Background

The primary mission of the PHS is to improve human health by increasing scientific knowledge related to health and disease through the conduct and support of biomedical and behavioral research. In pursuit of its mission, PHS supports a broad spectrum of research approaches, ranging from basic laboratory research to clinical research. This continuum of research activities creates a synergism essential to the effective advancement of knowledge. The synergy that exists among these research approaches is dependent upon the ability of PHS investigators to discuss and explore new ideas freely and openly. Under the Federal Technology Transfer Act (FTTA) of 1986, and Executive Order No. 12591, the PHS has been mandated to encourage and facilitate collaboration among federal laboratories, state and local governments, universities, and the private sector in order to assist in the transfer of federal technology to the market place. One vehicle for this collaboration is the Cooperative Research and Development Agreement (CRADA).

A CRADA is an agreement between one or more PHS laboratories and at least one other party, under which the PHS laboratories provides personnel, services, facilities, equipment, or other resources with or without reimbursement (but not funds to non-federal parties) and the other party provide funds, personnel, services, facilities, equipment, or other resources toward the conduct of specified research or development efforts which are consistent with the missions of the laboratory.

CRADAs confer intellectual property rights on PHS inventions. The PHS Model CRADA and PHS Model Materials CRADA (M-CRADA) are standard documents developed by PHS to facilitate the negotiation and approval process and to incorporate PHS policies on collaborative agreements and technology transfer.


Policy

General

The intent of Congress in establishing CRADAs was to promote national technological competitiveness and the rapid transfer of the fruits of innovation to the marketplace. CRADA research and development at the PHS should be directed to the development of biological and behavioral technology, products, and processes by transferring relevant knowledge acquired from PHS research efforts to state and local governments, universities, and the private sector.

Advances in biomedical and behavioral research depend on a continuum of research efforts, from those aimed at discovering new knowledge, to those aimed at expanding existing knowledge, to those aimed at developing new procedures and products. There is not always a clear distinction among these research activities to allow a concise definition of which activities are appropriate for a CRADA. All CRADAs must be consonant with the primary biomedical research mission of the PHS and the specific laboratory involved, ensuring that no aspect of that mission is compromised. For example, a proposed CRADA would not be appropriate if the fundamental mission of the PHS is compromised by creating, either explicitly or indirectly, more than minimal constraints on research freedom and communication.

Although there is no restriction on the topic of research appropriate for a CRADA, all CRADA research projects must be highly focussed and delineated and each proposed CRADA must be carefully assessed for its overall research objectives. In considering a proposed CRADA, PHS operating components will determine if the objectives of a proposed collaboration warrant the establishment of a CRADA or if its goals are more appropriately met through a procurement contract, material transfer agreement, cooperative agreement or other contractual mechanism. Also, the proposed collaborator's scientific and business capabilities will be assessed.

Prohibition on General Funding

A CRADA is not intended to be a general funding mechanism to support directed research in a PHS laboratory. The majority of a laboratory's resources should not derive from CRADAs. CRADA-derived funds may not supplant appropriated funds in supporting PHS research. They are to be used only to defray the cost of the project specified in the CRADA.

Laboratories must be prepared to address the impact on the ongoing research if a CRADA and related financial support is terminated unexpectedly. The sole purpose of a CRADA cannot be to support post-doctoral fellows and/or technicians, to obtain funds, or to purchase equipment and/or supplies. Conversely, the sole justification of a CRADA cannot be for a PHS laboratory to conduct research or tests for the collaborator.


Ensuring Research Freedom

PHS investigators generally are free to choose the subject matter of their research, consistent with the mission of their Institute and the research programs of their Laboratories. No CRADA may contravene this freedom.

CRADAs that explicitly attempt to direct PHS research are not appropriate. Additionally, in considering any proposed CRADA, attention must be given to whether directed research implicitly will be the net effect. For example, the greater the extent to which a laboratory's resources derive from a CRADA, the less likely it will be that the laboratory will pursue other research opportunities outside of the CRADA; the broader the scope of a CRADA research plan, the less able a laboratory will be to provide fair access and interact with others. The achievement of this balance will be considered in the decision-making process. Thus, consideration should be given to:

• a. the fraction of a laboratory's appropriated resources devoted to CRADA research;
  
• b. the fraction of a laboratory's total resources that derive from CRADA support, and the time and scope of work devoted to a given CRADA;
  
• c. the amount of time that any one investigator would give to one or more CRADAs;
  
• d. the number of CRADAs an investigator or Laboratory/Branch has with one company; and
  
• e. the number of CRADAs that any given company might have with the PHS and its operating components.

Scientific Communication and Dissemination of Research Results

It is fundamental to the mission of PHS that research results be published and discussed at public fora. Further, PHS scientists must operate within an atmosphere of scientific collegiality. Reasonable confidentiality requirements and brief delays in dissemination of research results are permitted under a CRADA, as necessary, in order to protect proprietary materials and intellectual property rights. CRADAs which in any way attempt to unreasonably restrict or constrain scientific interaction or the dissemination of research information will not be approved. In considering any proposed CRADA, consideration must be given to the possibility that the level of confidentiality associated with that CRADA project might, on balance, inappropriately impair the degree of openness necessary to maintain effective scientific communication and to serve the public interest.

Requirement of Intellectual Contribution by Collaborator

CRADAs are authorized only with collaborators who will make significant intellectual contributions to the research project undertaken or will contribute essential research materials or technical resources not otherwise reasonably available to PHS. CRADAs cannot attempt to direct or restrict research in a PHS laboratory. Sponsored research, such as routine, conventional testing, with no collaborative, intellectual contribution, is not appropriate for a CRADA.

Avoidance of Conflict of Interest

Pursuant to the CRADA-authorizing statute, every federal laboratory must ensure that there are no conflicts of interest in any CRADA. Extramural PHS staff scientists who administer grants and contracts may have an inherent conflict of interest that would preclude their participation in CRADAs. Intramural PHS scientists also may have conflicts of interest, in that they serve as a project officer on a contract or have authority over funding decisions in the course of their research. In both cases, the employee may have financial interests that would be affected by their proposed CRADA. Therefore, any conflict of interest--actual or apparent--must be addressed in the review and approval of CRADAs.


Fair Access to CRADA Opportunities

In compliance with the intent of the Federal Technology Transfer Act (FTTA) and the PHS Policy for Promoting Fair Access to CRADA Opportunities, the PHS shall ensure that outside organizations have fair access to collaborative opportunities, the licensing of federal technologies, and PHS scientific expertise, giving special consideration to small business and preference to those that are located in the U.S. and agree to manufacture in the U.S. products developed under the CRADA. Fair access to CRADAs is not to be considered as synonymous with the term "open competition," as defined for contracts and small purchases. Evidence of fair access or discussion of unique resource requirements should be maintained as part of the official IC CRADA file.

Companies can initiate the CRADA discussions by contacting a PHS scientist with whom they would like to work. Participants in CRADAs can include the individual PHS agency and one or more other parties (other agencies, state and local governments, non-profit and not-for-profit institutions, private corporations). A competitive process is generally not required in choosing a CRADA partner, although it is required by PHS fair access guidelines under limited circumstances. An agency may choose to use competition in a collaboration when interested parties are unknown or the technology/ project is such that competition is in the public's best interest. An announcement may be placed in the Federal Register or Commerce Business Daily with a selection made known to the responding parties. An ad hoc evaluation committee may be formed to review submissions, if appropriate.

A written CRADA document should be developed as soon as both participating scientists negotiate the Research Plan (the written description of the research and development project, including each party's contribution to the planned research and development). Federal laboratories may contribute staff, facilities, equipment, and supplies, but not funds. The collaborating party may contribute funds in addition to staff, facilities, equipment, and supplies. NIH has a model CRADA which is required and used as the basis for all negotiations with outside parties. The model CRADA contains three appendices: a) the Research Plan, b) Financial and Staffing Contributions of the Parties, and c) Exceptions or Modifications to this CRADA.

PHS scientists are required to fill out and attach a Conflict of Interest and Fair Access Survey form. The purpose of this form is to assure that a PHS scientist does not have a conflict of interest. regarding the CRADA research (such as consulting with the same company) and that proper consideration has been given to fair access guidelines.

Each PHS agency has a Technology Development Coordinator (TDC) who facilitates the drafting of an acceptable CRADA and related Appendices, advising the PHS scientist in the development of the overall agreement. The CRADA and Appendices are generally negotiated by the TDC in conjunction with the other party. The negotiated CRADA must be approved by the PHS scientist, the Laboratory or Branch Chief, and the Scientific Director. The TDC then forwards the agreement to the Office of Technology Transfer (OTT) and the Office of General Counsel for review, who then forward the agreement to the CRADA Subcommittee of the Technology Transfer Policy Board for final approval recommendation. Generally, all CRADAs containing exclusive licensing-related clauses must be reviewed by the agency's CRADA Review Subcommittee.



The Federal Technology Transfer Act provides for a 30-day period in which to disapprove or modify a CRADA after its finalization. When there are no changes required, the CRADA is signed and returned to the TDC at each PHS agency or institute. The TDC is responsible for obtaining the proper signatures required for execution by the company. Agreements have no mandatory term length and can be extended by the mutual agreement of the parties if there is no substantial change in the Research Plan. Because scientific objectives and circumstances change, it is essential to include in a CRADA a specific time period for financial accountability and provisions for early termination.

In order to expedite the commencement of the Research Plan, prior to final execution of the CRADA, an interim Letter of Intent may be signed with the company. Once an invention is made within the scope of a CRADA agreement, the OTT will negotiate the CRADA-related license with the commercial partner.