1. FDA's Medwatch program allows reporting of adverse events from medical products to help identify safety concerns, with reports on Zyvox and Levoxine/LANOXIN leading to label changes.
2. It is important to report serious adverse events, therapeutic failures, use errors, and product quality issues to the FDA to maintain the Medwatch system.
3. The iPLEDGE program imposed stricter controls on isotretinoin due to depression and suicide risks, requiring registration of prescribers, pharmacies, patients.
Health Canada Progressive Licensing - Professor Peivand Pirouzi
1. Post-Marketing Compliance
&
Health Canada Progressive
Licensing
Professor Peivand Pirouzi
2006
FDA/Health Canada Guidances
2. Reporting Adverse Events for Drugs, Devices,
Biologics and Dietary Supplements
FDA's Medwatch program allows health care professionals and consumers to report to the FDA
serious problems with the medical products they prescribe, dispense, or use. These reports,
along with follow-up investigations, can help to identify important safety concerns.
Take the example of the antibiotic Zyvox. Within the first six months of Zyvox's marketing, FDA
began getting MedWatch reports of myelosupression from clinicians who suspected that the
drug might be responsible. After investigating the problem, we worked with the manufacturer to
change the Zyvox labeling to warn about the potential for myelosuppression.
Sometimes MedWatch reports highlight errors in prescribing or administering medications. For
example, FDA received reports of patient injuries due to name confusion between LANOXIN, a
heart medication, and what used to be called LEVOXINE, a thyroid medication. As a result, FDA
asked the manufacturer to change the name of Levoxine, and now it's known as LEVOXYL,
which is less likely to be confused with LANOXIN.
The MedWatch system can also help detect problems with medical products other than drugs.
For example, FDA received two reports of pneumococcal eye infections in patients who'd
received corneal transplants. An FDA inspection identified numerous manufacturing problems,
which led the company to recall the implants.
3. Reporting Adverse Events for Drugs, Devices,
Biologics and Dietary Supplements
Of course, MedWatch reports by themselves can not usually establish a causal relationship between an adverse
event and a medical product - it may take a formal epidemiologic study to do that. Still, MedWatch reports are vital
in making sure that medical products are safe, because they provide a rapid signal to FDA that problems may be
occurring.
It is important to keep the MedWatch system working, and we can not do that without your help. Here are the kinds
of reports we need from you:
• First of all, we are asking that you report any serious adverse event that might be associated with a drug, biologic,
medical device, or dietary supplement. By "serious" we mean fatalities, hospitalizations, and medically significant
events. We're especially interested in serious adverse events that aren't listed in the product labelling.
• Secondly, report therapeutic failures - cases where the drug or device failed to work as it should. For example, let
us know if a patient has to switch from one brand of a drug to another because the original one was ineffective.
• Third, tell us about cases of use errors with medications or devices, including situations where the error may have
been due to poor communication, or to ambiguities in product names, directions for use, or packaging.
• And finally, we would like to know about product quality issues, such as suspected counterfeit products, defective
components, potential contamination, device malfunctions and poor packaging.
4. MedWatch: Reporting Adverse Events
1. FDA's Medwatch program allows health care professionals and consumers
to report to the FDA serious problems with the medical products they
prescribe, dispense, or use. These reports, along with follow-up
investigations, can help to identify important safety concerns.
2. It is important to keep the MedWatch system working, and we can
not do that without your help. Here are the kinds of reports we need
from you:
– Report any serious adverse event that might be associated with a drug, biologic, medical device, or
dietary supplement. By "serious" we mean fatalities, hospitalizations, and medically significant events.
FDA is especially interested in serious adverse events that aren't listed in the product labeling.
– Report therapeutic failures - cases where the drug or device failed to work as it should (e.g., if a patient
has to switch from one brand of a drug to another because the original one was ineffective).
– Report cases of use errors with medications or devices, including situations where the error may have
been due to poor communication, or to ambiguities in product names, directions for use, or packaging.
– Report product quality issues, such as suspected counterfeit products, defective components, potential
contamination, device malfunctions and poor packaging.
5. Stronger Risk Management Program for
Accutane (isotretinoin)
Isotretinoin is now a restricted distribution drug. This means that
wholesalers won't be able to distribute the drug, pharmacists won't be able
to dispense it, physicians won't be able to prescribe it, and patients won't be
able to receive it unless they register. Doctors, patients, and pharmacies
can obtain program information and register with iPLEDGE either online or
by telephone at 1-866-495-0654.
There is also a possible link between taking this drug and depression,
suicidality, and psychosis. And for that reason, FDA has strengthened the
labeling to help practitioners and patients identify and manage these risks.
Any patient being treated with this drug should be carefully monitored for
symptoms of depression, or suicidalility or psychosis. Patients should be
told to stop the drug and contact their health professional if they experience
any of these symptoms. Stopping the drug by itself, however, may not be
sufficient. Psychiatric evaluation and intervention may be needed to prevent
patients from harming themselves.
6. Stronger Risk Management Program for
Accutane (isotretinoin)
Revised October 28, 2005: The implementation dates of the iPLEDGE program have
been revised. The date by which wholesalers and pharmacies must be registered
/activated in IPLEDGE has been changed from November 1, 2005 to December 30,
2005. By March 1, 2006, only prescribers registered and activated in iPLEDGE can
prescribe isotretinoin and only patients registered and qualified in iPLEDGE can be
dispensed isotretinoin. Patients can begin registering and qualifying on December 30,
2005.
FDA has developed stronger requirements to prevent fetal exposure to the drug
Accutane (isotretinoin) along with its generic equivalents, such as Amnesteem, Sotret
and Claravis. Isotretinoin is used to treat severe, recalcitrant, nodular acne, but it can
cause serious birth defects if taken by pregnant women.
These requirements are now going into effect in a new program called iPLEDGE.
Under this program, wholesalers, prescribers, pharmacies and patients, both men
and women, must register. Also, women who are capable of becoming pregnant must
have two negative pregnancy tests before isotretinoin can be dispensed to them.
They also must have a negative pregnancy test each month while taking the drug.
7. FDA Studying Potential Safety Issues
with Several Drugs
FDA has informed the health care community about ongoing safety
reviews of several drugs. FDA is doing this as part of its commitment
to inform health care professionals and the public about its ongoing
drug safety reviews. Because this information is preliminary and
there is scientific uncertainty, FDA is not taking regulatory action at
this point, and is not advising health care professionals to stop using
the drugs. FDA is continuing to evaluate the safety of these
products, and will issue updates as more information becomes
available.
• CellCept (mycophenolate mofetil) and Myfortic (mycophenolic acid)
• Singulair (montelukast)
• Spiriva Handihaler (tiotropium)
8. New Rule Enhances the Safety of Human
Cells and Tissues
FDA recently finalized a new rule that's designed to increase the safety of human
cells, tissues and cellular and tissue-based products that are used for
transplantation. The regulations apply to a broad range of products, including bone,
ligaments, skin, corneas, and hematopoietic stem cells. They also apply to human
heart valve and human dura mater allografts. The rule requires that manufacturers of
these products recover, process, store, label, package and distribute them in a way
that prevents the spread of communicable diseases.
In this rule, FDA uses the word "manufacture" as an umbrella term to capture the
many different actions an establishment might take in preparing these products for
use. Many types of establishments may be involved in various steps from recovery,
donor screening and testing, to storage and distribution. If an establishment is
involved in any of the steps covered by the new regulation, FDA calls it a
manufacturer.
Prior to the new rule, there were some regulations in place to help assure the safety
of human tissue. But the new rule covers a broader range of products and has more
comprehensive requirements. This will help assure health care providers that the
tissue and cellular products they use are the safest available.
9. Reporting Adverse Events from Vaccines
Every year, tens of millions of vaccinations are given to children and adults in this
country to prevent serious infectious diseases. FDA and CDC work together to
monitor the safety of these vaccines using a registry known as Vaccine Adverse
Event Reporting System, or VAERS. The VAERS registry contains reports of adverse
events from patients, parents and health care providers, and it can help to identify
important new vaccine safety concerns.
Take the example of the rotavirus vaccine. During the first months after this vaccine
was approved, epidemiologists at FDA and CDC noticed 15 VAERS reports of infants
who had developed a particular type of intestinal obstruction after receiving the
vaccine. The reports signaled a potential problem, which led to further investigations.
As a result, the vaccination program was suspended, and then later, as
investigations verified the serious risk, the manufacturer voluntarily removed the
vaccine from the market.
10. Reporting Adverse Events from Vaccines
Of course, it takes multiple reports and thorough investigation to confirm a causal
relationship between an adverse event and a vaccine. Still, VAERS reports are on the
front line in making sure that vaccines are safe, by providing a rapid signal that problems
may be occurring.
Sometimes VAERS reports highlight errors in prescribing or administering vaccines. For
example, the VAERS registry was found to contain reports of 22 pregnant women who
had received live virus varicella vaccine by mistake after being exposed to chickenpox.
These women should have received a different product, varicella zoster immune globulin,
or "VZIG."
In this case, FDA and CDC worked with the varicella vaccine manufacturer to publish
details about the 22 cases. By publishing this information, we were able to alert health
care professionals of this potential mix-up, and thus help prevent future cases.
It's important to keep the VAERS system working, and we can't do that without your help.
We're asking that you report any significant adverse event that occurs after a vaccination,
even if you're not sure that the vaccine caused it. It's easy to report by internet, phone,
fax, or mail.
11. PHARMACOVIGILANCE AND RISK MANAGEMENT
THROUGHOUT THE PRODUCT LIFECYCLE
http://www.hc-sc.gc.ca/dhp-mps/homologation-licensing/develop/proglic_homprog_discus-eng.php
22. What is a Pharmacovigilance Plan?
A plan proposed by a sponsor
– for the ongoing evaluation of safety
signals identified with the use of a product
– to monitor at-risk populations which have
not been adequately studied
Plan may be developed at the time of product
launch or after a signal is identified
23. What is a Pharmacovigilance Plan?
A sponsor’s plan for an ongoing evaluation of safety
signals*.
May involve:
– Expedited reporting of serious adverse events
– Submission of adverse event report summaries at more frequent, pre-specified
intervals
– Implementation of active surveillance activities to identify adverse events that
may or may not be reported through passive surveillance
– Creation of registries or conducting patient/healthcare provider surveys
– Conduct of Pharmacoepidemiologic studies using cohort study design
* A safety signal is an apparent excess of adverse events associated with use
of a product
24. Post market Requirements and
Commitments
Post market requirement and commitment studies and clinical trials
occur after a drug or biological product has been approved by FDA.
Guidance for Industry (PDF - 456KB) (Post market commitment-
non-clinical). A separate Web site is available for post approval
studies for medical devices.
Website for Post market Requirements and Commitments
Database (FDA):
http://www.accessdata.fda.gov/scripts/cder/pmc/index.cfm?StartRow
=2&StepSize=1&Paging=Yes
25. The need
Regulatory agencies are increasingly proactive in seeking out
potential safety issues with marketed drugs
Political and social pressures have increased along with faster
communication channels
Litigation due to the lack of Pharmacovigilance can be devastating
for all concerned
Failure to practice pharmacovigilance can lead to the suspension or
withdrawal of license