[Code of Federal Regulations]
[Title 21, Volume 4]
[Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR250.201]
[Page 152-153]
TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
SERVICES
PART 250--SPECIAL REQUIREMENTS FOR SPECIFIC HUMAN DRUGS--Table of Contents
Subpart C--Requirements for Drugs and Foods
Sec. 250.201 Preparations for the treatment of pernicious anemia.
(a) The ninth announcement of the Anti-anemia Preparations Advisory
Board of the United States Pharmacopeia is concerned with the status of
the treatment of pernicious anemia. It clearly presents the following
facts:
(1) The Sixteenth Revision of the Pharmacopeia of the United States,
which became official on October 1, 1960, does not include preparations
intended for the treatment of pernicious anemia by oral administration.
(2) The U.S.P. unit for anti-anemia preparations no longer has any
significance.
(3) The U.S.P. Anti-anemia Preparations Advisory Board was
disbanded.
(b) On the basis of the scientific evidence and conclusions
summarized in the statement of the U.S.P. Anti-anemia Preparations
Advisory Board as well as pertinent information from other sources, the
Commissioner of Food and Drugs finds it is the consensus of well
informed medical opinion that:
(1) The parenteral administration of cyanocobalamin or vitamin
B12 is generally recognized as a fully effective treatment of
pernicious anemia. Parenteral cyanocobalamin preparations have not been
and are not authorized for use except by or on the prescription of a
duly licensed medical practitioner.
(2) Some patients afflicted with pernicious anemia do not respond to
orally ingested products. There is no known way to predict which
patients will fail to respond or will cease to respond to the treatment
of pernicious
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anemia with orally ingested preparations.
(3) The substitution of a possibly inadequate treatment, such as the
ingestion of oral preparations of vitamin B12 with intrinsic
factor concentrate, in place of parenteral vitamin B12
products for a disease condition as serious as pernicious anemia cannot
be regarded as safe in all cases.
(4) The development of the classical symptoms of pernicious anemia
that would cause a person to seek medical attention may in some cases be
delayed by oral ingestion of intrinsic factor. Pernicious anemia is a
disease that is associated, among other things, with a higher than
normal incidence of cancer of the stomach and that for the safety of the
patient, requires continuous expert medical supervision.
(5) With inadequate treatment there may be markedly deleterious
effects on the nervous system. It is well established that whereas the
development of anemia is completely reversible with adequate treatment,
the involvement of the nervous system may not be completely reversible
and thus may result in permanent damage.
(6) Some hematologists prescribe oral preparations of vitamin
B12 in the treatment of pernicious-anemia patients.
(7) Intrinsic factor and intrinsic factor concentrate serve no known
useful therapeutic or nutritive purpose except to the extent that they
do increase the gastrointestinal absorption of vitamin B12 in
patients with a deficiency or absence of intrinsic factor, which may
eventually lead to pernicious anemia. This conclusion does not apply to
diagnostic procedures using radioactive cyanocobalamin.
(8) Medical expertise is required for the diagnosis as well as the
management of pernicious anemia.
(c) The Eleventh Edition of The National Formulary and its first
Interim Revision include monographs for oral preparations of vitamin
B12 with intrinsic factor concentrate, establish a unit of
vitamin B12 with intrinsic factor concentrate, and provide
for a National Formulary Anti-anemia Preparations Advisory Board to
assign the potency of such preparations. This provides for the
availability of such oral preparations, standardized within the meaning
of the broad limits characteristic of the evaluation of such
preparations.
(d) Any drug that is offered for or purports to contain intrinsic
factor or intrinsic factor concentrate will be regarded as misbranded
within the meaning of section 503(b) of the Federal Food, Drug, and
Cosmetic Act unless it is labeled with the legend ``Caution--Federal law
prohibits dispensing without prescription.''
(e) Any drug for oral ingestion intended, represented, or advertised
for the prevention or treatment of pernicious anemia or which purports
to contain any substance or mixture of substances described in paragraph
(d) of this section (other than diagnostic drugs containing radioactive
cyanocobalamin) will be regarded as misbranded under sections 502 (f)(2)
and (j) of the act unless its labeling bears a statement to the effect
that some patients afflicted with pernicious anemia may not respond to
the orally ingested product and that there is no known way to predict
which patients will respond or which patients may cease to respond to
the orally ingested products. The labeling shall also bear a statement
that periodic examinations and laboratory studies of pernicious anemia
patients are essential and recommended.
(f) Under section 409 of the Federal Food, Drug, and Cosmetic Act,
intrinsic factor and intrinsic factor concentrate are regarded as food
additives. No food additive regulation nor existing extension of the
effective date of section 409 of the act authorizes these additives in
foods, including foods for special dietary uses. Any food containing
added intrinsic factor or intrinsic factor concentrate will be regarded
as adulterated within the meaning of section 402(a)(2)(C) of the act.
(g) Regulatory action may be initiated with respect to any article
shipped within the jurisdiction of the act contrary to the provisions of
this policy statement after the 180th day following publication of this
statement in the Federal Register.
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