rule was amended December 4, 1987
(Federal Register 52: 46075-46080) to exempt any drug regulated
by the FDA in the non-manufacturing sector from the requirement
to supply MSDS's.

established expiration date: 
The year that a drug was manufactured
by a National Cancer Institute contractor can also be determined
from the first two digits of the lot number (e.g. BV-87-301 and
UI-90-202 were manufactured in 1987 and 1990, respectively).
Any expired drug should be returned to the NCI Clinical Drug
Repository along with a completed Return Drug Form.

Preparation Information:
The recommended constitution and dilution directions are based on
formulation and solution stability studies performed on each drug.
0.9% Sodium Chloride Injection, USP, 5% Dextrose Injection,
USP, or 5% Dextrose in 0.45 % Sodium Chloride Injection, USP,
the most common infusion vehicles, are usually selected for
solution compatibility studies. The omission of other vehicles does
not imply incompatibility. The solution stability data which have
been developed are presented.

Infrequently, the formulation of a product is changed or a new vial
size is made available in between editions of this book.
Information in these monographs should not be used as a substitute
for the preparation instructions on the label of the product.

Compatibility:

Compatibility of the investigational agents with other drugs or with
antibacterial preservatives is not usually evaluated. Investigational
agents manufactured by the NCI are designed as single-use dosage
forms and admixture with other agents is, in general, not
recommended. Compatibility studies of selected investigational
agents in plastic are currently being conducted by NCI contractors.

recommendations are frequently based on accelerated shelf-life
studies at elevated temperatures. Each new lot of investigational
products manufactured by a National Cancer Institute is placed on
a shelf-life surveillance study. Generally, each lot is studied for
five years in the freezer (-10 °C) and recommended storage
conditions. Elevated temperatures are included as appropriate.
The NCI receives updated stability data every three months for the
first year, every six months for the second year and yearly
thereafter.

Many of the product monographs in this book include stability data
for temperatures higher than the recommended storage condition.
These data are provided to allow decisions on whether to use
products which may have inadvertently been stored above the
labeled temperature for short periods of time (e.g. a product which
is labeled for refrigerated storage which is left at room temperature
for a day or two).

Shipping:

Storage information is provided on the label. Occasionally,
product labeling requires refrigeration, but the product is shipped
without ice. These products are stable for short periods of time at
room temperature, but still must be stored under refrigeration upon
receipt.

Expiration Dating:

Older products carry an expiration date placed on the label, which
is based on real -time stability studies. The drug may be used
through the end of the month specified.

Newer drugs will carry only the manufacturing date; these drugs
are undergoing stability evaluation but do not yet have an


GENERAL INFORMATION

Product information is presented in a uniform manner. The
standardized format begins with the drug's labeled name as the
monograph title. When a United States Adopted Name (USAN)
is available, it is generally used. Otherwise, the name most
commonly applied to the agent, or in some cases the chemical
name, may be used. Other identification data presented include
the structural formula, CAS registry number, chemical name, any
common names other than those previously listed, the molecular
formula and the molecular weight.

The composition and packaging of the investigational dosage forms
are then described. Descriptive terminology for parenteral
products (e.g. "Sterile.....", ".... for Injection ") as defined in the
official United States Pharmacopeia is utilized.

NSC Numbers:

Each investigational compound studied by the NCI is assigned a
unique number. This universally recognized identification number
is called the "NSC" number, which refers to the former Cancer
Chemotherapy National Service Center. The NCI maintains its
files and data for each compound based on its assigned NSC
number. When information is requested on a particular NCI
compound, use of the NSC number will facilitate a response and
assure that both the requestor and NCI are referring to the same
compound. NSC numbers for special diluents have been added
where appropriate.

Stability and Storage:

Recommended storage conditions for the intact dosage forms are
presented in each monograph.