Document MJJKBNzeXYR7dK69vgpDE5yok

.December 21, 1973 ""'T T r w T r 1 K"lM HYLAND DIVISIO N TR A V E N O L LABO R ATO RIES, INC. Post Office Box 2214 3300 Hyland Avenue Costa Mesa, California 92626 (714) 540-5000 Hearing Clerk Food and Drug A dm inistration 5600 F ish ers Lane Rockville, M aryland 20852 Dear Sir: As m anufactu rers of biological products, holding establishm ent lic e n se n u m b er 140, we w ish to co m m en t on the P r o p o s e d Rule concerning A sb e sto s P a r tic le s in Food and D ru gs, published at 38 F R 27076 on S e p t e m b e r 28, 1973. We would like to point out that: 1. T h e r e is no e v id e n c e that a s b e s t o s in the q u a n titie s p u r p o r t e d to be p re se n t in so m e p a re n te ra lly a d m in iste re d drugs has ever cau se d a d v e r s e e ffects in hum an r e c ip ie n ts, despite the fact that a s b e s t o s has been a com ponent of m a t e r ia ls used in p r o c e s s in g such d ru g s for m an y d e c a d e s . The only evidence of ill effect follows exposure by inhalation and (possibly) by contact and ingestion, and then only following relativ ely high exposure b ecau se of o ccu p a tion or unusual environment. 2. A s b e s t o s is u b iq u ito u s , a s noted in the p r e a m b l e of the p r o p o s a l . 3. T h e r e i s no a c c e p t e d p r a c t i c a l m e t h o d to d e m o n s t r a t e the p r e s e n c e (o r, m o re im p ortan t, the a b se n c e ) of a s b e s t o s in p a r e n te r a l d ru g s. We have no objection, how ever, to attem pt to prevent u n n e c e s s a r y exposure to the p resen tly unknown h azard, providing that the quality and e ffic a c y of often life - s a v in g drugs a r e not im p a ir e d in such an attem pt. In accord an ce with this attitude, we have had an active project, *9 Hearing Clerk Food and D rug A dm inistration D ecem b er 21, 1973 Page 2 opened in O ctober 1972, to find w ays of elim inating a s b e s t o s and a sb e sto s- c o n ta in in g m a t e r ia ls fro m all s ta g e s of the p r o c e s s in g of the in jectab le p ro d u c ts we m a k e. We have no m e a n s to d e m o n s t r a t e eith e r the p r e s e n c e or a b s e n c e of a s b e s t o s in our p r o d u c ts ; th e r e fo r e the study h a s been d ire c te d s o le ly to the e lim in atio n of asbestos-containing m aterials (filters) so far as possible from all processing steps. Our injectable p ro d u cts a r e a ll d e riv ativ e s of hum an p la s m a and the diluents with which such pro du cts a s a r e furn ished in dry fo r m a re reconstituted for adm inistration. The diluents are all prepared with out the use of a sb e sto s or a sb e sto s - containing m a te ria ls. A sb e sto scontaining filters have been used for y ears to achieve the sh arp se p aratio n s of fraction s of human p la sm a proteins needed for purity and p h y s i c i a l s t a b i l i t y of p r o d u c t s and to r e a c h the fin a l p r o d u c t c l a r i t y required by present FDA regulations. Dozens of candidate substitutes for asbe stos - containing filter m ate rial have been found ineffective in our study. Only in recen t m onths has p a r t i a l s u c c e s s b e e n a c h i e v e d . We have b e e n a b le to u s e f i n a l m e m b r a n e filtration for all our products, and for som e products we have been able to elim inate a sb e sto s-co n ta in in g filters entirely. H owever, for other products, we have not yet been able to find an acceptable substitute during the p ro c e ssin g . We should again m ention that we have no inform ation a s to whether or not the num ber of a sb e sto s p a rticle s, if present, has been reduced by the final m em brane filtration. Although it is not c l e a r , the d e s c r i p t i o n of the F D A s u r v e y and study in the p r e a m b l e of the p r o p o s a l ( p a g e 2 7 0 7 7 , c o l u m n 3, to p a g e 2 7 0 7 8 to p of c o l u m n 1) s e e m s to s a y th a t a s b e s t o s w a s d e m o n s t r a t e d in m a n y products which w ere never exposed to a sb e sto s during p ro cessin g . Thus it m a y be futile to e x p e c t to a ch ie v e co m p lete a b se n c e of a s b e s t o s . '4 Hearing Clerk Food and Drug Adm inistration D ecem ber 21, 1973 Page 3 The p resen t FDA regulations and requirem ents for clarity and stability of p a r e n t e r a l l y - a d m i n i s t e r e d hum an p l a s m a d e r iv a t iv e s a r e b a s e d on what has been p o s s ib le with the use of a s b e sto s - containing f ilt e r s , not upon any knowledge of h arm fu l effects or lack of e ffe c tiv en e ss of p r e p a ra tio n s le s s c le a r or l e s s stable with r e s p e c t to the fo rm atio n of insoluble m a t e r ia l on aging. B a s e d upon the above con sideration s, we feel that the issu an ce of any regulation s such as those in pro p osed Section 133. 3 (j) is p re m atu re and should await: 1. P r a c t i c a l m e th o d s of d e m o n s t r a t in g and q u antitating a s b e s t o s p a r tic le s in such b io lo g ic a ls a s hum an p l a s m a derivatives. 2. Know ledge that the p r e se n t p r e p a r a tio n s, which m ay or m ay not contain v ery slight tra c e am ounts of a s b e s t o s , have any undesirable side effects attributable to a sb e sto s. 3. K n o w l e d g e a s to w h e t h e r o r not the p r e s e n t l y r e q u i r e d d egree of clarity and ph ysical stability a re needed for reason s other than esthetic. If it should be d e te rm in e d that so m e kind of re g u la tio n s in this m a tte r is needed, we have the following com m ents concerning the proposed fo rm of Section 133. 8 (j): F i r s t sen ten ce: T his sen ten ce would reg u la te the filte r, not the use of the filter, A better choice of sentence fo r m might be: " F i l t e r s w h i c h r e l e a s e f i b e r s s h a l l not be u s e d in the m a n u f a c t u r e -----------------. " Second sen ten ce: T h is d ir e c tly c o n tra d ic ts the f i r s t se n te n ce , say in g that such filters m ay be used under certain circu m stan ces. Further, dem onstration that som ething is not p o ssib le is an a lm o st im p ossib le ta sk ; the p o s s ib ilit y ch an ges with a d v a n c e m e n t of the a r t , a m a tte r l a r g e l y in the hands of the filte r m a n u f a c t u r e r s , not the b io lo g ic a l m an u factu re rs, although the latter adm ittedly can stim ulate the fo rm e r. Hearing Clerk Food and Drug Adm inistration D ecem ber 21, 1973 Page 4 Third and fourth sentences; The proposed requirem ent to furnish evi dence that the final (m e m b ra n e ) filter actu ally re d u c e s the content of a s b e s t o s p a r t ic le s s e e m s u n re a so n a b le , and we fee l it is am p le to require that such a filter be used. The dem onstration of reduction req u ires equipm ent not e a sily or usually available to a biologies m anu fa c tu re r, and the re fe re n c e cited is a lm o st entirely concerned with much larg er num bers of particles than might be expected under any condition in a p a ren teral solution. This proposed req u irem en t would requ ire proof only that safety or effectiveness is (or might be - a purely subjective conjecture) c o m p r o m is e d , It does not c o n sid e r that c la r ity and p h y sic a l stability, which a r e a p a rt of the p r e s e n t r e q u ir e m e n ts for our p ro d u c ts, m ight be affe cted with no e ffe ct on s a fe ty or e ff e c t iv e n e s s , yet p ro d u cts would not be sa tisfac to ry by p resen t r e le a s e stan dards. In su m m atio n , we fe e l that a g re a t d eal of inform ation needs to be gath ered b efo re reg u lation s such a s those p ro p o se d for Section 133. 8(j) can be considered. Respectfully, J o h n W. P a l m e r , P h , D. Vice P resid e n t and D irecto r of L a b o r a to r ie s gt HYLANI DIVISION T R A V ENN^^^^ BBppRRA T O R IE S , INC. TRANSMITTAL SLIP TO: / D A T F : ( ' L - 'L f - 7 ^ NOTE AND FILE NOTE AND RETURN N O TE A N D SEE ME PLEASE ANSWER FOR YOUR A P P R O V A L INVESTIGATE AND REPORT COMMENTS: PLEASE REPLY TAKE APPRO PRIATE ACTION PER YOUR REQUEST FOR YOUR SIGNATURE FOR YOUR INFORMATION JU ju u -d l p - {o ^ - ** * ^ r ji^ vf X rrt'V '' 'b _^/ -Y~ SIGNED