Tissue Processing

General Information

What is an Allograft?

An allograft is donated human tissue or bone that has been processed and prepared to aid in the surgical repair of damaged bones, tendons or joints.

Why use an Allograft?

Using allografts eliminates the need for a second surgical site to remove autograft bone or tendons, thus reducing the risk of infection and the pain and/or loss of function from that second surgical site. Allografts come in a variety of sizes, eliminating the guesswork that can come from the size and availability of an autograft. OR time is thereby reduced, as is the cost of the surgery.

Where do Allografts come from?

Allografts come from human tissue donors who have generously donated their bodies so that others may benefit.

Safety & Regulations

Parametrics Medical Commitment to Safety & Quality

The main goal of Parametrics Medical is to ensure the safety and quality of our products. All our procedures meet or exceed the standards set forth by the American Association of Tissue Banks (AATB) and the regulations set forth by the Food and Drug Administration (FDA). Parametrics Medical understands that every donation of tissue is an extraordinary gift that will improve the life of another. We ensure the highest standards in donor selection, beginning at the screening of potential donors, through the release and implantation of donated tissue.

Allograft Testing and Serology:

The following is a break-down of the progression of the tissue testing process:

• 1. Donor Screening
  • Obtain family consent to donate
  • Complete a medical questionnaire about the donor
  • Perform a physical examination
  • Pre-process donor blood and tissue
  • Determine donor eligibility by standards of a medical director
• 2. Tissue Processing
  • Each donor is processed individually to prevent cross-contamination. All processing surfaces are disinfected and rendered aseptic, and additional measures are frequently taken to reduce microorganisms, which may include soaking the tissue in an antibiotic solution.
  • Excess muscle and other extraneous tissue are dissected from the allograft with great care.
  • Osseous tissue is subjected to multiple detergent soaks and mechanical agitation to further decontaminate tissue and remove residual blood or lipids.
  • Large graft segments are processed to a predetermined form, based on size and type of allograft needed.
  • Once the allograft is cleansed and in the desired form, it is frozen, lyophilized (freeze- dried), hydrated, or cryopreserved.
• 3. Post-Processing Testing
  • Throughout the entire processing and packaging of tissue, environmental monitoring is conducted using sampling media to detect any possible microbial contamination. Sterility testing is done for every lot of processed tissue, in accordance with recognized industry standards.
  • Allografts are placed in quarantine, pending results of the final sterility testing. Both the processing department and medical director review final sterility tests. Once the desired test results are achieved, the allografts are moved from quarantine to await inspection by the Quality Assurance Department.
• 4. Post-Processing Inspection
  • Review of processing records
  • Review of inspection records
  • Review of final allograft sterility testing
  • Review of package integrity
  • Review of allograft appearance
• 5. Allograft is released for implantation upon satisfactory test and inspection results

Allograft Sterilization

Definitions

Sterile: The absence of detectable, viable microorganisms.

Sterility Assurance Level: The probability of a single allograft being non-sterile after being sterilized. A sterility assurance level (SAL) of 10^-6 means that there is a 1 in 1,000,000 probability that any bacteria survived the sterilization process. A SAL of 10^-3 means that there is a 1 in 1,000 probability that any bacteria survived the sterilization process. Only two processing methods can achieve SAL of 10^-6: electron beam sterilization or gamma irradiation. Aseptic processing can achieve a SAL of 10^-3.

Terminal Sterility: Sterilized in final packaging and delivered to the OR with a SAL of 10^-6.

Aseptic Non-Irradiated: Aseptic allografts are processed under strict conditions. These allografts are handled in a controlled environment in which the air supply, materials, equipment and personnel are regulated to control microbial and particulate contamination to acceptable levels. This method of processing relies on donor screening, laboratory testing and aseptic techniques to ensure the safety of the allograft. These allografts are typically referred to as non-irradiated.

Electron Beam: Electron Beam technology terminally sterilizes tissue without compromising the biomechanical properties of the collagen, while maintaining the Sterility Assurance Level (SAL) of 10^-6. Allografts processed with Electron Beam technology, undergo sterilization utilizing electrons. The electrons interact with a waveguide in a linear accelerator. The allografts undergo a validated process that subjects them to electrons for a period of seconds, as opposed to gamma irradiation, which typically takes 5-6 hours.

Available Sterilization Options

COLL-E-STRONG^TM: Coll-e-Strong allografts are Parametrics Medical’s trademarked electron beam sterilized tendons. This innovative processing methodology achieves a sterility assurance level (SAL) of 10^-6 without the use of gamma irradiation. Coll-e-Strong grafts provide Parametrics Medical’s best option of sterility, safety, and strength for surgeons and patients.

LO-RAD^TM: Lo-RAD allografts are Parametrics Medical’s trademarked low-dose gamma-irradiated tendons. These allografts are processed with an average exposure rate of 1.25 megarads which is among the lowest level of irradiation on the market. Studies suggest this level of irradiation does not negatively impact clinical results or biomechanical properties. The Lo-RAD processing methodology achieves an SAL of 10^-6.

NO-RAD^TM: No-RAD allografts are Parametrics Medical’s trademarked aseptically processed tendons. No irradiation is used in processing or after packaging. The No-Rad processing methodology achieves an SAL of 10^-3.

Allograft Preservation

Definitions

Preservation: Methods used to maintain the integrity of the tissue grafts for specified periods of time while maintaining their biological potential. There are five methods: fresh, frozen, freeze-dried, hydrated and cryopreserved.

Transit: Tissue storage temperatures must be maintained throughout the mode of transport ensuring the integrity and biological potential of the tissue. Major commercial carriers are used, and grafts are packaged and shipped in validated containers.

Storage: Varies based on the preservation method: Fresh – Refrigerated; Frozen – -40°C or colder; Freeze-dried (Lyophilized) – Room Temperature; Cryopreserved – -40°C or colder; Hydrated – Room Temperature

Reconstitution: The method of restoring a freeze-dried allograft to its original state according to the instructions for use provided within each container.

Fresh (Refrigerated Temperature – Above freezing 0°C to 10°C)

Preservation: Fresh allografts are immersed in nutrient culture medium with antibiotics. This method is used for short term storage only and is intended to preserve viable cells. Fresh grafts have a short-term shelf life.

Transit: Ice packs/blue ice/wet ice is packed around the fresh tissue in Styrofoam boxes to maintain validated, refrigerated temperature during transit.

Storage: Upon receipt, the allograft should have the appearance of floating in solution. (If the liquid appears frozen, the graft should be treated as unusable). Fresh grafts are packaged in plastic jars or pouches with a dual layer of sterility.

When the allograft arrives at the end-user facility, if the surgery is not immediate, remove allograft from the Styrofoam container and place in the refrigerator (NOT FREEZER) until surgery.

Preparation: Rinse the fresh graft to remove excess storage media. Submerge the allograft in sterile solution recommended in the Instructions for Use (IFU), and ensure the fresh graft remains moist prior to implantation.

Frozen

Preservation: Freezing the tissue at a temperature below -40°C is used for preservation of musculoskeletal tissue. These tissues are frozen at uncontrolled rates which does not allow for the viable cells to be maintained.

Transit: The allograft is shipped on dry ice in a validated shipping container to maintain the appropriate storage conditions.

Storage: Allografts are frozen at -40°C or colder up to allograft expiration.

Preparation: Submerge the frozen allograft in a room temperature, sterile, lactated ringer’s bath or similar solution with or without antibiotics.

Note: Solution from a warmer will denature tissues and render them unusable.

Cryopreserved

Preservation: Freezing of tissue at a controlled rate of 1 to 2°C per minute in the presence of a cryoprotectant solution (glycerol) and controlled by a computer with liquid nitrogen vapor as the coolant. This method is intended to preserve cell viability at a higher rate than frozen grafts.

Transit: The allograft is shipped on dry ice in a validated shipping container to maintain the appropriate storage conditions.

Storage: The allografts are cryopreserved with little or no solution and stored at -40°C, or colder.

Preparation: Submerge the cryopreserved allograft in a room temperature, sterile, lactated ringer’s bath or similar solution with or without antibiotics.

Note: Solution from a warmer will denature tissues and render them unusable.

Freeze-Dried (Lyophilized)

Preservation: Freeze-drying is the removal of water from a substance using a vacuum process, which turns the water in its crystalline form to water vapor without it ever passing through the liquid phase. This is very useful for the long-term preservation and storage of tissue. Tissue that is freeze-dried can be stored at room temperature for extended periods as well as transported long distances without the need for dry ice. Rehydration is required before the use of freeze-dried tissue.

Transit: Freeze-dried tissue is packaged to avoid breakage and is shipped at ambient temperatures.

Storage: All lyophilized allografts are maintained at ambient or room temperature unless otherwise specified on the package label.

Preparation: Submerge freeze-dried allograft into a room temperature, sterile, lactated ringer’s bath or similar solution, with or without antibiotics. This should be done as the surgery is beginning so that by the time the surgical site is prepared to receive the allograft, the tissue will be rehydrated.

Hydrated

Preservation: Tissue is suspended in a preservation solution at ambient temperatures.

Transit: Pre-hydrated tissue is packaged in a sterile pouch and is shipped at ambient temperatures.

Storage: All pre-hydrated allografts are maintained at ambient room temperature unless otherwise specified on the package label.

Preparation: Follow instructions for use. Most pre-hydrated tissue is ready-to-use, only requiring a brief soak in sterile solution prior to implantation, or ready for immediate use after removal from sterile packaging.

Storage Conditions for Commonly Transplanted Human Tissue

(AATB standards for Tissue Banking, Current Edition)