Form 2890-Stem Cell

Instructions for Completing NIH Form 2890

Request for Human Embryonic Stem Cell Line
to be Approved for Use in NIH Funded Research

OMB Approval 0925-0601
Expiration Date: 02/28/2010

Table of Contents

Introduction		Completing Form 2890
Submission through the NIH Form 2890 Website		Administrative Information
eRA Commons Registration		Stem Cell Line Information
Signing Official Authority		Adding Additional Related Cell Lines
eRA Commons support		Uploading Supporting Information
General Information about Submission		Supporting Information for NIH Administrative Review
Saving Data, FOIA, and Intent to Submit		Supporting Information for Working Group of the ACD Review
Form 2890 support		Assurance, Certification, Authority and Final Submission
Selection of Method of NIH Review		Final Submission and Email Confirmation
NIH Administrative Review		Printing Your Submission
Working Group of the ACD Review		Notification of NIH Determination

Introduction

NIH Guidelines on Human Stem Cell Research, effective July 7, 2009, establish a new NIH Human Embryonic Stem Cell Registry listing human embryonic stem cells (hESCs) eligible for use in NIH funded research. Only hESCs that have been reviewed and deemed eligible by the NIH in accordance with the Guidelines may be used in NIH supported research.

NIH Form 2890 is provided for the purposes of submitting information about hESC lines to the NIH, along with assurances and supporting documentation of compliance with the NIH Guidelines. NIH will conduct either an Administrative Review, or review by a Working Group of the Advisory Committee to the [NIH] Director (ACD). The Working Group of the ACD will make recommendations to the ACD, which will advise the NIH Director, who will make the final determination of whether a hESC line is approved for use in NIH funded research. All approved lines will be listed on the NIH Registry. The Registry will also contain basic information about organizations intending to submit lines to the Registry, lines pending NIH review and lines that have been reviewed.

Submission of hESC line through the NIH Form 2890 Web Site

NIH Form 2890 is a web-based form only, and must be submitted electronically through this web site: http://hESCRegApp.od.nih.gov/Login/.

eRA Commons Registration: An organization wishing to submit a hESC line for review must be registered in the eRA Commons. This is a one-time registration and is necessary for NIH validation purposes. Organizations may verify their current registration status by accessing the List of Grantee Organizations Registered in NIH eRA Commons at http://era.nih.gov/userreports/ipf_com_org_list.cfm. To register an Organization in the eRA Commons follow these instructions: https://commons.era.nih.gov/commons/registration/registrationInstructions.jsp. Note that a DUNS number must be included in the Institutional Profile. If your organization does not have a DUNS number you may obtain one from: http://fedgov.dnb.com/webform/displayHomePage.do.

Signing Official Authority: Requests may be submitted by the individual with a Signing Official (SO) role for the organization. Requests may also be submitted by another appropriate individual within an organization who has an eRA Commons UserID and password, provided that the SO approves the submission and provides the necessary certification and assurance via a signed letter on institutional letterhead, and attached as an uploaded document with the request. A sample letter (MS Word - 41 KB) is provided for this purpose. To log into the system and complete NIH 2890, the individual must provide his/her eRA Commons UserID and password. Once a Commons user enters a draft request, only that individual has the rights to edit and submit the request. However, the system provides a way to email copies of draft requests to the individuals of their choosing for review.

eRA Commons Support: For questions or problems concerning obtaining an eRA Commons account, please contact Commons Support at 1-866-504-9552, or email [email protected] and a customer service representative will be in contact with you.

General Information about Submission

Upon successful log-in to the NIH 2890 web site, you will be required to select the method of NIH review of your request. The two methods of review are Administrative Review, or review by the Working Group of the ACD. Your selection is based on a number of factors, including where and when the embryo from which the stem cells were derived was donated, and whether you are able to provide supporting documentation that the embryo was donated in accordance with Section II(A) of the NIH Guidelines.

Please use the Guidelines to determine the appropriate method of review. A cell line that meets the requirements of Section II(A) should be reviewed by NIH Administrative Review. Review by the Working Group of the ACD is only appropriate for:

• cell lines donated prior to July 7, 2009 which do not meet the exact specifications of Section II(A) but for which the embryos 1) were created using in vitro fertilization for reproductive purposes and were no longer needed for this purpose; and 2) that were donated by donor(s) who gave voluntary written consent for the human embryos to be used for research purposes, or

• cell lines from embryos donated outside the US on or after July 7, 2009 that do not meet the exact specifications of Section II(A) but for which the applicant believes the procedural standards of the foreign country provide protections at least equivalent to Section II(A) and were followed.

NOTE: NIH encourages you to select NIH Administrative Review if you believe that your cell line meets the Section II(A) requirements. If NIH determines that the line is not approvable under Section II(A), NIH will then refer the submission for ACD review under Section II(B) if the line is eligible.

It is important that you select the method of review carefully. Once you have made a selection you cannot change your selection without exiting the system and logging in again. You may contact the NIH Registry at: [email protected] and request that a submission be deleted.

Following your selection of method of review, you will be directed to complete the remaining sections of Form 2890, where administrative and stem cell line information will be entered, and you will upload supporting documentation for Administrative Review or review by the Working Group of the ACD.

Form 2890 provides the ability to submit multiple hESC lines in one submission, when all of the following circumstances are present:

1. the same organization is submitting all of the hESC lines;

2. the method of review for all of the hESC lines is the same (either Administrative Review or Working Group of the ACD review), and

3. the supporting information for all of the hESC lines included in the submission is exactly identical.

When multiple hESC lines are part of one submission, NIH will review the request as a single submission. If the request is approved then each hESC line will receive a separate NIH approval number and be listed separately on the NIH Registry. It is critical that the supporting information for all of the hESCs included in a single submission is identical.

The last section of Form 2890 is the Assurance, Certification, Authority and Final Submission section. If the Signing Official, who has direct or delegated authority to sign on behalf of the organization, is submitting the request, the authority, certification and assurance is provided electronically. If selecting review by the Working Group of the ACD, the SO will be required to indicate, by selection of the appropriate assurance, whether requesting review by the Working Group under Section II(B) or II(C) of the NIH Guide lines. If an individual other than a Signing Official is submitting the form, then the necessary authority, certification and assurance are provided in a letter that is signed by the SO and uploaded as part of the request.

Saving Data, Freedom of Information Act, and Intent to Submit

Users have the ability to save data to avoid a timeout of the session and potential data loss. When saving a draft, the system does not check to see that all data meets required validations. All data validations are performed when the “ Submit FINAL Registry Request" button is clicked. A session lasts approximately one hour, but each time the user clicks the "Save DRAFT for Further Editing" button, the session in restarted.

In addition, if you start a session and click the "Save DRAFT for Further Editing" button, then the session will be saved on the NIH server as a draft. You may come back at a later time or date and complete the submission. However, all drafts, including final submissions, are subject to the Freedom of Information Act.

All information submitted will be subject to the Freedom of Information Act. Do not submit any financial, commercial, confidential, or proprietary information. Do not submit consent documents with the personally identifying information of donor(s) of the embryos (the individuals(s) who sought reproductive treatment).

In order to provide the community with information about plans to submit a particular cell line, if you do not complete a session, and have clicked the "Save DRAFT for Further Editing" button, the name of the applicant organization (item 3) and the name of any stem cell lines that have been entered (item 6), will be posted on the NIH Registry under "Institutions Intending to Submit hESC Lines." If you decide not to complete the submission, please contact [email protected] and request that the draft(s) be purged and removed from this list. If you do not complete a session within 6 months after the initial entry date, then the draft will automatically be purged and removed from the list of institutions intending to submit hESC lines for review.

Form 2890 Support

Questions concerning the NIH Guidelines and use of Form 2890 should be addressed to the NIH Registry at: [email protected]. In addition, a Sample Web Version of the form is available for review; however, it is not an interactive form and you may not enter data into the sample.

Selection of Method of NIH Review

The two methods of NIH review, NIH administrative review and review by the working group of the Advisory Committee to Director of NIH (ACD), and the criteria and supporting information required for each are described below. A simplified decision tree (PDF - 15 KB) is also available to assist with your selection.

NIH Administrative Review

NIH Administrative Review should be selected if the organization has documentation related to the embryo donation that demonstrates compliance with all of the elements of Section II(A) of the NIH Guidelines. Regardless of where or when the embryo was donated, this option is available for all hESC lines for which there is supporting documentation. For embryos donated in the United States on or after July 7, 2009, compliance with Section II(A) is mandatory and therefore the only method of review available for such cell lines is NIH Administrative Review.

NOTE: NIH encourages you to select NIH Administrative Review if you believe that your cell line meets the Section II(A) requirements. If NIH determines that the line is not approvable under Section IIA, NIH will then refer the submission for ACD review under Section II(B) if the line is eligible. Examples of supporting documents may include for example, the consent for donation of embryos for research purposes, the consent for reproductive treatment (including the consent for cryopreservation of embryos, if applicable), and the research protocol or other document(s) demonstrating the relative timing of reproductive treatment and the donation of embryos for research purposes written policies, or other documents such as a copy of the Embryonic Stem Cell Research Oversight (ESCRO) or Institutional Review Board (IRB) or ethics committee approval to use the line or documentation of a committee's exemption from review.

The supporting information must provide evidence of compliance with each of the following elements of Section II(A) of the NIH Guidelines:

Element 1. hESCs were derived from human embryos that were created using in vitro fertilization for reproductive purposes and were no longer needed for this purpose.
Element 2. hESCs were derived from human embryos that were donated by individuals who sought reproductive treatment (donor(s)) and who gave voluntary written consent for the human embryos to be used for research purposes.
Element 3. All options available in the health care facility where treatment was sought pertaining to the embryos no longer needed for reproductive purposes were explained to the individual(s) who sought reproductive treatment.
Element 4. No payments, cash or in kind, were offered for the donated embryos.
Element 5. Policies and/or procedures were in place at the health care facility where the embryos were donated that neither consenting nor refusing to donate embryos for research would affect the quality of care provided to potential donor(s).

There was a clear separation between the prospective donor(s)’s decision to create human embryos for reproductive purposes and the prospective donor(s)’s decision to donate human embryos for research purposes. Specifically:
 
Element 6. Decisions related to the creation of human embryos for reproductive purposes should have been made free from the influence of researchers proposing to derive or utilize hESCs in research. The attending physician responsible for reproductive clinical care and the researcher deriving and/or proposing to utilize hESCs should not have been the same person unless separation was not practicable.
Element 7. At the time of donation, consent for that donation should have been obtained from the individual(s) who had sought reproductive treatment. That is, even if potential donor(s) had given prior indication of their intent to donate to research any embryos that remained after reproductive treatment, consent for the donation for research purposes should have been given at the time of the donation.
Element 8. Donor(s) should have been informed that they retained the right to withdraw consent until the embryos were actually used to derive embryonic stem cells or until information that could identify the donor(s) was no longer retained by the researchers, if applicable.

During the consent process, the donor(s) were informed of the following:

Element 9. The embryos would be used to derive hESCs for research.
Element 10.What would happen to the embryos in the derivation of hESCs for research.
Element 11. hESCs derived from the embryos might be kept for many years.
Element 12. The donation was made without any restriction or direction regarding the individual(s) who may receive medical benefit from the use of the hESCs, such as who may be the recipients of transplants of the cells.
Element 13. The research was not intended to provide direct medical benefit to the donor(s).
Element 14. The results of research using the hESCs may have commercial potential, and that the donor(s) would not receive financial or any other benefits from any such commercial development.
Element 15. Whether information that could identify the donor(s) would be available to researchers.

Working Group of the ACD Review

With the exception of embryos donated in the United States on or after July 7, 2009, review by the Working Group of the ACD is possible. The Working Group will review the materials as described below, and make recommendations regarding eligibility for NIH funding to its parent group, the Advisory Committee to the Director (ACD) of NIH. The ACD will make recommendations to the NIH Director, who will make the final determination of whether an hESC line is approved for use in NIH funding.

Embryos donated prior to July 7, 2009. Working Group of the ACD review is possible for embryos donated prior to July 7, 2009, in any country, under Section II(B) of the NIH Guidelines. Supporting information will be similar to that provided for Administrative Review (e.g., consent forms, written policies, or other documents such as a copy of the Embryonic Stem Cell Research Oversight (ESCRO) or Institutional Review Board (IRB) or ethics committee approval to use the line, or documentation of a committee's exemption from review).

Under Section II(B) of the NIH Guidelines, the supporting documentation must demonstrate that the hESCs were derived from human embryos:

1. that were created using in vitro fertilization for reproductive purposes and were no longer needed for this purpose; and

2. that were donated by donor(s) who gave voluntary written consent for the human embryos to be used for research purposes.

The Working Group will consider the submitted materials taking into account the principles articulated in Section II(A) of the Guidelines, HHS regulations for the Protection of Human Research Subjects (45 CFR 46 Subpart A), and the following additional points to consider: during the informed consent process, including written or oral communications, whether the donor(s) were:

1. informed of other available options pertaining to the use of the embryos;

2. offered any inducements for the donation of the embryos; and

3. informed about what would happen to the embryos after the donation for research.

Embryos donated outside of the United States on or after July 7, 2009. Working Group of the ACD review is possible for embryos donated outside the United States on or after July 7, 2009, under Section II(C) of the NIH Guidelines. Supporting documentation demonstrating that the alternative procedural standards of the foreign country where the embryo was donated provide protections at least equivalent to those provided by Section II(A) of the Guidelines will be required.

Completing NIH Form 2890

Please review the instructions below prior to completing the form, uploading supporting documentation, and final submission.

Remember that if you click "Save DRAFT for Further Editing" and do not complete the submission, the data entered thus far is saved on the NIH server as a draft and the name of the applicant organization (item 3) and the name of any stem cell lines that have been entered (item 6), will be posted on the NIH Registry under institutions intending to submit hESC lines for review.

Do not click the Back button to enter additional information or Refresh the screen. These actions can result in data corruption or data loss. Please remember to save your data often (every 10-15 minutes).

Administrative Information

1. Signing Official. Enter the name, phone number and email address of the Signing Official (SO, also known as the Authorized Organizational Representative). The SO must have designated or delegated authority to sign on behalf of the organization.

2. Submitter of Request.   If submitted by anyone other than the Signing Official, please enter the name, phone and email address of the submitter. In these cases, a copy of a letter signed by the SO must be provided as one of the documents in the Supporting Information section of the request form. See sample letter (MS Word - 41 KB) for appropriate language. In addition, users have the ability to send the SO or other individuals a copy of the draft request upon saving draft changes and from the main NIH Form 2890 selection screen in the "Edit Draft Request(s)" section. NIH questions about the submission will be emailed to both the Signing Official and submitter (if different).

3. Organization Name and DUNS Number. Enter the applicant organization name and DUNS number. This information should match the information in the eRA Commons account. You may verify the organization name and DUNS number at: http://era.nih.gov/userreports/ipf_com_org_list.cfm

4. Organization Address. Enter the applicant organization's address.

5. NIH Grant or Application Number. If there is an NIH grant or pending NIH application that would potentially use the stem cell line(s) that is(are) the subject of the request, please provide the numbers, using the following format: HL123456, AI654321, AG345678. If you are requesting approval for multiple stem cell lines, you may enter multiple application numbers. The response to this question will have no bearing on the NIH review or approval of the submission.

Stem Cell Line Information

6. Name of Stem Cell Line.  Enter the cell line's common or official name.

7. Cell Line Availability. Check yes or no to indicate whether the cell line will be available for use by the research community if approved for use in NIH funded research. NIH strongly encourages that hESC lines be made widely available to facilitate the advancement of new scientific knowledge. NIH Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources stress the importance of sharing unique research resources and dissemination of research tools to advance science and further discovery. Similarly, NIH Best Practices for the Licensing of Genomic Inventions encourage licensing policies and strategies that maximize access of genomic technologies.
   
   If you answer "yes" to item 7 you must complete items 8 and 9A. If a hESC line is approved for use in NIH funding, information entered into items 8 and 9 will appear on the NIH Registry.
   
   If it is unknown at this time whether the cell line will be available for distribution, check "other" and provide a brief explanation, e.g., unknown at this time, potentially available in the future, etc.

8. Restrictions (if any) on Use of Stem Cell Line. If there are any limitations on the use of the hESC line (e.g., no commercial use, in-vitro research only, diabetes research only), please describe those restrictions in the space available. If the line is approved this information will appear on the NIH Registry. Enter "None" if there are no restrictions.

9. Provider of Stem Cell Line. Enter contact information for researchers wishing to obtain the hESC line(s). You may provide the name of an individual, organization, or stem cell bank, and a phone number, email address or url. If the line is approved this information will appear on the NIH Registry. If the answer to Question 7 is "Yes", answer to 9A is required: 9B-D are optional.

10. Embryo Donation.  Indicate whether the embryo was donated in the United States or outside the United States, and the year in which the embryo was donated. This information may be relevant to the NIH review of the hESC line. The answers to item 10 will not appear on the NIH Registry.

Adding Additional Related Cell Lines

You may add additional hESC lines to your request. The method of review and the supporting information (see next section Uploading Supporting Information) must be precisely identical to the information for the hESC line identified in item 6.   If the method of review or any of the supporting information for another hESC would differ in any way (even in a non-substantive way), you must complete separate requests.

To add another cell line to your request, click “Add Another Cell Line with Identical Supporting Information.” You will automatically be routed to a confirmation page that your submission thus far has been saved. (Important Note: Be sure not to click the Back Button to enter additional data or to Refresh the screen. These actions can result in data corruption or data loss.) Scroll to the bottom and click “Continue to Edit Draft Request” and you will be directed to complete items 6-10 for another cell line. The new cell line will not be saved until you click one of the "Save DRAFT for Further Editing" buttons. You may repeat this process to add additional cell lines. When you have finished adding all the cell lines to be included in the submission, you will have the opportunity to upload one set of supporting documentation for all of the cell lines. When more than one cell line has been entered, you will have the option of deleting the last line saved, by clicking "DELETE Cell Line #_."

Supporting Information (Document Attachments)

11. Supporting Information. All requests for NIH review require that you upload supporting information. All supporting information must be in English.
    
    All materials uploaded and saved or submitted will be subject to the Freedom of Information Act. Do not submit consent or other documents with the personally identifying information of donor(s) of the embryos (the individuals who sought reproductive treatment).

In the event that you mistakenly upload an incorrect document, once you have uploaded documents and clicked "Save DRAFT for Further Editing" you will have the opportunity to delete any uploaded documents. Deleting a document removes the file from the NIH system. A copy will not be retained.

If the individual submitting the request is not a Signing Official (SO) with direct or delegated authority to sign on behalf of the organization, one of the attachments must be a letter signed by the SO. See the sample letter (MS Word - 41 KB) for appropriate language. If you are requesting NIH Administrative Review, check “other” in the Supporting Elements question for the letter of the SO.

Supporting Information for NIH Administrative Review. (If you did not select NIH Administrative Review, go to Supporting Information for Working Group of the ACD Review below.)

If you selected NIH Administrative Review, then you must provide information demonstrating compliance with each element of Section II(A). Examples of supporting documents may include for example, the consent for donation of embryos for research purposes, the consent for reproductive treatment (including the consent for cryopreservation of embryos, if applicable), and the research protocol or other document(s) demonstrating the relative timing of reproductive treatment and the donation of embryos for research purposes written policies, or other documents such as a copy of the Embryonic Stem Cell Research Oversight (ESCRO) or Institutional Review Board (IRB) or ethics committee approval to use the line or documentation of a committee's exemption from review.

Failure to provide documentation for any one element of Section II(A) will result in the cell line not being approved for NIH funding under the NIH Administrative Review process.

To upload supporting information:

• Click the "Browse" buttons to select a file from your computer. Valid document file type extensions are doc, xls, ppt, pdf, rtf, wpd, gif, jpg, txt or csv. Please convert MS Office 2007 documents (e.g., .docx, xlsx, .pptx) to MS Office 2003 format (e.g., .doc, xls, .ppt), prior to uploading.

• Provide a brief description (limit 100 characters) of the file (e.g., consent document, clinic policy, SO letter, etc.) in the box provided.

Select which of the 15 element(s) of Section II(A) of the Guidelines are supported by the document. You may choose multiple elements for each document. Up to 10 supporting documents may be attached. If you fail to select each of the 15 elements at least once, you will receive an error message that at least one of the elements is not checked and the system will not permit you to finalize your submission.

Supporting Information for Working Group of the ACD Review. Applicants are encouraged to provide, as document 1, a summary document explaining how the attachments address the materials that the Working Group will consider (see below).

If the embryos were donated prior to July 7, 2009, in any country, upload supporting information demonstrating that the hESCs were derived from human embryos:

1. that were created using in vitro fertilization for reproductive purposes and were no longer needed for this purpose; and

2. that were donated by donor(s) who gave voluntary written consent for the human embryos to be used for research purposes.

Additional information that will be relevant to the review of the Working Group includes documentation addressing the principles articulated in Section II(A) of the NIH Guidelines, the HHS regulations for the Protection of Human Research Subjects (45 CFR 46 Subpart A), and the following additional points to consider: during the informed consent process, including written or oral communications, whether the donor(s) were:

1. informed of other available options pertaining to the use of the embryos;

2. offered any inducements for the donation of the embryos; and

3. informed about what would happen to the embryos after the donation for research.

If the embryos were donated on or after July 7, 2009, in a country other than the United States, the supporting documentation is expected to demonstrate that the alternative procedural standards of the foreign country where the embryo was donated provide protections at least equivalent to those provided by Section II(A) of the NIH Guidelines.

To upload supporting information:

• Click the "Browse" button to select a file from your computer. Valid document file type extensions are doc, xls, ppt, pdf, rtf, wpd, gif, jpg, txt or csv. Please convert MS Office 2007 documents (e.g., .docx, xlsx, .pptx) to MS Office 2003 format (e.g., .doc, xls, .ppt), prior to uploading.

• Provide a brief description (limit 100 characters) of the file (e.g., consent document, clinic policy, SO letter, etc.) in the box provided.

Up to 10 supporting documents may be attached.

Comments

12. Comments. If there is any additional information you wish to provide regarding the submission, you may enter it here. If your comments exceed 1,000 characters and spaces, you may upload additional information as one of the attachments above and, if you are requesting an Administrative Review, please check "Other" for the supporting Elements question.

Assurance, Certification, Authority and Final Submission

The Signing Official (SO) registered in the eRA Commons is the only official with the authority to provide the necessary Assurance and Certifications. If the individual submitting the form is not the SO, one of the attached supporting documents must be a letter signed by the SO, which provides the required Assurance and Certifications. If the SO submits the form and has selected review by the Working Group of the ACD, there are two Assurance options; only one may be checked. If the individual submitting the form is not the SO, no Assurance, Certification and Authority boxes on the form should be checked; this information must be provided in the letter signed by the SO. The sample letter (MS Word - 41 KB) provides three assurance options; only one may be checked.

Final Submission and Email Confirmation

After clicking "Submit FINAL Registry Request" button, all data validations will be invoked. If any required data is missing, you will need to make any necessary corrections prior to it being accepted as final. Note that only partial data validation is performed when saving drafts, which allows you to have incomplete work-in-progress requests. Once all final validations are passed, you will receive an email confirmation and an NIH assigned request number that pertains to the submission.  The email will go to the Signing Official and to the submitter, if one is identified in item 2.

If you have questions concerning your submission, please contact the NIH Registry at [email protected], and reference the assigned request number. NIH will not edit any information provided as part of the submission.

The name of the organization submitting the request (item 3), the name(s) of the hESC cell line(s) provided in item 6, and the method of NIH review selected (Administrative Review or Working Group of the ACD) will appear on the NIH Registry under Submitted hESC Lines Pending Review.

Printing Your Submission

The email confirmation will include the entire text of the request, with all data you have entered and the names of the uploaded files. Print or save this email as a record of your submission.

Notification of NIH Determination

The results of the NIH review of the submission will be emailed to the SO and to the submitter, if one is identified in item 2.

NIH decisions are final and may not be appealed.  NIH will provide the reason(s) for non-approval.  If NIH determines that the line is not approvable under Section II(A), NIH will then refer the submission for ACD review under Section II(B) if the line is eligible.