Accreditation Standards



AABB AATB California CLIA
FACT FDA FDA BLA GMP
HTA IND ISO JACIE
Maryland NetCord New Jersey New York
PharmaStem TGA


AABB


AABB is a non-profit international association of organizations and individuals who are involved in transfusion and cell transplantation medicine. The list of AABB Accredited Cord Blood Facilities is on-line and updated regularly. AABB accredited facilities are inspected every two years. The AABB standards are updated on a two year cycle by subject matter experts to reflect the evolving nature of the field.

The AABB was founded in 1947 and is headquartered in Bethesda, Maryland, USA. Over the years they have developed voluntary accreditation standards for various types of blood banks, transfusion services, and laboratories. Originally named the "American Association of Blood Banks", the AABB is now international in scope and just calls themselves "AABB".

AABB accredited cord blood banks must perform the following medical tests upon banking cord blood:

  • - Family: health history
  • - Mother: test for HIV-I&II, Syphilis, Hepatitis B&C, CMV, HTLV-I&II
  • - Cord Blood: test for ABO, Rh, WBC, CD+34, red cell antibodies, bacterial or fungal contamination

When cord blood is released from an AABB accredited bank, AABB requires patient outcome reporting.

It is very important for parents to understand that AABB accreditation does NOT require a specific procedure for processing cord blood. The accreditation imposes quality objectives on the Standard Processes and Procedures but, except in a few instances, is not prescriptive. There is a great deal of variation in the laboratory practices among AABB accredited banks.

As of May 2005, AABB Standards require that the main cord blood collection should be stored with "integrally attached segments" for testing purposes. Most cord 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. By the time those standards became mandatory in January 2007, all the AABB accredited cord blood banks that had been using vial storage had switched to bag systems. However, older collections that were stored in vials are still acceptable for therapy if they are the best option for the patient.

AABB accreditation has been and is currently the standard most often used by family cord blood banks in the US and Canada.




AATB - 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 AABB, they maintain a voluntary accreditation program.

In the United States, for purely historical reasons, human blood and human tissue are regulated differently. The relevant accreditation for cord blood banks is AABB or FACT. 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.




California State License


California State requirements apply to any cord blood bank that collects, processes, stores, or distributes cord blood within California, controls these functions within California, accepts cord blood collections from California, or releases stored cord blood to California. Basically, in order to have any business in California, a cord blood bank must possess a California Biologics License.

The state of California has adopted the AABB Cellular Therapy Standards (current versions) for cord blood banks into their Health and Safety Code. The portions of the Health and Safety code (HSC) that may be relevant to cord blood banking include sections 1600 through 1630. If a cord blood bank also collects portions of the cord tissue, a California tissue bank license is required as well. The relevant HSC for cord tissue banking runs from sections 1635 through 1648. For more information about the California Biologics License, on-line resources provided by the California Dept. of Health include a FAQ and guidelines for a license application.

In late 2010 California passed a law authorizing a state initiative to collect cord blood donations for the benefit of the public health. The effort is run by California's Umbilical Cord Blood Collection Program at UC Davis, which has been setting up contracts with participating cord blood banks starting in late 2012 and continuing through 2014. The California Dept. of Health plays an important role in regulating the quality of these programs.




CLIA - Clinical Laboratory Improvement Amendments


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 that are registered with CLIA 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).




FACT - Foundation for the Accreditation of Cellular Therapy


FACT is a non-profit organization devoted to voluntary inspection and accreditation of cellular therapy facilities. The home page of their web site has a search engine to look up accredited banks by country. For example, here is the USA list of FACT Accredited Cord Blood Facilities. FACT accredited facilities are inspected every three years.

Whereas AABB grew out of the blood banking community, FACT grew out of the medical community. In 1996, FACT was formed as a merger of the separate standards of two medical societies: International Society for Cellular Therapy (ISCT) and American Society for Blood and Marrow Transplantation (ASBMT). Then, in 2004 FACT began to partner with NetCord, an international consortium of public cord blood banks, to administer joint standards and accreditation of cord blood banks. The FACT offices are located at the University of Nebraska Medical Center in Omaha, Nebraska, USA.

Originally, FACT only accredited public cord blood banks. The original FACT Standards required that the cord blood bank must have control over the cord blood collection site, which is only possible when collections are taken from fixed sites by dedicated personnel.

FACT currently accredits both family and public cord blood banks. In family banking, the collection site can be any clinic that delivers babies, and the collection person may be a doctor, nurse, or midwife. Some public cord blood banks have evolved to also accept mail-in donations collected by labor and delivery professionals who have taken an on-line training course. To accommodate this evolution in banking practices, the FACT Standards adopted since 2010 allow for non-fixed collection sites provided that the bank adequately trains the collectors and confirms that the shipping process protects the cord blood.

FACT Standards for family banks allow for a small number of relaxed criteria that take into account differences between family and public banking circumstances. For example, family banks have 72 hours after collection to process cord blood, whereas public banks must process cord blood within 48 hours after collection.

The FACT accreditation process is end-to-end, covering every aspect of cord blood handling from the moment of collection at the site where the baby is delivered, through the cord blood lab, and concluding with patient management at the clinical care site. Because of the emphasis on patient care, transplant physicians review inspection results before a bank is accredited.




FDA - Food and Drug Administration


This topic describes FDA registration, which is required of all cord blood banks that operate in the US. (The FDA license, called BLA, is the next topic.) The section of US federal regulations that gives the FDA authority to regulate cord blood is Part 1271 of the Code of Federal Regulations Title 21, or 21CFR1271. Cord blood falls under the rules for "Human Cells, Tissues, and Cellular and Tissue Based-Products" (HCT/P's).

Prior to 25 May 2005, the FDA only required family cord blood banks to be registered with them, and the list of FDA registered HCT/P establishments is on-line. Since then, the FDA also conducts inspections of family cord blood banks.

The FDA rules are also designed to prevent transmission of communicable diseases. The cord blood must be tested for the following diseases:

  • - Cord Blood: test for HIV-I&II, Syphilis, Hepatitis B&C, CMV, HTLV, CJD & vCJD
  • (Note that this list is almost identical to the maternal testing required by AABB and FACT)

As another safeguard against disease transmission, laboratories which process HCT/P's must follow current FDA standards of Good Tissue Practices.

In July 2012, the FDA posted their first-ever web page of cord blood information for consumers.




FDA BLA - FDA Biologics License Application


This topic describes FDA licensing, which is only required of public cord blood banks, ie. those that collect donations for use by patients outside the donor's family. The BLA requirement became effective in Oct. 2011, but as of Aug. 2012, only three of the public cord blood banks in the US had completed the difficult and expensive licensure process. Those public banks which are not yet licensed are being allowed to continue operations if they are "moving towards" licensure.

Many people who see news reports about the FDA licensure of cord blood banks are confused, and for good reason. Cord blood has been used in stem cell transplants since 1988, and by 2009 there had been over 20,000 cord blood transplants worldwide. From the perspective of hematologists and oncologists, cord blood transplants have become a standard therapy for patients. Yet, despite this long track record, the FDA had never officially approved cord blood transplants as a standard therapy or established a licensing standard for public cord blood banks. As a result, hospitals that provided cord blood transplants had to operate under clinical trial protocols, and some patient's insurance providers would not pay for cord blood transplants because they were labeled "experimental". Hopefully, the establishment of the FDA BLA license for cord blood will encourage more health insurance plans cover it and more oncology treatment centers provide it, so that patients will have more access to this therapy.

The FDA licensing requirements are not intuitive: The FDA operates on the philosophy that human cells are a "biologic product", or in other words a drug, whenever they are given to a person other than the donor. The Biologics License Application "is a submission that contains specific information on the manufacturing processes, chemistry, pharmacology, clinical pharmacology and the medical affects of the biologic product. If the information provided meets FDA requirements, the application is approved and a license is issued allowing the firm to market the product." (from the FDA glossary)

Hence, in plain language, the FDA BLA license requires that the public cord blood banks must operate their laboratories as if they are manufacturing drugs. Some of the requirements are sensible, like detailed requirements for laboratory sterility and for monitoring of batches on the production line (except here every single cord blood collection is a separate batch). But in some ways the drug analogy is not really applicable to cord blood, and that has caused a great deal of grief for cord blood bankers. For example, the FDA requires that each cord blood unit must be labeled with an expiration date. But cells that are cryogenically frozen remain viable for decades, and no expiration date has been scientifically established. Moreover, we do not have the technology to put a label on a unit that is already cryogenically frozen.

The FDA BLA license creates distinctions between cord blood that was stored before versus after the bank's BLA approval. The licensure is not retroactive, so when a public cord blood bank gets a license, it only covers their incoming cord blood collections, and their older cord blood inventory is not licensed. Nonetheless, if a patient needs a non-licensed cord blood unit (for instance if it is the best match to the patient), then it can be shipped for treatment if the hospital has an FDA-approved clinical trial (one that has IND) or if the cord blood was requested via the NMDP, which has a global IND for all their banks.

Another important feature of the FDA BLA license is that it only covers approved indications: a list of diagnoses for which the FDA recognizes cord blood transplants as effective therapy. Not surprisingly, the FDA list lags behind current clinical practice by several years. If physicians want to use cord blood from public banks for treatments that are not on the FDA BLA list, they must do so under a clinical trial IND label, regardless of whether or not the cord blood itself was banked under an FDA BLA license.

Finally, no innovation in cell therapy comes without press releases and marketing. Some (but not all) of the cord blood banks that have obtained their BLA license have given a name to their licensed cord blood "product": the NY Blood Center has named theirs HEMACORD (TM) and Duke Medical Center has named theirs DUCORD (TM). This leads laypeople to think that something new has become available, when it is really just a new label for the same cord blood transplant units that these labs produced before.




GMP - Good Manufacturing Practice


Good Manufacturing Practice for cellular therapy, known as cGMP, are standards that are usually established by the federal government. Hence they may be different in each country, which is why international standards have sprung up, such as JACIE in Europe.

In the US, the FDA establishes GMP standards. The FDA applies GMP standards to drugs and medical devices. The new FDA BLA licensing requires that public cord blood banks to handle cord blood as if it were a drug, and follow the GMP standards.




HTA - Human Tissue Authority


Cord blood laboratories operating in the UK must comply with government licensing requirements administered by a national agency called the Human Tissue Authority. The HTA maintains on-line records of HTA licensed establishments (updated every few months) and HTA inspection reports for licensed establishments. To help clarify their cord blood regulations, on 29 Nov. 2010 the HTA issued a Guidance document for establishments working with umbilical cord blood (30 page pdf).

The development of the HTA regulations goes back over a decade. In the US, human "blood" and "tissue" are regulated differently, whereas in the UK and the rest of Europe they are subject to uniform regulations. Tissue banks in the UK are regulated by the division of the UK Department of Health called the Medicines and Healthcare products Regulatory Agency (MHRA). They issued A Code of Practice for Tissue Banks (33 page pdf) in 2000, and it became compulsory after March 2004. Later in 2004, the Human Tissue Authority or HTA took over regulation of tissues intended for human transplant. The HTA licenses all UK establishments which remove, store, test, process, use or distribute any human cells that will be used to treat patients. Only tissue banks accredited by the HTA may supply tissues for therapy at National Health Service (NHS) hospitals.

The UK code of practice for tissue banks is consistent with EU standards established at the same time. On 31 March 2004 the European Parliament passed Directive 2004/23/EC (11 page pdf) titled "EU-Directive on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells". Compliance with this directive has varied among EU nations, but the UK was one of the first to establish fully compliant regulations.

HTA regulations are intended to ensure that cord blood is collected in a way that minimises risk to the mother and child and preserves the quality of the collection. Several aspects of those regulations are:

  • - The mother must give informed consent for the cord blood collection.

  • - The cord blood must either be collected in a facility that is HTA-licensed, or by a person who is working under a Third Party Agreement with an HTA-licensed bank. So long as the collection specialist is properly licensed, the collection may be performed by a phlebotomist, a doctor, or a midwife.

  • - However, the birthing centre is not obligated to allow a collection specialist hired by the parents to operate on their site.

  • - The complexity of the regulations about who may collect cord blood, and where they may collect, has led to some confusion - even to charges of "illegal" cord blood collections by phlebotomists who had not filed the correct paperwork. In an effort to clarify the rules, the HTA has established a separate web page on cord blood procurement.

  • - HTA-licensed facilities are inspected every two years. During a site visit, the HTA focuses on operational policies and procedures, inspection of premises, review of documentation, and in some cases interviews with staff at the establishment. If the HTA inspection report identifies shortfalls, they will be classified as 'Critical', 'Major' or 'Minor'.

  • - HTA facilities must be able to trace the path of a human specimen through their facility. This ensures that if there is a problem with a human tissue product, it can be traced back to other related batches.

  • - Cord blood can only be imported or exported from the UK under the authority of an HTA license or a Third Party Agreement with an HTA-licensed establishment.



IND - Investigational New Drug


IND status is granted by the US FDA. Via this status, new drugs and therapies that are not yet approved by the FDA can be administered in clinical trials. The IND is usually held by the institution that is sponsoring the trial.

Prior to the FDA BLA licensure of cord blood, US patients could only receive a cord blood transplant at a hospital that had an IND status for a clinical trial. Even today, cord blood that was frozen prior to the FDA BLA can only be released from the bank under an IND. Hence the NMDP, the agency that operates the US national network of public cord blood banks, holds an umbrella IND that covers their network. Also, the NMDP's IND allows them to ship cord blood from US banks to patients overseas, in countries where the treatment center does not have an IND. International banks who have an agreement with the NMDP under this IND may export cord blood to the US for patients whose best match is a unit from another country.

The IND is not required for family use of cord blood.




ISO - International Organization for Standardization


ISO is a very generic quality accreditation which may apply to any business or organization. An ISO accreditation indicates that the organization has well-documented procedures and follows those procedures. The motto of ISO is:

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

Although ISO does not have standards for cord blood banking, many cord blood banks have ISO accreditation on certain aspects of their operations. Here are examples of ISO accreditations that are held by some cord blood banks:

ISO 9001:2008 quality management systems
ISO 13485 medical devices
ISO 15189 medical laboratories
ISO 17025 testing and calibration laboratories




JACIE - Joint Accreditation Committee - ISCT - EBMT


JACIE is a non-profit body established in Europe for the purpose of accrediting providers of cell therapy. The JACIE standards currently apply only to stem cells derived from blood sources such as bone marrow, peripheral blood, and umbilical cord blood. The primary scope of JACIE accreditation is the use of blood-forming stem cells (known as Hematopoietic Stem Cells or HSC) and Therapeutic Cells (TC) to be used for blood diseases and cancers. There is a broader scope for their accredited laboratories, which may or may not include other types of blood-derived cells. The list of JACIE accredited centres can be downloaded.

JACIE was founded in 1998 by two professional societies: the International Society for Cellular Therapy (ISCT) and the European Group for Blood and Marrow Transplantation (EBMT). Since 2002 JACIE has also collaborated with the Foundation for the Accreditation of Cellular Therapy (FACT) to create international standards for providing cell therapy products.

JACIE's stated mission is to promote high quality patient care and laboratory performance through an internationally recognized system of accreditation. JACIE does not accredit cord blood banks. Their accreditation program focuses on transplant centers that administer cord blood (and other blood-derived cells) to patients. The scope of JACIE accreditation for the clinical use of cord blood is the same as FACT accreditation, particularly the end-to-end coverage of both laboratory practices and clinical care. However, their accreditation programs are administered separately.

The JACIE Accreditation Programme was recognized in 2011 by the European Commission under the Public Health Programme as an exemplary project. In January 2012, JACIE launched a survey of the different national regulations relevant to the JACIE Standards, and data for 9 nations has been reported as of summer 2012.




MD - Maryland State License


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

  • - Maryland permit must be renewed on an annual basis.
  • - Maryland requires an inspection. Accreditation by AABB will be accepted in lieu of state inspection.
  • - Bank must meet state specific requirements for personnel.
  • - Bank must meet state specific infectious disease testing requirements.




NetCord


The International NetCord Foundation (NetCord) is a non-profit association of predominantly public cord blood banks. NetCord banks have released more than 10,000 units of cord blood for transplantation in adults and children.

To ensure high and uniform quality of all cord blood units in its inventory, NetCord began collaborating in 1999 with the Foundation for the Accreditation of Cellular Therapy (FACT). New editions of the FACT-NetCord Standards are published at approximately three-year intervals to keep abreast of the latest developments and requirements of high-quality banking. Joint FACT-NetCord inspections of cord blood banks began in 2001. Today the Standards are universally recognized by stem cell transplant programs.

In addition to joint standards and accreditation with FACT, NetCord promotes studies and research on cord blood collection processes, the characterization and preservation of cells, ex-vivo expansion of placental and umbilical cord blood, and quality improvement of blood components for clinical cellular therapy. The collection and analysis of clinical and treatment outcomes data is coordinated with Eurocord and the Center for International Blood and Marrow Transplant Research (CIBMTR).




NJ - New Jersey State License


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

  • - New Jersey license must be renewed on an annual basis.
  • - A separate blood bank license is required for each permanent location of the bank.
  • - 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.




NY - New York State License


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 Collection, Processing, Storage and Distribution of Blood; Subchapter 13: Hematopoietic Progenitor Cells
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.
  • - New York is the only state whose health dept. conducts their own bank inspections. These state licensing requirements are the most rigorous in the nation.




PharmaStem License


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

The company PharmaStem claimed that all cord blood banks were using procedures for which they owned the patent. During the time period 2002 - 2006, PharmaStem attempted to force the family cord blood banks in the US to obtain patent licenses from PharmaStem and pay royalties to PharmaStem. In theory PharmaStem could have challenged public banks too, but hey had little financial incentive to do so. Four of the 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 who fought PharmaStem ran up legal bills, and those banks who signed licensing contracts had to abide by the terms of those contracts even after the patents were overthrown.




TGA - Therapeutic Goods Administration


In Australia, the preparation of stem cells for transplant is regulated by a government body called the Therapeutic Goods Administration. Cord blood banks are considered manufacturers of therapeutic goods, and cannot release cells for transplant in Australia unless they are licensed by the TGA. The TGA mandates compliance with the FACT-NetCord Cord Blood Standards.

Initially, family cord blood banks in Australia were only licensed to release cells for autologous use by the baby from which they came. However, there was no legislation prohibiting the use of privately stored cord blood for siblings, and it was allowed as needed on a case by case basis. Finally, the regulations were amended so that family bank licenses now cover sibling use of the cord blood as well.