CLC Provides FDA Guidance on Drug
Shortages Strategic Plan
(March 14, 2013)
March 14,
2013
Leslie Kux
Assistant Commissioner for Policy
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, Maryland 20993
Re: Food and Drug Administration Drug
Shortages Task Force and Strategic Plan, FDA-2013-N-0124
Filed Electronically at http://www.regulations.gov
Dear Ms. Kux:
The undersigned cancer patient, provider, and research
organizations appreciate the opportunity to provide advice
regarding the development of a strategic plan on drug
shortages. Our comments will focus on improving the
methods and timeliness of notice regarding shortages,
identifying and assessing alternative manufacturing sites and
entities for drugs and biologicals in shortage situation,
evaluating possible incentives for entities to begin or expand
manufacturing of drugs in short supply, and developing
strategies to assess and address the impact of shortages on
clinical trials.
During the last several years, diverse cancer community
stakeholders have described the significant impact of cancer
drug shortages on cancer care. Physicians have reported
the pressure to find alternative treatment options when critical
cancer drugs are unavailable; physicians, pharmacists, and
nurses have described hours spent managing shortages and finding
substitute drugs; patients have expressed their fears about
receiving a therapy that is described as less than optimal; and
clinical researchers have reported abandonment of studies
because a drug crucial to the trial was simply not available.
Pediatric
researchers have recently described the impact of drug
shortages on long-term health outcomes.A December 27,
2012, study in the New
England Journal of Medicine found that the substitution
of cyclophosphamide for mechlorethamine in the Stanford V
regimen for children diagnosed with high-risk and
intermediate-risk Hodgkin’s lymphoma was significantly less
effective.[1]Cyclophosphamide
was substituted only when shortages of mechlorethamine forced
the change.The
authors found that 75% of those treated with cyclophosphamide
enjoyed 2-year event-free survival, compared to 88% with
mechlorethamine.The
authors warn, “Our results suggest that even promising
substitute regimens should be examined carefully before
adoption; what might appear to be a suitable alternative
regimen may result in an inferior outcome – an intolerable
situation for young people with curable diseases.”
Shortages of drugs and biologicals result in intolerable
situations for both children and adults, and we urge that the
development of the strategic plan be approached with a sense of
urgency, creativity, and aggressiveness to find solutions to the
problem of drug shortages.
We will address several of the specific topics identified by the
Food and Drug Administration (FDA) in its Request for Comments.
1. New ideas to encourage high-quality
manufacturing and to facilitate expansion of manufacturing
capacity.
We
understand that in a number of cases, FDA has been able to
identify drug manufacturers who could respond to drug shortages
by expanding manufacturing capacity for current products,
opening facilities to begin manufacture of a drug or biological,
or resuming production of a drug or biological in cases where
manufacturing had been interrupted. These solutions have
been achieved primarily through aggressive and creative
management by FDA, combined with rapid action by responsive
manufacturers. We urge the agency, in developing its
strategic plan, to consider incentives that might provide
additional encouragement for manufacturers to resolve
shortages. These might include waivers of application fees
for new drug applications or abbreviated new drug applications
and additional (and possibly transferable) exclusivity for
products in the same therapeutic areas as the drug in
shortage. These options may be beyond the current
authority of FDA, but they might be evaluated in a strategic
plan to ascertain whether legislation would be necessary to
provide FDA authority to implement these reforms.
2. Incentives that federal
agencies, separately or in partnership with FDA, might provide
to prevent shortages.
We recommend that FDA evaluate steps that it and other federal
agencies might take to form partnerships not simply with each
other but with potential manufacturers to address or mitigate
shortages. The federal government has experience in
partnering with or funding industry partners for the manufacture
of vaccines. We urge that, as part of the strategic plan,
the past experience related to vaccine manufacturing be
evaluated and any promising models be considered for replication
to address shortages of drugs and biologicals.
3. Communications to alleviate
potential or actual shortages.
We recommend changes in the methods for communicating shortages,
and we urge that special attention be directed to 1)
communication with patients, and 2) collaboration with patient
organizations to strengthen outreach to patients who need
information about shortages. In developing the strategic
plan on drug shortages, FDA should consider the following
recommendations.
FDA
web pages should be improved so that patient navigation is
facilitated. We recommended that the web pages be
modified so that patients can search for products in a
shortage situation under categories including indication and
disease type. We also suggest that more information be
provided about the reasons for the shortage, so that
patients and their cancer care teams can make informed
decisions about alternative treatments. For example,
knowledge about the cause of the shortage will permit the
patient to make a decision to delay or alter treatment in
the short term or to make more complete changes with regard
to treatment.
FDA
should consider partnering with the National Cancer
Institute (NCI) or other offices and institutes at the
National Institutes of Health (NIH) to develop a fact sheet
or guidance document that patients could utilize in
discussions with their care team about alternative treatment
options if they are confronted with drug shortages. This
document might be in the form of a list of questions that
would guide decisions about alternative treatments.
The
agency should consider partnerships with patient advocacy
groups in the communication of drug shortages to those
groups’ constituents. FDA might evaluate a simple and
straightforward process through which organizations would
partner with FDA to send alerts about shortages to specific
patient populations. Partnering organizations should
be provided updates on numbers of shortages, shortages by
disease category, length of shortages, and other important
variables, to assist them in communicating with the public
about shortages and decision-making regarding treatment
alternatives.
Additional
communication strategies targeting patients and patient
organizations should be evaluated by FDA. These
communication options should include
social media and email communications targeted according to
disease category.
4. Impact of shortages on clinical
trials.
To assist in its decision-making related to management and
mitigation of the impact of drug shortages on clinical trials,
FDA should seek input from a number of agencies and
organizations. We recommend that FDA seek advice
related to drug shortages and clinical trials from NCI, which
has deep knowledge about clinical trials supported with NCI
funds; the FDA Office of Hematology and Oncology Products; the
Coalition of Cancer Cooperative Groups; cancer centers; and the
American Society of Clinical Oncology and other professional
groups. These organizations and agencies and others can
provide FDA advice about the impact of drug shortages on
clinical trials to date as well as guidance about how to manage
drug supplies going forward to ensure completion – rather than
abandonment – of clinical trials. We are recommending that
these entities be consulted during the development of the
strategic plan and that a mechanism be created for obtaining
ongoing input regarding clinical trials from these groups.
We understand that economic solutions, including possible
changes in the reimbursement for drugs that are in short supply,
are beyond the scope of this study. We believe that
changes in third-party payment may be necessary to address drug
shortages in a comprehensive and conclusive way, and we will
encourage those changes to the appropriate decision-makers.
We appreciate the opportunity to comment on the FDA drug
shortages strategic plan.
Sincerely,
Cancer Leadership Council
American Society for Radiation Oncology
American Society of Clinical Oncology
Bladder Cancer Advocacy Network
The Children's Cause for Cancer Advocacy
Fight Colorectal Cancer
International Myeloma Foundation
The Leukemia & Lymphoma Society
LIVESTRONG
Lymphoma Research Foundation
Multiple Myeloma Research Foundation
National Coalition for Cancer Survivorship
National Lung Cancer Partnership
Pancreatic Cancer Action Network
Prevent Cancer Foundation
Sarcoma Foundation of America
Susan G. Komen for the Cure Advocacy Alliance
Us TOO International Prostate Cancer Education and Support
Network
[1]Metzger
ML, Billett A, and Link MP.The impact of drug shortages on children with cancer
– the example of mechlorethamine.N Engl J Med 2012; 367:2461-2463.