Material and Packaging Compatibility in Medical Device Sterilization

When designing medical device products, sterilization should be considered as early in the development as possible to ensure the material challenges of the sterilization process on the product and packaging. AAMI TIR 17:2008 titled "Compatibility of materials subject to sterilization" is a very important reference.

EO is highly compatible with polymer-based, single-use medical devices, procedure kits and surgical trays. PVA, PGA, and PLA is not compatible with EO sterilization.

The Gamma irradiation process can modify polymers, add an ozone odor to the package contents, or cause some discoloring and embrittlement. Gamma irradiation also has undesirable consequences due to the potential production of toxic degradation products such as 4,4’-methylenedianiline (MDA) that can be produced when a high-molecular-weight polyurethane material decomposes as a consequence of irradiation. Polypropylene, PTFE, and polyacetals is not compatible with radiation sterilization.

A good summary of materials which can be used in Gamma ray irradiation is from Steris Company and Nordion.

Sterilization Methods of Medical Device

Sterilization of medical devices plays an important role in the product development although it is not heavily invovled or nealy not involved in academic research in universities. It need to be considered in the earlier stage of prototype development, which can avoid the complex or even failure in the later stage.

Sterilization is defined as a “validated process used to render product free from viable microorganisms.” Terminal sterilization is defined as the “process whereby product is sterilized within its sterile barrier system.” The terminal sterilization process is considered a manufacturing process step itself and usually takes place at, or near, the end of the manufacturing process.

The presence of microorganisms is expressed as a probability. While the probability can be reduced to a very low number, it can never with certainty be reduced to zero. This is why we use the term Sterility Assurance Level (SAL) to express a sterile claim. SAL is the probability of a viable microorganism being present on a product after sterilization. Normally expressed as 10^-n. 10^-3 or a 10^-6 value being used most frequently for sterilization. Common SAL for medical devices is 10^-6.

Sterilization is accomplished principally by radiation, chemical sterilants, steam under pressure, dry heat, and filtration or combinations thereof. General application and method of sterilization can be learned in Wiki. A more detailed Guideline for Disinfection and Sterilization in Healthcare Facilities can be found in Centers for Disease Control and Prevention (CDC)

It is important to distinguish sterilization from disinfection, which does not ensure the same security level and does not necessarily inactivate all forms of microorgan- isms – bacterial spores, for instance. 

A sterile medical device is one that is free of viable microorganisms. For a sterile medical device this can be achieved through:

• A terminal sterilization process
• Sterilization of components, followed by sterile filtration and aseptic filling into a sterilized container
• A combination of chemical/physical sterilization and aseptic processing
 

The choice of the sterilization method for medical devices depends on a number of factors including the type of material used in medical devices, the type of packaging materials (product packaging and final packaging), the number and type of microorganisms involved, and the classification of the item.

Medical Device Exhibitions

Although company website, online searching, and FDA database can provide a lot of information on the medical device company, exhibitions are still traditional and rich sources to learn medical device industry. Main exhibitions of medical devices are:

• Medica and Compamed
• FIME 
• Medtec
• China International Medical Equipment Fair
• Arab Health

More exhibition information can be found: http://10times.com/top100/medical-pharma

Summary on Format of 510(k) Premarket Notification Submission

After reading the FDA guidance for Industry and FDA staff: Format for Traditional and Abbreviated 510(k)s, a good summary on the format of an original 510(k) submission including sections and related regualtions, guidance documents, internet links which can be found in Chapter III of the guidance.

510(k) is a type of premarket submission that is intended to demonstrate that the device to be marketed is at least as safe and effective as a legally marketed device that does not require PMA. A legally marketed device is a device that was legally marketed prior to May 28, 1976, for which a PMA is not required, or a device which has been reclassified from class III to class II or I, or a device which has been found substantially equivalent through the 510(k) process. A legally marketed device is commonly known as the "predicate" device in 510(k).

FDA recommends that 510(k) submission includes the 21 sections preferaly in the sequence below:

1. Medical Device User Fee Cover Sheet (Form FDA 3601)
2. CDRH Premarket Review Submission Cover Sheet 
3. 510(k) Cover Letter
   
4. Indications for Use Statement
5. 510(k) Summary or 510(k) Statement
6. Truthful and Accuracy Statement
7. Class III Summary and Certification
8. Financial Certification or Disclosure Statement
9. Declarations of Conformity and Summary Reports
10. Executive Summary
11. Device Description
12. Substantial Equivalence Discussion
13. Proposed Labeling
14. Sterilization and Shelf Life
15. Biocompatibility
16. Software
17. Electromagnetic Compatibility and Electrical Safety
18. Performance Testing – Bench
19. Performance Testing – Animal
20. Performance Testing – Clinical
21. Othe

Multinational Companies for Contract Sterilization of Medical Devices

Terminal sterilization plays an important role in the development of medical devices. Medical device companies can access to the state-of-the-art sterilization facilities without investing in the equipment or labor required. Contract Sterilizers can be found in the database of FDA Establishment Registration & Device Listing. (Select contract sterilizer in establishment type).

The multinational companies that provide ethylene oxide, gamma ray or E-beam sterilization services in the different countries are:

• Synergy Health 
• Sterigenics
• IONISOS

Their websites have the rich resources to learn sterilization of medical device.