Pacific Bio Material Management, Inc.

1. Liquid Nitrogen Storage: Maybe not as cold as you think?
2. Scientists See Progress in FDA Stem Cell Trial Approval
3. Cold Update on Cold Chain Management
4. Novare Biologistics: Expanding Services in Sample Management and BioBanking
5. Industry Profile: George Melashvili
6. About our Sponsors

Liquid Nitrogen Storage: Maybe not as cold as you think?

Literature indicates that the optimal storage condition for maintaining viability and functionality for viable material, such as Peripheral Blood Mononuclear Cells (PBMCs), cell lines and tissue, is in the vapor phase of liquid nitrogen. Although temperature gradations within the vapor portion of a liquid nitrogen freezer are expected, the maximum temperature reached within the unit should remain at or below -140°C.

According to a validation study by BBI Biotech of liquid nitrogen containers used for storage of these specimens, temperature conditions within these vessels can vary widely (as much as 90°C) based on position within a unit, unit age, and type of access opening. Experiments demonstrate that there are several factors contributing to this temperature variation.

Contributing Factors

Previous studies determined that the acceptable temperature for storage of specimens in the vapor phase of liquid nitrogen is at or below -132°C, the Glass Transition Temperature of Water (GTTW). PBMC specimens stored above the GTTW may exhibit increased levels of apoptosis (Cosentino, et al., 2002). Specimen temperature may rise above the GTTW during the retrieval process if the specimens are not stored at or below –140°C. This maximum storage temperature was determined by performing an experiment using mock specimens, thermocouples, and BBI Biotech’s temperature mapping system.

Variations within a Freezer

In another experiment, the researchers examined multiple temperature points within a freezer, at each storage box height, using temperature probes.
Freezer units were chosen for this experiment by age and type of freezer opening. It was found that the type of access opening on the unit directly correlates to the range of temperatures found within that unit.
Two units, both 5 -6 years old, were used for comparison purposes. The whole open -mouthed unit had some temperatures that were warmer than -140°C, whereas the partial open -mouthed unit, manufactured in the same year, was able to maintain temperatures colder than -140°C within the entire unit. This experiment shows a direct correlation between the types of freezer opening to the temperature variation within the unit. The age of the unit may also have an effect on the temperature range exhibited by a unit.

Freezer Age Matters

There are several factors that lead to a liquid nitrogen unit’s ability to maintain proper temperature. BBI Biotech’s data shows that freezers decrease in their ability to maintain optimal storage temperatures at or below -140°C as they age. In addition, freezers manufactured with partial open -mouthed access maintain optimal temperatures more effectively th an freezers manufactured with whole open -mouthed access of comparable age. This data should be a primary consideration for collections where maintaining viability and functionality of PBMCs, cell lines and other viable material is required.

Conclusions

• Viable specimens must be stored in freezers capable of maintaining at or below -140°C to avoid crossing the glass transition temperature of water (-132°C) during the retrieval process.
• Liquid Nitrogen freezers that have a partial open-mouthed maintain lower temperatures than freezers with a whole open-mouthed.
• As freezers age there is an increase in the temperature variation between the top and bottom freezer box location in freezers of the same type.

Scientists See Progress in FDA Stem Cell Trial Approval

ISSCR Cautions Clinical Research Still at an Early Stage

The International Society for Stem Cell Research (ISSCR) shares in the excitement generated by the U.S. Food and Drug Administration's landmark decision to approve the first clinical trials using the products of human embryonic stem cells, yet advises the public to maintain realistic expectations at this early stage.

A milestone for the clinical application of stem cell research, the FDA sanctioned Geron Corporation to begin trials on patients with acute spinal cord injury. The ISSCR reiterates that the Phase I trial will focus on assessing the safety of using these cells in patients, a first step of many in determining whether this treatment can provide therapeutic benefit. Regardless of outcome, the knowledge gained from the trial will provide valuable insight for future studies as researchers continue moving stem cell research into the clinic.

"The go-ahead to test products of embryonic stem cells in patients is an important first step, but only the first step on a very long journey, " said George Q. Daley, immediate past-president of the ISSCR and associate director of the Stem Cell Program at Children's Hospital Boston. "We have so much more to learn about stem cells, and this first trial is only the beginning. We applaud Geron's hard work and diligence getting to this point."

The approval comes after an extensive review process, which echoes the responsible, regulated and external evaluation procedures called for in the ISSCR Guidelines for the Clinical Translation of Stem Cells, released last month.

"This is a great time for stem cell science," said David Scadden, co-chair of the ISSCR Clinical Translation Committee, director of the Massachusetts General Hospital Center for Regenerative Medicine, and co-director of the Harvard Stem Cell Institute. "The FDA has signaled that the safeguards are now in place to begin testing embryonic stem cell therapies. If the White House follows through with lifting restrictions on federal funding, we could see a great flowering of new research and an opportunity to see if these cells can deliver for patients."

Cold Update on Cold Chain Management

The cold chain distribution process is an extension of the cGMP environment that all drugs and biological products are required to adhere to, enforced by the FDA. As such, the distribution process must be Validated to ensure that there is no negative impact to the safety, efficacy or quality of the drug substance.

The cGMP environment begins with any/all things that are used to manufacture a drug substance and does not end until that drug substance is administered to a patient. Therefore, all processes that might impact the safety, efficacy or quality of the drug substance must be Validated, including storage and distribution of the drug substance.

Novare Biologistics: Expanding Services in Sample Management and BioBanking

Novare, the only cGMP compliant bio-repository in the New York area, is expanding its state-of-the-art sample storage, location management and transportation services to include:

• Informed Consent Management – For what purposes can samples be used
• Chain of Custody Management – Sample distribution for approved research
• Clinical Data Management – Web-based research data collection system that meets regulatory compliance requirements for
• HIPAA, Privacy and Security – enabling research by connecting the Phenotype to the Genotype
• Bio-banking Consulting – To assist our clients to assure Regulatory Compliance in Sample Management, through:
  • Infrastructure development
  • Technology solution selection
  • Creation of standard operating procedures and work practices

There is increasing scrutiny of the medical-legal-ethical challenges surrounding human tissue. Novare Bio-Logistics is on the forefront of helping its clients comply with these rapidly emerging regulations.

About Our Sponsors