By Mary Waters
Anyone who deals with the FDA should become familiar with the FDA Guidance for Industry and Review Staff Best Practices for Communication Between IND Sponsors and FDA During Drug Development. This Guidance represents FDA’s current thinking on the topic; its purpose is to describe some best practices and procedures for timely and effective communications between you and the FDA.
With the 2012 Prescription Drug User Fee Amendments (PDUFA) ACT, the FDA agreed to develop a dedicated drug development communication and training staff. Within CDER, MATTB’s (Manufacturers Assistance and Technical Training Branch) focus was to enhance the communications between the FDA and Sponsors during product development. Both CBER and CBER agreed to jointly publish this Guidance for industry and FDA review staff, gathered review staff’s suggested best practices, and incorporated input from interested parties to create this Guidance.
FDA Terms to Remember
Shall, must, required: These words or terms convey a statute or regulatory requirement.
Advisable, should, critical, may be appropriate, discourage, encourage, prefer, recommend, suggest, urge: These words or terms mean that something is suggested or recommended, but not required.
Guidance: Not legally enforceable, represent Agency’s current thinking, viewed only as recommendations unless specific regulatory or statutory requirements are cited.
FDA Regulatory Project Managers (FDA RPMs): Collectively, review division RPMs and specific functional area RPMs are referred to as FDA RPMs.
Regulatory Project Managers (RPMs): These RPMs oversee projects, processes, and programs; primary contacts for facilitating timely resolution of technical, scientific, and regulatory questions, issues, or other challenges between you and review teams.
Review Division RPMs: Primary point of contact for communications between Sponsor and FDA during drug development life cycle.
Do’s and Don’ts
• Do obtain authorization from your Sponsor (in writing) if you are an independent consultant before initiating contact with the FDA.
• Do reach out to the next level supervisor (division chief or branch chief) if you encounter challenges in obtaining feedback.
• Do establish a mutually agreeable communication strategy early in the relationship. FDA suggests a preferred method(s) (email vs telephone) and frequency of communications, and/or how to manage information requests (singularly or bundled; daily or weekly).
• Do not contact the FDA reviewers, team leaders, and senior management directly; instead, direct inquiries to the assigned FDA RPM who ensures your requests are communicated to review team members.
• Do not delay in responding to FDA information requests as this can negatively affect you in later development.
Types of Advice that Sponsors Seek
• Clinical pharmacology / pharmacokinetics
• Nonclinical pharmacology, pharmacokinetics, and toxicology
• Product quality
The FDA has stated that complex scientific or technical drug development questions should be directed to the FDA RPMs via either a submission or through the formal meeting request process.
Note, however, the FDA has also stated that their resources are limited, and strongly encourage Sponsors to seek answers first from other resources; or employ an independent consultant for assistance. Using this approach allows for resource conservation involving more complex and/or challenging issues.
General Expectations of Communications
The FDA realizes that timely and effective communication during the IND phase of drug development gives Sponsors information they need to help design studies/trials, in addition to product quality data intended to support future approval of a marketing application.
Note: Safety-related questions will be prioritized higher than routine inquiries.
Sponsors should realize that questions posed as simple or needing clarifying can sometimes be more than “routine”. When questions turn out to be complex and require significant review before an answer can be provided, they end up demanding significant resources and response time. The FDA suggests that these types of questions be posed in more formal situations (meetings/submissions).
Meetings can be formal between the FDA and Sponsors, such as face-to-face, teleconference, or with written response only (WRO). The FDA has written feedback timelines outlined in the PDUFA and BsUFA, as well as the FDA meeting guidances. Feedback from the FDA includes preliminary comments, final meeting minutes, and questions posed in the WRO request.
Submissions made to an IND during its life cycle may involve hundreds of supporting documents which could require variable degrees of review for which communication is needed with the Sponsor. Other submissions have regulatory-mandated timelines (e.g. safety-related submissions) or drug development submissions without a regulatory clock but are critical and may require a new protocol or a protocol amendment. In these instances, communications between the FDA and Sponsor is critical.
Other inquiries received via telephone, email or through a submission without a specific timeline which ask specific questions, the FDA RPM will attempt to acknowledge the communication within three (3) business days of receipt via telephone or email. The acknowledgment will include:
• The response within the acknowledgment time frame;
• The estimated time frame for division response to question(s);
• If questions will involve consultation with other parties, for example, policy questions where legal input is necessary;
• Recommendations to submit a formal meeting request; or
• Recommend that you contact another functional area in the FDA.
You will need to acknowledge receipt of FDA’s request either in writing or in other ways and provide to the FDA RPM an estimated response time.
Best Practices FDA Buzz Words
• Shall, must, require or requirement – these words convey a statutory or regulatory requirement•
• Advisable, critical, important, may be appropriate should consider, discourage, encourage, prefer, recommend, suggest or urge – these words or phrases convey advice, comments, or current FDA thinking.
Since the IND phase of drug development is typically a multiyear process, the FDA recognizes that new data will become available as well as new scientific and regulatory advances changes in clinical practice over time.
There are a number of ways to communicate with the FDA and this Guidance provides in-depth descriptions on each method.
The FDA website contains two pages that provide information for industry:
a) The FDA Basics for Industry web page can be found here:
b) Investigator-Initiated Investigational New Drug (IND) Applications web page includes links to information for investigators about submitting INDs to FDA and can be found here:
HartmannWillner is well versed in communicating with the FDA. In fact, we have completed hundreds of communications with FDA RPMs. If you need advice on how to write a question or want to set up a meeting, we are here to make that happen. Please contact us.