[Federal Register Volume 59, Number 220 (Wednesday, November 16, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-28193]
[[Page Unknown]]
[Federal Register: November 16, 1994]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 81N-0096]
Biological Products; Allergenic Extracts Classified in Category
IIIB; Final Order; Revocation of Licenses
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is issuing a final
order concerning most allergenic extracts classified in Category IIIB.
FDA is also announcing the revocation of product licenses and the
authorization to manufacture specific products under U.S. licenses for
allergenic extracts, as applicable, for most allergenic extracts
classified in Category IIIB. FDA is revoking the licenses of such
allergenic extract products for which the manufacturers have not
requested hearings. The agency has not, at this time, determined
whether to grant the one pending hearing request concerning Category
IIIB injectable Poison Ivy Extract. The license at issue in this
hearing request is not at this time being revoked.
DATES: The revocation of licenses is effective December 16, 1994.
Labeling changes were to be submitted to and approved by the Director,
Office of Biologics Research and Review by February 5, 1986, as stated
in the notice of opportunity for hearing of August 9, 1985.
ADDRESSES: Submit any additional labeling changes to the Director,
Center for Biologics Evaluation and Research (HFM-481), 1401 Rockville
Pike, suite 200N, Rockville, MD 20852-1448.
FOR FURTHER INFORMATION CONTACT:
Regarding this notice: Paula S. McKeever, Center for Biologics
Evaluation and Research (HFM-635), Food and Drug Administration, 1401
Rockville Pike, suite 200N, Rockville, MD 20852-1448, 301-594-3074.
Regarding licenses and labeling changes: Susan Barkan, Center for
Biologics Evaluation and Research (HFM-481), Food and Drug
Administration, 1401 Rockville Pike, suite 200N, Rockville, MD 20852-
1448, 301-594-2090.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of January 23, 1985 (50 FR 3082), FDA
announced its intention to revoke product licenses (hereinafter
referred to as the 1985 proposal), or the authorization of
manufacturers to produce individual products under their licenses for
the manufacture of allergenic extracts, for any allergenic extract
classified into Category IIIB. The proposed action was based on the
conclusions and recommendations of the Panel on Review of Allergenic
Extracts (the Panel), including the Panel's conclusions that data were
insufficient to classify certain products as safe and effective and
that the products have an unfavorable benefit-to-risk potential. The
conclusions and recommendations of the Panel are contained in a report
to the Commissioner of Food and Drugs which was reprinted in the 1985
proposal. Those products with insufficient data and an unfavorable
benefit-to-risk potential, which the Panel believed should not continue
to be marketed during the development of data to resolve whatever
safety and effectiveness questions exist, were classified in Category
IIIB.
FDA also announced in the 1985 proposal that the Panel recommended
that two products be classified into Category II (unsafe, ineffective,
or misbranded). However, the license for one of the products was
revoked at the request of the manufacturer during the Panel's review.
The other product had been classified as Category II for a specific
indication for immunotherapy that had not previously been approved by
FDA, and the agency is not aware of such immunotherapeutic use of the
product. Therefore, no action was proposed on the two products.
Many allergenic extracts were classified by the Panel in Category
IIIA, designating products for which the available data are
insufficient to determine whether the product license should be revoked
or affirmed and which may be marketed pending the completion of further
testing. Under Sec. 601.26 (21 CFR 601.26), all biological products
recommended for Category IIIA are to be reclassified into Category I or
Category II. The Panel established to reclassify Category IIIA
allergenic extracts has completed its review and submitted its
recommendations to FDA. The agency will announce its proposed response
to the recommendations for reclassification of Category IIIA allergenic
extracts in a future issue of the Federal Register.
In the Federal Register of August 9, 1985 (50 FR 32314), FDA
published a notice of opportunity for hearing (hereinafter referred to
as the 1985 notice), concerning specified allergenic extracts that the
agency had proposed for inclusion in Category IIIB in the 1985
proposal. Approximately 280 of the 1,600 generic allergens representing
almost 6,000 individual company allergenic extracts reviewed by the
Panel had been classified into Category IIIB. The 1985 notice included
a listing of all licensed manufacturers and the products classified as
Category IIIB.
A. Requests for Hearings
In response to the 1985 notice, FDA received four requests for
hearings from licensed manufacturers of allergenic extracts. The
following manufacturers submitted requests:
1. Antigen Laboratories, Inc., 30-34 South Main, P.O. Box 123,
Liberty, MO 64068, submitted a request for hearing dated August 30,
1985, on several unspecified products placed into Category IIIB for
diagnostic use. In a subsequent letter dated March 22, 1988, Antigen
Laboratories, Inc., withdrew its hearing request.
2. Barry Laboratories, Inc., P.O. Box 1967, Pompano Beach, FL
33061, submitted a request for hearing dated December 11, 1985, on its
Poison Ivy-Oak-Sumac Extracts, combined, injection in almond oil (Rhus-
All AntigenTM), License No. 119. At the manufacturer's request,
the establishment and product licenses issued to Barry Laboratories,
Inc., were revoked on January 19, 1988. The pending request for hearing
would have determined whether the product and establishment licenses
issued to Barry Laboratories, Inc., should be revoked. The request for
license revocation constitutes a withdrawal of the request for a
hearing, and consideration of the data is unnecessary.
3. Mulford Colloid Laboratories, Division of Lemmon Co., Inc.,
Cathill and Lonely Rds., Sellersville, PA 18960, submitted a request
for hearing dated September 5, 1985, on the Category IIIB
classification of its Poison Ivy Extract, injection in hydro-alcoholic
solution (Rhustox AntigenTM), License No. 102. At the
manufacturer's request, the establishment and product licenses issued
to Mulford Colloid Laboratories, Division of Lemmon Co., Inc., were
revoked on January 28, 1992. The pending request for hearing would have
determined whether the product and establishment licenses issued to
Mulford Colloid Laboratories, Division of Lemmon Co., Inc., should be
revoked. The request for license revocation constitutes a withdrawal of
the request for a hearing, and consideration of the data is
unnecessary.
4. Parke-Davis, Division of Warner-Lambert Co., 201 Tabor Rd.,
Morris Plains, NJ 07950, submitted a request for hearing dated
September 6, 1985, on the Category IIIB classification of its Poison
Ivy Extract, injection in almond oil, License No. 1. Parke-Davis
submitted data to support its request for hearing on its injectable
Poison Ivy Extract. FDA is reviewing the data submitted and has not yet
reached a decision on the request for hearing. Therefore, under 21 CFR
12.38(b), FDA will issue a separate notice regarding the hearing
request on the injectable Poison Ivy Extract produced by Parke-Davis,
Division of Warner-Lambert Co. The effective date of this notice does
not apply to this product.
B. Comments
The 1985 notice also requested comments regarding the 1985 proposal
to revoke product licenses for all allergenic extracts classified into
Category IIIB. FDA received approximately 1,700 comments in response to
the 1985 notice. All of the comments received concerning the Category
IIIB classifications were evaluated by FDA in developing the agency's
conclusions set forth in this order and notice. Summaries of the
comments and the agency's responses follow:
1. The majority of comments concerning the classification of
products into Category IIIB were testimonial in nature, most of them
form letters submitted by physicians and their patients. Most of the
comments expressed concern that some of the Category IIIB products
would no longer be available for medical use. No new and relevant data
that had not been previously available to the Panel or FDA were
submitted by the comments. A summary of these general comments related
to Category IIIB classifications follows:
a. Several comments supported the Category IIIB classification of
winged whole body hymenoptera insect extracts; several comments opposed
the classification of these products. Data were submitted in support of
the Category IIIB classification of these whole body extracts and in
support of the use of pure venom extracts rather than whole body
extracts for the diagnosis and treatment of insect sting allergy.
b. Over 1,000 of the comments, a majority of which were form
letters, opposed the Category IIIB classification of food extracts.
Some of the comments made reference to specific food extracts,
including food extracts not proposed for classification in Category
IIIB, and other comments referred to food extracts in general.
The 1985 proposal discussed the Panel report, which stated that
extracts of manufactured foods or undefined source materials which are
mixtures or whose composition may vary from time-to-time should be
discontinued (50 FR 3082 at 3247). The comments did not appear to
recognize that native, single food extracts were not classified in
Category IIIB and will remain on the market until reclassification
procedures are completed. All Category IIIB food extracts are derived
from processed foods or mixtures. Examples of processed foods or
mixtures are those that are canned or contain added chemicals or
preservatives.
Five of the comments opposing the Category IIIB classification of
food extracts referred to information in published journal articles.
None of the articles contained data or information demonstrating that
any food extract classified in Category IIIB is safe and effective for
the uses described in the products' labeling. The journal articles
failed to cite data with satisfactory controls, did not identify the
manufacturers of the food extracts, or used allergenic products in the
studies that were not Category IIIB products.
c. Many of the same comments that opposed the Category IIIB
classification of food extracts also opposed the Category IIIB
classification of trichophyton, oidiomycin, and epidermophyton
(T.O.E.)\1\ molds involved in dermatomycosis. A small number of the
comments opposed the Category IIIB classification of certain extracts
of animal epidermals, plant oleoresins, insects other than winged whole
body hymenoptera insects, and miscellaneous inhalants. Several of the
comments referred to specific products that were not classified in
Category IIIB and were not subject to the 1985 notice.
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\1\T.O.E. is a mixture of various species of the three genera of
dermatophytes: Trichophyton, Epidermophyton, and Microsporum.
---------------------------------------------------------------------------
Until data from further studies are developed to resolve questions
of safety and effectiveness, FDA cannot agree with the comments
opposing the final classification of Category IIIB allergenic extracts.
The Panel, with public participation, carefully reviewed the available
data on these products. The Panel concluded that further testing was
required and that because of questionable benefit and/or potential
risk, these products should be removed from the market until the
questions concerning their safety and effectiveness were resolved. The
comments submitted no additional data to resolve the remaining
questions. Applicable provisions of the Public Health Service Act and
the Federal Food, Drug, and Cosmetic Act and implementing regulations
require that biological drug products be demonstrated to be safe and
effective through adequate studies and that such products not be
misbranded. In the absence of adequate data, FDA cannot determine,
based on testimonials alone, that the statutory requirements have been
met.
2. One comment questioned whether sheep wool extract that is
prepared from unprocessed sheep shearings, rather than from processed
wool, should be classified as Category IIIB. Manufacturers of sheep
wool extract did not provide any data on the safety and effectiveness
of their products for diagnostic or therapeutic use. FDA is not aware
of any data to support distinguishing the safety and effectiveness of
extracts prepared from processed sheep wool from the extracts prepared
from freshly clipped sheep shearings. The 1985 proposal discussed
suggestions by the Panel that unprocessed source materials from sheep
be investigated (50 FR 3082 at 3179). Until appropriate studies are
performed to establish the safety and effectiveness of these extracts,
all sheep wool and other sheep epidermal extracts are classified as
Category IIIB.
3. Washington Homeopathic Pharmacy, Inc., submitted a comment to
the 1985 notice, asking FDA to permit the firm to market its
preparation of Poison Ivy Extract, License No. 392, (Homeopathic Rhus
Tox. 3X Pills) as a homeopathic preparation and not as a licensed
biological product. Subsequently, at the manufacturer's request, the
establishment and product licenses were revoked on August 5, 1994.
The Panel recommended placing this product in Category IIIB because
there was no evidence of effectiveness of the product for either
prophylactic treatment or treatment of active contact dermatitis.
However, the Panel stated that FDA may wish to consider this product
differently because it is a homeopathic remedy that is highly diluted
in accordance with homeopathic principles (50 FR 3082 at 3271).
In the 1985 proposal the agency recognized the Panel's suggestion
that FDA may wish to consider this homeopathic product differently. FDA
responded by proposing that ``* * * this biological product should be
subject to the same regulatory procedures as other Category IIIB
biologicals'' (50 FR 3082 at 3282). The 1985 proposal stated ``* * *
The regulations in Sec. 601.25 (21 CFR 601.25) make no separate
provision for standards of effectiveness for homeopathic drugs'' (50 FR
3082 at 3271). Because FDA has reviewed the data concerning the safety
and efficacy of Poison Ivy Extract, manufactured by Washington
Homeopathic Pharmacy, Inc., License No. 392, and determined that there
was no evidence of effectiveness for either prophylactic treatment or
treatment of active contact dermatitis, FDA is denying the
manufacturer's request to permit the firm to market its Poison Ivy
Extract, License No. 392, as an over-the-counter (OTC) homeopathic
preparation.
4. Several comments expressed the view that some Panel members were
biased regarding their recommendations for Category IIIB classification
of certain extracts and that the Panel did not represent a wide
divergence of responsible medical and scientific opinion from various
medical groups or societies.
FDA disagrees with these comments. The Panel members were selected
on the basis of their qualifications to review allergenic extracts to
determine if they are safe, effective, and not misbranded for their
labeled uses. The members were not selected as representatives of
various medical societies. The members have had experience with
allergenic extracts and are exceptionally well qualified in the fields
of allergy, immunology, pediatrics, and the proper methodology for
conducting scientific investigations. Most of the members are
physicians who were engaged in active medical practice during their
Panel membership. FDA believes that the expertise of the Panel members
qualified them to review the safety and effectiveness data related to
all allergenic extracts. FDA finds no reason to believe that the
members did not represent an appropriate divergence of responsible
viewpoints.
5. A number of comments acknowledged the need for additional
studies to be performed on certain Category IIIB products. Several of
the comments stated that certain food extract products are effective
when used with techniques that are not indicated in the approved
labeling of the products.
Additional studies need to be performed on any allergenic extract
classified as Category IIIB. The Panel reviewed allergenic extracts to
determine whether the licensed products are safe and effective for
their labeled uses. There are allergenic extracts currently approved by
FDA for use in the diagnosis and immunotherapy of immunoglobulin E-
mediated (IgE-mediated) allergy to the respective ingested food. The
Panel was not charged with reviewing food extracts for uses not
contained in the approved product labeling. Nevertheless, the Panel
considered the use of food extracts in both IgE and non-IgE-mediated
allergy. Food extracts were discussed at 16 of the 32 Panel meetings
and all persons who requested an opportunity to appear were given time
to appear before the Panel. Although the non-IgE-mediated uses
discussed in the comments were contained in the approved product
labeling, the lack of available data on such uses justifies the
Category IIIB classification of those food extracts of processed foods
or extract mixtures prepared from undefined and variable source
materials. If studies are conducted to determine the safety and
effectiveness of an allergenic extract for uses not indicated in the
current labeling, the data accumulated from the studies as well as
revised labeling and other necessary information should be submitted in
the license application. Guidance on study design may be found in the
recommendations of the Panel, as discussed in the 1985 proposal
concerning further testing (50 FR 3082 at 3116 to 3123), and FDA's
``Draft Guideline for the Design of Clinical Trials for Evaluation of
the Safety and Efficacy of Allergenic Products for Therapeutic Uses''
(53 FR 48727, December 2, 1988). Any person who is considering
performing further studies may wish to consult with the agency
concerning requirements.
6. One comment asked FDA to use the same standards for reviewing
Category IIIB products that reclassification panels used to reclassify
Category IIIA products, including establishing a new panel to review
them, if necessary.
The issue raised by this comment was addressed in the final rule
establishing the reclassification procedures under Sec. 601.26, which
was published in the Federal Register of October 5, 1982 (47 FR 44062
at 44065). The agency's position has not changed since publication of
that final rule. Products placed in Category IIIB differ from products
that had been placed in Category IIIA in that the Category IIIB
designation represents a finding that the potential risks of marketing
a product outweigh the potential benefits and, therefore, the Category
IIIB products should not be marketed pending the completion of
additional studies. However, interested persons may at any time submit
to the agency for evaluation evidence that would be appropriate to
support the relicensing of a Category IIIB product.
C. Manufacturers and Products Affected
The 1985 notice included a listing of the Category IIIB products,
most of which were classified by allergen, rather than by manufacturer
generically. Where the extract is licensed to a particular manufacturer
under a specific product license or the specific manufacturer's product
was reviewed by the Panel, the listing includes the name of the
manufacturer along with that specific extract. The other Category IIIB
classifications for products listed generically represent Category IIIB
classifications for the corresponding specific company products of each
licensed manufacturer of allergenic extracts. Some products were listed
generically in Category IIIB for therapy and in a different category
(Category I or Category IIIA) for diagnosis. Other products are
manufactured and approved only for immunotherapy. Some of the companies
produce only a few Category IIIB extracts or none at all. A company is
subject to this notice only to the extent that the company produces a
product or products classified in Category IIIB. The currently licensed
manufacturers of allergenic extracts are again being listed below, for
informational purposes only:
------------------------------------------------------------------------
Licensed manufacturer of allergenic
extracts License number
------------------------------------------------------------------------
Allergologisk Laboratorium A/S....... License No. 9271
Allergy Laboratories of Ohio, Inc.... License No. 407
Allergy Laboratories, Inc............ License No. 103
Allermed Laboratories, Inc........... License No. 467
Antigen Laboratories, Inc............ License No. 468
ALK Laboratories, Inc................ License No. 334
Delmont Laboratories, Inc............ License No. 299
EM Industries, Inc., Center License No. 193
Laboratories Division.
Greer Laboratories, Inc.............. License No. 308
Iatric Corp., Inc.................... License No. 416
Meridian Bio-Medical, Inc............ License No. 448
Miles Inc............................ License No. 008
Nelco Laboratories, Inc.............. License No. 459
Parke-Davis, Division of Warner- License No. 001
Lambert Co., Inc..
------------------------------------------------------------------------
\1\Approved by FDA on January 9, 1985.
Since the Panel completed its review, Cutter Laboratories, Inc.,
including its Hollister-Stier Laboratories Division, has become a part
of Miles Inc., and the combined operations are now licensed under
License No. 008. In the following discussions and listings the
references to specific products manufactured by Hollister-Stier
Laboratories, or by Miles Inc., apply to the products manufactured by
those companies at the time the Panel completed its review and prior to
the merger of the two companies. This notice of revocation of licenses
concerning any products manufactured by either of the two companies
during the Panel's review applies to the current company (Miles Inc.)
licensed under License No. 008.
In addition, 11 manufacturers that each held a license for the
manufacture of allergenic extracts when the Panel was meeting,
requested that their establishment and product licenses be revoked as
follows:
------------------------------------------------------------------------
Date of establishment and product
Manufacturer licenses revocation
------------------------------------------------------------------------
Purex Laboratories, Inc., (License August 4, 1977
No. 306).
Endo Laboratories, Inc., (License No. August 20, 1981
147).
Pharmacia Laboratories, Division of February 24, 1982
Pharmacia, Inc., (License No. 556).
Riker Laboratories, Inc., (License July 3, 1985
No. 372).
Barry Laboratories, Inc., (License January 19, 1988
No. 119).
Pharmacia AB, Inc., (License No. 752) October 1, 1991
3M Diagnostic Systems, Inc., (License November 12, 1991
No. 896).
Mulford Colloid Laboratories, January 28, 1992
Division of Lemmon Co., Inc.,
(License No. 102).
Washington Homeopathic Pharmacy, August 5, 1994
Inc., (License No. 392).
Merck Sharp & Dohme, Division of December 6, 1978
Merck and Co. (License No. 002)1.
Lederle Laboratories Division of August 11, 1976
American Cyannamid Co., (License No.
17)1.
------------------------------------------------------------------------
\1\These two firms remain licensed for other types of biological
products.
On November 2, 1984, Optimal, Inc., was approved for licensure of
allergenic extracts (License No. 992). At the request of Optimal, Inc.,
its establishment and product licenses were revoked on January 28,
1992.
On April 20, 1988, Hermal Kurt Herrmann was approved for licensure
of the Allergen Patch Test (License No. 1056). Similarly, on July 12,
1990, Kabi Pharmacia Operations AS (now known as Kabi Pharmacia
Services A/S, as of November 2, 1993), was approved for licensure of
the Allergen Patch Test (License No. 1110). Neither Hermal Kurt
Herrmann nor Kabi Pharmacia Services A/S, holds a license for
allergenic extracts.
The following listing represents the agency's final determination
of products designated as Category IIIB except for the IIIB product
discussed earlier for which a hearing request is pending. Products
listed in Category IIIB Extracts of Food are foods that are processed,
mixtures, or have undefined ingredients.
The allergenic extracts placed in Category IIIB for their
particular uses are listed as follows:
Category IIIB Extracts of Mammalian Origin
------------------------------------------------------------------------
Diagnosis Immunotherapy
------------------------------------------------------------------------
Angora Wool, Rabbit and Antelope Angora Wool, Rabbit and Antelope
Hair Mix. Hair Mix
Beaver Fur......................... Beaver Fur
Caracul Fur........................ Caracul Fur
Chamois Skin....................... Chamois Skin
Chinchilla Fur..................... Chinchilla Fur
Ermine Fur......................... Ermine Fur
Fox Fur............................ Fox Fur
Fur Mix............................ Fur Mix
Gerbil Fur......................... Gerbil Fur
Kolinsky Fur....................... Kolinsky Fur
Lamb, Black........................ Lamb, Black
Leopard Fur........................ Leopard Fur
Marmot Fur......................... Marmot Fur
Mink Fur........................... Mink Fur
Mole Fur........................... Mole Fur
Muskrat Fur........................ Muskrat Fur
Muskrat Fur (Hudson Seal).......... Muskrat Fur (Hudson Seal)
Nutria Fur......................... Nutria Fur
Opossum Fur........................ Opossum Fur
Persian Lamb Fur................... Persian Lamb Fur
Pony Fur........................... Pony Fur
Rabbit Hair (Fur).................. Rabbit Hair (Fur)
Raccoon Fur........................ Raccoon Fur
Sable Fur.......................... Sable Fur
Seal Fur, Alaskan.................. Seal Fur, Alaskan
Seal Fur........................... Seal Fur
Sheep Wool......................... Sheep Wool
Skunk Fur.......................... Skunk Fur
Squirrel Fur....................... Squirrel Fur
------------------------------------------------------------------------
Category IIIB Extracts of Food
------------------------------------------------------------------------
Diagnosis Immunotherapy
------------------------------------------------------------------------
Anchovy/Herring/Sardine............ Anchovy/Herring/Sardine
Angostura Bitters.................. Angostura Bitters
Apple Mix.......................... Apple Mix
Bacon.............................. Bacon
Bean Sprouts....................... Bean Sprouts
Beechnut (Fagus sylvatica)
Beer............................... Beer
Buttermilk......................... Buttermilk
Cascara Bark (Rhamnus purshiana)... Cascara Bark (Rhamnus purshiana)
Caviar............................. Caviar
Cheese, American................... Cheese, American
Cheese, Camembert.................. Cheese, Camembert
Cheese, Cheddar (American)......... Cheese, Cheddar (American)
Cheese, Cottage.................... Cheese, Cottage
Cheese, Limburger.................. Cheese, Limburger
Cheese, Mozzarella................. Cheese, Mozzarella
Cheese, Parmesan................... Cheese, Parmesan
Cheese, Pimento.................... Cheese, Pimento
Cheese, Provolone.................. Cheese, Provolone
Cheese, Romano..................... Cheese, Romano
Cheese, Roquefort.................. Cheese, Roquefort
Cheese, Swiss...................... Cheese, Swiss
Cherry, Mix........................ Cherry, Mix
Chewing Gum Base................... Chewing Gum Base
Chili Powder....................... Chili Powder
Chocolate.......................... Chocolate
Cider, Apple....................... Cider, Apple
Cocoa.............................. Cocoa
Cocoa (Hersheys)................... Cocoa (Hersheys)
Coca-Cola.......................... Coca-Cola
Coffee(Coffea arabica)
Cola............................... Cola
Cola-Glyoune
Cream of Tartar.................... Cream of Tartar
Curry Powder....................... Curry Powder
Dr. Pepper......................... Dr. Pepper
Gelatin............................ Gelatin
Grape/Raisin Mix................... Grape/Raisin Mix
Grape, Raisin...................... Grape, Raisin
Ham, Smoked........................ Ham, Smoked
Honey.............................. Honey
Honey, Pure........................ Honey, Pure
Lactalbumin........................ Lactalbumin
Lactalbumin, Cow's Milk............ Lactalbumin, Cow's Milk
Lettuce Mix (Lactuca sativa)....... Lettuce Mix (Lactuca sativa)
Licorice (Glycyrrhiza glabra)
Liver.............................. Liver
Milk, Condensed.................... Milk, Condensed
Milk (evaporated).................. Milk (evaporated)
Mint Mix (Peppermint (Mentha Mint Mix (Peppermint (Mentha
piperita) and Spearmint (Mentha piperita) and Spearmint (Mentha
spicata)). spicata))
Mull-Soy........................... Mull-Soy
Molasses........................... Molasses
Muskmelon Mix (Cantaloupe/Casaba/ Muskmelon Mix (Cantaloupe/Casaba/
Honeydew/Persian) (Cucumis melo). Honeydew/Persian) (Cucumis melo)
Mustard, Prepared.................. Mustard, Prepared
Oatmeal............................ Oatmeal
Olive Mix.......................... Olive Mix
Onion Mix.......................... Onion Mix
Pablum............................. Pablum
Mixed Peppers (Red and Green)...... Mixed Peppers (Red and Green)
Pepsi-Cola......................... Pepsi-Cola
Plum/Prune Mix..................... Plum/Prune Mix
Popcorn Seed (Zea Mays)............ Popcorn Seed (Zea Mays)
Postum............................. Postum
Prune, Dried....................... Prune, Dried
Raisin............................. Raisin
Root Beer.......................... Root Beer
Saccharose......................... Saccharose
Saccharin.......................... Saccharin
Seven-up........................... Seven-up
Squash (Cucurbita pepo) varieties.. Squash (Cucurbita pepo) varieties
Squash Mix......................... Squash Mix
Sugar (Beet) (Beta vulgaris)....... Sugar (Beet) (Beta vulgaris)
Sugar (Cane) (Saccharum Sugar (Cane) (Saccharum
officinarum). officinarum)
Sugar (Maple) (Acer saccharum)..... Sugar (Maple) (Acer saccharum)
Sweetbreads........................ Sweetbreads
Syrup, Pure Maple.................. Syrup, Pure Maple
Tea, Black......................... Tea, Black
Tea, Green......................... Tea, Green
Tea, Mixed......................... Tea, Mixed
Tuna Mix........................... Tuna Mix
Vinegar............................ Vinegar
Worcestershire Sauce............... Worcestershire Sauce
Yeast (Saccharomycetaceae)......... Yeast (Saccharomycetaceae)
Yeast Mix (Bakers/Brewers)......... Yeast Mix (Bakers/Brewers)
------------------------------------------------------------------------
Category IIIB Extracts of Miscellaneous Inhalants
------------------------------------------------------------------------
Diagnosis Immunotherapy
------------------------------------------------------------------------
Animal Feed Mix.................... Animal Feed Mix
Balsam Sawdust..................... Balsam Sawdust
Binder Twine....................... Binder Twine
Cattail............................ Cattail
Chalk.............................. Chalk
Cleansing Tissue................... Cleansing Tissue
Cottonseed
Dacron............................. Dacron
Derris Root
Dust, Alfalfa Hay.................. Dust, Alfalfa Hay
Dust, Alfalfa Mill................. Dust, Alfalfa Mill
Dust, Auto Upholstery.............. Dust, Auto Upholstery
Dust, Barley....................... Dust, Barley
Dust, Barn......................... Dust, Barn
Dust, Brome Corn................... Dust, Brome Corn
Dust, Chicken House................ Dust, Chicken House
Dust, Clover Hay................... Dust, Clover Hay
Dust, Combined..................... Dust, Combined
Dust, Furniture Upholstery......... Dust, Furniture Upholstery
Dust, Hay.......................... Dust, Hay
Dust, Prairie Hay.................. Dust, Prairie Hay
Dust, Kafir........................ Dust, Kafir
Dust, Lespedeza Hay................ Dust, Lespedeza Hay
Dust, Milo......................... Dust, Milo
Dust, Oat.......................... Dust, Oat
Dust, Pea.......................... Dust, Pea
Dust, Pencil....................... Dust, Pencil
Dust, Poultry...................... Dust, Poultry
Dust, Rice......................... Dust, Rice
Dust, Road......................... Dust, Road
Dust, Rye.......................... Dust, Rye
Dust, Soy Bean..................... Dust, Soy Bean
Dust, Timothy Hay.................. Dust, Timothy Hay
Dust, Wheat........................ Dust, Wheat
Excelsior.......................... Excelsior
Fiber Glass........................ Fiber Glass
Flaxseed
Glue............................... Glue
Glue, Animal....................... Glue, Animal
Glue, Fish......................... Glue, Fish
Glue, Liquid....................... Glue, Liquid
Glue, Powdered..................... Glue, Powdered
Lampblack.......................... Lampblack
Linen.............................. Linen
Newspaper.......................... Newspaper
Newspaper Mix (Printed)............ Newspaper Mix (Printed)
Newspaper/Newspaper Print.......... Newspaper/Newspaper Print
Nylon.............................. Nylon
Paper, Carbon...................... Paper, Carbon
Paper, Mix......................... Paper, Mix
Paper, Pulp........................ Paper, Pulp
Rayon.............................. Rayon
Rug................................ Rug
Smoke, Cigar....................... Smoke, Cigar
Smoke, Cigarette................... Smoke, Cigarette
Smoke, Tobacco..................... Smoke, Tobacco
Tobacco Smoke Mixture.............. Tobacco Smoke Mixture
Snuff, Mix......................... Snuff, Mix
Spanish Moss....................... Spanish Moss
Tobacco, Cigar..................... Tobacco, Cigar
Tobacco, Cigarette................. Tobacco, Cigarette
Tobacco, Mix....................... Tobacco, Mix
Tobacco, Pipe...................... Tobacco, Pipe
------------------------------------------------------------------------
Category IIIB Extracts of Plant Oleoresins
------------------------------------------------------------------------
Diagnosis Immunotherapy
------------------------------------------------------------------------
Poison Ivy Extract, injection in
olive oil (IvyolTM), manufactured
by Merck Sharp & Dohme, Division
of Merck and Co. At the request of
the manufacturer, this product
license was revoked on December 6,
1978.
Poison Ivy Extract, Poison Oak
Extract, and Poison Ivy-Poison Oak
Extracts (combined), injections in
alcohol, manufactured by Hollister-
Stier Labs., Division of Miles
Inc.
Poison Ivy Extract, Alum
Precipitated (Aqua Ivy apTM),
injection, manufactured by Miles
Inc.
Poison Ivy Extract by Washington
Homeopathic Pharmacy, Inc.
Plant Oleoresin (for oral use
only); Plant Oleoresins Used for
Patch Testing and Oral
Immunotherapy; Wild Plants, as
follows:
Aster (Callistephus)
Bitterweed (Helenium tenuifolium)
Black-eyed Susan (Rudbeckia hirta)
Burdock (Arctium)
Burweed marshelder (Iva
xanthifolia)
Chicory (Chichorium Intybus L.)
Cocklebur (Xanthium commune)
Dandelion (Taraxacum officinale)
Dog fennel (Anthemis cotula)
Fleabane (Erigeron)
Goldenrod (Solidago)
Ironweed (Veronia)
Ragweed, false (Franseria
acanthicarpa)
Ragweed, giant (Ambrosia trifida)
Ragweed, western (Ambrosia
psilostachya)
Sagebrush (Artemesia tridentata)
Sneezeweed (Helenium microcephalum)
Wild feverfew (Parthenium
hysteroporus)
Wormwood (Artemesia absinthium)
Yarrow (Achillae lanulosa)
Domesticated plants, as follows:
Chrysanthemum (Chrysanthemum x-
morifolium)
Coreopsis (Coreopsis)
Corn flower
Cosmos (Cosmos)
Dahlia (Dahlia)
Feverfew (Chrysanthemum parthenium)
Gaillardia (Gaillardia)
Lettuce (Latuca sativa L.)
Marigold (Tagetes)
Shasta Daisy (Chrysanthemum
maximum)
Sunflower (Heliantheae)
Tansy (Tanacetum vulgare L.)
------------------------------------------------------------------------
Category IIIB Extracts of Molds Involved in Dermatomycosis
------------------------------------------------------------------------
Diagnosis Immunotherapy
------------------------------------------------------------------------
Dermatophytin, Hollister-Stier Dermatophytin, Hollister-Stier
Labs., Division of Miles Inc.. Labs., Division of Miles Inc.
Dermatophytin ``O,'' Hollister- Dermatophytin ``O,'' Hollister-
Stier Labs., Division of Miles Stier Labs., Division of Miles
Inc.. Inc. `
``T.O.E.,'' Hollister-Stier Labs., ``T.O.E.,'' Hollister-Stier Labs.,
Division of Miles Inc.. Division of Miles Inc.
``T.O.E.,'' Antigen Laboratories, ``T.O.E.,'' Antigen Laboratories,
Inc.. Inc.
------------------------------------------------------------------------
Category IIIB Extracts of Insects (Whole Body)
------------------------------------------------------------------------
Diagnosis Immunotherapy
------------------------------------------------------------------------
Bedbugs
Bee, Bumble........................ Bee, Bumble
Bee, Honey; used for stinging Bee, Honey; used for stinging
insect anaphylaxis. insect anaphylaxis
Bee, Sweat......................... Bee, Sweat
Beetle, Blister
Beetle, Dermestid
Beetle, Japanese
Beetle, Ladybug
Black-fly.......................... Black-fly
Box Elder Bugs..................... Box Elder Bugs
Butterfly
Caterpillar........................ Caterpillar
Caterpillar (tent)................. Caterpillar (tent)
Citrus Mealy Bugs.................. Citrus Mealy Bugs
Clear Lake Gnats................... Clear Lake Gnats
Cricket
Cicada/Locust
Cockroach (species not defined)1
Cockroach, mixed (species not
defined)1
Daphnia
Flea
Flea, Dog
Flea, Cat
Flea, Mixed
Flea, Sand......................... Flea, Sand
Flea, Water (Daphnia pulex)
Fruit Flies
Gnat............................... Gnat
Gnat, Black........................ Gnat, Black
Grasshopper........................ Grasshopper
Hornet............................. Hornet
Hornet, Bald Face.................. Hornet, Bald Face
Hornet, Black and Yellow Mix....... Hornet, Black and Yellow Mix
Hornet, Japanese................... Hornet, Japanese
Horsefly........................... Horsefly
Horsefly/Stable Fly................ Horsefly/Stable Fly
Housefly
Household Insects.................. Household Insects
Leafhopper
Locust
Mosquito
Mosquito Mix
Moth
Moth/Miller
Sandfly............................ Sandfly
Screwworm Fly
Sow Bugs
Spider
Spider Mix
Stable Flies....................... Stable Flies
Tick Seeds......................... Tick Seeds
Triatoma
Wasp............................... Wasp
Wasp Mix........................... Wasp Mix
Yellow Jacket...................... Yellow Jacket
Stinging Insect Mix................ Stinging Insect Mix
------------------------------------------------------------------------
\1\This does not include properly labeled Cockroach extracts, e.g.,
Cockroach, American; Cockroach, German; Cockroach, Oriental. (See
discussion of reclassification below.)
D. Category IIIB Alum Precipitated Extracts
In addition, alum precipitated allergenic extracts (Center-
AlTM), licensed for use in immunotherapy only, to Center
Laboratories, Division, EM Industries, Inc., Hawthorne, NY 11050, are
placed in Category IIIB whenever the corresponding aqueous products are
classified as Category IIIB.
Alum precipitated allergenic extracts, (AllpyralTM) licensed
to Miles Inc., are placed in Category IIIB if the corresponding aqueous
products are classified as Category IIIB. The only exception to this
statement is that Alum-precipitated Allpyral short ragweed pollen
extract is classified as Category IIIB because the Allpyral short
required pollen extracts have been studied most extensively and
information suggests that this product is not effective even though the
corresponding aqueous extract is currently classified in Category IIIA.
E. Extracts Recommended for Category IIIB by the Panel, but Placed in
Category IIIA by FDA, Subject to Reclassification
The Panel recommended that extracts of Cockroach, American;
Cockroach, German; and Cockroach, Oriental be placed into Category IIIB
for immunotherapy and Category I for diagnosis. However, after the
Panel completed its review, new relevant data were published that
justify reconsideration of the generic classification of these
products. A copy of these published data has been placed on file with
the Dockets Management Branch (HFA-305), Food and Drug Administration,
rm. 1-23, 12420 Parklawn Dr., Rockville, MD 20857. The Panel on Review
of Allergenic Extracts (Reclassification Panel) recommended that
Cockroach, American; Cockroach, German and Cockroach, Oriental extracts
be placed in Category I for immunotherapy. Accordingly, licenses for
Cockroach, American; Cockroach, German; Cockroach, Oriental; and
mixtures consisting of such extracts are not at this time being revoked
pending reclassification into either Category I or Category II.
In addition, the Panel recommended that extracts of beechnut (Fagus
sylvatica), coffee (Coffea arabica), licorice (Glycyrrhiza glabra), and
butterfly be placed into Category IIIB for both diagnosis and therapy.
However, the data relating to these products were rereviewed by the
Reclassification Panel, which has recommended reclassification of these
products into Category I for diagnostic use. Therefore, FDA believes
that the licenses for these products for diagnostic use should not be
revoked at this time, pending review by the agency of the final report
of the advisory committee containing the recommendations for
reclassification.
II. Findings
Based on the Panel's report and recommendations published in the
1985 proposal, and the agency's review of comments received regarding
the 1985 proposal and affected products, the product licenses for
Category IIIB allergenic extracts affected by this notice and the
authorization of manufacturers to produce the specific products under a
general product license for allergenic extracts are revoked. Except for
the outstanding request for a hearing from Parke-Davis, Division of
Warner-Lambert Co., Inc., concerning its injectable Poison Ivy Extract,
injection in almond oil, and the pending reclassification of specific
cockroach extracts and extracts of beechnut, coffee, licorice, and
butterfly for diagnostic use, the revocation of licenses for the
Category IIIB products listed or discussed above represents the
agency's final action on those allergenic extracts recommended by the
Panel for classification into Category IIIB. Any allergenic extract
placed into Category IIIB and subject to this notice may not be
lawfully marketed for its Category IIIB indication(s) (diagnosis and/or
therapy). However, if a product is approved for diagnosis but
classified into Category IIIB for therapy, a manufacturer may continue
to produce and market that product for diagnostic use if the labeling
for the product is amended to reflect only the approved diagnostic use
of the product. Specifically, the container and package labels and the
``Indications and Usage'' section of the package insert must state
prominently, ``FOR DIAGNOSTIC USE ONLY.'' This statement should
immediately follow the proper name ``Allergenic Extract'' or
``Allergenic Extract Alum Precipitate,'' in the same size and type of
print as the proper name. The ``Indications and Usage'' section of the
package insert must also include a statement that the product has not
been shown by adequate data to be safe and effective for therapeutic
use. These labeling requirements will be reconsidered by FDA if a
manufacturer presents acceptable evidence obtained from future studies
demonstrating that such labeling is no longer appropriate. Labeling
amendments for such products were required to be submitted to and
approved by the Director, Office of Biologics Research and Review (HFN-
825), Center for Drugs and Biologics, by February 5, 1986. Under an
organizational change separating the Center for Drugs and Biologics,
labeling amendments are now submitted to the Director, Center for
Biologics Evaluation and Research (HFM-481), 1401 Rockville Pike, suite
200N, Rockville, MD 20852-1448. The authorization for a manufacturer to
produce a product for which the labeling is not changed will be revoked
upon the effective date of this order. Any biological product marketed
without an approved license is subject to regulatory action.
FDA notes that the lists of allergens in the published documents
related to the Panel's recommendations may not include all marketed
specific products, partially because of the various systems of
classifications that have been used. For example, because of the large
number of pollen extracts available (at least 777 different pollen
extracts are listed in manufacturers' catalogs), those extracts were
reviewed by the Panel according to the botanical family of the plant
producing the pollen. The list of products in the 1985 proposal did not
include each specific pollen extract marketed. Consistent with the
Panel's own review, FDA will consider the data and information that are
available for any product not included in the Panel's list of products
in determining the classification of such a product. Any manufacturer
that is uncertain whether one of its products is included in the
Category IIIB classification should request a decision on the product's
status from FDA. The request should be submitted in writing to the
Center for Biologics Evaluation and Research (address above).
Except for an outstanding request for a hearing from Parke-Davis,
Division of Warner-Lambert Co., Inc., concerning its injectable Poison
Ivy Extract, injection in almond oil, and the pending reclassification
of specific cockroach extracts and extracts of beechnut, coffee,
licorice, and butterfly for diagnostic use, the revocation of licenses
for the Category IIIB products listed or discussed above represents the
agency's final action on those allergenic extracts recommended by the
Panel for classification into Category IIIB. FDA advises that any
allergenic extracts placed into Category IIIB shall not be introduced
or delivered for introduction into interstate commerce for its IIIB
indications on or after (insert date 30 days after date of publication
in the Federal Register).
This notice is issued under the Public Health Service Act (sec. 351
as amended (42 U.S.C. 262)) and the Federal Food, Drug, and Cosmetic
Act (secs. 201, 502, 505, 701 as amended, 1050-1053 as amended, 1055-
1056 as amended (21 U.S.C. 321, 352, 355, 371)) 21 CFR part 12, 21 CFR
314.200, 21 CFR 601.7, 601.8, 601.25, and under authority delegated to
the Commissioner of Food and Drugs (21 CFR 5.10).
Dated: November 3, 1994.
William K. Hubbard,
Interim Deputy Commissioner for Policy.
[FR Doc. 94-28193 Filed 11-15-94; 8:45 am]
BILLING CODE 4160-01-F