Questions and Answers on
Exocrine Pancreatic Insufficiency Drug Products
1.
What is the Food and Drug Administration (FDA) announcing
today?
The FDA is announcing that all exocrine
pancreatic insufficiency drug products are new drugs and is
announcing the conditions for continued marketing of these drug
products. FDA previously announced that all pancreatic
insufficiency products must be available by prescription only.
These conditions relate to proving that pancreatic enzyme products (PEPs)
meet standards for quality, safety, and efficacy. At this time, the
FDA is requiring manufacturers of pancreatic enzyme drug products to
submit new drug applications (NDAs) and receive FDA approval to
market their products. The Agency has also determined that PEPs are
medically necessary and accordingly, is allowing manufacturers to
continue marketing and obtain approval of their products within four
years.
2.
What are these products used for?
PEPs aid in the digestion of meals in
patients who have diseases affecting their pancreatic function.
PEPs contain the ingredients pancreatin and pancrelipase, both of
which contain the enzymes lipase, protease, and amylase. These
enzymes break down fats (lipase), proteins (protease) and complex
carbohydrates (amylase) to allow absorption of these nutrients into
the body.
3.
Who takes pancreatic enzyme products in the United States
(U.S.)?
Patients who take these products are those with cystic fibrosis and
chronic pancreatitis conditions.
4.
What is Cystic Fibrosis (CF) and Pancreatitis?
Cystic
fibrosis (CF) is a genetic disease affecting approximately 30,000
children and adults in the United States. CF causes the body to
produce an abnormally thick, sticky mucus, due to the faulty
transport of sodium and chloride (salt) within the cells that line
organs such as the lungs and pancreas, to the outer surface of these
cells. The thick CF mucus also obstructs the pancreas, preventing
digestive enzymes from reaching the intestines to help break down
and digest food.
Pancreatitis is a disease of the
pancreas, affecting approximately 14,000-28,000 adults. Patients
with chronic pancreatitis lack sufficient pancreatic enzymes. This
lack of enzymes results in the body’s inability to properly digest
fat.
5. 5.
Why has FDA decided now to
regulate PEPs?
PEPs of porcine or bovine origin have been available in the
U.S. as prescription and
over-the-counter (OTC) products for the treatment of exocrine
pancreatic insufficiency in children and adults with cystic fibrosis
and chronic pancreatitis diseases since before the
enactment of the Federal Food, Drug, and Cosmetic Act of 1938. It was in
1938 that “new drugs” were required to be the subject of NDAs. FDA
has always regulated PEPs to the extent that it monitored the
labeling and manufacturing processes. With the exception of a PEP
approved in 1996, PEPs have been marketed without NDAs.
Over
the years, FDA has received reports of problems associated with
these drugs. Initially, the reports dealt with adverse events
associated with high doses of enzymes leading to strictures of the
intestines (narrowing of the digestive tract). More recently the
Agency has received a number of reports claiming that these drug
products do not have the expected therapeutic effect. There are
many reasons why certain products may be subtherapeutic, including
inactive ingredients or inadequate amounts of active drug in the
capsule.
FDA has
determined that more controls are needed in the manufacturing of
PEPs to ensure consistent potency and quality. Given that PEPs are
taken as maintenance
medications, avoidance of both over- and under-treatment is critical
to maintaining the health and well being of patients with CF or
chronic pancreatitis. This goal is best accomplished by having
products with consistent quality, potency and stability.
6.
Is there a public health crisis?
This announcement is not the result of
a public health crisis. The FDA is taking this action to ensure
that these drugs are manufactured to reproducibly high standards and
are demonstrated to be safe and effective. Manufacturers of PEPs
are being asked to submit marketing applications for their drug
products.
7.
Are groups that are likely to be impacted by this
proposed rule supportive of FDA's actions?
In a statement issued today by the
Cystic Fibrosis Foundation, the organization stated, "The Cystic
Fibrosis Foundation supports the FDA's announcement to require
pancreatic enzymes to obtain NDAs. The FDA's oversight will provide
assurance on the safety and potency of all pancreatic enzymes. It
also will improve the health of people with CF and help to address
adverse events reported by patients who take certain enzyme
products."
Cystic
Fibrosis Foundation Statement.
8.
If manufacturers do not submit marketing applications, will
there be a shortage of PEPs?
At this time there is no shortage of
PEPs, and the Agency does not anticipate any shortages as a result
of this announcement. The Agency recognizes that it will take time
for applicants to obtain approved applications. In an effort to
avoid a shortage, the Agency is providing manufacturers adequate
time to collect the data needed to submit an application. Manufacturers have 4 years to obtain approved applications. Currently there are 39 different formulations available
for patients.
9.
What should doctors do at this time?
Doctors should be aware that
manufacturers of PEPs must receive approval for their drug products
by 2008. If some current manufacturers do not receive marketing
approval or choose not to seek approval, patients may need to be
switched to other approved brands at that time.
10. What should I do if I am currently taking one of these
products?
Continue taking PEPs as prescribed by
your doctor. Because these products are taken as maintenance
medications, the FDA is taking this action to ensure their quality.
11.
Will I have problems if I stop taking pancreatic enzymes?
Yes. Because your body requires PEPs
for proper digestion, it is possible that if you stop taking your
medication you may have diarrhea or loose stools. Please talk with
your doctor before stopping or changing any medications.
12.
Are there any concerns about these products?
The Agency believes that the
pre-clearance of each product is necessary to provide patients with
the same quality, safety and efficacy that comes with all
FDA-approved products.
13.
Are these drug products available only by prescription?
Yes. The
FDA published a final rule on April 25, 1995 concerning
over-the-counter PEPs. It was determined that all PEPs had to be
marketed as prescription drug products and needed an approved NDA
for continued marketing.
14.
What about dietary supplements that contain pancreatic
enzymes? Will they remain on the market?
Under the law, FDA is not authorized to
require premarket approval of products legally sold in the United
States as dietary supplements. The Agency’s action in this matter
should have no impact on legally marketed dietary supplements.
15.
Are any of the PEPs FDA approved?
There
is one approved prescription PEP. The trade name of this immediate
release product is Cotazym. However,
the manufacturer, Organon, is not currently marketing the product.
16.
Will these products be recalled from the pharmacy?
No. FDA is not asking for a recall of
these products while manufacturers are applying for marketing
approval.
17.
Will my pharmacist continue to fill my prescription? May I
ask for a generic?
Yes,
your pharmacist will continue to fill your prescriptions. However,
pharmacists should be aware that these products have different
formulations. At this time, FDA does not have
sufficient data to determine
therapeutic equivalence of the drug products. Therefore, the
FDA does not recommend substitution of these products.
18.
What economic impact does FDA expect that this action will
have?
We do not expect prices
to change as a result of this action. Our economic analysis of this
action found that although some firms may choose to leave the
market, enough manufacturers would continue producing pancreatic
enzyme products that the market would remain competitive.
19.
How can I report a serious side effect to FDA?
You can report an adverse event the
following ways:
20.
Where can I get more information relating to PEPs?
Additional information can be obtained from the following
organizations:
National Digestive Diseases Information
Clearinghouse
2 Information Way
Bethesda, MD, 20892-3570
Phone: 1-800-891-5389 or (301) 654-3810
Fax: (301) 907-8906
http://digestive.niddk.nih.gov/ddiseases/topics/pancreas.asp
The Cystic Fibrosis Foundation
6931 Arlington Road, #200
Bethesda, MD 20814
Telephone: 301-951-4422 or 1-800-344-4823
http://www.cff.org/
National Library of Medicine, National
Institutes of Health
MedlinePlus: Pancreatic Diseases
http://www.nlm.nih.gov/medlineplus/pancreaticdiseases.html
FDA
Drug Information at: 888-INFO-FDA (888-463-6332)
E-mail Drug Information at:
druginfo@fda.hhs.gov
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Pancreatic Drug Product Info
Date created: April 27, 2004 |