The new article highlights the aspects related to the scope of information to be documented in the context of pathology peer review.

The Food and Drug Administration (FDA), the US regulatory agency in the sphere of healthcare products, has published a guidance document dedicated to pathology peer review in nonclinical toxicology studies. The document is non-binding in its legal nature, nor is intended to introduce new rules or impose new obligations, but rather to provide additional clarifications regarding the applicable regulatory requirements, as well as recommendations to be taken into consideration by medical device manufacturers, study sponsors and other parties involved in order to ensure compliance thereto. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the underlying legislation and has been agreed with the authority in advance.

The guidance itself is structured as a Questions-and-Answers document addressing the most important questions raised by the industry with respect to the existing regulatory framework.

Documenting the Review 

As it was mentioned in the previous article, the authority pays special attention to the way a pathology peer review should be documented. In particular, the authority additionally emphasizes the importance of ensuring that the related processes are duly documented. According to the guidance, when either a contemporaneous or a retrospective pathology peer review is part of a GPL toxicology study, the activity should be included in the study protocol or protocol amendment; the process should be guided by written procedures to establish the extent of the review and ensure the integrity of the study data. The authority also mentions that due to the fact the respective professional will be responsible for all the relevant data, the pathology report will reflect the study pathologist’s best scientific opinion and judgment regarding the diagnoses and pathological interpretations. 

As further explained by the FDA, the aforementioned review should be properly planned, performed, and documented. Furthermore, it should be subject to reporting in accordance with the respective regulatory requirements. The authority additionally emphasizes the importance of ensuring the appropriate written procedures are duly communicated to the healthcare professionals involved in the study itself. 

Based on the results of a peer review, a responsible person will have to prepare a peer-review statement to be included later in the final study report. The said statement should be signed and dated by the person responsible for the review. According to the guidance, the following details should also be included:

  • Who performed the peer review and the date(s) it was performed;
  • Whether the peer review was performed contemporaneously or retrospectively;
  • Whether the peer review was conducted in compliance with GPL regulations;
  • What tissues were examined microscopically, corresponding animal identification number, dose/treatment group, and the basis for their selection;
  • What format (e.g., glass slides or whole slide images) was used;
  • Whether the terminology, diagnoses, and interpretations used in the pathology report were agreed upon by both the study and peer-review pathologist(s);
  • Whether a narrative report prepared by the study pathologist was reviewed either prior to or during peer review (for contemporaneous review only);
  • What data and documents were utilized during the peer review (a listing). 

The authority also mentions that in case the pathologist conducting the peer review agrees with the conclusions made by a healthcare professional conducting a study itself, there will be no need to include a comprehensive analysis of the outcome. In such a case, it will be sufficient to include wording confirming that the peer review has been performed and that its results are in agreement with the results of the initial investigation. The FDA additionally emphasizes that any differences identified should be subject to a rigorous assessment. 

It is also important to mention that in case the pathologist conducting the study would decide to make changes to the diagnoses and interpretation based on the results of a contemporaneous peer review, these changes are not subject to documenting requirements related to the study pathology report. At the same time, the changes introduced based on a retrospective peer review should be duly documented.

Site Compliance with GLP Requirements 

Another question described in the guidance addresses the situation when a pathology peer review takes place at a site that does not have an established quality system as required under the GLP regulations. As explained by the authority, this is allowed under the applicable regulatory requirements, provided the integrity of the study is protected. Moreover, the said circumstances should be duly reflected in the respective protocol of the study, as well as in the final report, together with the details of the peer-review pathologist(s), including the name, affiliation, and work address. Apart from that, the details to be documented include the qualifications of the pathologist(s).


Other Aspects 

The guidance also provides answers to other questions that could be important for the industry in the context of peer review. In particular, the authority provides the following clarifications: 

  • The peer-review statement for a contemporaneous review can be signed by the peer-review pathologist before or after the study pathologist’s report is signed;
  • The signed peer-review statement should be included in the final study report;
  • The pathology report is the responsibility of the study pathologist and reflects that individual’s diagnoses and interpretations. 

In summary, the present FDA guidance provides an overview of the existing regulatory requirements in the sphere of pathology peer review in nonclinical toxicology studies in the form of a questions-and-answers document highlighting the key points that could be important for the parties involved. By the virtue of the guidance, the authority outlines the scope of information and details to be duly documented. 



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.