S.O.P. for Handling and Storage of Human Subject Study Reagents
Utilizing Recombinant DNA in Viral Vectors
Introduction:
The Recombinant DNA Committee recognizes that a growing number of investigational drug studies utilize recombinant DNA agents, many of which are administered in viral form. As stated in Section III of the NIH Guidelines for Recombinant DNA Research: "Institutional Biosafety Committee approval must be obtained from each institution at which recombinant DNA material will be administered to human subjects." It is the responsibility of the Recombinant DNA Committee to review the recombinant DNA component of these studies, and make a considered judgment regarding the safety issues relative to the investigational reagents. To aid investigators in preparing for review, the Committee has provided this S.O.P. on the safe handling and storage of recombinant DNA study agents involving viral vectors to be used in human subjects. This S.O.P. offers general guidelines, and is not intended to supersede any S.O.P. provided by study sponsors. The principal investigator is responsible for providing to personnel additional training addressing any hazards specific for the study reagent.
1. Inventory Control Procedures and Documentation
Investigators will provide a Recombinant DNA Inventory form that specifies the location(s) of the locked freezer, room and building, or Pharmacy, where the study reagent will be stored as well as names of individuals with authorized access. Unused study reagent and used vials with residual study reagent prior to disposal are to be kept under locked conditions at all times to limit either accidental or intentional release of materials. The investigator will maintain an up-to-date record of the quantities of study reagent at each storage site.
2. SOP for handling study reagents consisting of recombinant DNA in viral vectors
To minimize transportation between sites, study reagent will be shipped from the sponsor directly to the Pharmacy or laboratory storage site, where it will be unpacked, entered into inventory and stored under locked conditions. Packages will be inspected upon arrival for leaking containers or broken vials.
When transported from the Pharmacy or storage site to the administration site, the study reagent must be carried within a secondary, leak-proof, container displaying a biohazard label that identifies the reagent and the principle investigator responsible for the study.
Persons administering the study reagent must have completed the online recombinant DNA training course prior to the initiation of the study. Documentation of personnel training is required for initial approval of the protocol. Prior to handling the reagent, all personnel must receive additional training regarding the specific hazards of the study agent,.
Persons administering the study reagent must wear gloves and have the option of wearing a mask-face shield combination. Patients may also be offered the option of wearing a face shield, if the agent poses a potential danger when splashed in eyes or mucous membranes. If the study reagent is prepared in the pharmacy, the Pharmacist must complete the online recombinant DNA course and wear appropriate personal protective equipment while handling the study reagent. Persons handling the study reagent will wash hands immediately after preparing the syringes or injecting the patient.
Only luer-lock type syringe and needle combinations are to be used; empty syringes and needles will be disposed of immediately in sharps containers as per hospital protocol. Vials with residual study material are to be returned to locked storage, or discarded in hospital biohazard containers. Vials containing more than one milliliter of residual material should be inactivated with freshly-prepared 10% bleach solution prior to disposal.
3. Response to a Spill
A spill kit containing chlorine bleach, absorbent material and gloves will be maintained at each storage and administration site. The safety information sheet and MSDS should also be easily available at each site. If an employee is splashed with the study reagent on intact skin, he or she should immediately wash the area with soap and water, and if desired, report to Employee Health Services. If the material is splashed into eyes or mucosal surfaces (nose, mouth), he or she should use the eyewash station to rinse away the material, and report immediately to Employee Health Services, taking along the safety information sheet for the study agent.
In the event of a spill on an inanimate surface, people should be directed away from the area. The individual responsible should don appropriate personal protective equipment, at the minimum gloves and a lab coat. If a vial shatters on the floor, shoe covers, and an N95 respirator may also be necessary. Spilled material should be covered with paper towels or absorbent pads, which are then discarded in a biohazard container. The area must be decontaminated by carefully pouring a freshly-prepared 10% bleach solution (or undiluted bleach) from the edge to the center of the spill, exceeding the visible splatter zone. The bleach should be wiped up with paper towels of absorbent pads, again discarding contaminated material in the biohazard bag. The decontamination step should be repeated a second time. Because bleach is corrosive, the area may be rinsed with 70% ethanol, isopropanol or water after decontamination. Personnel must wash hands after cleanup is complete. Spills should be recorded in the study agent inventory, and reported to the Safety Office.
4. Disposal of study reagent vials
Used vials may be stored in a locked location, if the study sponsor requires review of the vials prior to disposal. Empty vials must be discarded in hospital biohazard containers. Unused material of a volume greater than one milliliter must be inactivated by exposure to fresh bleach solution at a final concentration of 10%, or by autoclaving, prior to disposal in a biohazard bag.
5. Laboratory safety inspection for site of study reagent storage
If the study reagent is not stored in the Pharmacy, the laboratory storage location must have passed an inspection by the Lifespan Safety Officer within the past year.
6. Reporting Requirements for Adverse Events
Study personnel will report adverse events to the Lifespan Office of Research Administration who will in turn notify the IRB and Recombinant DNA Committee.
7. Reporting Requirements for Change to Protocol Requests
Study personnel will submit requests for revision to protocol to the IRB and the Recombinant DNA Committee. Submission to the Recombinant DNA Committee must include a description of how the proposed change relates to recombinant DNA agents.
8. Public Relations consideration
It is recommended that the principal investigator, in conjunction with the study sponsor, prepare a potential press release statement in layman’s terms, describing the nature of the study. This may be used in the event of unanticipated community concerns, or public misperceptions regarding the study agent. All public relations information should be channeled through the Lifespan Media Relations Office.
Clinical study reagents page 3 of 3 01/09