[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.

-----------------------------------------------------------------------

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.
---------------------------------------------------------------------------

    \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