Alexander, Murray Seek Answers Following Contamination that Led to Indefinite Shutdown of National Institutes of Health Facility

WASHINGTON, D.C., June 5 – Senate health committee Chairman Lamar Alexander (R-Tenn.) and Ranking Member Patty Murray (D-Wash.) are seeking answers from Health and Human Services Secretary Burwell today, following news that at least six patients at the National Institutes of Health (NIH) Clinical Center received injections in April from an NIH-manufactured batch of albumin that contained contaminated vials.

News of the contamination was released yesterday by NIH, following a Food and Drug Administration (FDA) inspection last month that found serious problems at the NIH Clinical Center’s Pharmaceutical Development Section (PDS), which manufactures and manages drugs used to treat patients at the NIH Clinical Center.

“Because of the problems discovered during a recent inspection by the Food and Drug Administration (FDA), NIH has been forced to take the extraordinary step of suspending operations at PDS indefinitely,” the senators write in a letter to Burwell. “We request a prompt and detailed explanation of what went wrong and what is being done to address the situation and ensure the safety of patients receiving treatment at the Clinical Center.”

Problems discovered in the FDA inspection included physical design flaws in NIH’s recently renovated facility, improper cleaning and design protocols, insufficient employee training and quality control, and other instances of noncompliance with current manufacturing practices.

“NIH reported that it is suspending operations at PDS, preparing a corrective action plan, monitoring affected patients, seeking alternative sources of products for patients currently engaged in research protocols, and will be appointing an outside group to review NIH’s practices and to make recommendations,” the senators continued in the letter. “But these corrective actions—which may put patients’ treatments and critical research at risk while PDS’s operations are suspended—never should have been necessary in the first place.

“It is unacceptable that a facility that operates within the Department of Health and Human Services (HHS)—and holds itself out as a “[m]odel of excellence —has jeopardized patient safety by failing to live up to the same manufacturing standards that HHS expects other facilities to follow. We are particularly troubled that NIH failed to identify on its own the numerous problems in the PDS facility detailed by FDA inspectors, and that a complaint to the FDA and a site inspection were necessary before corrective action was taken.”

The senators are requesting a staff briefing from the department as soon as possible to address all issues included in the letter as well as a written response from the agency to ensure the senators have all of the information necessary to conduct congressional oversight of this incident.

Full text of the letter is below:

June 5, 2015

The Honorable Sylvia Mathews Burwell

Secretary

U.S. Department of Health and Human Services

200 Independence Avenue, SW

Washington, DC 20201

Dear Secretary Burwell:

We are writing with concerns and questions regarding the alarming news that at least six patients at the National Institutes of Health (NIH) Clinical Center received injections from an NIH-manufactured batch of albumin that contained contaminated vials. As detailed in a press release issued yesterday by NIH, the contamination is a likely result of improper manufacturing practices within the NIH Clinical Center’s Pharmaceutical Development Section (PDS), which manufactures and manages drugs used to treat patients at the Clinical Center. Because of the problems discovered during a recent inspection by the Food and Drug Administration (FDA), NIH has been forced to take the extraordinary step of suspending operations at PDS indefinitely.[1] We request a prompt and detailed explanation of what went wrong and what is being done to address the situation and ensure the safety of patients receiving treatment at the Clinical Center.

The Clinical Center is NIH’s research hospital, and the world’s largest hospital devoted exclusively to clinical investigation. As a leader in clinical research, it calls itself “America’s Research Hospital” and treated more than 10,000 new patients last year with a staff of approximately 1,200 physicians, dentists, and researchers.[2] PDS is responsible for managing the drugs used at the Clinical Center, and manufactures many of those drugs onsite in a facility that was upgraded in 2010 to “assure better alignment and continued compliance with FDA’s current good manufacturing practices.”[3]

Yesterday’s press release makes clear that PDS has fallen short of its objectives. In April, six patients were injected with albumin (which is used to administer the drug interleukin) from a batch that was later found to contain vials with a fungal contamination. The following month, in response to a complaint, FDA inspected the PDS facility and found serious problems that led to the contamination, including physical design flaws in PDS’s recently renovated facility, improper cleaning and design protocols, insufficient employee training and quality control, and other instances of noncompliance with current manufacturing practices. In response to this report, NIH has suspended operations at PDS indefinitely.[4]

NIH reported that it is suspending operations at PDS, preparing a corrective action plan, monitoring affected patients, seeking alternative sources of products for patients currently engaged in research protocols, and will be appointing an outside group to review NIH’s practices and to make recommendations.[5] But these corrective actions—which may put patients’ treatments and critical research at risk while PDS’s operations are suspended—never should have been necessary in the first place. It is unacceptable that a facility that operates within the Department of Health and Human Services (HHS)—and holds itself out as a “[m]odel of excellence”[6]—has jeopardized patient safety by failing to live up to the same manufacturing standards that HHS expects other facilities to follow. We are particularly troubled that NIH failed to identify on its own the numerous problems in the PDS facility detailed by FDA inspectors, and that a complaint to the FDA and a site inspection were necessary before corrective action was taken.

To address these concerns, we request a staff briefing as soon as possible and a written response to the following questions:

1.      When did NIH first become aware that (1) a batch of albumin that had been administered to patients contained contaminated vials, and (2) that there might be other manufacturing problems at the PDS facility? How did NIH become aware of these facts?
2.      Please provide the committee with the complaint that prompted FDA to inspect the PDS facility in May 2015 and the Establishment Inspection Report detailing FDA’s findings.
3.      Please explain how NIH identified which patients may have been injected with albumin from a contaminated batch. What is the likelihood that other patients not identified may have received injections subject to the risk of contamination? For those patients that NIH has identified as having received injections from the batch that included contaminated vials, please describe all steps that NIH is taking to ensure their safety, including but not limited to communications, monitoring, and medical treatment.
4.      Please describe the operations at NIH that will be modified or suspended as a result of the problems identified by FDA. Please also describe the steps being taken to bring PDS into compliance with current good manufacturing practices such that it can resume operations. What is the anticipated timeframe for resuming operations?
5.      Please describe the effects that the suspension in operations at PDS has had, or may have in the future, on (1) the availability of medication or treatment for patients, and (2) clinical trials, including blind and double blind studies. Please also describe what steps NIH is taking to ensure the continuity of care for patients who were receiving treatment with products manufactured by PDS, including patients currently scheduled to receive those products and other patients who have no immediate need for those products but may in the future.
6.       Please describe the process NIH has in place for investigating and responding to concerns (from employees, patients, contractors, or others) about safety issues at the Clinical Center, and whether any changes are being made in light of the problems identified during the May 2015 inspection.
7.      Please list all inspections that FDA has performed at PDS facilities in the last six years. For each inspection, please provide (1) the date of the inspection; (2) the purpose of the inspection; (3) inspection findings, including specific violations and recommended actions; and (4) any actions taken by PDS as a result of the inspection. In the last ten years, has FDA issued any Form 483s, warning letters or untitled letters regarding practices at PDS?

We look forward to your prompt response and to working with you to protect patient safety by ensuring that the drugs used to treat patients at NIH’s Clinical Center are manufactured according to the highest standards. To schedule the staff briefing, your staff may contact Lowell Schiller, Melissa Pfaff, and Grace Stuntz in Chairman Alexander’s office at (202) 224-6770, or Beth Stein at (202) 224-2931 and Andi Fristedt at (202) 224-7675 in Ranking Member Murray’s office.

Sincerely,

______________________________                                    ______________________________

Lamar Alexander                                                                    Patty Murray

Chairman                                                                                 Ranking Member

[1] NIH Press Release: NIH suspends operations in its Clinical Center Pharmaceutical Development Section (June 4, 2015), http://nih.gov/news/health/jun2015/nih-04.htm (“Press Release”).

2 NIH Clinical Center: Frequently Asked Questions, http://clinicalcenter.nih.gov/about/welcome/faq.shtml; NIH Clinical Center, http://clinicalcenter.nih.gov/index.html; NIH Clinical Center: Facts at a Glance, http://clinicalcenter.nih.gov/about/welcome/fact.shtml.

3 NIH Clinical Center Pharmacy Department: Pharmaceutical Development Section, http://www.cc.nih.gov/phar/
development.html (archived) (“PDS website”).

4 Press Release; FDA Form 483, Inspection of NIH Clinical Center Pharmacy (issued May 29, 2015), available at http://www.cc.nih.gov/phar/pdfs/483.pdf.

5 Press Release.

6 PDS website.

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For access to this release and Chairman Alexander’s other statements, click here.