Recent ACG FDA Committee Actions
- FDA Advisory Committees: Its Role and How To Contribute
- Accessing Food and Drug Administration resources in clinical practice: A primer for the practicing gastroenterologist
The inner workings of the Food and Drug Administration (FDA) can seem elusive from the realities of the day-to-day clinical practice. For the FDA to accomplish its mission, they have exclusive access to comprehensive and historical clinical trial data and a wealth of outcomes data. These data include the largest claims dataset covering over 227 million Americans, including patient-level data (2). Staying up-to-date with FDA communications is important as gastroenterologists and their patients look for guidance in areas of rapid innovation such as biosimilars(3), fecal microbiota for transplantation(4), and endoscopic bariatric treatments.
Click here for a summary of useful datasets and resources published on the FDA website which can enable gastroenterologists to stay current with regulatory guidance and access valuable FDA resources.
- Biosimilars in IBD: Slides from the 2017 ACG Workshop with the FDA and EMA
On October 23, The U.S. Food and Drug Administration (FDA) released a public bulletin on biosimilar drugs. The FDA has recently approved biosimilar products to treat conditions such as cancer, Crohn’s disease and colitis, irritable bowel syndrome, and more. But what are biosimilars? The FDA continues to roll-out educational materials for providers.
What are the practical implications for GI clinicians prescribing IBD medications?
ACG’s FDA Related Matters Committee hosted a public workshop with the FDA and the European Medicines Agency (EMA) and addressed the question of the practical implications for GI clinicians prescribing IBD medications at the WCOG at ACG 2017. The workshop compared the approval processes of biosimilar drugs in both agencies, with a focus on IBD. The EMA provided some insight from their history of approving biosimilar drugs in IBD. The FDA also provided some practical tips for ACG members and GI clinicians.
Check out the slides here:
Stephen Hanauer, MD
Professor of Medicine
Northwestern University Feinberg School of Medicine
ACG Past President
Sue Lim, MD
Medical Officer Team Leader
Division of Therapeutic Biologics and Biosimilars
Dr. Lim provided an overview of the FDA biosimilar approval process, with a focus on IBD. Click to view her slides.
Joachim Musaus, MD
Rheumatology, Respiratory, Gastroenterology & Immunology
Scientific and Regulatory Management Department
European Medicines Agency
Dr. Musaus provided an overview of the EMA biosimilar approval process, providing some history on EMA’s approval of biosimilars for IBD. Click to view his slides.
Tara Altepeter, MD
Clinical Team Leader
Division of Gastroenterology and Inborn Errors Products
Dr. Altepeter provided a practical overview of biosimilars in IBD and tips for ACG members. Click to view her slides.
- Biosimilars: The Need, The Challenge, The Future: The FDA Perspective (December 2014)
- 2014 American College of Gastroenterology (ACG) and U.S. Food & Drug Administration (FDA) Public Forum: Toward Improving the Quality of Colonoscopy and Evidenced-Based Bowel Preparation
On Monday, October 20th, ACG and the FDA held a workshop at the 2014 ACG Annual Scientific Meeting on clinical endpoints in bowel preparation products.
- ACG workshop with the FDA to review the efficacy in treating symptoms, the role of endoscopy, as well as managing eosinophils count
On October 22, 2012 the ACG FDA Related Matters Committee hosted a public workshop entitled Eosinophilic esophagitis (EoE): What are clinical endpoints for treatment and drug studies?
Joel E. Richter, MD, MACG
Robert Fiorentino, MD (FDA)
Joel E. Richter, MD, MACG, “Natural History of EoE”
Ikuo Hirano, MD, FACG, “Symptom Endpoint – What the Patient Wants”
Evan S. Dellon, MD, MPH, “Role of Endoscopy in Treating EoE”
Nirmala Gonsalves, MD, “Eosinophil Count and Criteria for EoE”
Robert Fiorentino, MD (FDA), “Review of FDA EoE Workshop (Sept 2012)”
Click here for the written transcript.
- How the FDA Manages Drug Safety With Black Box Warnings, Use Restrictions, and Drug Removal, With Attention to Gastrointestinal Medications
- “Feasibility of Mucosal Healing as a Clinically Significant Endpoint in Inflammatory Bowel Disease Clinical Trials”
American College of Gastroenterology and the U.S. Food & Drug Administration Joint Workshop
- The FDA’s Generic-Drug Approval Process: Similarities to and Differences From Brand-Name Drugs
Drug Shortages in Clinical Gastroenterology
- ACG is currently working closely with the FDA to help resolve the drug shortages many GI clinicians and practices are experiencing today.
Radiation and CT Scans
Recalls, Market Withdrawals, and Safety Alerts Important to GI
FDA Alert Regarding Duodenoscope Update From ACG FDA Related Matters Committee Chair Stephen B. Hanauer, MD, FACG
On Friday January 17th, the FDA sent out another safety alert–this time dealing with duodenoscopes, and how failure to correctly reprocess a duodenoscope could possibly result in tissue or fluid from one patient remaining in a duodenoscope when it is used in a subsequent patient–and warning that this can lead to patient-to-patient disease transmission. The FDA recommends that hospitals and endoscopy facilities transition away from fixed endcap duodenoscopes to those with newer design features that facilitate or eliminate the need for reprocessing. FDA continues to work with manufacturers to increase the supply of disposable cap duodenoscopes and the development of other new and innovative device designs that will further minimize or eliminate the risk of patient infection.
Read the January 17th alert regarding duodenoscopes here.
FDA Alert Regarding Lorcaserin Risks From ACG FDA Related Matters Committee Chair Stephen B. Hanauer, MD, FACG
On Tuesday, January 14th, the FDA sent out a safety alert to the public that “results from a clinical trial assessing safety show a possible increased risk of cancer with the weight management medicine Belviq, Belviq XR (lorcaserin).” The FDA is recommending that patients currently taking lorcaserin talk to their doctors about the potential risks that might be associated with the drug, which might include increased risk of cancer.
Read the January 14th alert regarding lorcaserin here.
FDA Recommends Transition to Duodenoscopes with Innovative Designs From ACG FDA Related Matters Committee Chair, Stephen B. Hanauer, MD, FACG
On Thursday, the U.S. Food and Drug Administration (FDA) issued a Safety Communication titled “The FDA is Recommending Transition to Duodenoscopes with Innovative Designs to Enhance Safety.” The FDA has provided an update on the mandated post-market surveillance study results for duodenoscopes used in endoscopic retrograde cholangiopancreatography (ERCP) since issuing the April 2019 Safety Communication. This Communication also provides additional recommendations and updates including the FDA:
- Recommending that hospitals and endoscopy facilities begin transitioning to duodenoscopes with innovative designs that facilitate or eliminate the need for reprocessing.
- Issuing new mandated post-market surveillance study orders to manufacturers of duodenoscopes with disposable endcaps to gather more information and verify that the new designs reduce the contamination rate. Upon completion of the post-market surveillance studies, the FDA expects the labeling on duodenoscopes with disposable endcaps to be updated with contamination rate data.
- Warning health care facilities that adenosine triphosphate (ATP) test strips should not be used to assess duodenoscope cleaning. To date, the FDA has not evaluated them for effectiveness for assessing duodenoscope reprocessing. Manufacturers of ATP test strips are advised to submit data to support the legal marketing of these strips for this use.
- Planning to convene the General Hospital and Personal Use Device Panel of the Medical Device Advisory Committee in late 2019 to further discuss duodenoscope reprocessing.
The FDA is also reminding patients that the risk of infection from inadequate reprocessing is relatively low and patients should not cancel or delay any planned procedure without first discussing with their health care provider.
Read the full safety alert here. ACG will continue to update members on important FDA alerts impacting clinical GI and our patients.
June 22, 2019
FDA: Fecal Microbiota for Transplantation and Risk of Serious Adverse Reactions Due to Transmission of Multi-Drug Resistant Organisms
In June 2019, the U.S. Food and Drug Administration (FDA) raised concerns of bacterial infections caused by multi-drug resistant organisms (MDROs) transmission during fecal microbiota for transplantations (FMT).
Two immunocompromised adults who received investigational FMT developed invasive infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E.coli). One of the individuals died.
FMT used in these two individuals were prepared from stool obtained from the same donor. The donor stool and resulting FMT used in these two individuals were not tested for ESBL-producing gram-negative organisms prior to use. After these adverse events occurred, stored preparations of FMT from this stool donor were tested and found to be positive for ESBL-producing E.coli identical to the organisms isolated from the two patients.
FDA’s recommendation: Patients considering FMT to treat C. difficile infection should speak to their health care provider to understand the potential risks associated with the product’s use.
Healthcare providers must obtain adequate consent for the use of FMT from the patient or his or her legally authorized representative. The consent should include, at a minimum, a statement that the use of FMT to treat C. difficile is investigational and a discussion of its potential risks. FDA is informing members of the medical and scientific communities and other interested persons of the potential risk of transmission of MDROs by FMT and the resultant serious adverse reactions that may occur.
Donor screening with questions that specifically address risk factors for colonization with MDROs, and exclusion of individuals at higher risk of colonization with MDROs. MDRO testing of donor stool and exclusion of stool that tests positive for MDRO. FDA scientists have determined the specific MDRO testing and frequency that should be implemented.
Read the FDA statement here
December 10, 2018
The FDA Provides Interim Results of Duodenoscope Reprocessing Studies Conducted in Real-World Settings: FDA Safety Communication
The FDA issued a safety communication titled “The FDA provides interim results of duodenoscope reprocessing studies conducted in real-world settings” to provide interim results from the ongoing mandated post-market surveillance studies (“522 study”) to inform patients, hospitals and health care facilities of higher-than-expected contamination rates with duodenoscopes after reprocessing.
February 1, 2018
Ocaliva (obeticholic acid): Drug Safety Communication – Boxed Warning Added To Highlight Correct Dosing
The FDA warns that the liver disease medicine Ocaliva (obeticholic acid) has been incorrectly dosed daily instead of weekly in patients with moderate to severe primary biliary cholangitis (PBC). To ensure correct dosing and reduce the risk of liver problems, FDA is clarifying the current recommendations for screening, dosing, monitoring, and managing PBC patients with moderate to severe liver disease taking Ocaliva. FDA is adding a new Boxed Warning, FDA’s most prominent warning, to highlight this information in the prescribing information of the drug label.
As a condition of approval, FDA required the manufacturer of Ocaliva, Intercept Pharmaceuticals, to continue studying the medicine in patients with advanced PBC. These clinical trials are currently ongoing, and FDA expects to receive results in 2023. FDA is adding the additional warnings to the drug label after receiving reports that Ocaliva is being given to PBC patients with moderate to severe liver impairment more often than is recommended in the prescribing information, resulting in liver decompensation, liver failure, and sometimes death. FDA recommends that providers should follow the Ocaliva dosing regimen in the drug label, which is based on calculating a Child-Pugh score in PBC patients with suspected liver cirrhosis before treatment to determine their specific classification and starting dosage. Dosing higher than recommended in the drug label can increase the risk for liver decompensation, liver failure, and sometimes death.
January 30, 2018
Imodium (loperamide) for Over-the-Counter Use: Drug Safety Communication – FDA Limits Packaging To Encourage Safe Use
The FDA announcement cautions “patients and consumers” to use as directed by your health care professional. The alert aims to be curbing over-the-counter abuse. Many ACG members prescribe this for patients, but with consultation with the patient and medical literature. The FDA alert specifically says “patients and consumers should only take the dose of loperamide directed by your health care professionals or according to the OTC Drug Facts label, as taking more than prescribed or listed on the label can cause severe heart rhythm problems or death.”
Important FDA News for GI
How to Obtain Domperidone
On June 7, 2004, the Food and Drug Administration (FDA) warned compounding pharmacies and other companies supplying domperidone that it is illegal to compound and sell domperidone in the U.S. The FDA also issued an ‘import alert’ advising FDA field personnel that they may detain shipments of finished drug products and bulk ingredients containing domperidone. These actions were the result of the Agency’s concern regarding public health risks associated with the use of domperidone.
Although FDA has determined that domperidone should not be compounded or used to enhance breast milk production in lactating women, there are patients with gastrointestinal (GI) disorders, such as severe gastroparesis or severe GI motility disorders, who are refractory to standard therapy and may benefit from the drug. In these circumstances, the FDA recognizes that the drug’s benefit may outweigh its risks.
Please click here to access the IND from the FDA website.
FDA Statement on IND Requirements for FMT – June 17, 2013
On Monday, June 17, 2013 the U.S. Food and Drug Administration (FDA) released a statement on IND requirements for fecal microbiota for transplantation (FMT). Specifically, the FDA announced that it would use discretion in enforcing IND requirements for treatment of refractory Clostridium difficile infection (CDI) by FMT. Please click here to read the statement.
ACG members should also know that the FDA will make a public announcement prior to any decision to re-enforce IND requirements for FMT or prior to other policy changes.
The FDA is also expected to release more formal guidance on FMT in the upcoming weeks.
The College continues to work with the FDA to help streamline this process, as well as the approval process for FMT. This includes drafting recommendations to the FDA, working through the ACG FDA Related Matters Committee as well as the College’s unique “ACG-FDA Liaison Council,” a group that meets with the FDA regularly to discuss issues important to the GI clinician.
What does this FDA announcement mean?
This is a change from the FDA’s guidance earlier this year requiring providers/facilities to obtain an IND for all FMT procedures and use.
- ACG members may interpret this announcement as the FDA allowing the use of FMT for refractory CDI without having to go through the administrative hurdles of obtaining an IND (or even an emergency IND).
- However, physicians/facilities must be able to demonstrate ‘informed consent’ on all FMT procedures where an IND was not obtained; this includes at minimum a discussion regarding the risks of the procedure and full disclosure that the procedure is still considered ‘investigational.’
- While this announcement eases burdens for both research and treatment of CDI, the FDA announcement applies to refractory CDI only. FMT for other research or treatment (IBD treatment) still requires an IND.
What are the risks commonly associated with FMT?
According to ACG physician experts, the most common risks are transient cramping (1-3 days), bloating gaseousness, altered bowel habit (constipation more than diarrhea), and low grade fever for no more than 12-24 hours.
Facilities performing FMT usually include the following risks in patient/donor consent forms:
- While donor-stool is screened and tested prior to the procedures, there may be an unintended transmission of infectious organisms (bacterial, viral fungal, parasitic) as well as an allergic reaction to the donor’s stool.
- There may be enhanced colitis activity in patients with underlying IBD.
- There are complication risks associated with use of a sigmoidscope or colonoscope (facilities use separate consent form).
- FMT is not intended for or an adequate colorectal cancer screening modality.
- The donor may be responsible for certain charges not covered by insurance.
- The donor’s stool and blood will be screened and tested, and the patient will be notified if the donor is ineligible based on the results of these tests. Patients may not know the precise reason for the donor’s ineligibility but the patient will know the list of screenings and tests performed on the would-be-donor’s blood and stool.
How do I complete an IND Form?
The IND form and instructions are below.
IND Form Instructions:
The FDA also provides “emergency use” INDs in certain situations. Please call the FDA at: 301-827-2000 (or the after-hours number at: 866-300-4374).
- Multi-Society Position Statement: Nonanesthesiologist Administration of Propofol for GI Endoscopy
- A glimpse at the future Food and Drug Administration: A summary of the FDA Amendments Act of 2007
Charles E. Brady M.D., Arthur A. Ciociola, Ph.D. and FDA Related Matters Committee
- Tysabri (natalizumab) Injection for IV Use FDA Public Health Advisory and Notification of Product Approval to Companies
- Cimzia Notification of Product Approval to Companies