Effective date: January 1, 2023

Table of Contents

• Policy Statement
• Who is Governed by this Policy
• Purpose
• Policy and Procedures
• Related Resources
• Contacts

Policy Statement

It is the policy of the Johns Hopkins University (“JHU” or “University”) that some types of research involving human pluripotent stem cells (“hPSCs”) being conducted by JHU faculty, staff, trainees, or students or involving the use of JHU facilities or resources shall be subject to oversight by the JHU Institutional Stem Cell Research Oversight Committee (“ISCRO”).  The following research is covered by this policy:

1. All research using human embryonic stem cells (“hESCs”);

2. All research using somatic cell nuclear transfer (“SCNT”) involving human cells;

3. Other hPSCs (e.g., human induced pluripotent stem cells [“iPSCs”] and human embryonic germ cells [“hEGCs”]) where the research involves:

a. Introduction of such cells into humans;

b. Introduction of such cells into the central nervous system of non-human primates;

c. Introduction of such cells into non-human animals and there is a reasonable possibility of the cells giving rise to gametes;

d. Derivation of gametes or embryos from such cells;

e. Formation of embryo models derived from such cells; or

f. In vitro culture of chimeric embryos (hPSCs introduced into non-human embryos).

Who is Governed by this Policy

All units of the University, excluding The Johns Hopkins University Applied Physics Laboratory

Purpose

This Policy sets forth the authority, responsibilities, and procedures of the ISCRO in its oversight for University research using hESCs, SCNT involving human cells, and other hPSCs under the circumstances identified in Policy Statement, Section 3 above (collectively, “Human Stem Cell Research”).

The primary purpose of the ISCRO is to provide ethical oversight for Human Stem Cell Research conducted at the University.  The ISCRO also conducts reviews for compliance with other applicable governmental regulations and University policies governing such research.

In addition, the ISCRO serves as an educational and consultative resource for researchers engaged in Human Stem Cell Research. Upon referral by an Institutional Review Board (“IRB”), the Institutional Animal Care and Use Committee (“IACUC”), the Institutional Biosafety Committee (“IBC”), the JHU School of Medicine Committee on Outside Interests (“COI”), the Reproductive Endocrinology and Infertility Tissues Committee (“REITC”), or the Maternal Fetal Medicine Tissue Committee (“MFMTC”), the ISCRO may review research protocols that the referring committee believes would benefit from such review.

Policies and Procedures

Part One: General Provisions; Standards and Procedures for Review

I. The Authority of the ISCRO

A. Initial Approval
The ISCRO shall have the authority to approve, require modifications to secure approval, or disapprove, all research activities that fall under its jurisdiction (see Policy Statement) for each school or division of the University. Human Stem Cell Research must be submitted to and approved by the ISCRO prior to being initiated. ¹

B. Continuing Oversight

1. Approved Human Stem Cell Research shall be reviewed by the ISCRO every year, or more frequently, as determined by the ISCRO on a case-by-case basis. The principal investigator (“PI”) is responsible for submitting the renewal application in a timely manner as specified by the ISCRO, preferably no later than six (6) weeks prior to the expiration date. PIs will be notified in advance of any specific renewal requirements. Failure to submit the application by the deadline may result in withholding or withdrawal of approval.

2. Renewal applications and Adverse Event Reports pertaining to the ISCRO approved research and submitted to a University IRB, IACUC, IBC, or COI must also be submitted to the ISCRO.

3. The ISCRO has the authority to review and approve, require modifications to secure approval, or disapprove, all amendments to previously approved human stem cell research subject to ISCRO oversight and conducted by the University.  No modifications to the ISCRO approved research shall be implemented prior to ISCRO approval of such modifications, except to the extent a deviation is necessary to prevent imminent harm.  Such deviations must nevertheless be reported to the ISCRO within five (5) days.

C. Monitoring of ISCRO Approved Research
The ISCRO or its representatives shall have the authority to observe and inquire about the conduct of any research activity subject to ISCRO oversight. This function includes the authority to review all records associated with the conduct of the research.

D. Restrictions, Suspension, and Termination of Research

1. The ISCRO shall have the authority to place restrictions on research activities that fall under its jurisdiction. The ISCRO will notify other relevant committees (e.g., IRB, IACUC, IBC, COI, and JHU institutional official(s), as appropriate, of any such restrictions.

2. The ISCRO shall have the authority to restrict, suspend, or terminate its approval of research that is not being performed in compliance with ISCRO requirements, applicable governmental regulations, and/or University policies, procedures, or guidelines. The ISCRO will notify the applicable JHU institutional official(s), as well as other relevant committees (e.g., IRB, IACUC, IBC, COI) of any such suspension or termination.

3. If a JHU sponsor or a JHU researcher (i.e., JHU faculty, staff, trainees, or students acting in their JHU capacity) participates as a co-investigator in research at a site outside the University that would be subject to ISCRO oversight if it were conducted at JHU, the ISCRO shall have the authority to restrict, suspend, and terminate the participation of JHU researchers in the research if that research is not in compliance with ISCRO requirements, applicable governmental regulations, and/or University policies, procedures, or guidelines. In such cases, the ISCRO will inform the responsible institutional official(s) at JHU and, as appropriate, the relevant official at each institution other than JHU involved in the research at issue of the action taken.

E. Review of Research within the Jurisdiction of the ISCRO by Other University Committees or Officials

1. Research requiring ISCRO review ordinarily will be submitted for review and approval by the ISCRO concurrently with submission of the research to any other JHU bodies (e.g., IRBs, IACUC, IBC, COI) that may have responsibility for oversight of other aspects of the research.

2. Research activities approved by the ISCRO may be subject to further review, modification of, approval and/or disapproval by all relevant bodies, such as the IRBs, IACUC, IBC, COI, and the applicable institutional official.  However, those committees and officials may not approve the conduct of research within the ISCRO’s jurisdiction if approval was previously withheld or disapproved by the ISCRO.

3. The ISCRO will make annual informational reports (e.g., number of applications reviewed, number approved, number for which approval was withheld or disapproved, and number involving human subjects) to the JHU IRBs.

F. Principal Investigator Responsibilities
The ISCRO requires that the PI of an ISCRO application must be a faculty member of The Johns Hopkins University who is compensated from the institution (including part time faculty); unpaid adjuncts may not serve as PI.  Others may serve as PI if determined to be appropriate by the ISCRO.

For research awarded to a JHU postdoctoral fellow (such as a Postdoctoral Fellowship award from the Maryland Stem Cell Research Fund), a JHU faculty mentor must submit a JHU ISCRO application as PI.  In this situation, the postdoctoral fellow should be listed as a co-investigator.  The PI must understand and accept the responsibilities and obligations associated with conducting Human Stem Cell Research.  PIs and co-investigators and other members of the research team must comply with applicable laws and regulations and University policies, procedures, and guidelines, and the determinations and requirements of the ISCRO.  PIs are responsible for training all study team members and for conducting the research at the University.

G. Education and Training
All study team members engaged in Human Stem Cell Research at the University shall complete educational activities related to the ethics of such research, as specified by the ISCRO.

II. Conflicts of Interest – ISCRO Co-Chairs, Members, and Consultants

A. Disclosure
ISCRO co-chairs and ISCRO members shall be required to disclose any conflicts of interest prior to the beginning of each ISCRO meeting.  Conflicts of interest include being a listed investigator, having a financial interest in the sponsor of the research or the technology being evaluated, having a conflict as defined by the applicable University or divisional policies on conflict of interest, or otherwise having any other conflict that might reasonably be perceived to inhibit a fair and unbiased review of the research.

B. Abstention from Deliberations and Decision Making
ISCRO members who have conflicts of interest with respect to protocols submitted for ISCRO review will abstain from participation in ISCRO deliberations and decisions relative to those protocols.  They will not be present during voting on such protocols.  However, such members may be consulted on and answer questions related to the research prior to deliberation and voting.

C. Consultants and Conflict of Interest Disclosure
Consultants (as hereinafter defined) shall also be subject to applicable policies on conflict of interest with respect to the study on which they are being asked to consult.

III. Prohibited Research*
In accordance with prevailing ethical and policy guidance and applicable law and regulation, the following categories of research are currently prohibited at JHU:

A. Research involving the introduction of hPSCs into human blastocysts;

B. Research involving the introduction of hPSCs into non-human primate blastocysts;

C. In general, research involving in vitro culture of any intact human embryo for longer than 14 days or until formation of the primitive streak begins, whichever occurs first²;

D. Breeding of animals that have or might have had hPSCs introduced into the germ line; 

E. Using gametes differentiated from human stem cells for in vivo reproduction; 

F. Gestating human stem cell-based embryo models in the uterus of a human or non-human animal; 

G. Gestating human-animal chimeric embryo(s) in the uterus of a human or non-human primate;

H. Transferring embryos following Mitochondrial Replacement Therapy (MRT) into a human uterus; and 

I. Human reproductive cloning³. 

IV. Standards for ISCRO Review
In conducting review of proposed research, the ISCRO will take into account considerations that include, without limitation, the following:

A. Procurement of Gametes, Blastocysts, or Somatic Cells for hPSC Generation⁴
For the purposes of ISCRO review, donors of human materials will be considered human research subjects (per 45 CFR 46), regardless of the context and manner in which the materials are procured.  The oversight of the procurement process, including provisions for informed consent, is under the purview of a properly constituted IRB.  Information about the process will be considered by the ISCRO in its deliberations.

The ethical and legal issues related to Human Stem Cell Research depend in part on the context in which human materials are procured (e.g., infertility treatment, research, clinical care).  The context of procurement may involve established standards such as the following that will be taken into consideration during ISCRO deliberations.

1. Ethical considerations for procurement of human materials in the context of clinical care, including:

a. Plans to ensure that an individual’s decision about donation will not affect the quality of care the individual receives;

b. Plans to ensure that infertility treatment teams will not generate more oocytes than clinically necessary; and

c. In the case of hPSCs derived from fetal tissue, plans to ensure that an individual’s decision about donation is separate from the decision to terminate the pregnancy.

2. Voluntariness of donor consent, including:

a. Plans to ensure that undue inducements will not be provided for donation (e.g., financial or special considerations for services); 

b. Plans to ensure that decisions to donate are made free from undue influence (e.g., the investigator and the attending physician responsible for the infertility treatment are not the same person). 

3. Informed Consent
In addition to the required elements of informed consent specified in 45 CFR 46. 116, the informed consent process and document must disclose the following, if applicable:

a. That procured human materials will be used to derive hPSCs for research that may include research on human transplantation;

b. That embryos will be destroyed in the process of deriving hPSCs;

c. That embryos will not be used to produce a pregnancy and will not be allowed to develop in culture for longer than 14 days from fertilization; 

d. That procured human materials might involve:

i. The introduction of the cells into humans;

ii. The introduction of the cells into the central nervous system of non-human primates;

iii. The introduction of the cells into non-human animals and there is a significant possibility of the cells giving rise to gametes;

iv. The derivation of gametes or embryos;

v. The derivation of organoids; or

vi. The derivation of embryo models.

e. That resulting cell lines will be genetically similar or identical to the donor;

f. That the hPSCs and/or cell lines might be used in research involving genetic manipulation of the cells or the mixing of human and non-human cells in animal models; 

g. That derived hPSCs and/or cell lines might be kept for many years;

h. Whether the donated material will be coded or de-identified prior to research use;

i. If the donors’ identities are retained (even if coded), whether donors can elect to be contacted to receive information obtained through studies of the cell lines;

j. That restricted and/or directed donation (e.g., to individuals or groups) are/is not permitted;

k. That the results of study of the hPSCs may have commercial potential and that the investigator and institution may benefit; however, the donor will not receive financial or any other benefits from any commercial development;

l. That the research is not intended to provide direct medical benefit to the donor(s);

m. That neither consenting nor refusing to donate embryos for research will affect the quality of any care provided to potential donors;

n. Risks to donors.

4. Third-party gamete donors 
Where blastocysts remaining after infertility treatment were created in whole or part with gametes donated by third-parties, procurement of the blastocysts for hPSC research requires informed consent from third-party gamete donors. The consent standards specified in IV.A.3 (above) apply to third-parties who donated gametes for infertility treatment as well as to individuals directly donating human materials for hPSC generation.

B. Transfer of Human Materials from Outside Entities for Human Stem Cell Research
To determine the scientific and ethical integrity of Human Stem Cell Research under its purview, the ISCRO must examine the circumstances under which human materials were (or will be) procured for use in such research and the details of the derivation of cell lines.  Applications for Human Stem Cell Research must include documentation of the provenance of all hESC lines and hPSC lines under ISCRO purview (see Policy Statement), whether the cell lines were imported into the University or derived at Johns Hopkins.  Such documentation must include evidence of IRB-approval of the procurement process, evidence of and adherence to basic ethical and legal principles of procurement, and compliance with applicable laws and regulations and University policies, procedures, and guidelines.

C. Derivation of hESCs
All protocols involving derivation of hESCs must describe:

1. Appropriate expertise of the research team in the derivation or culture of either human or non-human ESCs; 

2. The scientific rationale for the need to generate new hESCs, as well as the basis for the number of blastocysts used in the derivation process;

3. Any plans for compliance with an established set of good manufacturing practices (GMPs), and, if so, with which GMPs; and

4. How any new hESC lines will be derived, characterized, validated, stored, and distributed.

D. Transfer of hPSCs into Non-Human Primates
All protocols involving transfer of hPSCs into non-human primates must describe:

1. Why hPSCs are required in lieu of stem cells from non-human primates or other animals; 

2. Relevant animal work that precedes the proposed work; 

3. Quality control of the cell lines and their derivatives (such as genetic stability, absence of contamination); 

4. The developmental stage of the non-human animal to which the cells will be transferred; 

5. The procedures that will be used to assess whether the animal may acquire cognitive characteristics that are thought of as distinctly human, as well as how non-human primates will be evaluated (pre- and post-transplant); and

6. The procedures that will be used to assess whether the animal’s germline may be affected as well as how non-human primates will be evaluated (pre- and post-transplant).

E. Trials with Humans
All protocols involving trials involving hPSCs with humans must describe: 

1. Relevant pre-clinical testing with animal models;

2. Quality control of hPSC lines and their derivatives (such as genetic stability, absence of contamination);

3. Selection of subjects (e.g., the appropriateness of using healthy volunteers in early human trials); 

4. Risk of infectious disease (e.g., from cells cultured in mouse feeder layers); 

5. Risk of transfer of genetic disorders;

6. Risks of misdifferentiation, incomplete differentiation, mistargeting, tumor formation, and immune rejection; 

7. Risk of uncontrolled cell growth.

F. Privacy
Although the University IRBs and other University bodies have jurisdiction over the confidentiality of the identifying information of human research subjects, there may be cases in which identifying information is transmitted with hPSC lines for research that does not fall under the jurisdiction of any of these groups. Therefore, whenever hPSC research under ISCRO’s jurisdiction involves the transmission of identifying information on donors of gametes, blastocysts, hPSC lines, or somatic cells, protocols must describe any identifying information to be obtained and the steps taken to ensure that the privacy of donors is protected (e.g., how the requirements of HIPAA and any other applicable privacy laws and regulations will be met).

G. Justice
Human Stem Cell Research protocols involving human participants should describe mechanisms for subject selection.  The process for selection among groups and individuals to participate must be fair.

H. Collaboration with Other Institutions
Where JHU faculty, staff, trainees, or students acting in their JHU capacity, collaborate with a researcher at another institution, protocols must describe the oversight and review mechanisms at the other institution to ensure compliance with JHU’s policies, procedures, and guidelines related to Human Stem Cell Research.

V. Confidentiality of Review Process and Records
The review process and the records of the ISCRO will be maintained as confidential in accordance with applicable laws and regulations and University policies, procedures, and guidelines.

Part Two: ISCRO Organization, Responsibilities and Management

I. ISCRO Composition

A. Number
The ISCRO shall comprise at least ten (10) voting members, who shall collectively have adequate training and experience to promote the appropriate review of research activities pertaining to Human Stem Cell Research.

B. Standing Membership
The ISCRO shall include the following members:

1. JHU faculty scientists with relevant expertise (3);

2. JHU faculty ethicists/legal scholars (2);

3. A JHU faculty member with expertise in clinical transplantation (1);

4. A JHU Faculty member with expertise in reproductive endocrinology/infertility (1);

5. JHU faculty co-chairs (2), one with relevant expertise in science and one with relevant expertise in ethics;

6. A non-institutional member (i.e., an individual who has, and whose immediate family members have, no direct occupational affiliation with the University) (1);

7. A representative of the University’s Office of General Counsel, ex-officio/non-voting (1); and

8. A representative of the JHU School of Medicine Office of Research Administration (ORA), ex-officio/non-voting (1).

C. Alternate Members
The ISCRO may include standing alternate voting members to serve in the absence of regular voting members.  Each alternate voting member shall have expertise similar to that of the regular voting member for whom they are serving as a replacement.  The alternate voting member shall assume all of the responsibilities of the voting member for whom they are serving as a replacement.  Alternate voting members may attend ISCRO meetings without serving as replacements for a regular voting member; however, in this capacity, alternate members may not vote.  The co-chairs may appoint a designee to act as chair, in the event neither is available for a convened meeting.

D. Consultants
The ISCRO may consult individuals with special expertise in human stem cell research or with a specific community perspective (“Consultants”), whether internal or external to the University.

II. ISCRO Appointments and Terms

A. Appointment of Co-Chairs
The co-chairs of the ISCRO shall be appointed by and report to the School of Medicine Vice Dean for Research.

B. Term of the Co-Chairs
The term of the ISCRO co-chairs shall be two years, with the option of appointment renewal for additional two-year terms.

C. Appointment of Members
The ISCRO co-chairs shall recommend potential members of the ISCRO to the School of Medicine Vice Dean for Research.
The members of the ISCRO shall be appointed by the School of Medicine Vice Dean for Research in consultation with the JHU Vice Provost for Research.

D. Term of Members
Members will be appointed to a two-year term on the ISCRO.  Initial appointments may be made for one or two years.  Voting members may be reappointed to subsequent two-year terms, depending on the member’s interest and the needs of the ISCRO.  The term of a member appointed to fill a vacancy created by a resignation will end at the time that the former member’s term would have ended.

III. Management and Responsibilities of the ISCRO

A. General Management
The ISCRO shall be managed as determined by the School of Medicine’s Vice Dean for Research and Vice Dean for Clinical Investigation (“Vice Deans”). The Vice Deans shall ensure that adequate facilities, equipment, and resources are available to support the ISCRO.  The Vice Deans shall be responsible for providing an appropriate level of administrative support to the co-chairs of the ISCRO and the ISCRO members.  Management on a day-to-day basis shall be carried out under the direction of the ISCRO co-chairs and administrative/management staff.

B. Overall Responsibilities
The ISCRO shall be responsible for:

1. Providing oversight of JHU faculty, students, trainees, or staff or involving JHU facilities, regardless of the source of funding, who conduct Human Stem Cell Research, as provided in this Policy;

2. Providing consultation to researchers working with and University committees reviewing all types of human stem cells; 

3. Maintaining a database of research protocols reviewed;

4. Maintaining a registry of all ISCRO approved hESC lines;

5. Auditing ISCRO approved research, and restrict, suspend, or terminate ISCRO approval of research determined not to be conducted in compliance with applicable laws and regulations and University policies, procedures, and guidelines; 

6. Reviewing, on a routine basis, current ISCRO policies, and assuring appropriate revisions to these policies as new, applicable laws and regulations and University policies, procedures, and guidelines are implemented; and

7. Developing and disseminating pertinent education and training programs for University researchers involved in the conduct of research that falls under the ISCRO’s jurisdiction.

C. Responsibilities of the Co-Chairs
The ISCRO co-chairs shall lead the ISCRO’s review of Human Stem Cell Research.  In addition, the ISCRO co-chairs shall:

1. Oversee recruitment, training, continuing education, and retention of ISCRO members;

2. Recommend appointment and dismissal of ISCRO members to the School of Medicine Vice Dean for Research;

3. Oversee the ISCRO’s development and implementation of appropriate policies, procedures and guidelines for the conduct of research pertaining to Human Stem Cell Research;

4. Preside over ISCRO meetings and communicate ISCRO questions, decisions, and directives to researchers working in the area(s) that fall under the ISCRO’s jurisdiction;

5. Have authority to request audits of research projects that fall under the ISCRO’s jurisdiction and to notify Institutional Official(s) in the event of any suspension or termination;

6. Represent the University at national and local meetings related to ISCRO activities and the ethical conduct of hPSC research, as appropriate and as resources permit.

D. Responsibilities of the Members
ISCRO members shall:

1. Review and evaluate proposed Human Stem Cell Research in a manner that is consistent with the Policies and Procedures of the ISCRO; and

2. Attend convened meetings, participate in deliberations, and, as applicable, vote. Members are expected to attend at least 80% of all meetings and membership may be revoked if a member is unable to attend a sufficient number of meetings. 

E. Resignation or Termination of Chairs and Members

1. Co-Chairs
The School of Medicine Vice Dean for Research shall have the authority to terminate the appointments of the ISCRO co-chairs.
Resignation of co-chairs membership shall be submitted, in writing, to the School of Medicine Vice Dean for Research and the co-chairs.

2. Members
ISCRO members may be dismissed by the School of Medicine Vice Dean for Research due to a failure of the ISCRO member to attend a sufficient number of meetings, actively participate in ISCRO functions, and/or otherwise fail to uphold the roles and responsibilities of an ISCRO member as provided herein.

Resignation of ISCRO membership shall be submitted, in writing, to the School of Medicine Vice Dean for Research and the co-chairs.

IV.Continuing Education

A. The ISCRO shall maintain a website that includes ISCRO Policies and Procedures, ISCRO approved hESC lines, the online ISCRO application, and a training module.

B. ISCRO members shall be provided education related to the ethical, legal, scientific, and policy issues associated with human stem cell research.

* This list may be revised from time to time to reflect changes in prevailing ethical and policy guidance and applicable law and regulation.

¹ Research already approved by the ISCRO must be in compliance with this revised policy no later than one-year from its implementation date or sooner with any amendments or annual review applications.

² In compelling cases and after consultation with the applicable institutional official(s), such research may be permitted subject to any additional requirements imposed by such official(s) and the ISCRO.

³ Pursuant to Maryland State law, a person may not conduct or attempt to conduct human cloning.

⁴ Contracts, material transfer agreements, or other agreements procuring such materials must be submitted to the applicable research administration office and/or Johns Hopkins Tech Ventures (“JHTV”), as applicable, for review and signature.

Contacts

Policy Clarification and Interpretation
Office of General Counsel
Phone: 410-516-8128
Web Address: https://www.jhu.edu/general-counsel/