Thank you for joining us for another episode of the Guidance Recap Podcast. The Guidance Recap Podcast provides highlights for FDA guidance documents straight from the authors. My name is Kylie Haskins, and I am the host for today’s podcast. In today’s episode, I am excited to be talking with Rick Wasko, a biologist in CDER’s Office of Study Integrity and Surveillance. He will be sharing some thoughts with us on the newly published draft guidance titled, “Translation of Good Laboratory Practice Study Reports: Questions and Answers.” Welcome, Rick! Thank you for speaking with us today.

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For listeners less familiar with this topic, can you describe the role of the Good Laboratory Practice study report in the pharmacology/toxicology review process and provide some of the reasons that FDA issued this guidance?

Sure. Every year, the FDA receives study reports from all over the world in support of research and marketing applications for FDA-regulated products. Title 21 of the Code of Federal Regulations, Part 58 “Good Laboratory Practice for Nonclinical Laboratory Studies” is more commonly referred to as the FDA GLP regulations.  Thus, studies conducted under these regulations or similar principles for instance, from the Organization for Economic Co-operation and Development (also known as OECD), are referred to as GLP studies.  GLP studies include but are not limited to nonclinical toxicology, safety pharmacology, and device safety studies received by different FDA Centers.

The GLP study report is vital for safety reviews, shedding light on potential safety concerns and toxic effects of FDA regulated products. It helps determine human risks based on nonclinical studies, aiming to pinpoint possible toxicity, set a safe human trial starting dose, and highlight safety monitoring parameters.

Many of the study reports come from non-English speaking countries, and these study reports are translated to English by the sponsor, testing facility, or another contracted entity.

During the review and evaluation of these translated study reports, we have found that the translation practices are inconsistent across the industry with some common areas for improvement identified. A few examples of issues we have seen are:

• The translation of the final study report from its native language to English may not accurately reflect the raw data.
• We have seen inaccurate translations, including misspellings and typographical errors, omissions, mislabeled parameters, different tables from the original report, among other issues.  
• On several occasions, we have seen compliance to the FDA GLP regulations claimed in the translated study report but not within the original signed report.  For instance, the relevant regulation of the country where the study was conducted was listed in the original study report.
• In addition, the practice of signing and dating the translated study report is not consistent and can be confusing.

We developed this translation guidance to provide FDA’s recommendations to hopefully lead to a more consistent approach to the translation process and produce higher quality translated GLP study reports submitted to the FDA.

Let’s get into more specifics about the recommendations provided in the guidance. What expertise is expected of the translator(s)?

We would like to establish expectations for the person who performs the report translation. The translator should possess the education, training, experience, or combination thereof in English and the native language, and should have relevant medical and scientific knowledge. While the translation needs to be performed by a qualified person, it does not need to be performed by a translation service that specializes in translating documents into English.

Why is it necessary to have a translation statement accompany the translated GLP study report?

The translation statement signifies the translator’s obligation and responsibility that the translated study report is a truthful, accurate, and complete representation of the original study report. The translation statement is a separate document from the study report. The statement should be signed by the translator and indicate who performed the translation and the date that the translation was completed.

Translation statements are crucial when provided with translated GLP study reports for several reasons:

• The first reason being accuracy and authenticity: The signed statement from the translator(s) provides assurance that the translated document is an accurate, truthful, and complete representation of the original GLP study report. This is crucial as even minor inaccuracies or omissions in translation could lead to misinterpretation of the data, which could then potentially impact decision-making processes based on these reports.
• The second reason being accountability: The inclusion of the translator's name, affiliation, and qualifications helps to establish the translator's credibility and expertise. This provides a level of assurance about the quality of the translation, as well as accountability if any issues were to arise.
• The third reason being timeliness: The date of the translation is necessary to document when the translation was completed and ensure that the most recent version of the document has been translated.

What are established written procedures for translating GLP study reports?

Importantly, as with other aspects of GLP studies, the sponsor, nonclinical laboratory, or contractor who performs the report translation should have a standard operating procedure (typically referred to as an SOP) for the translation process. The SOP should include requirements for the qualifications of the translator, requirements for the documentation associated with the translation activity, such as the translation statement, verification of the accuracy of the translation, and completeness checks. The purpose of the SOP is to ensure the translated nonclinical data submitted to FDA are reliable.

What are the guidelines for retaining the translated GLP study report?

Although the translation of GLP study reports is outside of the scope of the GLP regulations, title 21 of the Code of Federal Regulations parts 58.190 and 58.195 discuss the requirements for the retention of GLP study records, and FDA recommends that the translated study report be retained with the original study report. In addition, we recommend communications related to the translation should also be documented and retained.

Is it necessary to translate the amendments to the GLP final study report separately from the original report?

Yes, each amendment to the original GLP study report should be translated as a separate document. This will help FDA reviewers compare the translated study report and associated amendments to the original documents written in the native language and ensure that the translated GLP study report is an accurate and complete reflection of the original GLP study report.

Is the translation of GLP study report tables and appendices required?

Yes, the tables and appendices, including contributing scientist reports, should be accurately and completely translated from the original documents. We have seen missing data tables and contributing scientist reports, as well as errors within the tables of the translated study report.  Accurately translated tables and appendices will help to ensure reliable and complete data are submitted to the FDA.

What completeness check is recommended for the translated GLP study report?

The complete translated GLP study report should be reviewed by a second person (such as another individual at the testing facility or sponsor), independent from the translation activities, to check the report format, tables, and figures for completeness. This is to ensure a completeness check is performed by someone who has “a fresh pair of eyes” and whose perspective might more easily identify discrepancies than the original preparer. The review for completeness should be performed on the final version of the translated GLP study report.

Is it necessary for the translated GLP study report to have signatures?

No, in fact we recommend that the translated study report not contain any signatures. The reason for this is because we often see different practices for signatures in the translated study reports. Some translated study reports have no signatures or dates; some contain the typed signatures and dates that appear in the original report; other translated study reports are signed and dated by the Study Director and Quality Assurance reflecting when the original study report was finalized or when the report was translated. These inconsistent practices cause confusion.

The recommendation in this guidance is that the translated study report should contain the typed names of the individuals who signed the original reports such as the Study Director, Quality Assurance and contributing scientists along with the dates listed in the original study report.

Is there a plan to expand the guidance to include other study reports submitted to FDA?

In the future, FDA may update this guidance or issue a new guidance to add questions and answers regarding the translation of other study reports submitted to FDA in support of marketing authorizations as appropriate.

For our final question, what are a couple of key items that you especially want listeners to remember?

The GLP study report is vital for FDA reviewers, shedding light on potential safety concerns and toxic effects of FDA regulated products. It helps determine human risks based on nonclinical studies, aiming to pinpoint possible toxicity, set a safe human trial starting dose, and highlight safety monitoring parameters. This guidance was generated to help sponsors and nonclinical laboratories ensure that the translated GLP study reports are accurate and complete when submitted to FDA to support the safety evaluation. So, I just want to emphasize some key points in this guidance: translation should be performed by a qualified person, a translation SOP should be established and followed, the translated reports should be accurate and complete, and signatures and dates from the original study report should be typed into the translated study report.

Finally, I would like to thank my FDA working group colleagues from CDER, CBER, CDRH, CVM, CFSAN, ORA, and CTP. We had thoughtful discussions during the development of the guidance, which hopefully produced a clear, concise document for our stakeholders to reference.

Rick, thank you for taking the time to share your thoughts on the draft guidance Translation of Good Laboratory Practice Study Reports: Questions and Answers. We have learned so much from your insights on this document. We would also like to thank the guidance working group for writing and publishing this draft guidance.

To the listeners, we hope you found this podcast useful. We encourage you to look at the snapshot and to read the guidance.