BACKGROUND INFORMATION
These guidelines have been developed to ensure the sterility and effectiveness of drugs when secondary containers are used for compounding, diluting, or transferring drugs and compounds to be administered by injection to animals.
RESPONSIBILITIES
It is the responsibility of the Principal Investigator to ensure that all personnel working with animals adhere to these guidelines when using secondary containers for compounding, diluting, or transferring drugs and compounds.
DEFINITIONS
Secondary Containers: Vials, bottles or tubes used for storage of drugs or compounds that have been moved from their original container for purposes of transferring, diluting, or compounding.
Transferring: When drugs or compounds are taken out of the primary container and placed into a secondary container (e.g., drugs in glass ampules).
Diluting: When drugs or compounds are mixed with a diluent to achieve a working concentration (e.g., antibiotics or analgesics for use in rodents).
Compounding: When drugs are mixed with one or more drug or diluents (e.g., mixture of ketamine with xylazine and diluent).
PROCEDURES
Types of Secondary Containers
Secondary containers are most commonly used for drugs or compounds that are:
- Removed/withdrawn multiple times from the same container
- Diluted or compounded and then administered aseptically (single or multiple draws)
The best type of container for secondary use is a vial with a septum in the cap (search septum or crimp top vial on a scientific supply website) that allow for the contents to be removed aseptically with a sterile needle and syringe. The sterile drug or compound is transferred/dispensed into the vial using aseptic technique. . The top of the septum should be disinfected with 70% alcohol prior to use. As a second choice, a red capped (untreated) blood collection tube can be used as a secondary container.
The use of screw capped tubes should be avoided as it is difficult to remove the contents aseptically.
The secondary container material must be compatible with the drug or compound and its intended use. Container material requirements:
- Does not react with the drug or compound (e.g., glass, polypropylene, or polycarbonate plastic).
- Opaque if light sensitive material is to be stored (e.g., covered with foil, brown glass)
- Supplies are sterile or able to be autoclaved.
Labeling
Any drug or compound transferred to a secondary container must be labelled as follows:
- Name and concentration of each ingredient, including the diluent.
- Total amount/volume in the container
- For transferred solutions the expiration date of the drug or compound
For diluted or compounded solutions, secondary containers must also include the following:
- The preparation date
- The expiration or use by date
- Cannot extend past the earliest expiration date of any of the components.
- Should be no longer than 30 days from preparation for compounds or dilutions, unless published or vendor- provided scientific data can demonstrate a duration of efficacy longer than 30 days.
- EXAMPLE: Compounded Ketamine anesthetic cocktails have a use by date of 6 months (or the earliest expiration date of any drug in the compounded solution, if < 6 months) on a basis of the publication Taylor, BJ et al.2009. Beyond-use dating of extemporaneously compounded Ketamine, Acepromazine, and Xylazine; safety, stability, and efficacy over time. JAALAS 48:718-726.
For controlled substances, per DEA Guidelines, the inventory must reflect all disbursements and the label must include the following:
- The total amount/ volume and lot number of each controlled substance.
- The total amount/ volume of the combined drugs
- The concentration of each drug (mg/ml)
- Date of preparation
- Date of expiration or use by date, whichever is earliest.
Exceptions:
The following compounds are exempt from this Guidance:
- Test compounds that are prepared for single use and will not be stored past this use.
- Test compounds that are available in small quantities (<0.5 ml), such that use of a septate vial poses a risk of losing the contents in the rubber septum.
- Test compounds that consist of hazardous materials (BSL-2/3, CSL-2/3, radioisotopes), such that the additional handling needed to place the material into a septate vial increases the risk of accidental exposure.
These compounds must be prepared and handled using sterile technique, as appropriate. All containers must be identified with a description of the contents. Note that this exception does not apply to veterinary drugs, i.e., anesthetics, analgesics, or euthanasia drugs.
REFERENCES
Click
here for a downloadable image showing examples of appropriate containers and labels.