Enhancing FDA’s Evaluation of Science to Ensure Chemicals Added to Human Food Are Safe (Pre-Workshop Materials)
Pre-Workshop Materials

DEVELOPING AND REVIEWING TEST GUIDELINES

Round 3 of the small group discussions will focus on developing and reviewing test guidelines. These guidelines establish the objectives, general design and endpoints of guideline-based studies. When FDA determines that a test method has been validated and provides useful understanding of the safety of a food additive, it includes the protocol in its Redbook guidance and explains how it should be used. Once this is done, food manufacturers, expert panels and consultants conducting their own safety assessment or preparing a petition to FDA are expected to conduct guideline-based studies consistent with the guidance.
While FDA is our priority, we also want to keep in mind the other organizations that review and approve relevant test guidelines. The most important are the Organisation for Economic Co-operation and Development (OECD) and, to some extent, the Joint FAO/WHO Expert Committee on Food Additives (JECFA).

FDA’s presentation at the end of Day 1 and its document on the Redbook in the back of the binder should help you better understand how it reviews and approves test guidelines. The panel presentation on alternative methods to animal testing at the beginning of Day 2 should provide insights into how the system handled a new set of test guidelines.

In Round 3, we are continuing to expand our focus, moving stepwise from specific endpoints in Round 1 to study design in Round 2 and, now, to the incorporation of new or improved study designs into FDA’s guidance. Unlike Rounds 1 and 2, we will not focus on a handful of hot topics. In this round, we want to look broadly at all aspects of the issue. To make the discussion more productive, we have divided the issue into two parts:

1. Developing test guidelines for review: How are new or improved draft test guidelines developed, validated, funded and submitted to FDA (or another organization) for its consideration?
2. Reviewing and approving test guidelines: How does FDA (or another organization) review, manage and approve new or improved draft test guidelines?

Given the breadth of the topic and the importance of having small enough groups to ensure that all participants will be heard, we will have two small group discussions going on simultaneously in each of these two parts.

All groups should also consider whether implementing a step-by-step procedure following the OECD model would be useful and practical under FDA’s Good Guidance Practices, and which steps can be taken to make these procedures efficient.

BACKGROUND

The Redbook is an FDA Level 1 guidance document under 21CFR 10.115 Good Guidance Practices. At 21 CFR 10.115, FDA describes the procedures to participate in the development of guidance documents. Any person, institution, stakeholder or agency can

1. Provide input on guidance documents
2. Suggest areas of guidance development
3. Submit drafts of proposed guidance documents
4. Suggest revision or withdrawal of any guidance document.

Once a year, FDA publishes in the Federal Register a list of possible topics for future guidance document development or revision. Before and after preparing a draft for a new Level 1 guidance document like the Redbook, FDA seeks public comments in response to the notice, reviews them and incorporates them into the final guidance document as appropriate.

OECD has defined procedures for the creation of new guidelines and updating of current test guidelines under the Test Guidelines Program; these procedures are described in “Guidance Document No. 1 for the Development of OECD Guidelines for Testing of Chemicals.” See Figure 2 for a flowchart of the procedures.

Governments, industry, public interest groups, the scientific community, the European Commission or the OECD Secretariat can submit proposals to develop or update test guidelines. The submission form contains a detailed description of the project and supporting documentation (such as regulatory need, validation status, relevance and reliability) and describes the work plan (deadlines, deliverables and milestones). OECD guidelines and documents are available at no charge online.

The information provided at the time of proposal submission describes

• foreseen or existing regulatory need for such a test (or update)
• contribution to international harmonization of data requirements
• scientific arguments indicating the importance of the test or the modifications
• animal welfare considerations indicating the advantages of the proposed test/procedure with respect to animal use/discomfort without loss of essential information
• a rationale indicating the advantages of the proposed test/procedure with respect to reduced costs without loss of essential information
• supporting documentation; e.g., on the performance of the test method, validation status, or the reliability and relevance of the method.

Read Full Section: Small Group Discussion Round 3 (PDF)