[Federal Register Volume 62, Number 60 (Friday, March 28, 1997)]
[Notices]
[Pages 14917-14918]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-7912]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
[Docket Nos. 95P-0262 and 96P-0317]
Citizen Petitions Concerning Therapeutic Equivalency Ratings
Between Tablets and Capsules; Request for Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; request for comments.
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SUMMARY: The Food and Drug Administration (FDA) is requesting comments
on two citizen petitions that ask the agency to revise its current
policy concerning therapeutic equivalency ratings between tablets and
capsules. The petitions propose that a tablet and a capsule containing
the same active ingredient in the same dosage strength that have been
demonstrated to be bioequivalent be listed as therapeutic equivalents
in the publication ``Approved Drug Products with Therapeutic
Equivalence Evaluations.'' FDA is seeking public comment in order to
assist the agency in deciding whether to revise its current policy.
DATES: Submit written comments by June 26, 1997.
ADDRESSES: Written comments to the Dockets Management Branch (HFA-305),
Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, Rockville,
MD 20857.
FOR FURTHER INFORMATION CONTACT: Christine F. Rogers, Center for Drug
Evaluation and Research (HFD-7), Food and Drug Administration, 7500
Standish Pl., Rockville, MD 20855, 301-594-5644.
SUPPLEMENTARY INFORMATION: The publication ``Approved Drug Products
with Therapeutic Equivalence Evaluations'' (the Orange Book) identifies
drug products approved on the basis of safety and effectiveness by FDA
under the Federal Food, Drug, and Cosmetic Act. The Orange Book also
contains therapeutic equivalence evaluations for approved multisource
prescription drug products. These evaluations are prepared to serve as
public information and advice to State health agencies, prescribers,
and pharmacists, to promote public education in the area of drug
product selection, and to foster containment of health costs.
For two drug products to be listed as therapeutically equivalent in
the Orange Book, the products, among other criteria, must be
pharmaceutical equivalents. FDA regulations define pharmaceutical
equivalents as follows:
Pharmaceutical equivalents means drug products that contain
identical amounts of the identical active drug ingredient, i.e., the
same salt or ester of the same therapeutic moiety, in identical
dosage forms, but not necessarily containing the same inactive
ingredients, and that meet the identical compendial or other
applicable standard of identity, strength, quality, and purity,
including potency and, where applicable, content uniformity,
disintegration times and/or dissolution rates.
(see 21 CFR 320.1(c))
Tablets and capsules containing the same active ingredient in the same
dosage strength are defined as pharmaceutical alternatives rather than
pharmaceutical equivalents. Pharmaceutical alternatives are defined as
follows:
Pharmaceutical alternatives means drug products that contain the
identical therapeutic moiety, or its precursor, but not necessarily
in the same amount or dosage form or as the same salt or ester. Each
such drug product individually meets either the identical or its own
respective compendial or other applicable standard of identity,
strength, quality, and purity, including potency and, where
applicable, content uniformity, disintegration times and/or
dissolution rates.
(see 21 CFR 320.1(d))
[[Page 14918]]
Pharmaceutical equivalents and pharmaceutical alternatives are defined
similarly in the Orange Book. Under these definitions, a tablet and a
capsule cannot be rated as therapeutic equivalents in the Orange Book
even if they have been demonstrated to be bioequivalent.
FDA has received two citizen petitions asking the agency to revise
the current policy that does not permit tablets and capsules to be
rated as therapeutically equivalent. Kleinfeld, Kaplan and Becker
(Kaplan) submitted a petition dated August 11, 1995, that asks FDA to
take the following actions: (1) Revise the Orange Book to specify
therapeutic equivalence evaluations for products that contain the same
active ingredient, but are in a different solid oral dosage form (i.e.,
tablets and capsules); (2) change the Orange Book designations
``Tablet, Oral'' and ``Capsule, Oral,'' to ``Solid, Oral''; and (3)
change the definitions of ``Pharmaceutical equivalents'' and
``Pharmaceutical alternatives'' in FDA's regulations in 21 CFR 320.1(c)
and (d) and in the Orange Book to accommodate the requested changes.
The petition suggests, as an alternative, that FDA could rule that
tablets and capsules are the same dosage form (i.e., solid oral) and
are thus pharmaceutical equivalents. Under the latter approach, grant
of a suitability petition (under section 505(j)(2)(C) of the act (21
U.S.C. 355(j)(2)(C)) and 21 CFR 314.93) would not be a prerequisite for
FDA to approve a tablet form of a capsule product, or vice versa.
The National Association of Pharmaceutical Manufacturers (NAPM)
submitted a citizen petition dated August 27, 1996, requesting that
``FDA deem all solid oral dosage form drug products (e.g., tablets and
capsules) as the same dosage form, which, upon a showing of
bioequivalence, will be considered in all respects to be
`pharmaceutical equivalents.''' NAPM argues that tablets and capsules
are ``more properly regarded as a single dosage form, i.e., solid oral
dosage forms.'' Both petitions assert that there is no scientific basis
for distinguishing between tablets and capsules that have been
demonstrated to be bioequivalent.
Recently, the issue of whether tablets and capsules can be listed
in the Orange Book as therapeutically equivalent has taken on added
significance. Some innovator firms, whose period of marketing
protection (either through patent or exclusivity) is about to expire,
have succeeded in delaying generic competition by, for example,
voluntarily withdrawing the new drug application (NDA) for the tablet
formulation of a product and submitting a second NDA for the drug
product in capsule form. In such a case, if there are already filed
abbreviated new drug applications (ANDA's) for the tablet product,
these ANDA's cannot be approved immediately upon expiration of the
innovator's period of market protection. Before these ANDA's can be
approved, an interested party must file a petition asking the agency to
determine whether the innovator product was withdrawn for reasons of
safety or effectiveness. The agency must then determine that the
product was not withdrawn for these reasons, publish that
determination, and relist the product in the Orange Book. Even after a
withdrawn product has been relisted in this way, generic competition
may still be affected. For example, if physicians continue to write
prescriptions by brand name rather than by generic name, substitution
of the generic tablet for the brand name capsule may not be permitted
under the applicable State drug product selection statute.
FDA is soliciting public comment on the two citizen petitions
discussed above. Among the questions the agency would particularly like
to see addressed are the following:
1. Should any potential change in current FDA policy be limited to
permitting bioequivalent tablets and capsules to be listed as
therapeutic equivalents in the Orange Book, or should FDA regard
tablets and capsules as the same (i.e., solid oral) dosage form?
2. What would be the implications of regarding all tablets and
capsules as the same dosage form?
3. Is there a sound scientific basis for the current distinction
between tablets and capsules?
4. What would be the impact on patients of rating bioequivalent
tablets and capsules as therapeutically equivalent, or of adopting the
term ``solid oral'' as a dosage form? Are there reasons for some
patients or health care practitioners to prefer either tablets or
capsules?
5. How would listing tablets and capsules as therapeutic
equivalents in the Orange Book affect current substitution practices
under State drug product selection statutes? What would be the impact
on drug selection by formularies?
6. What would be the economic impact of various proposed changes?
7. How would FDA action in this area relate to United States
Pharmacopoeia (USP) monographs?
Interested persons may, on or before June 26, 1996, submit to the
Dockets Management Branch (address above) written comments regarding
this notice. Two copies of any comments are to be submitted, except
that individuals may submit one copy. Requests and comments are to be
identified with the docket numbers found in brackets in the heading of
this document. The NAPM and Kaplan petitions and received comments may
be seen in the office above between 9 a.m. and 4 p.m., Monday through
Friday. Copies of the citizen petitions may be requested in writing
from the Freedom of Information Office (HFI-35), Food and Drug
Administration, 5600 Fishers Lane, Rockville, MD 20857.
Dated: March 21, 1997.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 97-7912 Filed 3-27-97; 8:45 am]
BILLING CODE 4160-01-F