CBI is keenly aware of the ethical, regulatory and legal issues surrounding the collection of human biospecimens. Our policy supports our fundamental values with the continuous goal of maintaining the donor’s integrity, autonomy and privacy.

CBI follows a strict internal bioethical policy that can be summarized as follows:

1. All specimens are legally procured within standard of care practices and under the laws and regulations of the country of acquisition and in accordance with the US laws related to use and procurement of human tissue specimens.
2. GCP/HIPAA compliant
3. PHI - All human specimens and relevant clinical data are fully de-identified and suitable for commercial research and development
4. Sites serve as Honest Brokers
5. Full consent and the IEC/IRB approval for prospective collection will be obtained
6. Patients/donors do not receive any form of remuneration for their specimens

LEC/IRB Approval

Collection Protocol is approved by local EC or IRB every 1 to 3 years depending on a site.

Compliance

• CBI conducts and manages collection of the biospecimens in compliance with all applicable laws, statutes and regulations (GCP, FDA, ISBER best practices).
• CBI is compliant with the Health Insurance Portability and Accountability Act of 1996 (HIPAA) and its implementing regulations (45 CFR Part 46 et seq., and Parts 160 and 164).
• Collection sites must follow GCP rules and comply with all ethical regulations of the country in which the samples are collected. All collection sites are accredited medical facilities that are subject to internal hospital regulations as well as regulations of the country of procurement.
• Site Coordinators and Principal Investigator must ensure that the study is conducted in accordance with the principles of Good Clinical Practice. The signed agreement with the sponsor and the investigational plan (SOWl) as provided by the sponsor must follow the country-specific regulations.
• CBI operates in accordance with the Declaration of Helsinki and the principles of ICH GCP. Likewise, our Source Sites provide us documentation that they also comply with Declaration of Helsinki and the principles of ICH GCP. This includes, but is not limited to the 13 points below.

1. Conduct trials according to: Ethical principles from DoH, Consistent with GCP Applicable regulatory requirement(s).
2. Before initiating, weigh risks against benefit (participant and society).
3. Rights, safety, and well-being of trial subjects prevail over interests of science and society.
4. Adequate nonclinical and clinical information on investigational product to support proposed trial.
5. Scientifically sound clinical trial; clear, detailed protocol.
6. IRB-approved protocol (for all studies including cosmetic studies)
7. Medical decisions – responsibility of a qualified physician.
8. Each team member should be qualified by education, training, and experience for his/her trial tasks.
9. Freely given informed consent from every subject prior to participation.
10. Storage, recording and handling of all clinical trial info such that it is accurately reported, interpreted and verified.
11. Protect confidentiality of records; respect applicable privacy and confidentiality rules.
12. GMP manufacturing, handling and storage of IP. Use in accordance with approved protocol.
13. Implement quality systems and procedures to assure the quality of every aspect of trial.

CBI Site Coordinators & Site Management

To insure proper and ethical biospecimen procurement CBI Site Coordinators are assigned to one or more collection sites. Site Coordinators communicate directly with Principal Investigators (PIs) whose responsibility is to recover material of interest and temporarily store it at the hospital storage facility.

CBI Site Coordinators responsibilities include:

1. Conducting regular PI training in proper sample, PHI, and clinical information handling
2. Reviewing SOPs with PIs and other hospital staff involved in the biospecimen collection
3. Conducting unannounced audits of facilities, tissue samples storage facilities and storage files of medical documentation
4. Insuring that each project is well understood by the PIs and other involved staff
5. Providing written Project Descriptions, applicable SOPs and timeframe for completing the project
6. Conducting regular checks and providing regular reports to Sponsor on project progress
7. Insuring proper chain of custody - documentation of the chronological movement of samples from the time of collection through shipment, receipt, possession, handling, processing, analysis and final storage.
8. Insuring safe and well documented shipment of all biomaterials to the CBI Sorting Facility in Maryland

Honest Brokers

Honest Brokers are Principal Investigators at Source Sites acting on behalf of CBI to collect and provide health information to Site Coordinators in such a manner that it would not be reasonably possible for the Site Coordinators or others to identify the corresponding patients directly or indirectly. The Honest Broker cannot be a Site Coordinator. The information provided to the Site Coordinators by the Honest Broker may incorporate linkage codes to allow for information collation and/or subsequent inquiries (i.e., a “re-identification code”). However, the information linking this re-identification code to the patient’s identity must be retained by the Honest Broker and subsequent inquiries are conducted through the Honest Broker.

Informed Consent

Obtaining Informed Consent is a critical part of our Biospecimen Procurement and Handling Policy.

The following is a summary of our most important policies related to Informed Consent:

1. Securing informed consent directly from donors or next-of-kin is conducted before any collection or study-related procedure takes place.
2. Informed consent must be prospectively obtained from the participants or their legally authorized representatives. Information must be conveyed in understandable language.
3. Subjects must be given sufficient opportunity to consider whether they want to participate.
4. Consent must be given without coercion or undue influence.
5. Subjects will not give up legal rights or be given the impression that they are being asked to do so.
6. Information provided to donors from whom samples are acquired must make it clear that:
   1. the donation is voluntary
   2. samples of surplus surgical tissue and/or biofluids (such as blood, urine, etc.) will be collected for research purposes only.
   3. personal information (name, date of birth, etc.) associated with these samples will be coded.
   4. the samples will be used for various tests for research purposes, and may be stored for an unspecified period of time for future studies
   5. the samples and data may be used by commercial companies and third parties
   6. prospective donors have the right to withdraw consent without any consequences
   7. the samples are a gift and donors shall have no intellectual property rights or financial gain from any inventions or products derived from use of their specimens
   8. steps will be taken to protect their personal identity
   9. specific types and quantities of samples and data to be collected will be itemized.
   10. collection procedures may include possible risks, inconveniences and sides effects for the donor. These risks will be explained to the donor’s satisfaction prior to consent.

Protected Health Information (PHI)

Throughout the project demographic and clinical data associated with the donors medical record move through several levels of de-identification before being received by the Sponsor.

Level 1 - Principal Investigator on site. To the PI the data is not de-identified. Since the PI is the physician who is personally involved in treating the patient, the PI will code the data and de-identify it. In this case PI acts as Honest Broker (discussed above)

Level 2 - CBI Site Coordinator. To the Site Coordinator the data is anonymised (i.e. direct identifiers have been removed from the information rendering it impossible to identify the individual. If samples and data are not fully anonymised then they are considered traceable to an individual, ie. coded)

Level 3 - CBI Project Manager. For all intents and purposes the data at this level is fully de-identified (direct identifiers have been removed from the information rendering it impossible to identify the individual without the use of extreme and inappropriate efforts.

Level 4 - CBI Sponsor - the end user. At this point the PHI is 4 steps removed from the patient and it is absolutely impossible to be traced back to the donor by any means other than contacting CBI Project Manager, who will have to trace it all back to CBI Site Coordinator and then PI.

It’s important to note that if additional information is requested by the end user, it is possible to trace all coded identifiers back to the patient and collect additional clinical or other data. This information will also come de-identified to the Sponsor and donor’s PHI will be safely protected.

De-identification Standard (as stated in U.S. Department of Health & Human Services)

The following identifiers must be removed:

1. Names
2. All geographical identifiers smaller than a state, except for the initial three digits of a zip code if, according to the current publicly available data from the Bureau of the Census: the geographic unit formed by combining all zip codes with the same three initial digits contains more than 20,000 people; and the initial three digits of a zip code for all such geographic units containing 20,000 or fewer people is changed to 000
3. Dates (other than year) directly related to an individual
4. Phone numbers
5. Fax numbers
6. Email addresses
7. Social Security numbers
8. Medical record numbers
9. Health insurance beneficiary numbers
10. Account numbers
11. Certificate/license numbers
12. Vehicle identifiers and serial numbers, including license plate numbers;
13. Device identifiers and serial numbers;
14. Web Uniform Resource Locators (URLs)
15. Internet Protocol (IP) address numbers
16. Biometric identifiers, including finger, retinal and voice prints
17. Full face photographic images and any comparable images
18. Any other unique identifying number, characteristic, or code except the unique code assigned by the investigator to code the data

Monitoring

CBI is responsible for setting up, monitoring and closing out all studies with full documentation. As a part of the monitoring process, an audit of case report forms against de-identified patient records may be requested; the principal investigator must agree to facilitate the access to and review of the required documents.

Source Site auditing is conducted by the CBI Site Coordinators as discussed above.