The article provides an overview of the regulatory requirements regarding the sterility information to be included in the premarket submission. 






The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a guidance document dedicated to the submission and review of sterility information in premarket notification (510(k)) submissions for devices labeled as sterile. The document is intended to provide additional clarifications regarding the scope of information to be submitted, as well as recommendations to be considered by medical device manufacturers applying for marketing approval. The authority also mentions that the guidance document is non-binding, and is not intended to introduce new rules or impose new obligations. Moreover, an alternative approach could be applied, provided such approach is in line with applicable legislation and has been agreed with the authority in advance. 

The document outlines the scope of information to be submitted when applying for marketing approval concerning sterility and pyrogenicity. The guidance also contains references to the FDA-recognized voluntary consensus standards the manufacturers may use when demonstrating compliance with the applicable regulatory requirements. 


Regulatory Background 

The authority acknowledges the increasing number of requests for marketing approval related to medical devices intended to be supplied sterile, while sterilization methods used are different from the usual ones. However, the authority already has sufficient information about some of the novel sterilization methods, so they could be considered to be established. At the same time, the methods and approaches used to ensure the sterility of medical devices are subject to continuous development and improvement, so the assessment methods should be continuously improved as well. Thus, when describing the applicable sterilization methods, the authority uses the terms “novel” and “established”. As further explained by the FDA, novel sterilization technologies carry a substantial risk of inadequate sterility assurance if not conducted properly; consequently, compliance with Good Manufacturing Practice (GMP) for devices sterilized using these technologies should be closely evaluated. The inefficient sterilization process will expose patients to additional risks. Hence, manufacturing facilities conducting sterilization activities should be subject to rigorous inspections to ensure the proper effectiveness of sterilization processes. 

The scope of the document addresses the matters related to 510(k) applications for medical devices intended to be supplied sterile. At the same time, the scope of the guidance does not cover:

  • Sterilizers;
  • Processes based on microbial exclusion, rather than microbial inactivation;
  • Processes intended to sterilize medical devices that incorporate materials of animal origin;
  • Processes that incorporate the use of liquid chemical sterilants;
  • Processes intended to be used by reprocessors of single-use devices, as well as operations with medical devices intended to be reprocessed in healthcare settings. 

The authority also mentions that the existing regulatory framework for sterilization methods used for medical devices is set forth by regulation 21 CFR Part 820. 

Sterilization Methods: Key Points 

As it was mentioned before, all sterilization methods could be divided into the following groups: 

  1. Established Sterilization Methods, which are also divided into two categories, namely: 
    1. Established Category A, which covers the methods that have a long history of safe and effective use as demonstrated through multiple sources of information such as literature, clearances of 510(k)s, or approvals of premarket approval (PMA) applications, and satisfactory QS inspections. Furthermore, the authority mentions that such matters are also addressed in the respective voluntary consensus standards. 
    2. Established Category B includes other established methods which are, however, not covered by the standards, but are still described in detail in numerous sources. The data relating to the actual effectiveness of such methods are already available for the FDA and are sufficient to make regulatory decisions. 
  2. Novel Sterilization Methods are defined as newly developed methods for which there exists little or no published information, no history of comprehensive FDA evaluation of sterilization development and validation data through an FDA-cleared 510(k) or approved PMA for devices sterilized with such methods, and no FDA-recognized dedicated consensus standards on development, validation, and routine control. Thus, this term applies to methods that haven’t been assessed rigorously by the authority. This group includes, inter alia, sterilization methods based on the use of a chemical sterilant, or a combination of chemicals that haven’t been approved by the FDA before. Apart from that, the group also covers methods based on specific processes that haven’t been reviewed properly by the authority. According to the guidance, examples of such methods are high intensity or pulse light, microwave radiation, sound waves, or ultraviolet light.  


Sterilization Information 

The document further describes in detail the scope of information to be included in an application for marketing approval depending on the type of sterilization methods used, as the information the authority expects to receive will differ. 

For instance, the information provided concerning an established sterilization method should include:

  • A description of the sterilization method;
  • A description of the sterilization chamber if not rigid, fixed;
  • The sterilization site;
  • In the case of radiation sterilization, the radiation dose;
  • For chemical sterilants, the maximum levels of sterilant residuals that remain on the device, and an explanation of why those levels are acceptable for the device type and the expected duration of patient contact. 

Apart from the details outlined hereinabove, the manufacturer should provide a detailed description of the way the sterilization cycle is validated, accompanied by references to the respective voluntary consensus standards. 

According to the guidance, the scope of information to be provided in the case of novel sterilization methods should be more substantial. In particular, the information to be provided should include: 

  • A comprehensive description of the sterilization process;
  • The method used to validate the sterilization cycle;
  • The validation protocol; and 
  • The sterilization validation data. 

The authority also mentions that the applicant should provide references to published scientific literature, while the authority reserves the right to request additional information, should it be necessary to assess the effectiveness of the sterilization method subject to review. 

In summary, the present FDA guidance describes an approach the authority applies concerning sterilization methods and evaluation of their effectiveness. The document also highlights the key points related to sterilization that should be addressed in an application for premarket approval. 







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