FDA Warning Letters: How to Navigate FDA’s Website

May 10, 2011

FDA Warning Letter

One of the Many Exhibitors at the
ACRP Conference

FDA Warning Letters, and some thoughts on critical and creative thinking, conclude my reporting from the Global Conference for ACRP – the Association of Clinical Research Professionals – held last week at the Washington State Convention Center in Seattle. During the conference it became apparent that many people, including FDA employees, have a difficult time searching for Warning Letters on FDA’s website. The Warning Letter section is an absolute mess. So I thought I would provide a few simple search tips to help find Warning Letters for GCPs. Unfortunately cGMP Warning Letters are more difficult, but the tips still help. Then I would like to tell you about an interesting session I attended on critical and creative thinking.

When searching for FDA Warning Letters, the link is below, scroll down and choose to “Browse Warning Letters by SUBJECT.” You will be presented with the alphabet. Click on “C” and then scroll down past all the “cGMP” categories until you reach “Clinical Investigator” where you will find the majority of GCP Warning Letters.

FDA Warning Letters

Searching for FDA Warning Letters

They will be listed in alphabetical order. There is a “Sort by:” option. Choose “Letter issued DESC” from the drop down menu. You will then have most of the GCP Warning Letters with the most recent listed first. You can also choose as subjects: Clinical Investigator – Sponsor; Bioresearch Monitoring; IRBs; Sponsor Obligations; and “IDE….” for medical device Warning Letters. There are several ways of listing for each category. You can sort by “Letter Issued DESC” for each category. There are five GLP categories plus Good Laboratory Practices. Go figure.

FDA Warning Letters

There were a number of interesting sessions that I attended at the ACRP meeting. I wanted to tell you about Critical Thinking in a Regulated Environment, because it can be so darn difficult. Kirk Mousley described critical thinking as producing ideas and then evaluating ideas. Citing Iris Verdi he described creative thinking as original, imaginative, and uncommon. He discussed that creative thinking comes through different avenues: it is often a revisement of something that already exists (evolution); a combination of two or more ideas (synthesis); or just a different way of looking at things, asking yourself, “how else can I look at this?”

FDA Warning Letters

How Can I Look at This Differently?

Mousley also discussed the barriers to creative thinking including “not part of an approved process” (SOPs). He noted that the regulatory process itself discourages critical thinking by imposing a “process mentality.” He countered that by suggesting that you build into a process the encouragement of critical thinking. And he pointed out the myth that “every problem can only have one solution or one right answer.” One of the points that I emphasize when doing a root cause analysis of a problem identified during a CAPA process is that you should Always Look for More Than One Root Cause.

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On The Blogroll: The FDA Lawyers Blog discusses a variety of interesting issues including bioequivalence data, litigation tactics, and Victory for Embryonic Stem Cell Researchers.

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FDA & OHRP Hold Regulatory Forum at ACRP Meeting in Seattle

May 1, 2011

FDA OHRP regulatory forum

Jerry Menikoff of OHRP & Jean Toth-Allen of FDA

FDA and OHRP both presented at a Regulatory Affairs Public Forum at the ACRP Global Conference on Sunday, May 1st.Speaking for FDA were Leslie Ball, MD, Director of the Division of Scientific Investigations (DSI) which initiates the majority of Bioresearch Monitoring inspections at FDA. Also from FDA was Jean Toth-Allen, PhD, Biophysicist, Office of Special Medical Programs. Jerry Menikoff, MD, JD, spoke on the panel as the Director of the US Office for Human Research Protection. The Association of Clinical Research Professionals hosted the forum in a setting more reminiscent of a TV game show than a professional panel that was complete with theme music and multi-colored columns highlighting the stage. However the questions posed were the ones on everyone’s minds and the speakers gave some good answers.

Please note that the Plenary Session on the Regulatory Affairs Public Forum was recorded and is available on the ACRP website for free.

One question brought up the issue of sponsor oversight of outsourced clinical trial responsibilities. Toth-Allen said that the sponsor is ultimately responsible for all of the clinical trial responsibilities and only CROs are specifically mentioned in the regulations. She emphasized the need to have SOPs in place covering how they are going to oversee contracts of vendors and what the contracts should cover. Leslie Ball said that DSI had an increased focus on sponsor and CRO inspections.

Dr. Ball said that she thinks sponsors should look at three qualities when selecting vendors:

1. The overall capability of the organization and staff.

2. That contracts clearly point out who is responsible for specific responsibilities.

3. That the sponsor oversees the vendor’s activities while the trial is ongoing.

OHRP FDA regulatory forum in Seattle

When Does FDA Inspect?

Another area of interest was when and where FDA would inspect. Both Leslie Ball and Jean Toth-Allen said that FDA was focusing more on inspections during the actual conduct of the study and not just when a sponsor makes an application to the agency.

Dr. Ball said that with the shift to more sponsor/CRO inspections that FDA inspections were looking at sponsor oversight of ongoing trials. She also said that DSI was developing a risk-based site selection tool that looked at three different levels. First, at the application level, did the application pose certain risks that FDA needed to consider. Then at the trial level, tending to focus on pivotal trials. Then at the site level, were there complaints or a history of non-compliance. She also said that they were looking at data from the application such as the rate of subjects dropping out or very high or very low rates of adverse events.

FDA OHRP regulatory forum

Dr. Leslie Ball, FDA

Dr. Ball also emphasized that FDA looked at what they considered important, specifically data integrity for primary efficacy endpoints or key safety indicators, and oversight by the sponsor. She noted that many things that are routinely listed on a Form FDA 483, Inspectional Observations, such as study drug accountability sometimes didn’t find their way to a Warning Letter that focused on items of significance to the approval of the application.

Another interesting discussion was on the topic of online informed consent forms, which are beginning to appear. Jerry Menikoff said it depended on the nature of the study when an online consent might be appropriate. Jean Toth-Allen spoke of the need for a verification process, that the online consent was given by a real person.

FDA regulatory forum Seattle

Discussion on Electronic Medical Records in
Clinical Trials

Finally the panel discussed electronic medical records (EMRs). All three panelists supported the use of EMRs. Toth-Allen said that if an EMR is used in a clinical trial then the institution needs to provide access to verify the record, that it was not acceptable to for monitors to be told that you can’t see it, which elicited a hearty round of applause from the many monitors in attendance. Dr. Ball noted that there were a lot of advantages to EMRS. “You can actually read them,” she said. She also emphasized that EMRs should have the same criteria for clinical trials, that they should be ALCOA– Attributable, Legible, Contemporaneous, Original and Accurate. She also said that although they may not need to be Part 11 compliant, they did need to have an audit trail so that all changes to the record could be traced.

To view the Regulatory Forum visit the
ACRP Website on the Plenary Sessions

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On the Blogroll: RegBlog on all things regulatory from the University of Pennsylvania Law School. Covers much more than FDA

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On The Blogroll: Applied Clinical Trials Blog discusses,
“It Takes a Village: Recruiting Latino and Hispanic Patients.”


ACRP Meets in Seattle for 2011 Global Conference

April 29, 2011

ACRP Seattle

ACRP Meets in Seattle for 2011 Global Conference

Seattle, WA plays host to the Association of Clinical Research Professionals’ (ACRP) annual Global Conference. ACRP is one of the larger professional organizations focusing on clinical trials and expects 2,000 participants. It will be the first time I have attended their Global Conference and I am looking forward to it. There will be sessions on “Introduction to Imaging in Clinical Trials” and on “Distance-Based Learning for Foreign Study Coordinators.” GxP Perspectives will be there for the entire conference (the pre-conference workshops have already begun) and among the sessions I look forward to is “Comparative Effectiveness Trials.” I am going to try to blog at least twice during the conference on issues I think are of concern to GxP Perspectives readers. If I am super industrious maybe I will blog from the ACRP Global Conference every day.

Here is a new feature that ACRP is offering:ACRP is pleased to announce that for the first time ever, two live-feed Plenary Sessions from the ACRP Global Conference & Exhibition will be broadcast FREE of charge. Join us May 1 for the Regulatory Affairs Public Forum featuring representatives from global regulatory agencies addressing issues facing clinical trials. Join us May 2 for Innovation & Global Health, a discussion by Tachi Yamada, MD, President, Global Health Program, Bill and Melinda Gates Foundation.

For more information visit the ACRP Website on the Plenary Sessions

ACRP clinical trials

Do You Have a Guest Commentary for
GxP Perspectives?

Another highlight will be the May 1st session on “Your Site Doesn’t Need 60 SOPs, But How Many Does It Need?” The speakers are Christine Pierre, RN and Steven Steinbreuck, MPH and the author of a Guest Commentary on GxP Perspectives on Informed Consent Requirements. Remember, I am always looking for a good Guest Commentary. Send me a note and ask me how-

Leave a Comment to Submit a Guest Commentary!

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On the Blogroll: Top 40 Websites (and Tweeters) on the FDA, by FDAZilla (Yes, we made the list.)

Moriah Consultant’s Blog – Commentary by Michael Hamrell, one of the conference speakers
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GxP Perspectives LinkedIn Group

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Conferences: Pharma/Bio Boot Camp on the eTMF on 20-21 May 2011 in Philadelphia


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