NATIONAL CENTER FOR DRUGS AND BIOLOGICS 

FOOD'AND DRUG ADMiNISTRATION 

, PUBLICHEALTfl,SERVICE 

DEPAR~NT OF H£ALTMANn HUMAN,SERVICES , ,"'" '" ',' ,': ,:; '. ',,-. 

Panel on Review of 'Allergenic Extracts 
 

Category IlIA Reclassification, Final Report 
 

December 1983 
 

The Panel on Review of AllE!rgenic Extrac~s was re-establishedon . ;,.' -.' 

March 2, 1982 by a notige in the FEDERM.-,Rt:GISTER (47 FR 876). The 

Panel was reconvened to. rrr~l~ssify all~8signeci products previous'l,.y , 

J _ . " designated by review panels or FDA as Category IlIA". Categ~ryllIA 

applies to those licensed produ~ts judg~d to fall under the 4escription 

of 21 CFR 601.25 (e)(3), ~eaning thatt~e available data were sufficient 

to classify as ,~.afe and effective, but that the products shouldrf!Diain 

on the market p,ending further t~~ til13. Th.:: Category IlIA designaticrn 

was based on a£~vQ.F~ble potential ~nef1t-to-risk judgment. Reg""l.,a'" 

tions removing tne'C'ategory IlIA option and est'ab!ishing S~ctio'n 601.4:~: 

were published in, tRie FEDERAL REGISTER of Octobel:' 5, 1982 (~7 FR 4406'2;). 

The products assign~!1 to this Panel are the Polyvalent Bacterial < ' 

Vaccine (wit~ no U,_,-8. $tandard of Ppt'ency);ticens~,d to Cut~er La'i??racodes (42 F.R 582~.Q)AP'd _!ill products clasli!ified in C~tego~y IlIA , ',~ ~ ":.: .~_ .~, '. 1 ':.' -. ':.-""~ • • _,,;". 

in the report of ,t:he ::;'a~~l,~p. Review of All~tgenic E~tracts ,final f > ,.' • ',",>- , '. ' 

report of March 13, J~81, ~s ann!'unced in the Ap:ri1. 21, 1981 FEDERAL 

REGIST;ER (46 FR 22806.>. • • ~ .< -." • -". -.. ,"~"" 

The Commiss:f.oner of FOQd and Drugs i appointed the folloWing l'·anel , . ~. " ; 

members: 

Chairman, Paul M. Seebohm, M.D., Professor,Dep~rtment : '_1 ,...- I '. 

of Internal Medicine, Executive Associate Dean, C()11ege 

of Medicine, University of Iowa, Iowa City, Iowa. 
( 

-2­ ~, ~'.; 

". '. ,~: 

Elliot F • Ellis ~;<:,~i~'i;<;;f~9~~"~O,~'.:pn4· Chairman, Oepart­

,inent of pediatric~, S'Eai~ Untv~t~it:1 df N~i;tci~it'~t Buffalo, 

Childrens .. a9~,pii~f;B~~f4~9, (N~J"yO,:"k.~ :" ,.{ .' .." ~,L".· •. .'-, ~' ':<,;,~ _i ~"._'" .,:, '~'.;.' .,' ,'. " .:.'- " 

Clifton T. FurUkawa~~.D. ,clirilcal Associate Professor 

bf';PeJi~t:tics~ tin:f'v~fstty 6f w~~Kl.rigt()n~;'si!atHe/WaSl\ihtt~n. 

~iphHaie t Ii.f)., ;tiiriid!l:;'As~rj t~nt Prbfesso~'; of.' i

t~te~~iM~(Hcine, ~n!ia~;unf~~r~ity ~M~dicai' C~nter~ 

. '\ . ". .J. 

:""ba~id A.';I:~vY,M.]j~ ,.jp~6f~s~6r;cif imkulo16ky &'Infec­


. tious i'Di~eases', .Scho~i ofHygi~he a:riaiPublic H~~ith, johns 


>.:.) , ·.r ~,,;,'''.',. '; }.)., l~,'_,;- ., ';:i ~':. . ,. ". ·.·.1::." ,,," "<. ':".' •

Hopkins University,Baltimore, Maryland. 
 

""Fioyd J. &iv~~~~,' M~D. ,}'Ph~D~, A~so~i~te }ftofessor 
 

. olMedicin~ and Chai~~ ofAi1erg;:iIoward' btd.ver~ity; . . .

liosp:l.t:~f~iq~shington, D~C. 

Thom~~ t. vari Metre, Jr.; M.]).; AssOCiate 'Professor 

of MediCine, Johns ·Ho~k.ins Uriiv~'~slfy,;Physld.~~ inCharg~, 

A11~rgy .clinic,j~hnsIlopk:in~;Hosp:ital,'Bal't1more, Maryland. 

me} Corts~mef ti.!Hsbn R~presentat:l.v'e~as Mrsj~; B'arb~taMaet~yictah, ;.. 

261 Ringgoid Street, WaynEisboro,' Periilsylvaliia~ The"Industry Liaison 

Repr~;~~lit1ti~~' was Lowell ~eie~ni~k'~"ph;jj. ,nit'ector, Resekrchand 

Development, New Products Evaluation, Allerganph~:fm'~c:etiH.ca·ls, 'tne-., 

I~i~~~ dait¥~th:ta.·· ;Rgberi(i~' R~lstrian,"~.n:.~ ch.n:l.c~i .Pr~fe:ssor of 

Medicine and Pediatrics, State University of New York, served as'i:! 

consulta~{ ~o the panei:'tlay 's'i'sk,'J6fH~~ of S(d.~nt'tfi~Ad~isors & 

Consultants:':Nadonal"Center lor"Drugs'an'd" Bi6i~~fhs se~vea'- a~j Ex'~cutive 

,. ~'. Secretary. 
-3­

The Panel held reclassification meetings on November 19-20, 1982, 

February 18....19, 1983 and June 3~4, 1983. 

In the October 5, 1982 announcement, interested persons were 

requested to submit any new data for consideration by the review panel. 

A data submission was' received from Mi.les Pharmace~ticals, Division 

of Miles Laboratories, West Haven, Connecticut, in support of their 

"Allpyral" line of alum-prec:1.pitated allergenic e~tracts. A letter 

was received from Center Laboratories, Port Washington, New York, 

calling attention to information in support of the safety of ahuninum, 

a component of their "Center-Al" line of alum-precipitated allergenic 

extracts. 

Regarding the criteria for effectiveness, the October 5, 1982 

notice stated that it will be the obligation of the' Panel conducting 

the reclassification review to reexamine the scope of evidence currently 

available regarding the effectiveness of allergenic extracts and deterridne what the current practices are for the responsible assessment 

of their effectiveness. Furthermore, the Panel was charged with determining whether these contemporary: standards are readily applicable to 

each type of product under review. The standards should be consistent 

with av.ailable technology and readily obtainable through the use of 

clinical and laboratory methodol~gy that has already been recognized by 

the general scientific ~ommunity as practical and applicable to the 

products under review.· 

The Panel was asked to. recommend which products should be designated under §601.25(e)(l), called "Category I" and ~601.25(e)(2), 

---? called "Category II." An option was provided under §601.25(e)(2) 
ferthosept6duct'sre'cemmended:to'be designated as ·safe arid presump­ .,. 

-,. 

tively effective and to' remain on the tJiatketpend1:ngcoiDplet1en of 

further 'testing "bec8usetne're 1sa"colftpell'ing' tDedi(:alneed and 'no 

suitable 'alternative thl!rapeutie,prephylactic, ot' diagnestic s·gent 

needs ~ This· option was called '!Categery IIA. '!.. 

A. STANDARDS FOR PRODUCT CATEGORIZATION 

The Cede of'Pederal R.egulations • Title 21,'Sectien 601.25· (d) 

defines thestartdards·fer safety, effectiveness and labeling that:are 

to' be used by review panels in determining ,their recemmendatien for' 

the continued er discClntinuedmarketltig of currently marketed bt;elegics. 

It states that prcef 'of safety sheuld censiSt ef adequate tests to' show 

thebiolegical'preductis safe, including results ef Significant human 

experience durf,rtguse. lnthe case of, allergenic extracts , there has 

beert signif.fcant hliwmexperience which generally has -demonstrated that 

they are safe when prudentlY-administered. Serieus and fatal reactiens 

have eccurred follewing erters 'iIi dosage inassociatiOriWith their use 

iriboth diagnosis and treatment. The humber of stlchadvetse reactions 

has been few'cenSidering them±lliens of deses given 'annually over a 

peried·of-S6me70years~ "There are ,however; cencerns abeut the pctentia! t'oxi'city iQfsubstancesthat may be adi1ed to aIl~tgEmic extracts 

to' medify abserptien er in some ether manner affect their !ntigeriicity'. 

Currently,alumiriumis-aii ingredlertt'about'which fhere is· the greatest 

s~fety concern because'of'!tsalleged ass6Ciad6n-~t:h ortttigerteslsin 

.animals and pathologic ,findings in liumariBwnh·A1zhei~et·' sdisease:. 
-5­

Except for alum-precipitated allergenic extracts, safety was not 

judged to be a flignificant factor in the evalutionof ... Category IlIA

products when they are used in accordance with proper labeling instructions concerning the possibility of severe anaphylactic reactions. 

In contrast to safety, proof of effectiveness for the diagnosis 

and treatment of immunoglobulin E-medl,ated (IgE-mediated) allergies 

was the II14jor consiqerC}tion for the reclassification of the Category 

IlIA products into Cat~gory lor" II. In its reports of M,arch 13, 1982, 

report the Panel required evidence of adequate clinical investigation to 

classify a product into Category I. Chapter 601~25 (d)(2) provides 

several exceptions for the requirement of controlled clinical investigations when such investigations are not reasonably applicable to the 

biologic l'roduct or essential to the validity of the investigation and 

states that an alte"rnate method of investigation is adequate to substantiate effectiveness. 

Alternate methods suggested are: 

"Serological response evaluation in clinical studies 

and appropriate animal and other laboratory assay evaluations 

may be adequate to substantiate effec·tiveness where a. previously accepted correlation between such data and clinical 

effectiveness already exists." 

For example, if in fact clinical improvement in ha:yfever.were 

found to relate to the blood level if IgG antibody to a particular 

allergen, then one might r~late the capacity of an allergen to induce 

IgG antibody in a human to its clinical effectiveness. Although such a 

correlation between antigenicity of an allergen .to clinical effectiveness 
-.6­

hasnotbeene-stabiishe'd, 1 t is true thatt 'allergens shownto'be effec­

~,. .~,~,,., _ ' . :," ".:':-. -r,: ,- ,. ,'~ _:' _ .':.' r"., J' " '_ :' ': _. : ., - " ,- __:: . . tive in con'trci'fled clinfcliH tri'a1s 818'0' 'inducr('"spec1f1C:: tgG ant'ibodies. 

'SeroldgfEal resports 1venesstldgh't be 'used asamfriimurnrequitement 

in the' teticissificationdf lIrA; ptodtl'cis'.AlJ:ergeits'without a'nti'" 

geIrl.citf atenotiikely to be~linically effect:1"e. 

'ThetegulatloncOntinues : '''Investigatiorl,f iria:Y'be cot1:ob~rated by 

parti$11ycdritir6h~d" or urtcdrttroil.ed' 's'tud:f.es, dJ'chisberi:t ~d c:tinica1 

studie~'b:5"qi1a'l:tf'i~dexperts, ilrld repotts'of significant numan e~t... 

, 'iehJed\h~:fn.gmatket'1ng ." 

"'''Thi{'Panei 'considered' definitions of' these lateermetllods. 

'" 'iparda1ly controlled" cou1d'oie'an 'i:h~, 'pat+ertf is 'blinded to the 

identity 'of the study triater'ials, but the physidan"is riot, otv:f.ce Versa. 

1'1:: 'could aiso'meanthat the patient 'a pre-treittril~rtt condition is com­ " \ 

pared tohla cOnd:l.dondtiting treatment and/orhispost-tteat1l1ent condition. 

An "uncontrolled study" couldntean··a Clin:f.cal trial in which all 

patients took the sam~treatmE!nt; and the outcome was 'evaluated by 

the pliy'si~ian';;observersb'ased on the degree·bfimpro~emEmt reported by 

the patierits.· 

A "documented clinicaIstJdy·i by a. :iqtialified ~xpert" coula be a 

report of cases which appeared to be improved ot 'not i1ftprov~d as a 

result 'of their treatment .j Sucn studies couid be e:f.therplittichiy 

contfg±l~d ~ruricori.tro1:ied as stat~d above.'i'hetwo'comp&n~rit~ of this 

m~thodwere regJrdedas ind:i.stinguishabi~, that is, th~ qiiaiityof the 

. expert "fuust ·be judged by the quAiity·· of th~ d6cutn~rited study ahd vic~· 

, 

;j~t-sa~ ·:AvAlid~tudY appear1ftg in a peer-revie~~d journAl aricldescdbtng a series of patients ~ho are reactive ,to allergens and in whom 
-7­


injection therapy results in clinical improvement would constitute the 

· " 

'~ 

most important evidence for effectiveness. 

After considering the above criteria and the guidance in the preamble of the October 5, 1982 FEDERAL REGISTER, the Panel developed the 

following guidelines for recommending that a Category IlIA product be 

reclassified into Category I rather than Category II for diagnosis 

of IgE-mediated allergic disease: 

(a) The accumulated evidence indicates that the extract is safe. 

(b) The extract is derived from a well4fefined source materi.a1. 

(c) The extract has definable or measurable constituents and is 

capable of being standardize~. 

(d) The extract has been'demonstrated to be effective by skin 

testing in appropriately allergic and nonallergic subjects and/or by 

radioallergosorbent testing (RAST) with appropriate sera. 

(e) In lieu of (d) it is acceptable if tl1e extract is closely 

analogous to products shown to be effective. 

(f) The product is properly labeled. 

For Category I for use in immunotherapy of IgE-mediated allergic 

disease; 'the above criteria for diagnoSis must first be. met. In addition, an extract must be als,:, demonstrated to be effective for immunotherapy by a valid clinical study or by analogy with products for which 

effect,iveness has been shown. 

Category II· was recolninended for those products judged as not 

meeting the above criteria. In reviewing the 'conditions in §601.26(c)(2) 

the Panel does not believe this section applies to any of the products 
~8-

and #s~ase~~l1d~r .F~vlel!1~ 11l~.refore;n9 prodJ1c:~$a:t;e !r~comrpe~ded fot

-, 

. '1> 

Category I IA. 

B~ POLLENA.l.LERGENIC eXTRACJ'S ( , 

empl,oy~~L tr~q~en~ly .fqr ;d1agno~is 9f, a,lleJgi~ dj,sealile. vere classHie~, in 

Categ9;I.'Y I for di~gn9s1s".~n· ~J1.ep,rev1ous:.Panel reppr~ because P1;1blished 

studies indicated that they were effect1,v~ Jor d1aggos~s. '1.1:lerem~imJer 

were classified J.n Cfi:te~qt:YJ~IA, for d,ia,gn9~is becaus,e they had pot been 

sho~ .t9 )~~ effec~i v~ for .di~g'9,Olilis by avaUd cont.roH~d pUllli~lled 

accepted by practicing allergists or by the,(lllth()rs of ~tandard, 

allergy te:x;tboQks as, effective far,diagtJosis. They fall into tWQ groups 

which 

" 
 

/

; arei,d,entified in'l'abl,es 1 and 2. 

a. Group A. Group A .1", comprised of e~tracts afpollenswbich 

are r,el,a,t;::ed bot~~~cally;t;:o poll,ens i.n e~tracts w1:lichwere classified in 

Category I for diagnosis in the ,previous Panelrepo;J:'t •. ' A good e:x;a:mpl:e 

is southern ragweed (Ambrosieae bi4entata)e:x;trac;:t~hichJs.,closely 

reJ,B;tE:lcl to various ragweed extracts in, Catego.!"y, I f.or dia~ods ..The 

Panel is of t,he : '" opin;i,on 

", >. 

"that the most '. appropriate, ~, diagnostic allergenic 

extractfo,r a patiell.t, allergic tq a specific pollen~:pecies ·ts gen-, 

. e~a,1*ya,n e?tt;r~~t of,t;hat.~pec;i.fi,c speci~s ,of, pqll"en. ,Thqs, for all. 

allergic patient living where southern ragw~,ecl:gro~saIlc:L whqtsact1.1,slly 

.pollen , - . -~ ,'. i.s.8,pprop~:iateand . ; - . ". .'. - ".shouldbea;vailablefor ' '-, '.' '-. . - , us~ in dj,;agtJ:t)si$.

Thp~~h, ~y defillitipn, extracts of. ,po;l;L,ens in Gategpry l;II.t\.for M.a,g... 

nosis have not been proven effective, many of those pollens are related 
-9­


to others which have been proven effective in a valid study. The Panel or',. 

presumes that the Category IlIA diagnostic extracts listed in Table 1, 

if they were properly standardized, could be proven effective for the 

diagnosis of patients sensitive to those specific pollens if valid 

studies were done. Howev'er, such studies may never be accomplished 

because of the small demand for most if not all of the extracts in 

Category lIlA for diagnosis in Table 1. 

RECOMMENDATION. The Panel recommends that when properly standardized, 

those pollen extracts previously placed in Category IlIA for diagnosis 

and listed in Table 1 be reclassified into Category I for skin test 

diagnosis. 

b. Group B. Group B is comprised of extracts of those pollens 

which are not related botanically to pollens in extracts classified in 

Category I for diagnosis in the previous Panel report. A good example 

is the extract of common cattail (Typha latifolia). In these instances, 

there is no published evidence which indicates that pollens in these 

families are responsible for IgE mediated allergic diseases with symptoms of respiratory tract allergy such as hay fever. Neither is there 

evidence that positive skin tests and/or radioallergosorbent tests can 

be obtained with the specific pollen extract. The Panel is of the 

opinion that the field of allergy would be served best by taking such 

extracts off the market until there are studies which demonstrate that 

positive skin tests in patients are correlated with evidence of symptoms of respiratory tract allergy after exposure to the pollen. Such 

studies would demonstrate also that IgE-mediated respiratory allergy to 

these pollens does, in fact, exist. 
-10­


RECOMMENDATION. The Panel recommends th~ pollen extracts listed 

, ,.. ' ­

in Table 2 which were in Category ItIA be reclassified into Cate~ory tt 

for skin test diagnosis. 

2. Pollen extracts for immunothera.py. Few pollen extracts were 

classified in Category I for i.mmunotherapy in the previous Panel report 

because only these ~ew had been shown to be effective for immunotherapy 

I in appropriately controlled published studies. Many were classified in 

Category lIlA for immunotherapy. These Category IlIA extracts had not . . . .. 

been shown to be effective by ~ontrolied studies but rather they have 

been accepted by allergists and by the authors of standard allergy 

textbooks as effective for diagnotis a1\d immunotherapy. In some instances, they have been proven effective for diagnosis in a valid study. 

The extracts which were in Category IlIA for immunotherapy fall into two 

groups which are identified in Tables 1 and 2. 

--t " 

a. Group A. Group A Is comprfsed of extracts classified in the 

previous report in Category I for diagnosis, plus those classified previously in Category IlIA for diagnosis which are now recommended for 

reclassification into Category I for diagnosis of IgE-mediated allergic 

diseases such as hayfe'ver and asthma~ The Panel presumes that any 

properly standardized extract which is effective for such skin test 

diagnosis and, which contains an adequate amount of the significant 

allergens, is safe when properly employed and could be proven effective 

for immunotherapy by a valid clinical study. The Panel recognizes that 

controlled studies have not been done with these extracts because such 

studies are difficult, costly and time-consuming. Where a weed (e.g., 
-11­


short ragweed), a grass (e.g., timothy and orchard) ,or a tree (e.g .1, 

." 

mountain cedar) pollen extract has been teste! in an appropriate manner, 

it has been shown to be effective for immunotherapy. 

RECOMMENDATION. The Panel recommends that the extracts listed 

in Table 1 which were previously in Category lILA for immunotherapy 

be reclassified into Category I for immunotherapy. 

b. GroupB. Group B is composed of extracts classified in the 

previous report in Category IlIA for diagnosis and now recommended for 

reclassification in Category II for immunotherapy. For these extracts 

(listed in Table 2) the Panel has found no appropriate, published 

evidence which indicates that these pollens are responsible for IgE­

• mediated allergic diseases with symptoms of respiratory tract allergy. 

Neither is there evidence that positive skin tests and/or radioallergosorbent tests can be obtained vith the specific pollen extract. The 

Panel is of the opinion that the field of allergy would be served best 

by taking such extracts off the market until properly controlled studies 

are accomplished which prove that they are effective for diagnosis. 

Such studies should demonstrate also that IgE-mediated respiratory tract 

allergy to these pollens does, in fact, exist. When and if proven 

effective for skin test diagnosis, these extracts could be placed in 

Category I for immunotherapy as were the extracts in Table 1. 

RECOMMENDATION. The Panel recommends that the extracts listed in 

Table 2 which were previously in Category IlIA for immunotherapy be 

reclassified in Category II for immunotherapy. 
:-12­


....

. " _	not inclusive or all IIUltki!ted,pr,oducts ~ pil'rtiailyibecause .0'£ the various systems of classifications that. have been used. There£ore, the 

PaneL recommends that the FDA Office of Biologics Resea.rchandReview 

accept sitidlar evidence as ment;-ioned.above in considering the inclusion 

of other extracts of pollens .in>theindiVidua1 nufactur.er s U.cefUle. 

! " 
TABLE 1 

Pollen Extracts Recommended for Category I!! 

Previous Category 

Taxonomic Recommendations 

Classification Common Name Diag- Immunonosis therapy 

COMPOSITAE FAMILY COMPOSITE, SUNFLOWER 

Ambrosieae Ragweed Tribe 

Ambrosia artemisiifolia 

syn. A. elatior short: ragweed 

A. trifida 	 giant ragweed 

A. bidentata 	 southern ragweed .,) 

\, 

A. 	 psilostachya 	 western ragweed 

A. 	 confertiflora syn. franseria false or 

confertiflora or tenuifolia slender ragweed 

A. 	 a,canthicaJ;pa syn. Franseria 

acanthicarparpa bur ragweed 

A. deltoidea syn. F. deltoidea rabbit bush " - A. dumosa syn. Franseria dumosa bU,rroweed 

A. amhrosiaides syn. Franseria 

AmbJ;osiaides .canyon ragweed 

(Taxonomic Name not Supplied) wooly ragweed 

1/ Category I for skin test diagp,osia and immunotherapy. 

I 

I 

IlIA 

I 

IlIA 

IlIA 

IlIA 

IlIA 

IlIA 

IlIA 

IlIA 

IlIA 

IlIAIlIA 

IlIA 

IlIA 

IlIA 

IlIA 

IlIA 

I 
TABLE " I-con. ./',. Pollen Extrac1:8 Recommert1i~a for Category I 

-;.. " Previous Category

Taxonomic Recommendat ions 

Classl,fication. Common Name Diag- ImDiUno~ 

nosis th~.rapy :,~ '-'~ ':: ." ~;~. 2 .: 

COMPOSITAE FAM:q'.Y~-C(m, ..'CQf1l'OSIT]!:, SJINFLOWER 

Iva "',Ragweed Tribe ............ 
 

Iva xanthifolia syn. cyclachaeJl~t. 

xanthifolia burweed Marsch elder '. 'lIlA' 

I':. annua syn. ciliata toUgh marsh elder utA 

I. ftutescens high' tide bush IlIA iIU 

1..\"microcephala ILIA 

!.~,artgustifo11a IlIA ;t,tn 

I. toxensis lItA " TiIA 

I. axillaris poverty weed 'IlIA 

I. acerosa 'IitA 'ITIA 

I.rievadensis tttA.•··].];t1\.'.' 

I.' 'ambrosiaefo'li a IltA '"tIIA 

Hypienoclea Winged ragweed' IlIA' " IlIA 

Dicoria "',i'tIA 

'. ~ . 'c1!'i'c:oria cocklebur 

(.' ,_ ,,1". _"j Anth'enildeae Tansy'Tribe ;- ;' 

Arthemisia common sage brush I ILIA 

A. fi1ifo11a IlIA""
-15­

TABLE l--con. , ,r'

• Pollen Extracts Reco~nded for Category I 
-16­

.,. '. PollertExtracts,RecotJUnei'ldedfor Category I 

Previous Cate~ory 

T~xonotni,c Recommendations 

C1as's1£fca t ion Diag;;"; 'Immuno'" 

nosis therapy 

AMARANTHACEAE FAMILY 

Amaranthus retrof1exus 

A.' P~lmer1 

/ 

1 

!.. spinosus 

Other Amaranthus species 

Acrtida tamariscina 

CHENOPODIACEAE FAMILY 

Salsola pestifer 

Salsola species·, 

Kochia scoparia 

(

'-. 

Chenopodium album 

Chenopodium spedes 

Atriplex species' 

Bet4'w1garis, . 

CANNABINACEAE FAMILY 

Canriabis 

Hu~lus 1upu1us 

H. japonica 

cOllllnOn, rough, or redroot pigweed I IlIA 

carelessweed, Palmer's 

~iilaranth I rItA 

spiny amaranth I 

None 

western water hemp ,IlIA 

CHENOPOD, GOOSEFOOT 

Russian thistle I UtA 

burning bush, Mexican 

firebush, summer cypress I IlIA 

1amb's-quarter I IlIA 
 

None None 
 

saltbush IlIA tllA 
 

sugar beet I fitA 
 

hemp I iitA 

hop, common I IlIA 

hop, Japanese I IlIA 
-17­

TABLE 1--con. .,. 

'", 

Pollen Extracts Recommended for Category ! 

Previous Category 

Taxonomic Recommendations 

Classification CotlUllOn Name Diag- Immuno... nosis therapy 

PLANTAGINACEAE FAMILY 

Plantago lanceolata 

P. 	 major 

P. rugel 

POLYGONACEAE 	 FAMILY 

Rumex acetosella 

R. crisp!!!. 

R. obtusifolius 

R. hymenosepalus 

GRAMlNEAE FAMILY 

Festuceae 	 Tribe 
 

Bromus mollis 
 

B. inermis 

B. carinatus 

B. secalinus 

B~ rigidus 

Other Bromus species 

Festuca elatior 

F. rubra 

F. ovina 

PLANTAIN 

English plantain 

BUCKWHEAT 

sheep or red sorrel 

dock, curley 

dock, bitter 

canaigre 

GRASS 

brome, soft chess 

smooth brome 

California brome 

brome chess 

ripgut grass 

meadow fescue 

red fescue 

sheep fescue 

I 

IlIA 
 

IlIA 
 

I 

lIlA 

IlIA 

I 

I 

I 

I 

I 

None 

I 

I 

I 

IlIA 

IlIA 

lIIA 

IlIA 

lilA 

lIlA 

IlIA 

IlIA 

IlIA 

IlIA 

IlIA 

None 

IlIA 

IlIA 

IlIA 

1114 
l 

-18­


, 

.. ,.

Previous Category 

Taxonomic Recommendl:ltiQns 

Classiiication , CO"'moJl Name Diag-. t~no;" 

nosis "therapy 

GRAMlNEAE FAMILY--con. 

Festucease Tribe 

Daetylis glo~erulata 

Poa'prat;ensi$ 

P. 	 compressa 

P. annua 

P~ ttivialis 

Hordese 	 Tribe 

Agrbpyron repens 

A. Smithii 

Triticum aestivum 

Hordeum jubatum 

H., ,nfurinum 

Lblium perenne 

L'~nfultifloru'ln 

L.lf,ementuluui 

Se~a1.e cereale 

Averie~e Tribe 

Kolaus lanatus 

AVella fatua 

GRASS 

orchard, cocksfoot 

June, meadow 

,Canad,~ bluegrass 

apnual bluegrass 

r01,lgh,bluegrass 

ClHB:ckgrass, couchgrass 

western wheatgrass 

wheat 

fo~tail barley 

mOllSt! barley 

pe,rennial ryegrass 

I,talian ryegrass 

;c,l~r}lel 

rye 

veJ,.yet? Yorkshire fog 

wild oat 

I I 

I I,IIA 

I lUA., 

I lIlA 

I IlIA 

I ~lJ4\. 

I :UlJ. 

I lIlA .­

I :UIA 

I IlIA 

I IlIA 

I IlIA 

I III1\. 

I IlIA --,". 

I IlIA 

I IlIA. 
-19­

TABLE l--con. 

Pollen Extracts Recommended for Category I 

Previous Category 

Taxonouiic Recommendations 

Classification Common Name Diag- Immunonosis therapy 

GRAMlNEAE FAMILY--con. 

Aveneae Tribe 

A. barbata 

A. sativa 

Koeleria cristata 

Agrostideae Tribe 
 

Phleum pratense 
 

Agrostis alba 
 

Chlorideae Tribe 
 

Cynodon Dactylon 
 

Boutaloua 
 

Phalarideae 	 Tribe 

Anthoxanthum oderatum 

Phalaris minor 

P.arundinacea 

P. canariensis 

Paniceae 	 Tribe 

Digitaria sanguinalis 

Paspalum 

GRASS 

slender wild oat 

cultivated oat 

western June grass • 

timothy 
 

redtop 
 

Bermuda 
 

grama 
 

sweet vernal 

Mediterranean canary 

reed canary 

canary 

crab 
 

dallis 
 

I IlIA 

I IlIA 

I IlIA 

I I 

I IlIA 

I IlIA 

IlIA IlIA 

I . IlIA 

I IlIA 

I !IIA 

I !IIA 

I IlIA 

I IlIA 
-20­


Pollen EXtracts Recou!mended for C~tegory 1 

Previous Category 

Taxon6tnic Recommend'atiat\s 

Classiffeation Common Name Mag- clmmurio'" 

nosis therapy 

GRAMlNEAE FAMILY--con. 

Andropogoneae Tribe 
 

Sorghum halepense 
 

,[. Vulgare 
 

Trip~~acrae Tribe 

CONIFERAE FAMI~Y 

• Cupressinae 

Juniperus sabinoides (mexicana) 

j. virginiana 
 

.J.bermudiaria 
 

J. Pinchotii 

j. osteosperma 
 

J; 1Jlonosperma 
 

,'.. 

Other Junipurus species 

Cnamaecyparis Lawsoniana 

Cupressus arizonica 

C•. sempervirEms 

GRAsS 

J6hnson 

sorghum 

I 

IlIA 

IlIA 

IlIA 

maize, Indian corn, corn 

CONIFER 

I 

Junipers, CyPresses and Cedars' 

IlIA. 

mountain cedar 

red cedar 

BerlliUda cedar 

red....berried juniper 

·Utah juniper 

orte~eede4 juniper 

Port Orford cedar or 

cypress 

Arizona cypress 

Italian or Mediterranean 

cypress 

I I 

tlIA ~ .IlIA 

IlIA .. IlIA 

IlIA IlIA 

IlIA lIlA 

IlIA lIlA 

Norie None 

IlIA III 

"1 II.IA· 

I IlIA 
-21­


TABLE 1--con. 
 "/',. Pollen Extracts Recommended for Category I 

Previous Category 

Taxonomic Recommendations 

Classification Common Name, Dlag- Immunonosls therapy 

CONIFERAE FAMILY--con. 

Cupresslnae 

C. lusltanica 

C. macrocarpa 

C. torulosa 

Cryptomeria japonica 

Libocedrus dacurrens 

Thuja 

Abietineae 

Picus 
 

Picea 
 

Abies 
 

Tauga 
 

Taxodineae 

Taxineae 

CASUARINACEA FAMILY 

Casuarina 

SALICACEEAE FAMILY 

Salix 

CONIFER 

Junipers. Cypresses and Cedars 

Mexican or Portugese 

cypress I IlIA 

Monterey cypress I IlIA 

Indian incense cedar I IlIA 

Japanese cedar I IlIA 

incense cedar IlIA tlIA 

white cedar, arborvitae IlIA IlIA 

Pines, spruces, and firs 

pine IlIA IlIA 

spruce IlIA IlIA 

firs IlIA IlIA 

hemlock IlIA IlIA 

Bald cypress and sequoias IlIA IlIA 

Yews IlIA lIIA 

BEEFWOOD 

Australian pine I IlIA 

WILLOW, POPLAR 

willow IlIA IlIA 
-22­

TABLE 1-1:on. '/ 

.~ 

Pollen Extracts Recommend'ed lor Category,. I 

Previous Category 

TaxO'ijollQ,¢ Recommendat,:i;o.ns, 

C1assifi·ca:tion Common Name Diag­ . ;Immti.rtonosis therapy 

SALICACEEAE FAMILY 
 

Populus albus 
 

P. tremuloides 

P. d'eltioides 

P. nigra 

JUGLANDAGEAE FAMILY 

/ Jugla:ns californica 

J. nigra 

J. cinerea 

J. regia. 

Othet.Juglans species 

carya.pecan 

C. ova:ta 

C. glabra 

C. myristicaefotmis 

Other earya species 

BETULACEAE 	 FAMILY 

Betula' 

Alnus species (, 

WILLOW, POPLAR 

poplar, white or silver 

poplar, aspen 

poplar, cottonwood 

poplar, Lombardy 

WALNUT, HICKORY 

California black walnut 

black walnut 

butternut 

English walnut 

peca:n 

shellbark hickory 

whi·teheart hickory 

nutmeg hickory 

BIRCH 

birch 

alder 

I IlIA 

I IlIA 

I IlIA 

I lIlA 

I IlIA 

I lIlA 

IlIA trIA 

IlIA IlIA 

I .IlIA 

I IlIA 

I IlIA 

I IlIA 

None None 

I -: , IlIA 

IlIA .~. IlIA 
-23­

TABLE l--con. 

Pollen Extracts Recommended for Category I 

Previous Category 

Taxonomic Re commendati()O$ 

Classification CotmJlOn Name Diag- Imml.lrionosis therapy 

BETULACEAE FAMILY--con. 

Carpinus 

Ostrya species 

CoryIus 

MYRICACEAE FAMILY 

Myrica cerifera 

FAGACEAE FAMILY 

Quercus species 

Fagus grandifolis 

F. 	 sylvatica 

ULMACEAE 	 FAMILY 

Ulmus americanus 

U. rubra 

u. 	 glabra 

u. 	 pumila 

u. crassifolia 

u. serotina 

u. racemosa 

u. alata 

BIRCH 
 

American hornbean, 
 

ironwood 

ironwood, hop-hornbeam 

hazelnut, filbert 

BAYBERRY 

wax myrtle 

BEECH, OAK 

oak 

American beech 

European beech 

ELM 

American elm 

slippery elm 

English elm 

Chinese elm 

cedar or scrub elm 

September or red elm 

cork elm 

winged elmIlIA IlIA 

IlIA IIIA 

IlIA lIlA 

IlIA IlIA 

I IlIA 

IlIA IlIA 

IlIA IlIA 

I IlIA 

I IlIA 

I IlIA 

I IltA 

I IlIA 

I IlIA 

I IlIA 

1 IlIA 
TABLE l--cQo • 

'r

.... Pollen Extrac;ts Recommended fpr Category I 

Previous Category 

Taxoriomlc Recommendations 

ClssS'ifi'dat·ion ..;.-~~ .: Common Name niag-I_rio'"

nosis, '.therapy 

ULMACEEAE FAMILY--con. 

Planera wate~ elm I IlIA 

Ce~t isoccidetltalis hClckberry lIIA IlIA 

Argentine hackberry 

or tala IlIA IlIA 

OLEACEAE FAMILY O~IVE. 

Fra~1tlus americana white ash I II~ 

F. pennsyvanica red ash I lIlA 

F. tEp~ana gre.~~ ash I lIlA 

F. velutina mountain ash I IlIA 

91:'egcm ash I IlIA 

Other Fraxinus species Non~ None 

olive I IlIA 

IlIA IlIA 

PLATANACEAE FAMILY SYCAMORE 

Pla1;:an~s occidentalis common <!"" • native sycamore I IlIA 

P. Qrientalis ori~ntal plane tree I IlIA 

1:. acerfolia London plane tree I IlIA 

f.. r.acemosa we~tern sycamore I IlIA 

HAMAMELIDACEAE FAMILY SWEE'J; GUM 

Liguidambar styraciflua sweet gum IlIA IlIA 

( 
-25­

TABLE I-con. 

. " 

Pollen Extracts Recommended ·for Category I 

Previous Category 

Taxonomic Recommendations 

Classification Common Name Diag- Immunonosis therapy 

ACERACEAE FAMILY 

Acer saccharinum 

A. 	 rtegundo 

A. 	 rubrum 

A. 	 platanoides 

A. 	 pseudoplatanus 

A. 	 saccharum 

TILIACEAE 	 FAMILY 

Tilia americana 

T. europaea 

MIMOSACEAE' FAMILY 

Acacia 

Prosopis juliflora (syn. glandulosa) 

SIMARUBACEAE FAMILY 

Ailanthus altissima 

MORACEAE 	 FAMILY 

Broussonetia papyrifera 

Morus alba 

Morus rubra 

Maclura pomifera 

MAPLE 

silver maple 

box elder, Manitoba maple 

red maple 

Norway maple 

sycamore maple 

sugar maple 

LINDEN 

American linden (lime, 

basswood) 

European linden 

MIMOSA 

Acacia 

mesquite, kiawe 

AILANTHUS 

tree of heaven 

MULBERRY 

paper mulberry 

white mulberry 

red mulberry 

osage orange 

I IlIA 

I IlIA 

I ILIA 

I lIIA 

I IlIA 

I IlIA 

I IlIA 

I IlIA 

IlIA IlIA 

I IlIA 

I IlIA 

I IlIA 

I lIlA 

I IlIA 

I IlIA 
-26­

TAStE < l--:cpn.

-,­

Pollen Exttac'ts 'Recommended for ,;Category I 

Previous Category 

Taxonomic ," Recommenda,tiona 

Class'if-ica.'iion COllUllOn Name Diag~'v,; ;Immuno,.. 

noBis therapy 

URTICACEAE FAMILY NETThE 

Urti.cadioica (syn. U. gracilis) 'great nettle IlIA 

U. urens " dwarf nettle I IlIA 

Pat\ietaria officinalis wall-pellitory I lILA 

• 

( 

.",' 

! 

! -......,- .. 
-27­

TABLE 2 

Pollen Extracts Recommended for Category II 

Previous Category 

Taxonomic Recommendations 

Classification Common Name Diag- Immunonosis therapy 

CYPERACEAE FAMILY SEDGE 

Carex sedge lIlA lIlA 

JUNCACEAE FAMILY RUSH 

Luzula wood rush lIlA lIlA 

TYPHACEAE FAMILY CATTAIL 

Typha latifolia common cattail lIlA lIlA 

!.. augustifolia narrow leaf cattail lIlA lIlA 

ARECACEAE'FAMILY PA"J.JJ../ 

Phoenix dactylifera date palm lIlA IlIA 

Sabal cabbage palm IlIA IlIA 

II (Following completion of the Panel Review, letters were received 

from two physicians in Palm Springs, California in support of palm 

pollen extracts, stating that strongly positive skin reactions to 

palm pollen extracts occur and that palm pollen sufficiently disperses 

in the environment to cause symptoms. This suggests that it may be 

appropriate to designate palm pollen extracts in Category I. 'As 

with other new information which is submitted following the Panel 

----' .. 

meetings, the FDA will consider available data before making final 

! • 

1 category designatioys.) 
-28­

I 

C. EXTRACTS OF KAMMALlAN AND AVIAN ORIGIN ,

.1 

1 

1. Extracts ofmalDJlial1an Qrigin for diagnosis. ,Tile mammalian 

',", ;""r"'~''',''';,'",:, ',," ; 

I 

exttacts JDOS,t frequently employed for diagnosis of allergic diseases 

(i.e., cat, dog and horse) were 'classified in Category I for diagnosis 

irithe original Panel report ,beqause studies acceptable to thePan~1 

indicated that they were effecqve and safe for diagnosis of IgE-uaediated 

allergies. 

, 

The remainder of these ma~lian Category lILA extracts are ! ! 

,.e~plpY~4'. fQJ:" ::dl~~~qsf~ •• ~~j~:'~~;f1~;}j~~:f"',~~~,~J~:()~"i~~:,b~,"'~~':'~~E~,f~~,~'?,j:}:~,>,,;;,<;;:/> ".;>:,,; , 

Bec~X~~t~:y•had' nbtbeei1' ~ho~':t'~':~s~f~'a~d"~f fe~t 1;~f ~'~'di~;osi~iX'><' ,', 

by studies judged adequate by the Panel, most of them were classified in , I 

Category lILA for diagnosis except those from processed furs which were " ',I 

in Category IIIB. These CategorJy lIlA diagnostic extracts tend to fall 

, I 

into two groups. 	 1 ( 

a. Group A. Group A iS~xaC,'~,:,n"',,Oed.edinOsfomeextracts whose compo~~tion 

and allergenfcity have been ~n, detail. ' The composition 

and 	 allergenicity of extracts OfiI cow, guinea pig, mouse, rabbit, and 

I 

rat hair, hair and dande,r and/orl pelt ,have been studied in some detail, 

as noted in the Panel's Orig~nall report. There is conclusive evidence 

! that extracts in this group cont in one or more potent allergens and 

that each is capable of inducing a typical IgE-mediated wbeal and flare '"i " -	 ;' I' 

skin reaction in individuals wit a well-documented history of allergy 

1'.. ; ,',';:' c .. :, ".. I .. 	 " "', 

to the particular animal species: in question. However. none of the 

; "", ,I ,',,' , :": " " , " , 

reported studies' ai~d at provin~ their efficacy for' diagnos18 is vlth­

, ,!;' 'J,: ,,' 

out fault. Nevertheless. the Pa~el i8 of the opini~n that properly .. I. 

standardizedpreparations,~f exttacts from these five anJ.ulspecles ! 
-29­


would be proven safe and effective for diagnosis of specific allergic 
 

-'"
 -. sensitivity in appropriate pa_tients. However, such studies may not be 

accomplished because the demand for these extracts is relatively limited 

and because the high cost of these studies would make them impractical. 

The Panel is of the opinion that, if properly manufactured and standardized, their safety and efficacy would be equivalent to these extracts previously classified in Category 1 for diagnosis. 

b. Group B. Group B is composed of extracts whose composition 

and/or allergenic potency is largely unknown. The allergenicity of some 

of them has been demonstrated in only a small number of specifically 

sensitive individuals according to descriptions in a few pub1i~hed 

reports of uncontrolled studies or in one or another allergy textbooks, 

that is, it is based on anecdotal evidence. 

For most of these extracts, it would be difficult to assemble 

enough individuals who are sufficiently sensitive to the animal in 

question to conduct an adequate study of their safety and efficacy. 

Nevertheless, by analogy with extracts in Category I-for diagnosis, the 

Panel is of the opinion that, if properly manufactured and standardized, 

safety and efficacy would be equivalent to those previously classified 

in Category I for diagnosis. 

There are exceptions to this statement, namely, with reference to 

human dander extracts, human hair extracts and extracts of leathers. 

The published evidence for the existence -of IgE-mediated sensitivity of 

humans to allergens of human origin is not convincing. Likewise, the 

(

, 
." seJlSitiv,~ty toh\llJlan allergens 1s equ1voc:8~. ·f.eathers are prepared trom -;. .: -:: ' , . .~: . _ .'-' '", - _ \ . . ~ i . , " : '.' - ,- " . .; .,_" ..... -: : :.'_ " : -, ," "~ '-.' \" " .' .'. "'. ,c. • .' 

.ant,Jll81~*ins py ta?ning. or a si,~lar denat\lring proce~~ which r,es\llts in 

the :1nc,(u:pora,tion oJ vari<;l\lS ctll'!micals in,to the., ski.ns. Th,erefore, where 

i ta,ct~alJ;yexi.sts ,sens!tivity to leatlle~ may be d\le to these ..add1 tives ;. - ,. - .' '. . , " -,. - -: -, 

and n.otto the native~IDID:8HaIl proteins. , .": ' ., 

RECOMMENDAT}:ONS. ~e Panel. r.ec9mmends. ~ha,t.'with .theexception of 

extracts of ~u~n ~ander,. ~.uman hair and le~thers, pr0J)erly standardized 

reclas,sif:ied :into Ca~E!gory ,1f.or 4i,agno~.is ('r:abl~ 3). Bre.eds mar ~ 

specif,ied J~l~ho~ghthe,re .~s .. H,t~l~ ev;tdencej\ls.tifyingthi;~. :tt is 

rec,o~m,e;Ilded tj:lat extracfs .of h~man daIlder,' human h,air f1~d leather.s b¢ 

{ reclassified into Category II f.or diagnost~ (Table 4)., '\ 

c., ,:Extra,cts of. ;pJ:'9ces~~dJ\lr,!.3. In the Panel's .original,. r.eport, 

extracts .ofpr.ocessed furs, were clas"sifi.ed.inCategory IUB for d,.;f.a,g.. ~' ., _ ) ~-';.' - 1:' _:';, '.- ,.'. . .:;" .: _, " .:.. . . _, - . _ . ; . . .' '. ',; ..' '.. - -". ~. 

nosis. It il;l J:l'1t! op:i.qion .o;th~ Panel t.ha,t t;h~r~. is non~w ra:v:l,cl~;nC7~i!, 

to sug~~t;:I,t ,that proc~~~gq ~u+l?at;r~~e :$,ou;r~~ Qt.sp,e~ira!3~P,~};f:f,Jc 

al1ergenicsubstan,cel;l. ... __-~ L ,. ",' _, .;.} ;". .~' - - : ,"' " ", T\1ePalld _ _ ", !.~. ,"':<, +e~Qgnizep _. . ., ' _ thatEloJIie '.'.' or • . , the ... ~x;tr~~t:s . -. . 

listed in Table 1: might be prepa;red Jr~~.pr:pces,s~d flP;S eV:.en .t:hough 

data originally submitted by the manufacturer!:!, d:i.d not ident:f"fy the, 

source materials as prq~e~sed {~rs.anq, thus" thi,s :i.~.emph~s:l"z~~ ,in 

Table 3. '.~. ",- ' ,: f _ <" 

2. Extrac,t,s. Qi,roalllmaliaJl odi:Lnfor. iJllllN,llothe~~w. ,:ti91l1a~li~p 

ext+acts ~ere classifie,d,1:n Ca,t;egory, ,1; f,qri,1D.IIlt.lllotherapyi,n th~ PaI}e;t's 

or~ginal report because none had been shown to be safe and effective 

{ 
-31­

for immunotherapy in studies acceptable to the Panel. Recent placebo0/ 

controlled studies of immunotherapy for allergy to cats and/or dogs. 

including one that has been reported as an abstract <Ohman, J. L., 

Double Blind Trial of Immunotherapy in Cat Induced Asthma, Journal of 

Allergy and Clinical Immunology, 71 (Supplement):91, 1983) and another 

in progress in Scandinavia suggest significant clinical improvement 

following administration of an extract of known potency. 

Moreover, extracts of cat, dog and horse have been shown previously 

to be effective for diagnosis and were placed in Category I for diagnosis. They were regarded as probably effective for immunotherapy and 

were placed in Category IIIA for immunotherapy. Extracts that were 

classified in Category IlIA for diagnosis in the Panel's original report 

were also classified in Category IlIA for therapy. The Panel recognized 

\ 

that the appropriate studies have hot been done (and may never be done) 

with most of these extracts because such studies are difficult, costly 

and time-consuming. The Panel believes that if the presently available 

evidence for safety and efficacy of cat extract is confirmed by additional evidence, then any properly standardized, potent mammalian extract that is effective for diagnosis likely would be proven effective 

for immunotherapy if an adequate placebo-controlled study were conducted. 

RECOMMENDATION. The Panel recommends that extracts of the mammalian 

species that previously were in Category I for diagnosis or are 

now being reclassified into Category I for diagnosis be reclassified in 

Category I for immunotherapy (Table 3). Breeds may be specified but, 

as for diagnosis, there is no evidence to j~stify a requirement for 

breed identification. Mammalian extracts that are now classified in 
-32­

Category I! for diagnosis sbouldbe reclassif1edinto Category: It for 

.... 

.,. .. ~ \. 

f 

\. 

3. E~tracts.ofavial\.'or1gin fordiagnosh. Extracts of eigh~ 

avian.species (canary, chicken, duck, goose,para.keet,<parrot; pigeon 

and t~+key.) areempl9yed with varying frequE!ncies for diagnosis in t., .. 

patients with. all.erg1c. di!ieases • These· ~t:ractswere classifiet;i in. 

Category IlIA for.di,~gnosis in thE! Pa,nel. '8 original report, because 

reports ofacceptablest:udies indicating theiJ," safety and ef.f1cacy were 

not availal?le to the Panel. 

The.re is 'l:'ePorted a,necdota,l evidence that various feather extFacts 

can ind,uce posi~iveskin tE!st reactions in individ)..lals whp, are clinical;ty sensi~iv;e to birds, sllch as birds kept as pets in their homes. . 

The }lane I regards this as an in(licat:1on of the e~istence o~IgE-mediated 

al,l.e1;'gy to the avian species.· HoweYer, there i~ inadequate,evidence on 

the cpmposition and allergenic po~ency of thelOJe extracts and on their 

safety" and efficacy for 4:i.agnpsis. The' Panel' is, neve)fthe}ess, of the 

opinion that if proper!y stanqardized extracts were available they w(;lUld 

prove safeaJ).d.effect;lve ;ordiagnosis. '!'he Pall!;!l is alsoo£ the opinion t;hatthefi~ld ,..of allergy .would. Pe well served if ac;1eqlJate studies 

were cPllducted ~th standardized featl:l.er extracts. 

RECOMMENDATION. The Panel recommends that defined avian extracts 

Category I for d:i.agIl.,?sis. Poprly defineci; ex,·t:l:'acts . .-sq.ch a~ a JIQ.x of, 

"featlu~rsand ,lillt" '. an4. "tp!xed feathers", .I'Ihoul4 be" recla.ssified into 

Category Il for diagnosis ,. 
-33­


4. Extracts of avian origin for immunotherapy. No avian extracts .,.j 

were classified in Category I for immunotherapy in the Panel's original 

report because none had been shown to be safe and effective for immunotherapy. In fact, there is a gross lack of information about their use 

in treatment of proven allergy to the feathers of one or another avian 

species. Nevertheless, the Panel presumes that if potent, properly 

standardized feather extracts can be proven effective for diagnosis of 

allergic sensitivity in such patients, then by analogy with extracts of 

other defined inhalant allergens, placebo-controlled clinical studies 

might demonstrate that feather extracts are safe and effective when 

employed properly for immunotherapy. The Panel regards it as imperat~ve 

that a clinical trial of at least one standardized feather extract be 

conducted to prove this assumption. However, feather extracts in gen­

, 

eral have been accepted by allergists and by the authors of early 

standard allergy textbooks as effective for immunotherapy, and the Panel 

believes that they should continue to be available for this use. 

RECOMMENDATION. The Panel recommends that extracts of defined 

avian species previously. classified in Category IlIA for immunotherapy 

should be reclassified into Category I for immunotherapy (Table 5). 

Poorly defined extracts such as the mix of "lint and feathers" and 

"mixed feathers" should be reclassified into Category II for immunotherapy (Table 6). 

{ 

~ '-. ­
-34­

TABLE 3 

"/ 

Mammalian Extracts R~commended fot Category I' 

Extract 

Beaver (not processed fur) 
 

Camel (not processed fur) 
 

Cat 
 

Chinchilla (not processed fur) 
 

Cow 
 

Deer 
 

Dog 
 

Elk 
 

Fox (not 'processed fur) 
 

/ 	 Gerbil 

Goat 

Guinea pig 

Hamster 

Hog 

Horse 

Leopard (not processed fur) 
 

Mink (not processed fur) 
 

Monkey 
 

Mouse 
 

Muskrat (not processed fur) 
 

Rabbit (not processed fur) 
 
-35­

TABLE 3--con. . ,. 

" Mammalian Extracts Recomme'nded for Category I 

Extract 

Racoon (not processed fur) 

Rat 

Skunk 

Squirrel (not processed fur) 

• 
...~6

TABLE 4. - ,. 

to' 

Ma~11an Extrac.I:.~Recom~nded.f(>:r Category II 

Extract 

Human dander 

Human hair 

Leathers 

TABLE 5 

Avian Extracts Recommended for Category I 

Extract 

Feathers, canary 

Feathers, chicken 

Feathers, duck 

Feathers, goose, 

Feathers, parakeet 

Feathers, pigeon 

Feathers, turkey 

TABLE 6 

Avian Extracts Recommended for Category II 

Extract 

Feather, lint, mixed 

Feathers, mixed 

C,-,' 
 
-37­

D. MOLD ALLERGENIC EXTRACTS 

1. Mold extracts for diagnosis. Six mold allergenic extracts 

which are employed frequently for diagnosis of allergic diseases 

were classified in Category I for diagnOSis in the previous Panel 

report because appropriate controlled published studies indicated 

that they were effective for diagnosis. These extracts were of the 

mold genera listed below. 

Alternaria 
 

Cladosporium (Hormodendrum) 
 

Helminthosporium 
 

Aspergillus 
 

Penicillium 
 

Mucor 
 

No attempt was made by the Panel to determine which species or strains 

of these mold genera were to be employed in the Category I diagnostic 

extracts. 

The remainder of the mold extracts listed were classified in 

Category IlIA for diagnosis. Although many of these Category lilA 

extracts,have been accepted as effective for diagnosis by practicing 

allergists and by the authors of allergy textbooks, the Panel was unable 

to find appropriate published evidence which unequivocally proved that 

these specific mold extracts were actually effective for ·diagnosis. The 

difficulty related in part' t<?finding proof that clinical exposure to a 

specific mold produced symptoms of allergic disease which were due to 

that specific mold. Whereas there was abundant evidence which indicated 
I 

-:38­


that exposures to other airborne a~lle~gens such as pollens and animal aller­ .-'" , -':'»'.' :~~ Y ,1 '.-:. - ~ "' •• - .', • .. :i r < 

... ,~ 

that an individual pati~nt, was expos~d to a ~pecific, species or genera j. • C"" r .", ,,' '" , .<~ (, • 

. of mold in \:lis natural environment and that this exposure induced the 

symptotIJ,S of Allergic disease wJlich were present in the patient at a '-' .. ' '." ,'-. , ,~, ," ," 'rpartic",lar time. As with ce~ain pollens, examination of the ambient :~. .- \.~-/ " • . .~ -., .'1'-; '." : 

air indicated that a patient usually sustained exposure to multi~~e. 

molds at the same time. Therefore, in the absence of conclusive evidence of diagnostic effectiveness, the Panel based it;s judgment;s con­ .' "."' • • "- f 

"'~-' . 

cerning the classification of mold extracts on knowledge (1) of the 

immunology and aerobiology of molds, (2) of the data concerning positive " r! < -.} 

skin tests and RAST in patients living in environments in which airborne 

molds are -abundant from time-to-time, and (3) of evidence that such ~: ,­

pa:ti,ents may su,ffer alle):'gic symptoms when specific molds can be de­ o •••t. '-,"~ ",:. - <:: : ":; ,~:.'_- ; ,.' ,- : ,: -,,", -, .,' >,:,i -. ,,{ : 

Table 7 lists mold extracts for which there is evidence of both 

recotllffi,e~d,s, tr~at, al~e7g~Il:ic: ex~ra.~t~of these molds be pl,B;ced in Ca~egory 

.~or, 4;~gn~~is. ,~ ',' '.

Ta9JT';;~ ~ist;~ )llold extra~~s for ~hich;~~~ fa.nel so _~ar ~as no~ 

s,~en su~~i'7~1'!1;t evi1~llce ,of bot'l) clinics.I e:ltl'0su;-e to; the llU)ld genera 

ang, ,p<?s:p:,iye, sk;Il; tests 1;0 eJft;t"aFtSQfthe.:vaJ:!~t1s ~P;~!7~ ()f :tl,1e m9:t!i 

genera •. The Pa,nel recommends that allergenic extracts of these mo;l.ds be ..""'~ , f',--.' : ..: -.:.(,! ~~'~'; """- '.> '."',' ~ .. ',,:": ,::,' ;,. ,'. » 

.pJ"a,~,edinCat~go,+y;IJ: f0:J:', d~~gn()sis unJ,ess or until app;ropr~a,t:e, evi~;~nce 

of effectiveness is found. 
~39

2. Mold extracts for immunotherapz. No , "

mold extracts were classi­ If' 

Hed in Category I for immunotherapy in the previous Panel report 

because the Panel found none which had been shown to be effective for 

immunotherapy in valid controlled published clinical trials. Those 

extracts listed in Table 7 were classified in Category IIIA for immunotherapy because they had been accepted by practicing aller~ists and 

standard textbooks as effective for diagnosis and immunotherapy_ The 

Panel has recommended that those extracts in Table 7 be classified in 

Category I for diagnosis _ As stat.ed previously, when certain pollen 

extracts have been tea ted adequately, they have been shown to be ef fective for immunotherapy. The Panel presumes that any properly standardized sufficiently potent mold extract which is effective for skin 

test diagnosis and is safe when properly employed for immunotherapy 

might be proved to be, effective for immunotherapy by appropriate controlled studies. The Panel recognizes that such studies have not been 

done with these extracts because such studies are difficult, costly and 

time-consuming and standardized mold extracts have not been available 

for testing. 

RECOMMENDATION. The Panel recommends that extracts listed in Table 

7 be reclassified in Category I for immunotherapy. 

The mold extracts listed in Table 8 have been recommended for Category 

II for diagnosis for the reasons listed on the previous pages. The 

Panel recommends that extracts listed in Table 8 be reclassified in 

Category II for immunotherapy_ 
Mold Extracts Recommended for CS,tegory I 

Ai t~rnarfa tenuis 

Aspergillus clav8tuB 

Aspe~gillhs fundgatu's 

Asp~ig:i.lluB glaucus 

Aspergillus nidulans 

Aspergillus niger 

Aspergillus sydowi 

AsperglluB ierre~s 

Botryd.s· cinerea 

Candida albicans 

C~phalosporitimacremonium 

Cephalothecfum roseum 

Chaetom!um globos~rit 

Cladosporium fulvum 

Cladosporium herbarum 

Curvularia spicifera 

EPlcciccum nigrum 

Fus~rium 'vasfnfec'tum 

Fusariuul 'foseum 

Gliocladium fimbriatum 

Refeioencet!l whIch 
 

Demonstrat!! Exposure 
 ·to)'Rold. Genera· 
 

r, 1,9, 11 
 

1, 3, 9, 11 
 

1, 3, 9, 11 
 

1, j~9, n 
 

1, 3,9, 11 
 

1, 3, 9, If 
 

1, 3, 9, 11 
 

1, 3, 9,. n 
 

1, 3, 11 
 

1, 11 
 

3~ 8, 11 
 

1, 11 
 

1, 

\ 

3, 11 
 

1, 3, 9, 11 
 

1, 3,9, 11 
 

3 
 

1, 3 
 

i, 3, 9, 11 
 

1, 3, 9, 11' 
 

3 
 

References which 
 

Demonstrate Positive 
 

Skin Test 
 

tb'Mold SJ)1!cies 
 

2,5, 11 
 

10 
 

2, 9, 11 
 

2, 11 
 

2, 11 
 

29
 , 

2 
 

2', Ii 

2, n 
 

11 
 

9, 10, n 
 

2, 11 
 

4, 11 
 

4, 11 
 

2, 5 
 

2 
 

:2 
 

11 
 

2 
 

*Positive skin tests to these mold genera only 
-41­

TABLE 7--con. -/ 

Mold Extracts Recommended --for Category I 

References which 

References which Demonstrate Positive 

Demonstrate Exposure Skin Test 

to Mold Genera to Mold Species 

Helminthosporium interseminatum 1, 3, 9, 11 2 

Monilia sitophilia 1, 3, 11 2, 9, 11 

Mucor plumbeus 1, 3, 11 9, 11 

Mucor racemosus 1, 3, 11 2, 11 

Mucor spinorus 1, 3, 11 11 

Mycogone sp. 3 2 

Nigrospora sphaerica 3, 11 2, 11 

Paecilomyces variota 3 2 

Penicillium biforme 1, 3, 9, 11 2 

Penicillium carmino-violaceum 1, 3, 9, 11 2 

Penicillium intricatum 1, 3, 9, 11 2 

Penicillium luteum 1, 3, 9, 11 2 

Penicillium notatum 1, 3, 9, 11 2, 11 

Penicillium rubrum 1, 3, 9, 11 9 

Phoma herbarum 1, 3, 11 2 

Phoma betae 1, 3, 11 11 

Pullularia pullulans 1, 3, 11 2, 11 

Rhizopus nigricans 1, 3, 9, 11 2, 11 

Rhodotroula glutinis 1, 3 2 

Saccharomyces cerevisiae 1, 9, 11 2, 10, 11 

Spondylocladium sp. 3, 9 5 
-42­

TABLE 7-con. 

'/ 

MQldE~tracts Recommended--for Category I 
 ;,~. ":" ,"t ;". '. 

References which 
 

References which Demonstrate Positive 
 

~monstrate Exposure Skin Test 
 

to Mold Genera to Mold Species 
 

Sporobolomyces, roseum 3, 11 11 
 

Stemp~ylium botryosum 1, 3, 11 2, 5 
 

Trichoderma viride 1, 3, 11 2, 11 
 

Trichothecium roseum 11 11 
 

( 
 
-43­

TABLE 8 .,. 

.~, 

Mold Extracts Recommended for Category II 

Absidia capillata 

Achorion schoenleini 

Acrothecium spp. 

Anacystis 

Beauvaria bassiana 

Bispora antennata 

Chlanydomyces diffusus 

Chlorella 

Colletotrichum 

Cryptococcus sp. 

Cryptococcus diffluens 

Cryptococcus laurentii 

Cryptococcus terreus 

Cunninghamella elegans 

Dematium nigrum 

Epidermophyton 

Epidermophyton floccosum (inguinale) 

Epidermophyt9n rubrum 

Fomes sp. 

Geotrichum 

Geotrichum (Oospora) 

Geotrichum oidium 

Lycopodium 

{ 

Microsporum 
." ... 

';;44­

Mold Extracts Reco~nded'fot Category II 

Microsporum audouinii 

Microsporum canis (lanosum) 

Microsporum gypseum 

Monotospora lanuginosa 

Mycelia sterilia 

Mycogone sp. 

Mycotypha dichotoma 

Neurospora crassa 

Oidiodendrum sp. 

Oidiodendrum oospara 

( Papularia arundinis 

Phyco~cetes 

Phycomyces blakesleeanus 

Pleospora sp. 

Podaxis sp. 

Poria sp. \ 

ScopulariopsiS 

Scopulariospsis brevicaulis 

Sporotrichum 

Sporotrichum pruinosum 

Stachybotrys atra 

Streptomyces 

Streptomyces griseus f 
-45­

TABLE8--con. -/

.,. Mold Extracts Recommended for Category II 

Syncephalastrum racemosum 

Tetracoccosporium 

Thamnidium 	 elegans 

Trichophyton 

trichophyton cutaneum 

Trichophyton gypseum 

Trichophyton interdigitale 

Trichophyton mentagrophytes 

Trichophyton purpureum 

Trichophyton rubrum 

\ 	 Trichophyton {achorion} schoenleinii 

Trichophyton tonsurans 

Trichophyton yiolaceum 

Typhula 

Verticillium albo-atrum 

(. / 
""'46­

", REFERENCES '''' 

(1) Van der W~rf, P. J., "Hold Fungi and Bronchial 

Asthma, a Mycological and Clinical Study," Charles c. Thomas, 

Springfield, Ill., 195~. 

(2) Prince, H. E., G. H. Meyer, "An up-to-date 

Look at Mold Allergy," Annuals of Allergy, 37:18, 1976. 

(3) Prince, H. E., M. B. MorrOtoT, "Skin Reaction 

Patterns to Dematiaceous Mold Allergens," Annuals at' 

Allergy, 29:535, 1971. 

(4) Morrow, M. B., G. H. Meyer and H. E. Prince, 

'. "A Summary of Air-borne Mold Surveys," Annuals of 

Allergy, 22:575, 1964. 

(5) , Prince, H. E. and Co-authors, "Molds and B"acteria 

in the Etiology of Respiratory Allergic Diseases. XXI. Studies 

with Mold Extracts Prepared from Cultures Grown in Modified 

Synthetic Media, A Preliminary Report," Annuals of Allergy, 

19: 259, 1961. 

(6) Prince, H. E., C. E. Arbesman, E. D. Seilers, 

P•. T. Pettit, E. A. Brown and M. B. Morrow, "Mold Fungi 

in the Etiology of Respiratory Allergic Diseases. XII. Further 

Studies with Mold Extracts," Annuals of Allergy, 7:597, 1949. 

(7) Graveson, S., "Identification and Prevalence of 

Culturable Mesophilic Microfungi on House Dust from 100 Danish 

Homes," Allergy, 33:268, 1978. 

\ 

I 
-47­

(8) Blumstein, G.!., "Mold Allerg~'. II. Clinical 

Analysis," Annuals of Allergy, 3:341, 1945. 

(9) Pennington, E. S., "A Study of the Incidence 

of Air-borne Molds and of Skin Sensitivity to Molds," 

Southern Medical Journal, 33:931, 1940. 

(10) Brown, G. T., "Hypersensitiveness to Fungi," Journal 

of Allergy, 7:455, 1936. 

(11) Warren, W. P., B. Rose , "Air-borne Fungi and 

Respi ratory Allergy," A Montre.al Study, Canadian Medical 

Association, 99:827, 1968 • 

• 
-48­


Basidiomycetes: Rusts, smuts ~ and I!I.1shroom spores. Since the ,/ 

Panelcompletedit;s or1g1rtalrepott~thete il'ss'''be'en additional information dealing with allergy to basidlonij~ce:tes: 

Symington (Ref. 1) reported on eight workers!n a food manufacturing company who had rhinorrhea, dyspnea atad wheezingwt'th preparation of dried mushroom soup. Five'fiad' varYing degtee~of pos'1.t:f.;'\*e 

ilDIDfid:l.ate skin tests fo dried U1ushioom extract and "i6ur had positive 

inhalation challenge tests. ' Precipitating antibodies couldn6tbe 

detected. 

Two abstf'actswere presented at the meeting'ofthe American Academy of 

Allergy, Montreal, Canada, March 1982. Lehrer {Ref. 2) reported that an 

extract of spores of the mushroom Chlorophyllum molybetium coll~cted 

from the field caused positive skin tests in 12 of 66 atopic patierits 

with perennial allergic sYmptoms; 5 of the 12 patients had a positive 

RAST as well. An extract made from the mycelial form, grown in vitro, 

did not cause positive skin test reactions. Using crossed radioimmunoelectrophoresis, 7 of 23 precipitating antigens were shown to bind IgE 

from patients' sera. In New Orleans, spores from basidiomycetes can 

account for up to 20-30% of the total spore and pollen count, and allergic symptoms in some patients appear to be,related to this exposure, 

although a firmly established cause and effect relationship has not 

been proved. 

Santilli, et al. (Ref. 3) reported that they were able to elicit 

immediate skin reactions with extracts of basidiospores (including Agaricus, 
-49­


Coprinus, FiJligo, Lycoperdon, Scleroderma, Ustilago and sooty mold) 

in individuals who have allergic symptoms, including asthma,coincident with high environmental spore counts. 

In two Japanese journals (Refs. 4 and 5) two cases of asthma from 

occupational exposure to spores (Cortinellus shitake and Lentinus 

edodus) were reported. The disease was not the mushroom workers' lung 

type of extrinsic allergic alveolitits with precipitins. 

This additional evidence allows the following mushrooms to be 

included in the list of identified basidiomycetes wh+ch will produce 

allergic reactions: Lentinus, Agaricus, Lycoperdon, Scleroderma, and 

Fuligo. 

No reports were found on the use of extracts of basidiomycetel;l 

in immunotherapy. 

It should be noted that there are 10,000 to 20,000 more members of 

the basidiomycete class that are yet to be studied and evaluated. For 

industrial exposure as in the above references, material present at the 

industrial plant may be the best source material to extract, so commercial allergenic extract will not be as useful or specific (e.g., it may 

be a dust of the product rather than of the spore of the mushroom). 

RECOMMENDATIONS: (a) The basidiomycetes extract groups listed in 

Table 9 should be in Category I for diagnosis if spores, are used as the 

source material. Other members of the class should not beinclude,d 

generically, since it appears that th'is group of substances has a low 

degree of cross-reactivity and data on other members are not available •. 

--~..--. 

(b) Even though there are no data, other than · a few anecdotal 

comments, about immunotherapy with extracts of members of this group, 

// 

,.... 
( 
 

'( ) .' --' 

-'SOby analogy \rlthother'tlirborneallergenCs ~a'Od Uspores ar,(!uied, ' '," 

as the sourcematet'ial' then' thes,eextracts sho'tildbe inCategotj 

I for immunotherapy. 

TABLE'9 

BilSidiomYcete:Spore Extracts' Recommended,f0t:Category I 

Barley smut -Ustilagobordel 

- Ustilagonuda 

Corn smut ... Ustl1agb i zea4!' 

Milletstntit -UstiIago cta1nefi 

Oat smut "'l:1st:llag()avert~e 

Rye smut - Urocyst!s occulta

• 

Sorghunismo.t -Sphacelothecal:iorghl' 

Sphacelotheca cruenta 

Wheat: slniJt - 'rl1let1a trit:ici" 

'';;; Tflletfa ie~is' 

~ Us t11:~gd'; boO! tid ' ' 

Rust'';;', Puc'C1rtfli;gr~Udil:(stH t:t.~i 

Mushroom 	 ';'Agaricus, Cantharelltis ,~' ChlorophyiltiIIi; COprinus~ 

- Ftust111atuni, 'FuHgo;' Htphb16ma, . tihtitt1l6," Lycdpertlc)n, 

~ P1.eutotus, Scleroderma 

F~.'., -. 

",.-. Yeast ';":;')ti1:h~tf8ps±s'; 

" 

; ': ,~ ,'" 
-51­


REFERENCES 
 

(1) Symington, 1. S., J. W. Kerr and D. A. McLean, "Ty~ I 

Allergy in Mushroom Soup Processors," Clinical Allergy, Vol. II, 

p. 43-47, 1981. 

(2) Lehrer, S. B., R. O. de Shazo, B. T. Butcher, 

L. Aukrust and J. E. Salvsggio, "Skin Reactivity and 

Ig! Antibodies to Basidiomycete Extracts in Allergic 

Individu$ls," Journa~ of Allergy and Clinical Immunology, 

69:97, 1982. 

(3) Santilli, J., Jr., D. G. Marsh, R. P. Collins, 

J. F. Alexander, Jr., and P. S. Norman, "~asidiospore 

Sensitivity and Asthma," Journal of Allergy and Clinical 

Immunology, 69:98, 1982. 

(4) Kondo, 0., "A Case of Cortine11us Shitake Spore 

Asthma," Japanese Journal of Allergy, 18:81, 1969. 

(5) Shichijo, et a1., "A Case of Bronchial Asthma 

Caused by Mushroom Spore of Lentinus Edodus," Journal of 

the Japanese Society of Internal Medic:i.. ne, 58:405, 1969. 
~52

E. MISCELLANEOUS INHALANT ;ALLERGENIC EXTRACTS 

'For the itl1ergEmic extracfS of the tHscellan'eousirlhalant substances, the Panel'" relied on the ,data in the Panel 'sOrigfnalr'eport. 

Generally, an extract previously placed in Category·IitA fot' diagnosis 

is reclassified iri'to Cad~gotY'I for diagtiosis when 'there is 'adequate 

evidence that the sdbstance~b '.i11erg~rlic (Table 9). 'Among'the extracts 

originally in CategorY I for· diagnoSis, there "care a fewwhic'h 'can also 

be recommended for, ,Category' 1 fo.r iinmunothetapy,tr:~b1e 10). Ho*ever, 

the remainder of the extracts in Category I for diagnosiSha:ve'been 

recommended for'CategotY II for therapy because (1).' there are no published reports of thedrftse and (2) avoIdance of the bffendinga1lergen 

is sufficient,~ For COmpleteness, Tabl¢30 aHH) includes severai·extracts 

which were in Category I in the Panel's original report .T~ble',A! lists 

extracts of mis'cellJ:ineous substahces'which are recominended' fo~ Category 

II. 

For grainelevat6r,'du·st~'grad.ri mill, dust and girain.duE;.tmix, 

which has settled on high rafters should be the original source material. Locations where only one or two species of grains are processed 

are inappropriate. As soon as possible after storage, the material 

should be screened, defatted, and stored at freezing tempera~ures or 

otherwise handled ,to limit the presence of weevils, mites, other insects, endotoxins, and mycotoxins until ready to be-extracted. Dialysis 

and acetone precipitation may be useful in the manufacturing process. 

l/ / 
-52­

E. MISCELLANEOUS ~NHALANT ALLERGENIC EXTRACTS 

For the allergenic extracts of the miscellaneous inhalant substances, the Panel relied on th~ data in the Panel's original report. 

Generally, an extract previously placed in Category IlIA for diagnosis 

is reclassified into Category I :for diagnosis when there is adequate 

evidence that the substance is allergenic (Table 9). Among the extracts \ 

originally in Category I for diagnosis, there are a few which can also 

be recommended for Category I for immunotherapy (Table 10). However, 

the remainder of the extracts in Category I for diagnosis have been 

recommended for Category II for immunotherapy because (1) there are no 

published reports of their use for immunotherapy and (2) avoidance of 

the offending allergen is suffic~ent therapy. For completeness, Table I 

10 also includes several extracts which were in Category I in the Panel's 

Q tlglna~i·~port. Tabl~ rllhi~reitt..1¢t~ of.. tni$qel'18ll~Qu'~~~b~t,a.~,¢i~Y 

which are recommended for Catego~y II. 

For grain elevator dust, grain mill dust and grain dust mix, 

I 

several conditions were recommen~ed to provide better assurance of a 

I safe, more consistant product. ine dust which has been ai~borne and 

which has settled on high rafter should be the original source material. Locations where only on or two species of grains ~re processed 

are inappropriate. As soon as p ssible after storage, the asterial 

should be screened, defatted, an~ stored at freezing teaperatures or 

i 

I otherwise handled to limit the presence of toieevils, mites, other In~ 

sects, endotoxins, and' myCotoxin~ un.til ready to be extracted. Dialysis

and acetone precipitation may be! useful in the manufacturing process. 

i 

i 

i 

1 
-53­

T.uLE 10 

Miscellaneous Inhalant AllergetUcExtracts 

. 1/ Caeegory.' Recommendat,ionsSkin Test ImmunoDiagnosis : therapy 

Algae I I ~ :..\". 

Castor bean 1 11 

Cotton l:f,nters (1) I 

Cottonseed (1) (II) 

Derris root 1, (II) . ~ ,..~ .. ," . , ' ". 

• 

Dust,' grain ~.levator (grain,m1ll 

d).Js.t o1;"grai,n dust mix) I I 

Flax.se~d .(.1) (II) 

I.'; II 

Gum Arabic or Acacia I 11 

Gum Ind,;i4. (Kflraya) ·(1) II 

" (1) IT 

Ipe~ac. , I II 

Monsanto . enzyme (B •. Subdlis', 

, Novoenzyme ), , 

Orris;, root, 11 
 

Pyrethrum; 
 II 

l/Category I reco'mmendations' irtpa-rerithesis wei-~ iit Cat~g8'ry t inthe 

Panel's original report. Category II recommendations in par,enthes;i.s were 

.' in .' Category II'IB in the odginal report. ,- " ,... ,.' .... " ',.' 
-54­ .,. TABLE lO--con. .~ 

Miscellaneous Inhalant Allergenic Extracts 

Recommended to Remain Licensed 

Category Recommendationsl! 

Skin Test ImmunoExtract Diagnosis thera~y 

Silk, raw (I) I 

Tobacco leaf (unmodified) (I) II 

Wood dust, cedar and red cedar (I) II 

Wood dust,·cocabola (1) II 

Wood dust, red oak (I) II 

Wood dust, white oak (1) II 

Wood dust, padauk (I) II 

1/ Category I recommendations in parenthesis were in Category I in the 

Panel's original report. Category II recommendations in parenthesis 

were in Category IIIB in the original report. 
·A1mc)ril hulls 

Chicle 

Chicory 

Coconut fiber 

Cotton 

Cotton, aged 

Cotton gin dust 

Fern spores 

Flax fiber 

Gum carbo 

Hemp dust 

Jute· 

Kapok 

Lavendar 

Lycopodium 

Malt 

Psyllium seed 

Rapeseed 

Rose spp. 

Sea moss 

Senna 

Sisal 

-55­

TABLE 11 

Miscellaneous Inhalant Allergenic Extracts 
 

Recommended for Category II 
 

For Diagnosis and Immunotherapy 
 

'\ 1." 

/ 
-56­ ';

... 

TABLE ll-con. 
 

Miscellaneous Inhalant Allergenic Extracts 
 

Recommended for Category II 
 

For Diagnosis and Immunotherapy 

Tobacco leaf, cured 

Wood dusts: 

Busal 
 

Beech 
 

Birch 
 

Cottonwood 
 

Elm 
 

Fir 
 

Fir, Douglas 
 

Fir, red 
 

Fir, white 
 

Hemlock 
 

Mahogany 
 

Maple 
 

Pine, white 
 

Pine, yellow 
 

Redwood 
 

Spruce 
 

Tamarack (larch) 
 

Walnut' 
 

( 
-57"; 
 

:1 

\ 

F. HOUSE DUST EXTRACTS 

House dust extracts are prepared from source materials which 

have not been precisely defined and, therefore, fail to meet the first 

requirement the Panel established to qualify for Category I 

classification. By 'their nature, house dust extracts are not of constant composition. :Because of this inconsistency, it is not possible 

to assure that any two batches of house dust are alike. Furthermore, 

it is doubtful that this will ever be possible unless collection and 

extraction methods can be devised which will produce batches of known 

composition so that standards can be developed. The chemical composition of house dust extracts has not been determined. They are known 

to contain multiple antigens, but an antigen unique to house dust 

has not been shown conclusively. 

Never~heless, there is adequate evidence for the need in practice 

of an extract with the characteristics of house dust. It is generally 

recognized that there is a small proportion of patients who give clear~ 

cut histories of allergy to house dust and who react to house dust extract 

by skin and/or serological tests, but who do not have positive skin 

test reactions to available extracts of severa:l known allergenic components of 

house dust. The reasons for this are not clear. While it is the goal 

of the conscientious allergist to be as specific as possible in diagnosing and treating the allergies of each patient, in practice it is not 

feasible to perform all of the diagnostic testing necessary to do this. 

Therefore, house dust extracts fulfill a need in the diagnosis and 

" ,­

treatment of allergic disease. However, there is nOestandard of potency

• 

for house dust extracts. They are currently produced on a W/V or PNU 

./

" 
~58

basis. Extracts with equal W/V or PNU designations may differ in bio­ < 

logic activity by more than a thousandfold. This is a major fault which 

will be considered in the Panel's recommendations. 

The safety of house dust extracts as used in diag~osis and therapy 

has not been studied systematically, but extensive marketing experience 

and human use appear to have demonstrated their safety. 

The specificity and sensitivity of these extracts for the diagnosis 

of IgE-mediated allergy to components of house dust cannot be established unless and until standardized preparations are available. 

The effectiveness of house dust extracts in the treatment of 

sensitivity to house dust cannot be established for the same reason. 

Recommendations: 

House dust extract is recommended to be placed in Category I for 

skin test diagnosis notwithstanding the fact that the source material is 

not well defined and each product is a mixture varying from batch-tobatch. 

By a 6 to 1 vote of the Panel members house dust extract was recommended for Category I for use in immunotherapy. The dissenting opinion 

reflected several concerns of the Panel. Although there are some reports in the literature which suggest that house dust extract may be 

useful in therapy, other reports show it to be ineffective. Because of 

a lack of knowledge of the components used in the reported studies, 

these data could not be applied to current production batches of house 

---.-­ dust extracts. 

Several recommendations are repeated from the original Panel 

/

report. 
-59";' 
 

(1) Collection. Various environments are suitable for the collec-:­

tion of these source materials. The collector should maintain a record ,", :; j' 

of the actual location from which each sample of source material was 

collected. The sites and method of collection of the source material, 

for example, by vacuuming, should be approved by the FDA. 

(2) Processin~. Upon receipt of the source material from the 

supplier, it should be inspected by the manufacturer and should meet 

standards for this product established by the FDA. When required, it 

should be sieved upon receipt from the supplier to remove contaminating 

debris. 

(3) Storage. The source material should be stored under condi.,.. 

tions approved by the FDA. Particular attention should be given to 

the temperature and humidity during storage, and to the duration of 

stor~ge. 

(4) The manufacturer must indicate the general nature of the 

source on the label. For example, "a mixture of mattress and carpet 

dust". Only extracts made from source materials obtained from houses or 

similar establishments (e.g. hotels) or their .appurtenances should be 

labeled "house dust extract." Due to the observed wide variation in 

potency which ma~ occur from batch,-to-batch, a warning should appear on ;;., , 

the label. For example: "Warning,.potency may vary from batch-to­ _ ~ ~_ Ci . 

i [ 

batch, thel."efore, equivalent doses measured by W/V or PNU may differ. 

This mustbe considered when changing a patient to a new lot number." 

Based on its previous review of this subject a~d___4iscussions at . 

the most recent Panel meeting,the Panel added the following conditions: 

a. No house dust source material should be collected from areas 

where pet animals, particularly cats or dogs, are kept. 

,.. 
-60­


b. House dust source material should not be collected from areas ',' ." 

where detergents or pesticides have been used within the previous two 

weeks. 

c. House dust source material should have low levels of mite and 

other insect infestation detectable upon microscopic examination. 

d. House dust source material should be stored in a manner to 

inhibit bacterial, mold, and insect growth. 

e. House dust extracts should be tested for mycotoxins, particularly aflatoxin. 

f. House dust extracts should be limited to low levels of endo..,. 

toxin as specified by the FDA • 

• 

g. No extraneous additives should be used to "fortify" these 

extracts. 

It is &lso suggested that a sufficient number of lots of extract 

should be skin tested to assure consistency and to ultimately determine 

whether there is a clinical syndrome which can be attributed to house 

dust per se and in which people are skin test-positive at relatively 

high dilutions of these extracts. 
-61­
 l.f 

,,­

... 

G. INSECT EXTRACTS 

Insect extracts were reviewed again in the same groups as in the 

original Panel report; i.e., extracts for insect sting allergy t extracts for insect hite allergy, and extracts for insect inhalant 

allergy • 

1. venom. The only insect extract ~~~~~~~~~~~~~~~~~~

for imnrunotherapy of insect sting allergy in Category IlIA in the original Panel report was the extract of the whole body of the fire ant. j , . 

Venoms of the winged hymenoptera such as bees, wasps, yellow jackets and 

hornets were marketed as safe and effective products after the initial 

Panel review and were not addressed by the Panel. Whole body extracts 

of the winged hymenoptera were placed in Category IIIH based on pub';" 

lished evidence of their ineffectiveness. However, limited observations 

· ,-' ",< :}; 

mentioned in t1:te original Panel report suggest that whole body extract 

of the fire ant may be effective in the diagnosis and treatment of fire 

ant-sensitive individuals. Observation of a control group of untreated 

individuals is lacking and corraborative immunological studies are not 

available. Nevertheless, because of the published evidence it, is recommended that whole body fire ant extracts be placed in Category I for 

immunotherapy. 

2. Extracts for allergy to insect bites. 

a. Fleas. Reactions from flea bites are primarily large local 

reactions. As mentioned in the original Panel report, many of these 

r'eactions are delayed in onset as is the reaction found when skin testfng with flea extract. There is no present documentation that reactions 

to flea bites have an IgE pathogenesis. It is recommended that flea 
-&2­


extracts be placed in Category II for diagnosis and therapy as currently 

labeled for use in IgE-mediated allergic disease. One Panel member 

believed the extract should remain on the market for use in the diagnosis of delayed hypersensitivity to the flea bite. 

b. Mosquito. The original Panel report concluded that mosquito 

extracts 	 may have some diagnostic value irl' confirming the delayed local 

, 

reactions which some individuals ha,re had following mosquito bites, but i 

that an IgE pathogenesis for this type of reaction has not been established. It is. recommended that mosquito extracts be placed in Category 

II for diagnosis and therapy as currently labeled for use in IgE-mediated allergic disease. One Panel member believed the extract should 

• 

remain on the market for use in the diagnosis of delayed hyper- . 

sensitivity to the mosquito bite. 

c. Deerfly. Deerfly extract was placed in Category I for skin 

test diagnosis in the original Panel report. Based on studies reviewed 

in the earlier report, it is recommended that deerfly extract now be 

placed in Category I for immunotherapy. 

d. Bedbugs. Based on studies cited in the original Panel report, 

extracts of bedbugs are recommended for Category I for skin Test diagnosis. (Bedbug extracts are in Category IIIB for therapy in the original 

Panel report). 

e. Kissing bug. Kissing bug (Triatoma) extracts were placed in 

Category I for skin test diagnosis in the original Panel report. There 

is evidence in one study which suggests that an extract of the salivary 

glands of this insect is effective for immunotherapy (Ref. 1). Therefore, it is recommended that kissing bug extract be placed in Category I 

for immunotherapy. 
-6:3­


3. Extracts for inhall1nt allergy to insects • 

. ,a.Cagd1,s .f1y~C~d~i{:1 ,fly e;x;tra~tw~~ p~~ced in Gategory I 

£or8\4:in tes.~ diagnos~s .in. the ()ngtn~l Panel,r,eport. B~sed on; the 

stt1di~s reviewed in that. report, it is recommended ,that caddis fly 

extract be placed in Category I fo~ immunotherapy_ 

b•. May:f.1y.May fly extract was in •Category I for skin test 

diagnosis tn the original. Panel report.' B~u~ed on,the,studies reviewed 

~here, it isreco~nded that May .fly ex:tract be placed in Category I 

fO,r:immuno~,herapy!, 

c. Aphid. Aphid extracts were pla~ed i.nCCitegory I for skin. teg t 

diagnosis in the, original Panel I'eport. Usein~herapy is analogous 

to t,he,abq,veext.ract;s. It 'is ~eComI!lendec;i ·that aphtd .extractbe placed 

in Category, I for, immunotherapy". 

/ 	 d. Bee. The evidence supporting the use of whQle body extract in 

inhalant allergytQ ,;bees was,,discussed "i,nthe origt,nal .Ea,nel report. If 

it is not effective for bee stiI)g4),ler,gy,4eap:l,t·~ widespi;~HJ,A' previc>us 

us.efor th1:s pu.rpo~.e.lt\ is :r:'ec.Qmmended ·that· whole body bee 'extracts 

labeled for ,use in the d:iagnosis and tr.eat.ment of inhalant allergy be 

placed in Category I. 

e. Cockroach. Cockroach extracts were in Category If,orskin 

a·change based on ,new,ev:l,pellce avaitlab1e :In inanuscrlptand published as 

th~ abstract (Ref,. 2}.,,· In ,llpatie'nts, the, ;symp:tonr ·and medi'ca'tion, 

f 

scor:esc;iecreasedsignificarttlyfo1l9wing llnmiunotherapy ·for two years." 
-64­


The sensitivity of basophil histamine release ~eclined on the average ',. 

350 fold during the same period. It is unclear if the same lot of 

antigen was used for all assays and the use of controls was not documented. Nevertheless, the Panel now recommends Category I for immunotherapy. 

f. Mite (Dermatophygoides). The extensive literature dealing 

with house dust mite was discussed in the Panel's original report where 

it was recommended that specific mite extracts be placed in Category I 

for skin test diagnosis. The Panel now recommends that the house dust 

mite extracts of D. fariniae be placed in Category I for immunotherapy 

as there is growing evidence of their efficacy. 

g. Moths and butterflies. Extracts of moths were in Category I 

for diagnosis in the Panel's original report while extracts of butterflies were in Category IIIB. Evidence from a study in Japan (Ref. 3). 

indicates that butterfly extracts are effective for diagnosi~ in patients who experience symptoms upon significant exposure to butterflies. 

The Panel recommends that extract of butterfly be placed into Category I 

for diagnosis. There was insufficient evidence to justify reclassification of extracts of moths and butterflies from Category IIIB for 

immunotherapy. 

h. Other extracts for inhalant allergy to insects. The reCOmmendations for the other extracts for insect inhalant allergy, listed 

in Tables 11 and 12, are based on information in the Panel's original 

report. The Panel recommends that when there is evidence that the 

insect is the cause of IgE-mediated allergic reactions in humans, these 

other extracts be placed in Category I for diagnosis. 
::".65­


Although exposure to many of these insects is rare, occupational con­ '" . 	 . . ., ~~ :' I>.! 

tacts account for much of the reported evidence. These other extracts 

should be placed in Category II for immunotherapy because of a lack of 

evidence that the products are effective or safe. Where the Panel could 

find no information, that a specific insect is responsible for an allergic reaction, the extract has been recommended to be' placed in Category 

II for both diagnosis and immunotherapy. 

REFERENCES 

(1) Marshall, N. A., and D. H. Street, "Allergy to 

Triatoma protracta, I. Etiology, Antigen Preparation, 

Diagnosis and Immunotherapy," Journal of Medical Ent.omology, 

19:248~252, 1982. 

c. 	 "i .'

(2) Kang, B., J. Johnson, B. S. Chang and J. L. Chang, 

"Blocking Antibody and Efficacy of Immunotherapy in Cockroach 

Asthma, .. Allergy and Clinical Immunology, 69:132, 1982. ! ~ ~ - r '.. '".' 

(3) 	 Kino, T., and S. Oshima, "Allergy to Insects in Japan,'· 

Journal of, and Clinical Immunology, 61:10-16, 1978.
.,.66­

·r

.,. 

TABLE 12 
 

Insect Extracts 
 

Recommended to Remain Licensed 
 

Category RecommendationsJ! 

Extract Skin Test ImmunoDiagnosis therapy 

Aphid 

Bedbugs 

Bee, honey (whole body) 

Beetles (identified) 

Butterfly 

Caddis fly 

Crickett 

Cicada/locust 

Cockroach, American 

Cockroach, German 

Cockroach, Oriental 

Daphnia 

Deer fly 

Fire ant 

Flea, water (daphnia pulex) 

(1) 

I 

(I)1./ 

(I) 

11.1 

(I) 

I 

I 

(I) 

(I) 

(1) 

(I) 

(I) 

(I) 

(I) 

I 

(II) 

IY 

( II) 

(II) 

r 

(II) 

(II) 

I 

I 

I 

(II) 

I 
 

I 
 

(II) 

. 11 Category I recommendations in parenthesis were in Category I in the original panel.report. Category II recommendations in parenthesis were in 

Category IlIB in the origtllal panel report. 

21 Forinhalent insect allergy • 

. .' 31 Extract of butterflies was in Category IIIB in the original report. 
-67­ -

',.,­

TABLE 12-con. 

'Insect Extracts 

Recommended to Remain Licensed 

Category Recommendationsl! 

Extract Sldn Test '1l1iiJn.inoDiagnosis therapy 

Fruit fly I (II) 

House fly (I) crr) 

Ki'ssing bug (1) T 

Leafhopper I (II) 

I 

\, 	 May fly (I) I 

Mexican bean weevil I 1 

Mite (Dermatophygoides farinae) (I) I 

Mite (Dermatophygoides farinae) (I) I 

Mite (D. pteronyssirius) I I 

Moth I '(Ii) 

Moth, miller I (II) 

Mushroom fly (I) I 

Screwworm fly I (II) 

Sow bugs I (II) 

<~~ I. Spider 	 I (II) 

, '1/ CategoI'Y Trecom~ndatiortE; inparetlthesiswere'1n Categ6ry I in the 

or:l.giriaf" p'ane'i 'report ~ Caf~gbry ''Ii rec&1ilittidat iottE; iIi 't>ar~nthes is were 

ft-n Category IIIB in the otfgitlElI panel rept;5te~' " , , " -- ~~'. , 
-68­


oJ"

.. 
 TABLE 13 
 

Insect Extracts 
 

Recommended for Category Ill! 
 

For Diagnosis and Therapy 
 

Flea 

Flea, Dog 

Flea, Cat 

Flea, mixed 

Mosquito 

Spider mix t 

1../ This table does not include extracts listed in Category IIlB in the 

original panel report. 
-69­

'" • 'FOOD EXTRAct'S 

In conducting the reclassification of foq.d extracts, the Panel ',. 

noted caref~11y its original and current charge to review the safety and 

effectiveness of the assigned products ,for use accordin~ to the way they 

are labeled. There was no new information subm.itted by the manufacturers 

for the Panel to consider in i,ts reclse,sification of Category lIlA food 

extracts. 

Food extracts for skin tes t diagnosis. Many food extracts we~:e 

considered in the previous Panel report to be effective as an aid in ,. 

the diagnosis by skln test of IgE-mediated allergic disease. In,con'" 

sidering the evidence in that ,report and in other articles (Refs .,1 

through 6) and in applying the standards of effectiveness recommended by 

the Panel in:this report for the reclassification of the Category lIlA 

{ extracts; most food extracts are recommended for Category I for this 

\, 

use. Applying these standards, each extract should: (1) be obtained 

from a well defined source; (2) be capable of being standardized as 

shown by identifiable and measurable allergenic constituents (which 

remain intact during the dating period); and (3) be shown to induce 

positive skin test reactions in individuals with IgE-mediated food 

allergy and negative reactions in those persons without such allergies. 

Many food extracts were recommended for Category I, even if they were 

derived from exotic foods unlikely to be consumed by humans on more than 

a sporadic basis. Requirement number (2) is not presently fulfilled 

with the great majority of food extracts but is theoretically possible 

with many of them. 
-70­


Almost all mixtures and processed foods, e.g. Angostura Bitters, 

soft drinks (e.g., Coca~ola, 7-Up) and simplE! chemicals (e.g., vinegar), were classified into Category IlIB in the original Panel report. 

Three products reviewed in the original report, heechnut, roasteo coffee 

bean and licorice extracts, were not clearly defined and were originally 

placed in Category IIIB. However, if the FDA can ascertain that a 

disc!ete plant substance rather than a processed form is the source 

material, extracts of these substances should be reclassified in 

Category I for skin test diagnosis. 

The recommendations for the reclassification of food extracts for 

skin test diagnosis of IgE.;...,nediated allergy are listed in Tables 14 

and 15~ Table 15 lists four food extracts previously classified in 

Category IlIA which are recommended for Category II for skin test diagnosis. Three of these (beef heart, cod liver, and grapefruit peel) 

represent extracts of anatomical parts of an approved food, i.e., beef, 

cod, and grapefruit, and therefore are considered redundant. The 

fourth, black/white pepper, is a mixture. 

Because the Panel believes that the use of allergenic extracts as 

defined in its previous report have been demonstrated to be effective 

only for use in connection with IgE-mediated allergy, the Panel recommends that the labeling of allergenic extracts of foods should clearly 

state that they are intended for use in the diagnosis of this type of 

disease only. Furthermore, the labeling should indicate that allergies 

to food substances may 'be of ingestant and, in some cases, inhalant 

nature. 
-71.,. 

Food e~tr.acts for ill)DlUnotherapy • The Panel recommends that all 

food extracts ,be reclassified ipto, Cat,egory II for ilDlJlUnotherapy of 

I~E,:-uIedi~te<;l allergic diseaae ~en exposure to the food is by ingestion. . The rf:!4!H)1l~ for t hia decfsionare:" (1 )the,re is llO generally 

ac~ei>table evidence supporting ~he use of allergenic extracts of 

foods as therapeutic agents"ei~her orally or parenterally"•.for • • ," • "_ - '" I ',_' ,"" 

ingestant IgE-mediated allergy, ;while in .coptrast suct) studies do 

e.xist for severd inhala,nt alle~ge.~ ;(2) avoldance otal,lergens 

to which an individual is sens1.tive is. a. fu.ndamental pr:l,nciple in 

allerfY management (this is usu~Uly possible for most foqd apergens 

most of' the time); and (3) food ,extracts are 1Il0re likely than otl;1er 

classes of extracts to induce, a ;systemfc anaJ>hylax~8 whenl,lse.d in 

immunotherapy. This latter conclusion is based o~ the evidenc,e . I" 

1 

reviewed in the original Pane1.r.eport. ~ ...... ' 7-. < ~ c". " •. 

I 

Several physicians and memlrers, of the publ:f.c ap~ared ,before .- ~ " .' . ; r -. -:', .,,- : i' 

'the Panel in support of the use 1of .a~lerge~c.extra~ts ot fC),od~ 

in the treatment of "food intole;rances .," Rei>resen,t.atives9f the
 !.,.:' . 

Society for Clinical Ecology, thr: American Acad~my of ~tolary~~c . ,.","" 

",<,,:;:,~,; .'.l41~,~~Y.,- '~nd' ~l!e 'f~ll o~~e'~~'~~~,r~ :;S~~~~~tx ~~~~;~}.~ :,pU~::',.~ :~h~ "::., :'.::. : ' ..~: ...:·;:·';L'i::·:'~:'···· 

Panel meetings and submitted infprmation (Ref.erences 7 through 44) :j: ' ....., 

I 

'\ 

I 

I 
-72­


mos~,--l..y "relating to the use of allergenic extracts of food substances by ' .... -:'" 

"provocation" testing and "neutralization" treatment. They stated that 

food intolerance is primarily nonIgE-mediated, and may have both 

immediate and delayed clinical and immunological features. They also i 

stated that for patients with f90d intolerance who as a practical matter 

can not avoid the offending foo~s, they support the use of allergenic 

i 

extracts of foods in ameU.orati9g and preventing a variety of conditions 

which they believe are caused by food. Examples of these conditions as 

described in their documentation include otitis media, hyperkinetic 

syndrome in children, behavioral abnormalities, asthma, milk 

intolerance, headaches, and lary~geal edema. 

It was noted by the Paneltnat most of the discussions by the 

!

I . 

speakers from the three 80cietie~ and the written material they supplied 

to the Panel had to do wi th technlques employed by some physicians in 

theii medical practices but did fiot represent evidence from studies 

supporting allergenic extracts a~ made and labeled commercially and as 

under review by the Panel. Sevep of these references were on "environ­

! 

mentally triggered" conditions u~related t~ allergenic extracts of foods 
-73­

and unrelated to any topic within the charge to the Panel. F.ight references 

'/ 

were on "mechanisms involved'," none of which contained evidence of an , , )' , ~.; 

immunological relationship between a specific food extract and its 

labeled use in treatment. Three of the references were co~~mentaries on J .- ( 

other reviews of the use of food extracts. Several other ref~rE7nces 

contained reports of case histories or testimonials of individual physicians f .' "'~"; 

rather than controlled studies. The few art~~le~ that w~re in some 

manner referred to as reporting controlled studies .. did not contain I, '.''- .. 

information demonstrating that any specific, well-charact~rizf!!d .food " • ";;' ~" ~',' .-./: "i <"I ::. ':-, -.: ," ,- • .~", ~~ '. :.\';' , , . 

extract being revie.wed· by the Panel is safe and effect.~ye fo.r.\1~e in J 

immunotherapy as labeled by the manufacturers.• ~; ,f ,. .,' ". • c ::: ' ,~ 10;' /i .- -',,' i" - ,­

The Panel's charge is to .consider the evid~ncepertairin~ to.. t~e ; ;, ;', < : r " .~ ~. 

approved labeled indi~ation~ of allergenic e.xtr~ct~. "Neutra1~zation" ., :":,1, C''.; 

tr:eatment of. fQ~d intp1«jlFa1i\CeS fo~.~o~~lgj~g1'qv~~aMon" t~st~ng ~sai:l 

{ 

\ unapproveq use of these products. The Panel has . ne:vertpele~§,;cC;>nsidered ~ i" ·"""1"< 'i' -.~".', .',:':" 't.{·:.-·.~:~-·~i {~:, ;.,<-;',:;j,·.2~_J.: -,". ,.-,' .J:.- .. " .;...J-}."" • c,_. ~ , 

all ~~.:l1e evi,4e~?~:.~Vblllil;.t~d.,t?:~pe~~f~pf'! rffi,ietp~1f ,i,~,,~uI'Rq1;t:l:I. th.~.> 

a'p'p1;'o;ved ,iI}J:li~c,t,,~!9~s qf .J9pdiext<~C;;.fs Jpr.I~E!"'jD\ESpi.E\t:.e,~.ia),l~.rgy;~ . :;': ~'. ~_,' _, .I, "'.,. \ .• "_'" '. ,;,-• .' ':.' _' "" "',' .' .' ." '.' -.C" - - -,. ~ -. ' • 

.r~~~~d .,ex~r,~7t:,s~.fo~J;~~~ .. fnunllnc;>thE!ra.p¥ oJ ~gE:'t1l,ed;ifl;t~d 'Ii),,~e,r:gy .In'\sQlIIe 

instances the. data did not even relat~ to allergenic extracts or to 

an immunological relationship between a food extract and its labeled use. 

The material submitted by the three societies therefore does not 

alter the Panel's conclusion that food extracts should be placed in 
 

Category II for immunotherapy. 
 

L 
-74­

TABLE 14 -". 

Food Extracts Recommended for Category I fo'r Skin Test DiagnOsis.!.! 

Abalone: Haliotidae species 

Alfalfa leaves: Medicago sativa 

Allspice: Pimenta officinalis 

(Almond: Prunus amygdalus) 

Anchovy: Engraulis encrasicholus 

Anise: Pimpinella anisum 

Anise seed 

(Apple: Malus pumila) 

Apricot: Prunus armeniaca 

Arrowroot: Maranta arundinacea 

Artichoke: Cynara scolymus 

(Asparagus: Asparagus officinalis) 

(Avocado: Persea americana) 

(Banana: Musa paradisiaca sapientum) 

(Barley: Hordeum vulgare) 

Barracuda: Sphraena barracuda 

Basil: Clinopodium vulgare 

Bass 

Bass, Black: Micropterus species 

Bas.s, Florida red 

Bay leaf: Laurus nobilis 

Bean, broad: Vicia faba 

JJ Extracts in parenthesis were in Category- I for skin test diagnosis 

in the original panel report. 
-75­

TABLE1Z.~on. -,­

.,. 

. Food Extracts Recommended for Category tior Sldn Test Diagnosts 

Bean, castor 

Bean kidney, red kidney: Phaseolu8 vu;lgar!s 

Bean, kola 

Bean, Uma: Phaseolus limensls 

Bean, mung 

Bean, navy 

(Bean, pinto) 

(Bean, string/green 

Bean, string/wax 

Bean, yellow/wax 

Beechnut: Fag~s sylvatica 

Beef meat: Bos species ( 

Beet: Beta vulgaris 

Beet, sugar, vegetable 

Blackberry: Rubus occidentalis 

Black-eyed pea: Vigna sinensis 

Blueberry: Vaccinium corymbosum, pennsylv~mi'c~m . 

or other species 

(Blue fish: Pomatomus saltatrix) 

Boysenberry: Rubus ursinatus loganobaccus 

Brains, calves 

(Brazil nut: Bertholletia excelsa) 
-7fr. 

TABLE 14--con. · 

-,.,. 

Food Extracts Recommended for Category 1 for Skin Test DiagnosisBroccoli: Brassica oler.acea italica 

Brussel sprouts: Brassica oleracea gemmifera 

(Buckwheat: Fagopyrum sagittatum) 

Cabbage: Brassica oleracea capitata 

(Cacao, whole bean: Theobroma cacao) 

(Cantaloupe: Cucumis melo cantalupensis) 

Caraway seed: Carum carvi 

Cardamom: Elettaria cardamomum 

-J. 

(Carp, Cyprinus corpio) 

Carrot: Daucus carota 

(Casein) 

(Cashew nut: Anacardium occidentale) 

Catfish 

Catfish, bullhead 

Catfish, channel 

Cauliflower: Brassica oleracea botrytis 

Celery, Apium graveolus 

Chard : vulgaris dcla 

Cherry 

-Cherry, bing: Prunus avium 

Cherry, choke 

Cherry, red sour: Prunus cerasus 

(Chestnut: Castanea dentata 
-77­


TABLE 14-con. 


Food Extracts Recommended for Category I &r SkinTes t Diagnosis 


Chicken meat: Gallus gallus 


Chicle 


Chicory: Chichorium intybus 


Chili. pepper 


Chives: Allium schoenoprasum 


Cinnamon: Cinnamomum zeylanicum 


Citron: Citrus medica 


(Clams, hard shell ~ Venus mercenaria 


soft shell - Mya arenaria) 
 

Cloves~ Caryophyllus aromaticus 
 

Coconut: Cocos nucifera 
 

(Codfish: Gadus callariu~ 

{ 

~i. Collards: Brassica oleracea acephala 

Coffee: Coffea arabica (roasted bean) 

(Corn: Zea mays) 

(Corn, sweet·: Zea mays saccharata) 

(Cotton seed: Gossypium species seed) 

(Crab: Crustacea species) 

Cranberry: Vaccini.um macrocarpon 

Crappie: Pomoxis species 

Crawfish: Cambarus virilis and bartoni 

Croaker 

l, 
 
-78­


TABLE 14--con. 
 

.,. Food Extracts Recommended for Cate~ory I for Skin Test Diagnosis 

Cucumber: Cucumis sativu8 

Cumin seed: Cuminum cyminum 

Currants: Ribes species 

Currant, Red: Ribes rubrum 

Dandelion leaf: Taraxacum officinale 

Date: Phoenix dactylifera 

Dill: Anethum graveolens 

Dill seed or leaves 

Duck meat: Anas platyrhynchos 

(Egg, white: (Chicken, Gallus galluse)) 

(Egg, whole) 

Egg, yolk 

Eggplant: Solanum melongena 

Elk meat: Cervus canadensis 

Endive: Cichorium endivia 
 

Fig: Ficus carica 
 

Filbert nut (Hazelnut): Corylus species 
 

Fish, white 
 

(Flounder) 
 

Frog meat: Rana species 
 

(Garbanzo (chick-pea; Cicer arietinum) 
 

Garlic: Allium sativa 
 

Ginger: Zingiber officinale 
 
-79­


TABLE 14--con. 
 

Food Extracts Recommended for Category I for Skin Test Diagnosis
 .. 

Goat meat: Capra species 

Goose meat 

Gooseberry: Ribes hirtellum 

(Grape: Vitis species) 

(Grape, concord: Vitia labrusca) 

(Grape, Rieber: Vitis vinifera) 

(Grape, tokay) 

(Grape, white) 

(Grape, white seedless) 

Grapefruit: Citrus paradisi 

(Gum, acacia: Acacia .senegal) 

(Gum, karaya) 

Gum, chicle 

(Gum, tragacanth: Astragalus species) 

Haddock: Melanogrammus aeglefinus 

Halibut: HippoglossuB species 

Herring: Clupea species 

Hickory nut: Carya species 

(Hops: Humulus species) 

Horseradish: Armoracia rusticana 
-80­

TABl.E 14-eon. ·,. .,. 

Food Extracts Recommended for Category I for Skin Test Diagnosis 

Huckleberry: Gavlussacia baccata 

Juniper berry: Juniperus communis 

Kale: Brassica oleracea acephala 

Kohlrabi: Brassiea oleracea caulorapa 

Kola nut: Cola acuminata 

(Lactalbumin, alpha, cow) 

(Lactoglobulin, beta, cow) 

Lamb (sheep) meat: Oris vigrei 

Leek: Allium por.rum 

Lemon: Citrus limonia 

Lentil: Lens culinaris 

Lettuce: Lactuca sativa capitata (iceberg) 

Lettuce leaf: Lactuca sativa crispa (leaf) 

Llcorice: Glycyrrhiza glabra 

Lime: Citrus aurantifolia 

Liver, beef 

Liver, chicken 

Liver, pork 

Lobster: Homarus americanus 

Loganberry: Rubus ursinus loganobaccus 

Mace: Myristica fragrans 

(Mackerel: Scomber scombrus) 
.. ;~ 

Food Extracts Recommended for. Categ.ory I for SkillT~9t Oia,gnosis 

Malt 

(Mango: Mangifera indica) 

Maple, syrup/sugar: ----..;...;., Acer saccharum ..........--.... 
 

Marjoram: Majorana hortensis 

(Melon, honeydew) 

(Milk, cow's (whole): species milk) 

Milk, goat's: Capra species milk 

Millet grain 

Mullet: Mugil cephalus 

Mulberry, red: Morus rubra 

Mul berry, black: Morus rigra 

Mushroom: Basidiomycetes (with species defined) 

Mustard greens: Brassiea j~ncea 

Mustard seed: Brassica hirta 

Nectarine: Prunums persica 

Nutmeg: Myristica fragrans 

Oat, whole ground: Avena sativa 

Okra: Hibiscus esculentus 

Olive, black: Olea europaea - ripe 

Olive, green: Olea europaea - green 

Onion: Allium cepa varieties 

(Orange: Citrus sinensis) 

Oregano: Origanum vulgare 
-82­

TABLE 14-con. 

Food Extracts Recommended for Category. I oor Skin Test Diagnosis 

(Oyster: Ostrea virginica) 

Oyster plant/salsify: Tragopogon porrifolius 

Papaya: Carica papaya 

Paprika: Capsicum annuum 

Parsley: Petroselinum cirspum 

Parsnip: Pastinaca sativa 

Pea, black eyed 

(Pea, green English: Pisum sativum) 

(Peach: Prunum persica) 

(Peanut: Arachis hypogaea) 

(Pear: Pyrus communis) 

(Pecan: Carava illinoensis) 

Pepper, black: Piper nigrum 

Pepper, Cayenne: Capsicum annuum 

Pepper, green: Capsicum frutescens 

Pepper, sweet: Capsicum frutescens 

Peppermint: Mentha piperita 

(Perch: Perea flavescens) 

(Perch, lake) 

(Perch, sea) 

Persimmon: Diospyros virginia 

Pheasant: Phasianus torguatas 
;~.83

TARLE 14"'"-con. 

-/ 

:Food, Extracts Recommended',for'Category If'or Skin Tes't Dia:g:nOSis 

Pigeon (squab): Columbidae species 
 

Pickerel: Esox species 
 

Pike: Esox lucius 
 

Pike, walleye: Perea 
 

Pimento: Pimenta officinalis 
 

(Pineapple: Ananss comosus) 
 

Pistachio nut: Pistacia vera 
 

Plum: Prunus domestica 
 

Plum, blue 
 

• 	 Plum, red 

Poke greens: Phytolacca americana 

Pollock 

( Pomegranate: Punica granatum 
 

Pompano: Trachinotus carolinus 
 

Poppy seed: Papaver somniferum 
 

Pork 
 

(Potato, red Irish: Solanum tuberosum) 
 

Potato, sweet: Ipomoea batatas 
 

(Potato, white Irish: Solanum tuberosum) 
 

Prune, fresh 
 

Psyllium seed: Plantago pysllium 
 

Pumpkin: Cucurbita ~ 

Quail: Colinus virginianus 
 
-84­

TARLE 14--con. 

Food Extracts Recommended for Category I (or Skin Test Diagnosis ',. 

Quince: Cydonia oblonga 

Quince seed 

Rabbit: Lepus species 

Radish: Raphanus sativus 

Raspberry: Rubus species 

Raspberry, black: Rubus occidentalis 

Raspberry, red: Rubus idaeus 

Red snapper: Lutjanus campechanus 

Rhubarb: Rheum rhaponticum 

(Rice: Oryza sativa) 

Rice, wild 

Rosemary: Rosmarinus officinalis 

Rutabaga: Brassica napobrassica 

Rye: Secale cereale 

Safflower seed: Carthamus tinctorius 

Sage: Salvia-officinalis 

(Salmon: Oncorhynchus species) 

Sardi.ne: Sardina pilchardus 

Savory: Satureia hortensis 

(Scallops: Pecten irradians) 

(Sesame seed: Sesamum indicum) 

(Shad: Alosa sapidissima) 

( , ~/ 
Food Extract:s"RecommEmaedfor':Category[urr Skin Test Diagnosis , 

(Shrimp: Peneus set-iferus) 


Smelt: Osmerus mordax 


Snail: Helicidae species 


(Sole: Achirus fasciatus) 


Sorghum: Sorghum vulgare species 


(Soybean: Glycine max) 


Spearmint: Mentha spicata 


(Spinach: Spinacea oleracea) 


Squash, acorn 


Squash, banana 


Squash, summer 


Squash, tomato 


Squash,.- turnip 


Squash, water cress 


Squash, zucchini (Italian) 


Squirrel: Sciurus.species 


Strawberry: Fragaria species 

Sunfish (bluegill): Lepomis species 

Sunflower seed: Helianthus species 

Swiss chard: vulgaris cicla 

'. Swordfish: Xiphias gladius ;... 

(Tangerine: Citrus nohilis) 

Tapioca: Manihot esculenta 

{ 

~~ .. 
-86­

TABLE14--con. 

Food Extracts Recommended for Category I t-or Skin Test Diagnosis 

Tea: Thea sinensis (if variety is defined) 

Thyme: Thymus vulgaris 

(Tomato: Lycopersicon esculentum) 

Trout: Salvelinus (if species is defined) 

Trout, Gulf or speckled 

Trout, lake: Salvel!nus namaycush 

Trout, rainbow: Salmo irideus 

Tuna: Thunnus species 

Turkey (meat): Agriocharis ocellata 

Turmeri~: Curcuma ~onga 

Turnip: Brassica rapa 

Turnip greens 

Vanilla bean: Vanilla planifolia 

Venison (deer): Odocoileus species 

(Walnut, black: Juglans nigra) 

(Walnut, English: Juglans regia) 

Watercress: Lepidium sativum 

(Watermelon: Citrullus vulgaris) 

(Wheat, whole: Trtticum species) 

Whitefish: Coregonus clupeifprmis 

Whiting: Merlangus merlangus 

Yam: Dioscorea alata . 

Yeast, Bakers' (if species is defined) 

. Yeast, Distillers' (if species is defined) 
~B7

}fABLE'1'5 4' 

Food Extracts Recommended fot" Categoryll for 'skftr'TestDiagrl'osis·!/ 

Beef heart 

Codl1ver 

Grapefruit peel 

Pepper, black/white: Piper nigrum 

1 

- This table does not include food ext,rse:t's whfchwe'rein category IIIB 

in the original panel report. 

REFERENCES 

(1) Bock, s. A., J. Buckley.','A. llb1:st ana C. D.May, 

'·Proper Use of Skin Tests with Food Extract's ln'Diagnosis of 

Hypersensitivity to Food in Children," Clinl'cal Altet"gy', 

7:375-383, 1977. 

(2) Bock, S. A., W. Y. Lee., 1.~ Re'iirlgio, A.Holst 'and 

C. D. May, "Appraisal of Skin Tes'ts wi:Ui' Fb~od .Extrabts'for' 

Diagnosis of Food Hypersensitivity,',' GH.nicai",Allergy~ 

8:559-564, 1978. 

(3) Aas, K., "The Diagnosis of·:FIype'rsens,itiv1ty to 

Ingested Foods," Clinical Allergy:;8::39~50~ 1978. 

(4) Bjorksten, F., A. 'Sackinan, K.A. J:.. Jarvinen" 

H. Lehti, E. Savilahti, P. Syvafieni,and:"T:~ /Karkkall.riim~ . 

"Immunoglobulin E Specific to Wheat and:itye;F16ufProteins," 

Clinical Allergy, 7:473-483, 1977. 

(5) Bernstein, M., J. H. 'Day, A~We1sh;; "noubl€-bi:i:nd 

Food Challenge in the Diagnosis of Food Sems:lti';'ity in th~ Adult," 

( 
 Journal of Allergy and Clinical Immunology, 70:205-210, 1982. 
-88­

(6) Kidd, J. M., S. R. Cohen, A. J. Soeman and -,,­

-,.. 

J. N. Fink, "Food-dependent Exercise-induced Anaphylaxis, 

Journal of Allergy and Clinical Immunology, 71:407-411, 1983. 

(7) Miller, J. R., "A Double-Blind Study of 

Food Extract Injection Therapy: A Preliminary Report , " 

Annuals of Allergy, -38: 185-191, 1977. 

(8) Rapp, D. J., "Double-Blind Confirmation and 

Treatment of Milk Sensitivity," The Medical Jountal of 

Australia, 1: 571-572, 1978. 

(9) Rapp, D. J., "Weeping Eyes in Wheat Allergy," 

Transactions, American Society of Ophthalmologic and 

Otolaryngologic Allergy, 18:149-150, 1978. 

(10) Rapp, D. J., "Food Allergy Treatment for 

Hyperkinesis," Journal of Learning Disabilities, 12(9): 

608-616, 1979. 

(ll) O'Shea, J. A., and F. Porter, "Double-Blind 

Study of Children with Hyperkinetic Syndrome Treated 

with Multi-Allergen Extract Sublingually," Journal of 

Learning Disabilities, 14(4):1981. 

(12) King, D. S., "Can Allergic Exposure Provoke Psychological Symptoms: A Double-Blind Test," 

Biological Psychiatry, 16(1):3-17, 1981. 

(13) Rea, W. J., I. R. Bell, C. W. Suits, et al., 

"Food and Chemical Susceptibility After Environmental 

Chemical Overexposure: Case Histories," Annals of Allergy, 

41:101-110, 1978~ 

{ 

\. 
, -89­


(14) Rea, W. J., "Envlx:on~ental1y Triggered Thrombophlebitis," ~':, 1'-'. ' 

'r 

.... Annals of Allergy, 37:~01-l09, 1976. , ~ '!' , 

(15) Rea, W. J., "Environmentally Triggered Small 

Vessel Vasculitis," Annals of Allergy, 38:245-251, 1977. 

(16) Rea, W. J., "Environmentally Triggered Cardiac 

Disease," Annals of Allergy, 40:143-251, 1978. 

(17) Rea, W~ J., D.. PeteTs~ R. Smiley, et a1., "Recurrent 

Environmentally TriggeTed Thrombophlebitis: A Five Year 

Follow-Up," Annals of Allergy, 47:338-344, 1981. 

(18) Rea, W. J., "The Environmental Aspects of Ear, 

Nose and Throat Disease: Part I," J.C.E. O.R.L &Allergy, 

41(7) :41-56, 1979. • 

(19) Rea, W•.J., "The Environmental Aspects of 

Ear, Nose and Throat Dis.ease: Part II," J.C.E. O.R.L. 

,. 

&

Allergy, 41(8/9):41-54, 1979. 

(20) Shambaugh,G. E., Jr., "Serous Otitis: Are 

Tubes the Answer?," Unpublished Manusct;ipt • . ­

(21) Waickman, F. J., "A Double-Blind Study of the 

Sublingual Provocative Food Test," Unpublished Manuscript. 

(22) Rea, W. J.~ R. N. Podell, M. L. Williams, 

E. Fenyves, D. E. Sprague and A. R. Johnson, 

"Intracutaneous Neutralization of Food Senitivity: A 

Double-Blind Evaluation," Unpublished Ma~uscript. 
-90­


(23) Mcr~vern, J. J., Jr., D. J. Rapp, R. W. '/',. Gardner, O. R. O'Rannion, P. Peters, K. Painter 

and S. Perica, "Doub1e-Rl1nd Studies Support Reliability 

of Provocative-Neutralization Test," Unpublished Manuscript. 

(24) Rapp, D. J. and J. J. McGovern, Jr., "Immunologic Diagnosis and Treatntent of Hyperkinesis in Childhood," 

Unpublished Manuscr:1.pt. 

(25) O'Shea, J. A., toA Five-Year Clinical Study Treating 

Infants with Cow's Milk Intolerance with a Milk Extract," 

Unpublished Manuscript. 

(26) Rea, W • .I., "Laryngeal Edema," Unpublished 

Manuscript. 

(27) Bellanti, J. A., L. S. Nerurkar and J. W. 

Willoughby, "Measurement of Plasma Histamine in Patients with 

Suspected Food Hypersensitivty," Annals of Allergy, 47(4):260­

263, 1981. 

(28) McGovern, J. J., Jr., J. L. Laxaroni, P. Saifer, 

A. Levin, D. J. Rapp and R. W. Gardner, "Clinical Evaluation 

of the Major Plasma and Cellular Measures of Immunity," Orthomolecular Psychiatry, 12(1):60-71, 1983. 

(29) McGovern, J. J., Jr., R. W. Gardner, 

K. Painter and D. J. Rapp, "Natural Foodborne Aromatics 
 

Induce Behavioral Disturbances in Children with Hyperkinesis," 
 

International Journal for Biosocial Research, 4(1): 49-42, 
 

1983. 
 
, , 

Pod~ll,R~ N., 

-91­


(30) 'McGOvern, J. J.'~ Jr., J. A. Utzaroni, M.F. , - Hicks, J. C. Adler; and P. c1eary, "Food and 

Chemltal 'Sensitivity: Clinical and Immunological 

Cortel~'t~s," International F~od Allergy" SYmPosium III , 

Boston, Massachusetts, October 1980, l1npubl1sh'e'd" Hanuscri pt. 

(31 )' 'Trevino, R. i., "!mmunologic' MechaTds~ 'in the 

Production of Food Sensitivities," The Lamgoscope, 91: 

1913.;..1936', i981. 

(32) McGOvern~ ;].J., J. A. Lazaro~i and D. J. Rapp, 

. ~ .

"Environmental Agents and Immune Dysreguiation," Unpublished 
 

Manuscript. 
 

(33) McGovern J. J., J. A. Lazaroni, J. C. A(her, M. F. 
 

Hicks and P. Cleary~, "Laboratory and Clinical Diagnosis of 
 

Immune C61ilpiex'Disorders in Food and'Chenrlcal :Allergy, " 
 

unpubiished'Manuscripf.; 
 

(34) McGovern J. j., Jr., and R. W. Gardner, "eNS Effect 
 

ofPh~ft§l CompotJndsinFoods," Unpublished 'Mail~~cript. 

(35) F6rmanR., -;.A cfi 1:1que ofE"alua~ion Studies of 

Sublingual a.nd Intracutaneous Provocative Tests for Food 

, Allergy," Medical Hypbtheses, 7:'10i 9..;,;.1027," 1981.; 

(36) FortMnR., "Medfcsl ReSistance ,to Innovation, II Medical 

, 

"C6ntrove~ies in Aiiergy: A Critical 

Review of' the Methods' 6f Pr6vocatiort and'Neutraliz~tion, " 

unpublished Manuscript. 
-92­

(38) Miller, J. B., "Food Allergy, ',;provocative 

Testing and Injection Therapy," Charles C. Thomas, 1972. 

(39) Mandell, M. and A. A. Conte, "The Role 

of Allergy in Arthritis, Rheumatism and Polysymptomatic 

Cerebral, Visceral and Somatic Disorders: A Double-Blind 

Study," Journal of the International Academy of Preventive 

Medicine, 7(2):5-16, 1982. 

(40) King, D. S., "Can Allergic Exposure Provoke 

Psychological Symptoms? A Double-Blind Test," Biological 

Psychiatry, 16(1):3-17, 1981. 

(41) Rapp, D. J., "Food Allergy Treatment for Hyperkinesis," Journal of Learning Disabilities, 12(9):808-616, 

1979. 

(42) Rapp, D. J., "Weeping Eyes in'Wheat,Allergy," 

1ransactions, American Society of Ophthalmologic & Otolaryngologic Allergy, 18(1):149-150, 1978. 

(43) Rapp, D. J., "Double-Blind Confirmation and 

Treatment of Milk Sensitivity," The Medical Journal of Australia, 

1:571-572, 1978. 

(44) Draper, W. L. "Food Testing in Allergy," 

Archives of Otolaryngology, 95:169-171, 1972. 

( 
 
I. ALUM-PRECIPITATED ALLERGENIC EXTRACTS 
 

Alum-prec1p1.tated al1ergenic extracts and adjuvants were discussed 

extensively in the original Panel report. In addition to the conclusions in that report, more recent information on the possible role of 

aluminum in dementia has been reviewed during meetings of the Panel. 

Mclachlan and DeBoni (Mclachlan, D. R. and V. DeRom, "Aluminum in Human 

i 

Brain.Disease - An oJrerview, "Neurotoxicology, 1:3-16, 1980) reviewed 

the role of aluminum in brain disease, examining the circumstantial 

. . . 

evidence implicating aluminum as a· possible cytotoxic factor in processes assbC::l:ated with neurofibrillary degeneration'of the Al~heimer 

type. They emphasized that at least two important areas require inten.. • 

sive further investigation: thebiologicai state of aluminum wi~hin the 

',. r 

nucleus and the chemicaliderttif:!.cation of the polypeptide subunits of 

the Alzheimer paired helical filaments. There seems no doubt that 

aluminum occurs in elevated concentration in a number of abnormal hrain 

, ._. I ,,;:' 

conditions,howeve£, the critical question of whether it is pathogenetic 

or the result of disease remains unanswered. 

Although higher brain levels of aluminum in lHltients have been 

as'soclat:ed withde'mtmtia~ eVidertce of its causal relationship is still 

circumstantial and the Panel did not find sufficiently compelling 

evidence to recommend a change in th~ permitted leveis of aluminum in 

allergenic extracts • However, thePanelreconiriiend'~lhat the ·la.'beling of 

alum-prec1pitated allergenic extracts should include a warning that they 

should not be used in patients with Alzheimer's disease, Down's Syndrome or renal impairment. 

(;, 
 
-94­


The Panel has reviewed evidence dealing with the use of aluminumcontaining adJuvants in immunotherapy for aller~ic disease. 'In some 

instances, immunological and clinical evidence reviewed in the original 

Panel report suggests results comparable to those following the use of 

aqueous extracts. The margin of difference is not great and falls far 

short of the enhancing effect which might be expected from the la-rger 

nomirtal doses of extract that can be administered wi th alum. Nevertheless, the prinCiple embraced by adjuvant therapy is sound and its 

further development should be encouraged. 

Alum-precipitated Allergenic extracts, (Center-AI"'), Center 

Laboratories, Inc., Port Washington, New York. These alum-precipi tated 

allergenic extracts are prepared from aqueous extracts by formation of 

an aluminum hydroxide precipitated complex. They are licensed for use 

in immunotherapy only. The conclusions and recommendations of the 

original Panel report concerning comparable safety and efficacy remain 

unchanged. However., on further review by the Panel, the data still do 

not support conclusively the claims of clinical or immunological superio-rity of Center-AI over aqueous allergenic extracts. The Panel therefore recommends that each alum-precipitated allergenic product for which 

Center Laboratories, Inc., is licensed be placed in the same generic 

category as the corresponding aqueous product. 

Alkaline:pyridine extracted alum:precipitated allergenic extracts 

(Allpyral"'), Dome Laboratories,· Division of Miles Laboratory,West 

Haven, Connecticut. Allpyral"" products are prepared from nondefatted 

source materials by an alkaline extraction procedure employing pyridine. Comments made earlier about the safety of alum-precipitated 

( 
 
-95­


cons,idf}ration, oughtto,b~g1""en tothe,saiety and particularly the 

•,e:~,fectiven,eEls of these alterta.d allergens although,bas,ed on uncOQtroUed 

clini,calobse,rvations, t'he1;'e appeara to beat least no ,greater risk to 

~heir ;\1sein theirapythan to the, uSe of the cQrx.:e'sponding aqueo,u8,allergenic 'ex,tracts'.A,fter3,Oyea1:'sof elWeti;encew1,thove,r200m111ion 

d08,~8,of .ulpyral11! extract8, there is to date no c11n1,caleviden,ceto 

suggest an incre,ased1,ncidel.'lce,ofoncogenicQ,r neuropat;hicconditions 

among the patients receiving this form of )treatment as noted, in the 

previous Panel report. 

Da;t;a,on, effe~t:iveness,werereviewed1n the ,Paq.el's 0r;,iginalrep,ort. 

110rerecenelythe i.mmunogeJ1;l:cityof Allpyral Wl grass ,pollen extract 

(containing both orchard and ti1!lothy), ,wss;tested l,n ,Sw,ede,n(by Drs. Lars 

( 

du~inga:l.,.year course of treatment.' Spe'cificIgE antibody levels 'rose 

in'!tlal,lYsndlaterfell, 'andspecif,ic IgG antibody levels 'increased 

during anclfel1 foll;ow:ing, trtratJJ:lent'. This suggests that thi's A11pyral 

grass extract isi1l11IlUnpgenicin allergic patients. 

;~n the, Panel'sorigina.l r~p():rt" evidence :w~s revi'ewed for fi;ve 

Allpyral grass pollen e~tI!:acts, the jillergenici~ty, ofwh:lichwas appaI'~ 

ep.~ly'p:ot 'des;t,r9Yi,edQY the;al1tllline;~pY1:';tP~Jleext::r~q,t~01l:.pl"o~es!9 ~'. These < - ,'.' • .- _< .,' - • -':v. '_.' ­

wereorc!t,~rdGc.p~ksfQotJ, t';lmql:hy, ,me:adow. fes:elle ;p.er;enn1alI'ye., 's,nd 

velvet. (Yor}tshtrefog). ,Allp'yralextract~s ·of these five 'grass' pollens 

are recoIl,ltnend.edforC~tegory I. Simila,revide.nce is not available·,for 

ot:her'A11pyr!ilpollen~wold;, dust or animale~tracts. 

c' 
-96­

The Panel's original report recommended that Allpyral- short rag­ .~. .,. 

weed pollen extract should be placed in Category IIlB, because the bulk 

of the evidence available at that time suggested that this extract was 

not effective. With the demonstrated loss of antigen E of short ragweed 

by the alkaline-pyridine extraction process, there is the concern that 

active antigens in other pollens, molds, etc. might. likewise be destroyed in the preparation of their respective AllpJ,ral products. Rowever, since these active fractions have not been identified for most 

allergens, it is difficult to be sure whether they are affected by the 

Allpyral process or not. Although patients receiving Allpyral have 

generally been reported to have been improved, there is inadequate• 

evidence to put these preparations into the same category as their 

aqueous counterparts. The Panel recommends that the remaining Allpyral 

extracts be placed in Category II unless new evidence is furnished that 

the allergens are not destroyed in the extraction process. 
J.PLANT OLEORESINS 

•..,,;., ';c_ iF :.' O:-;;.:'--:~; ; {~.;}):;:...?t ,.,,' 

Considering the almost universal susceptfhility of manto contact 

dermatitis given sufficient exposure to chemical and plant organic 

compounds, it is recommended the Category IIIA plant oleoresin ex­

, 

tracts currently available for patch testing be placed in Category 

I and made available for clinical diagnosis. 

On the other hand, oral immunotherapy has only been tested and .. ~'" 

proven to be effective for a urushiol standardized preparation. Extracts of poiSon ivy and pOison oak should be placed into Categoryl 

for oral immunotherapy if the conditions in the original Panel teport 

are met, that is, if the proquct is shown to contain an ade<luate amount \._ i 

of urushiol and an effective dosage schedule is substantiated by appro­ ~: ,- .-,. 

priate effectiveness data. It is recommended that all other oral ,-}; , 
 

~.' . 
 

oleoresin products be placed in Category II. (Injectable poison ivy, 

( 

\ oak, and sumac extracts for use in immunotherapy were in Category IIIH 

J;, : . ~ '~ .--;- ; 

in the original Panel report.) 
-98­

K. BACTERIAL VACCINE AND BACTERIAL ANTIGENS .,.

.,. .. 

WITH NO U.S. STANDARD OF POTENCY 

The Federal Register November 8, 1977 (42 FR 58266), summarized the 

Panel on Review of Bacterial Vaccines and Antigens with No U.S. Standard 

of Potency Report and the FDA's response. The final order was published 

January 5, 1979 (44 FR 1544). 

Cutter Laboratories, HollisteJ;'...Stie.J;' Divis.ion's Mixed Res.p.iratory 

Bacterial Vaccine (MRV) (licensed as "Polyvalent Bacterial Vaccines with 

No U.S. Standard of Potency") which was in Category IlIA has continued 

to be offered for sale and was assigned to this Panel for rec.1as.si~ 

fication. As stated on page 58317 in the No,vember 8~ 1977 notice, the 

Category lIlA products could "remain on the· market and thei,r licenses 

remain in effect on an interim basis provided that;: (1) group. A strept.o,;" 

! coccal organisms and their derivl;itiv.:es" where present, are removed, and 

\ 

(2) satisfactory potency standards are developed and acce.ptab,le s'f$ndards are developed and acceptable data bas.ed. on scientifically so~hd 

studies (as recommended in the panel report) ~ s,u,bmitted to demort$tra.~e 

efficacy in humans." 

Although the manufacturer remov:ed the group A stJ;'eptoco'ccal organisms and began some preliminary st~dies fOir. MRV, since 1977' there has 

been no better definition of indications fo.r the use OI thi$ px:oduct e; 

Neither are there recognizable criteria fo;r se;lect10n of Patients or. 

d:o~ag>e. No double-blinded controlled studies have been performed or 

even started since the Panel made its r:ecomJ;Denqattons in 1977 .. 

(

,--,. 
,.:.\ 

With no demonstratfi!d effectiveness, the pQnel with one dissenting 

vote recommends that Cutter Laboratories, Polyvalent Bacterial Vaccines ~,:f ., 

with "No u.s. Standard of Potency" be reclassified fro", Category lIlA to 

Category II. one Panel member recommends Category I for diagnosis 

and immunotherapy because in his experience a rare patient will react 

with an itilmediate skin test response and seemingly w111benefit from 

immunotherapy. 

( 


:<' 

I