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Overcoming Obstacles to Tissue Sterilization Validation: What Manufacturers Need to Know

Feb 21, 2022 | Medical Device Testing, Microbial Identification, Microbiology, Regulatory, Technical Expertise

Sterilization validation is necessary to bring tissue-based products to market. The U.S. FDA requires it, whether the device functions in vivo or in vitro, so understanding how to ensure sterility is critical. When it comes to living tissue, the process carries an even bigger imperative because sterility level could mean the difference between life and death.

A 100% sterile device is neither realistic nor possible, so manufacturers must ascertain and set an appropriate sterility assurance level (SAL) to assess bioburden. SAL measures the probability of a single living microorganism surviving after sterilization, and a SAL of 106 is the acceptable standard. This SAL threshold means no more than one microorganism in one million is present after sterilization. There can be no margin for error when dealing with tissue-based products, so understanding bioburden is mandatory.

Methods of Tissue Sterilization Validation

Sterilization validation requires strict timelines for bioburden testing to verify the proper sterilization method. Tissue is typically sterilized using heat, irradiation, or chemicals, and each requires its own process. Gamma irradiation is a common sterilization method that has a long and successful track record of reducing bioburden. Radiation dosage follows Association for the Advancement of Medical Instrumentation (AAMI) guidelines to reach the lowest SAL.

Electron beam (e-beam) is an alternative to gamma irradiation and has been used for decades to sterilize sutures, gloves, gowns, masks, etc. It is only just starting to be used in tissue sterilization. While researchers cannot sterilize as much material as they can when using gamma, e-beam is a quicker, more cost-effective and eco-friendly option.

When choosing a sterilization method, understanding the modality’s impact on tissue is critical. Researchers must be keenly aware of all factors that elevate the bioburden load of a donor’s microflora when they conduct validation. These factors include:

  • Raw materials used to package or clean the product
  • The location in which the product was processed or collected
  • Seasonal variations present where the tissue was collected

Bioburden Knowledge is Non-Negotiable

Fully understanding bioburden is critical when conducting tissue sterilization validation. Scientists must establish bioburden before they can substantiate a sterilization dose. It requires microbial identification and characterization for aerobes, anaerobes, fungi, spore formers and other organisms. The presence of these elements helps establish bioburden, and a history of successful dose audits will determine the frequency with which they are conducted. Dose audits are small validations required quarterly at first, but the cadence and frequency can vary over time.

It is easy to run amok when measuring bioburden levels simply because dilution or correction factors reduce detection tests’ accuracy. These factors can increase bioburden and result in validation failures. Failures create additional steps which squeeze timelines, so it is essential to establish a clear sterilization protocol from the beginning. This removes uncertainty and makes sterilization methods easier to monitor and ensure the lowest possible SAL.

The dose substantiation study is pivotal in tissue sterilization validation because it determines the minimum level of radiation necessary to achieve the required SAL. Lot testing begins only after the study and SAL are complete. The entire tissue sterilization validation process includes writing a customized protocol for each product, working with a testing laboratory and finding an irradiator. A dose substantiation study can take up to three months, so expect the unexpected when planning deadlines. The timeline could stretch even thinner if there are new tissue products in the process for which bioburden has not been previously established.  

Avoid Timeline Pitfalls

When a sterilization method for tissue-based products is validated, many are then monitored through quarterly dose audits. Success is essential because failing two audits can require revalidation. This adds costly delays that can compromise a product’s release date.

Efficient time management is crucial for tissue sterilization validation. Conservative timelines provide the necessary flexibility when the unexpected occurs. Simply put, the biggest obstacle a manufacturer faces is a tight or poorly planned deadline. Three more obstacles manufacturers must consider include:

  • Sample availability: Tissue samples can be very limited. The time it will take to replace a tissue-based product is completely unknown. These products need to be handled with extreme care.
  • The product: Different tissue types all carry different bioburden levels. Some microorganisms can be resistant to radiation. Tissue types have varying expiration dates after processing. It is essential to know these factors before validation begins.
  • Travel timelines: Recovered tissue products have a shelf life—some are longer than others, but they all expire. Tissue must arrive at its destinations on time and intact. Transportation must be timely, and your laboratory partner should be prepared to receive and begin processing the tissue immediately upon receipt.

Tissue sterilization validation has unforgiving timelines, so manufacturers must anticipate and plan for unforeseen delays. Leave as much time as possible to assure optimal success. Before beginning the tissue sterilization validation process, always work with an experienced and accredited lab testing partner who shares the same goals, values and mindset.

As a global company with operations across Asia, Europe, and North America, WuXi AppTec provides a broad portfolio of R&D and manufacturing services that enable global pharmaceutical and healthcare industry to advance discoveries and deliver groundbreaking treatments to patients. Through its unique business models, WuXi AppTec’s integrated, end-to-end services include chemistry drug CRDMO (Contract Research, Development and Manufacturing Organization), biology discovery, preclinical testing and clinical research services, cell and gene therapies CTDMO (Contract Testing, Development and Manufacturing Organization), helping customers improve the productivity of advancing healthcare products through cost-effective and efficient solutions. WuXi AppTec received AA ESG rating from MSCI in 2021 and its open-access platform is enabling more than 5,600 collaborators from over 30 countries to improve the health of those in need – and to realize the vision that “every drug can be made and every disease can be treated.”

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