The new article highlights aspects related to the software used to manufacture patient-matched guides and also biocompatibility-related matters.

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 patient-matched guides to orthopedic implants. The document provides an overview of the applicable regulatory requirements as well as additional recommendations to be considered by medical device manufacturers and other parties involved in order to ensure compliance. At the same time, provisions of the guidance are non-binding in their legal nature and are not intended to introduce new rules or impose new obligations. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the existing legislation and has been agreed upon with the authority in advance.


The scope of the guidance covers, inter alia, aspects related to the software used in the course of the, development of patient-matched guides, which could be proprietary or off-the-shelf. According to the guidance, this software ensures that a pre-operative plan is developed and correctly implemented within the guide design parameter; while adequate software performance testing provides assurance that the software operates as intended to ensure accurate and reproducible results for the compatible implant system(s). In this respect, the authority also refers to a separate guidance document dedicated to the content of premarket submissions for device software functions, which outlines the scope of documentation the authority expects the applicant to submit. 

According to the guidance, an applicant should submit a detailed description of the software used in the course of pre-operative planning and guide design. The authority additionally emphasizes that the above applies to both original products as well as changes to existing products already on the market. Furthermore, changes to the software will require additional validation and verification in line with the respective Design Controls. In certain cases, the changes would trigger new submission requirements. In this respect, the authority refers to a separate guidance document describing the approach to be applied when determining whether a new 510(k) submission is required for the software changes, as well as the one dedicated to the PMA supplement decision-making process. 

The authority also acknowledges that sometimes third-party software could be used in the course of the guide’s design. In such cases, the appropriate requirements related to the use of off-the-shelf software should be followed, including those related to cybersecurity matters for medical devices that require connection to a network when used for their intended purpose. With respect to the latter, the authority encourages the parties involved to follow the recommendations outlined in the guidance document dedicated to the content of premarket submissions for the management of cybersecurity in medical devices. 

Under the general rule, the documentation provided by the applicant with respect to the software used should be sufficient for the authority to assess the way the software is used, its functions, and the risks associated.


Due to their nature, patient-matched guides contain patient-contacting materials; consequently, the characteristics of such materials should be subject to a rigorous assessment from a biocompatibility standpoint. Thus, medical device manufacturers should determine the biocompatibility of any and all patient-contacting materials the device in question contains. Should the composition of the device subject to review be identical to that of a similar device already on the market, the appropriate reference could be provided in order to demonstrate compliance with the applicable regulatory requirements. As it is mentioned by the authority, for some device materials, it may be appropriate to refer to either a recognized consensus standard or to a Letter of Authorization (LOA) for a device Master File (MAF). 

Should the medical device manufacturer be unable to identify a product already placed on the market that has a similar location and duration of contact, as well as the intended use, while also utilizing the same materials, a biocompatibility risk assessment should be duly conducted, with its results to be provided to the authority. As explained by the FDA, the assessment should explain the relationship between the identified biocompatibility risks, the information available to mitigate the identified risks, and any knowledge gaps that remain. Thus, the medical device manufacturer will be responsible for identifying any testing required to address the remaining risks.

In terms of biocompatibility, the authority refers to a guidance document dedicated to the application of International Standard ISO 10993-1, which outlines the types of testing to be carried out in order to  properly address biocompatibility-related matters. As further explained by the FDA, the biocompatibility assessment should include the following endpoints:

  • Cytotoxicity;
  • Sensitization;
  • Irritation or intracutaneous reactivity;
  • Acute system toxicity;
  • Material-mediated pyrogenicity. 

Moreover, since patient-matched guides are sometimes manufactured with the use of additive manufacturing technology, the respective aspects should also be addressed properly when assessing biocompatibility-related matters. Apart from that, it is important to implement sufficient quality control to ensure the materials used do not adversely impact the overall biocompatibility of the product in question. In this respect, the authority refers to the guidance document dedicated to technical considerations for additively manufactured medical devices. 

In summary, the present FDA guidance provides additional clarifications regarding the special considerations related to the software used to manufacture patient-matched guides and also biocompatibility matters to be taken into consideration by medical device manufacturers in order to ensure the safety and proper quality of their products. The document also contains references to other relevant guidance documents addressing specific aspects that manufacturers should familiarize themselves with.

How Can RegDesk Help?

RegDesk is a holistic Regulatory Information Management System that provides medical device and pharma companies with regulatory intelligence for over 120 markets worldwide. It can help you prepare and publish global applications, manage standards, run change assessments, and obtain real-time alerts on regulatory changes through a centralized platform. Our clients also have access to our network of over 4000 compliance experts worldwide to obtain verification on critical questions. Global expansion has never been this simple.