Laboratory Accreditation

 AABB (formerly known as the "American Association of Blood Banks") is a non-profit international association of organizations and individuals who are involved in activities related to transfusion and transplantation medicine.   They were founded in 1947 and are headquartered in Bethesda, Maryland.  Originally an "American" association, the AABB is now international in scope and just calls themselves "AABB". 

AABB offers various types of voluntary accreditation.  They have an on-line list of  AABB Accredited Cord Blood Facilities.  Some cord blood banks are not AABB accredited for cord blood, but are instead listed as AABB Accredited Hematopoietic Progenitor Cell (HPC) Facilities.   Technically,  the HPC accreditation is only for adult sources of stem cells, collected from bone marrow or apheresis of peripheral blood, not for cord blood.  

AABB accredited facilities are inspected every two years.  

To some extent, AABB and FACT are competing to be the most prestigious accreditation for cord blood banks.  The private cord blood banks were not eligible for FACT accreditation before 2009 (see the FACT section below), and therefore when you look through a table of family banks and their accreditation, the one that is most common in the United States is AABB.

AABB accredited cord blood banks must perform the following medical tests:
family: health history
mother: test for HIV-I&II, Hepatitis B&C, CMV, HTLV-I&II, Syphilis
cord blood: test for ABO, Rh, WBC, CD+34, red cell antibodies, bacterial or fungal contamination

It is very important for parents to understand that AABB accreditation does NOT require a specific procedure for processing cord blood.  The accreditation is like a quality review of the Standard Operating Procedures (SOP): does the bank have clearly defined procedures, do they follow them, do they maintain accurate records?  It does not mandate what those SOP are, and there is a great deal of variation in laboratory practices among accredited banks.

AABB has always required reporting of patient outcomes when products are released from an AABB accredited bank.

As of 1 May 2005,  AABB updated their cord blood accreditation criteria and required all banks to be re-inspected.  The revised standards now require that the cord blood should be stored with "integrally attached segments" for testing purposes.  Most blood bankers interpret the "integrally attached" criterion as requiring AABB banks to use bags for long term storage, where the tube leading into the bag can have sections crimped to hold integrally attached testing segments.  The new AABB standards became mandatory in January 2007.  By then, those cord blood banks which had been using vial storage had switched to bag systems.  

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The American Association of Tissue Banks (AATB) is a non-profit association of organizations and individuals who are involved in activities related to transplantation of cells and tissues.  They were founded in 1976 and are headquartered in McLean, Virginia.   Like the American Association of Blood Banks, they maintain a voluntary accreditation program.

However, for purely historical reasons, in the United States human blood and human tissue are regulated differently.  The relevent accreditation for cord blood banks is AABB.  The laboratory of a cord blood bank may also hold AATB accreditation if they are also engaged in tissue banking.  For example, sperm banking is considered tissue banking and is eligible for AATB accreditation.

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A cord blood bank must meet these California State requirements if it operates within this state, accepts collections from the state, or releases cord blood units to the state.

Bottom line:  California has legally adopted the AABB standards, therefore a California Biologics License is equivalent to AABB accreditation.

Relevant regulations:

1.   California Health and Safety Code:  Sections 1600-1647
2.   California Code of Regulations - Title 17:  Sections 950-1028 Production and Distributions of Biologics, Licensure.
3.   California Business and Professions Code:  Sections 1200-1327 (Also S 650-657 for billing, S 119 & 125 for license offenses).
4.   AABB Stds for Blood Bank and Transfusion Services - 25th Edition
5.   AABB Standards for Cellular Therapy Product Services - 3rd Edition
6.   Clinical Laboratory Improvement Amendments (CLIA) Regulations
   

Accreditation required: California Biologics License: Product - Hematopoietic Progenitor Cells, Cord Blood

• Initially this license was required for banks that had a permanent location in the state of California. It is now required from out of state banks as well.
• License must be renewed every two years.
  
• California requires an initial inspection; but they will accept accreditation by a private, non-profit accrediting organization approved by the state (i.e. AABB) in lieu of state inspection.
• Repeat inspections occur every two years and are unannounced.
  
• Bank must meet state specific requirements for personnel.
• Bank must meet quality system requirements.

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The CLIA are US federal laws passed in 1988 which apply to any laboratory that performs any patient testing.  They are not a quality accreditation, they are a basic legal requirement.  They are not specific to cord blood banking at all.

Laboratories which are registered with CLIA do get inspected every two years.  The cost of CLIA validation is paid by the laboratory and the program is managed by the US Centers for Medicare & Medicaid Services (CMS).

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The Foundation for the Accreditation of Cellular Therapy (FACT) is a non-profit organization devoted to voluntary inspection and accreditation in the field of hematopoietic cell therapy.  Their offices are located at the University of Nebraska Medical Center in Omaha, Nebraska.  The parent agencies of FACT are:

• International Society for Cellular Therapy (ISCT; founder)
• American Society for Blood and Marrow Transplantation (ASBMT; founder)
• International Society for Hematotherapy and Graft Engineering (ISHAGE; merged with ISCT)
• Netcord international consortium of leading cord blood banks (joined 2004)

In the mid-1990's, FACT coallesced the separate standards of ISCT, ISHAGE, and ASBMT.  In 2004, FACT began cooperating with NETCORD to revise the cord blood accreditation standards.  The first FACT Cord Blood Standards generated in cooperation with Netcord were finalized in Spring 2006, and since then cord blood banks are gradually being accredited under the new system.  As of October 2009, 19 cord blood banks are accredited by FACT, 8 of them in the US, and 28 applications are pending. 

There is a FACT website search engine to check the accreditation status of a given facility or to identify accredited banks in a country or state.

FACT accredited facilities are inspected every three years.

Historically, FACT accreditation was oriented towards public cord blood banks which regularly release units for transplant.  The original FACT standards required the  cord blood bank to have control over the collection site, such as those public banks which have dedicated collection teams working in a limited number of sites.  Private cord blood banks could not apply for FACT accreditation because in family banking the collection site can be any clinic that delivers babies, and the collection person may be a doctor, nurse, or midwife.

Family cord blood banks can now obtain FACT accreditation.  Beginning 20 Jan. 2009, amendments to the FACT Third Edition Standards allow for non-fixed collection sites.  The revisions to account for issues unique to private banking are carried much further in the FACT Fourth Edition Standards, which will be released 1 Jan. 2010 and become effective 31 March 2010.  The Fourth Edition Standards are written in such a way that both public and private cord blood banks must meet the same stringent requirements to achieve FACT accreditation.

The main remaining distinction between FACT and AABB accreditation is that, while AABB primarily inspects the processing laboratory, FACT inspection is end-to-end from the collection site to the clinical patient management, and the inspection team includes a transplant physician.

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The Food and Drug Administration regulates cord blood under the category of  "Human Cells, Tissues, and Cellular and Tissue Based-Products " (HCT/ P's).  The division of FDA which regulates HCT/P's is the Center for Biologics Evaluation and Research (CBER).  The section of FDA regulations pertaining to cord blood is 21CFR1271.  Since 2004, the FDA has formulated a Tissue Action Plan which consists of these 3 rules: 

1. As of 21 Jan 2004, all cord blood banks are required to register with the FDA.  Any cord blood bank which has a laboratory should be on the web page of FDA Registered Establishments.
2. The second rule was published 20 May 2004 and became effective 25 May 2005.  It pertains to donor eligibility.  In the case of cord blood, the donor is the baby.  This rule requires more screening of donors for communicable diseases.  Previous FDA standards only required screening for HIV 1&2 and Hepatitis B&C.  Now cord blood must also be screened for syphilis, CJD, and vCJD,  HTLV, and CMV.
   
3. The final rule establishes FDA standards of current Good Tissue Practice (GTP) for laboratories which process HCT/P's.  This rule was published 19 Nov 2004, became effective 25 May 2005, and is intended to prevent contamination or cross-contamination during the handling of HCT/P's. 
   

These 3 FDA rules only apply to cord blood processed on or after the effective date of 25 May 2005.  The final rule allows the FDA to inspect cord blood laboratories to determine compliance with the provisions of 21 CFR Part 1271.  In the summer of 2009, the FDA began conducting surprise inspections of family cord blood banks.

This finishes the summary of FDA regulations for cord blood which is banked for family use.  When a patient receives cord blood from an unrelated donor, as would be the case with a public cord blood bank, the hospital at which the patient is treated must have a clinical trial registered with  Investigational New Drug status (see the IND section).

Finally, when stem cells from cord blood are manipulated to become part of a drug, they must be processed under GMP regulations, which are summarized below.

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FDA licensing of cord blood therapies is a completely separate topic from FDA regulation of cord blood banks.  As described in the previous section, the regulations for banks are well-defined and have become progressively stricter over time.

To this day (Aug 2009), cord blood transplants (CBT) are still not "licensed" by the FDA, but are given under an "investigational new drug" (IND) status.  In other words, a transplant doctor can only offer patients CBT if the doctor's hospital has an IND.  This is why some doctors do not counsel their patients about this option.  Also, patients' insurance companies sometimes use this loophole to deny coverage for a CBT on that grounds that they are "experimental" therapy.  Clearly, patients would have more transplant options and better reimbursement for them if the FDA would license CBT. 

An amendment to the Stem Cell Therapeutic and Research Act of 2005 required the FDA to report on requirements for licensing cord blood units, within 90 days of the passage of the bill.  That was Dec. 2005, and the FDA has reported on this subject many times since, but CBT are still not licensed.

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Good Manufacturing Practice (GMP) is an FDA standard that is somewhat more strict than their Good Tissue Practice (GTP).  The latest FDA rules (see the FDA section) regulate cord blood as an HCT/P and require cord blood to follow GTP, but not GMP.  The GMP are usually applied to drugs and medical devices, which must be sterile.  Cord blood which is "minimally manipulated" is not sterile.

However, when cord blood stem cells are separated and "manipulated" they fall under FDA guidelines for drugs and medical devices, and must be handled in a lab which follows cellular GMP, or cGMP.  Two examples are: cord blood whose stem cell count has been expanded prior to infusion, or cord blood stem cells which are used as vectors for gene therapy.

A review of FDA guidelines for cord blood was presented at the 9/23/2006 ISCT meeting.

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A cord blood bank must meet these Illinois State requirements if it operates within this state, accepts collections from the state, or releases cord blood units to the state.

Relevant regulation:
Title 77:  Public Health, Chapter I: Dept Public Health, Subchapter d: Lab & Blood Bank, Part 470: Sperm Bank & Tissue Bank Code
Accreditation required: Ttissue bank registration

• Registration must be renewed on an annual basis.
• Bank must meet state specific infectious disease testing requirements.

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Cord blood transplants from unrelated donors are regulated by the FDA under Investigational New Drug status, and therefore public cord blood banks must file an IND application.

Much of the medical community views the IND status of unrelated cord blood transplants as a hindrance to their widespread use for transplant patients who cannot find a matching adult donor.  In April 2005, the Institute of Medicine released a report from the Committee on Establishing a National Cord Blood Stem Cell Bank Program.  Among the key findings of the IoM Report was Recommendation 4.4:

"The Food and Drug Administration should move promptly to establish a system of licensure of cord blood units intended for clinical transplantation. As an interim measure until a licensure process is established, all banks participating in the National Cord Blood Stem Cell Bank Program should operate under an investigational new drug application."

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ISO is a very generic quality accreditation which may pertain to any business or organization.  For example, the US National Aeronautics and Space Agency (NASA) has ISO accreditation.  The motto of ISO (yes, they have a motto) is:

• Say what you do,
• Do what you say
• Be able to prove it

Hence, an ISO accreditation indicates that an organization has well-documented procedures and follows those procedures.  Internationally, many cord blood banks have ISO accreditation.

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A cord blood bank must meet these Maryland State requirements if it operates within this state, accepts collections from the state, or releases cord blood units to the state.

Relevant regulation:
Title 10: Dept of Health and Mental Hygiene, Subtitle 50: Tissue Banks
Accreditation required: Tissue bank permit

• Permit must be renewed on an annual basis.
• Maryland requires an inspection. However the state will accept accreditation by a private, non-profit accrediting organization approved by the state (i.e. AABB) in lieu of state inspection.
• Bank must meet state specific requirements for personnel.
• Bank must meet state specific infectious disease testing requirements.

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A cord blood bank must meet these New Jersey State requirements if it operates within this state, accepts collections from the state, or releases cord blood units to the state.

Relevant regulation:
New Jersey State Sanitary Code; Chapter 8; Section 8:8 Collection, Processing, Storage and Distribution of Blood; Subchapter 13: Hematopoietic Progenitor Cells
Accreditation required: Blood bank license

• A separate blood bank license is required for each permanent location of the bank.
• License must be renewed on an annual basis.
• Bank must be made available for state inspection but no mandatory timeline is imposed.
• Bank must meet state specific requirements for personnel.
• Bank must meet state specific testing requirements (infectious disease testing and sample quality testing).
• Bank must meet quality system requirements.

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A cord blood bank must meet these New York State requirements if it operates within this state, accepts collections from the state, or releases cord blood units to the state.

Relevant regulation:
New York State Health Regulations NYCCR Title 10, Volume A-1, Part 58 Clinical Labs & Blood Banks, Subpart 58-5 Hematopoietic Progenitor Cell Banks
Accreditation required: Tissue bank license

• Initially a provisional license is issued.
  
• License must be renewed every 4 years (or more frequent for provisional license).
• Bank must be made available for state inspection but no mandatory timeline is imposed. Note that an inspection usually occurs during the provisional status, and the permanent license is only granted after successful inspection.
• The state may also change the bank’s status to provisional at any time, usually in response to deficiencies noted during an inspection. Permanent status is then granted after deficiencies are corrected.
• Bank must meet state specific requirements for personnel.
• Bank must meet state specific testing requirements (infectious disease testing and sample quality testing).
• Bank must meet quality system requirements.
• The New York licensing requirements are very rigorous and the permanent license is one of the most difficult state accreditations to earn.
  

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A PharmaStem license is NOT a medical accreditation; it pertains to Patent Law.  It has no bearing whatsoever on the quality of the medical procedures performed by a cord blood bank. 

PharmaStem claimed that all cord blood banks were using procedures which they had patented.  During the time period 2002 - 2006, PharmaStem attempted to force the family cord blood banks in the US to buy patent licenses from PharmaStem.  Four family banks fought PharmaStem: CBR, CorCell, Cryo-Cell, and ViaCord.  All the others capitulated and took out licensing contracts.  Eventually, in 2006 the PharmaStem patents were completely overthrown.  Nonetheless, all the family banks suffered financial losses because of this conflict.  The four banks which fought PharmaStem ran up legal bills, and those banks which signed licensing contracts had to abide by the terms of those contracts even after the patents were overthrown.