Document 912b0Ge1DkLdOY9MMZgBOgLep

OtfanicA, 7125 N CLARK. STR EE T CHICAGO. ILLINOIS 60626 312 - 764-6700 M arch 17, 1976 O ffice of the H earin g C lerk Room 4-6 5 Food and D rug Adm inistration 5600 F ish e rs Lane R o ck ville, M aryland 20852 G en tlem en : Re: F ed eral R eg ister V ol. 41, N o. 31, 2-13-76, p . 6888 R eg ard in g the P ro p o sed R u les su b p a rt D , "E q u ip m en t", regu lation 211.72, p a ra g ra p h s a , b and c in the above p u b licatio n , we w ould lik e to comment on th is su b je c t re la tiv e to o u r m an u factu re of R ep o sito ry C orticotropin Injection USP XIX (o u r NDA # 1 0 -831). In the h eat degradation of g elatin , w hich is u sed a s a re p o sito ry veh icle in R epository C orticotropin , a v ery m inute amount of mucoprotein is precipitated as a haze. We re m o v e the h a z e b y filte r in g the h e a t d e g r a d e d g e la tin th ro u g h an a sb e sto s filte r. A fter the gelatin h as been p o lish e d b y filtratio n the ap p ro p ria te amount of corticotropin con cen trate is ad d ed to the gelatin an d the g e la tin c o n c e n tra tio n , v olu m e a n d p o te n c y a r e a d ju s t e d to 100% o f the la b e le d p o te n cy fo r th e p a r t ic u l a r s tr e n g th in v o lv e d ( i . e . , 40 u n it o r 80 u n it p e r m l . ) . T h e p r o d u c t in g e la tin a t 2 5 C i s then filtered through a sterile 0.45 m icron m illipore m em brane for sterilization p r io r to fillin g in to s t e r ile v i a l s . Upon exam ination of the gelatin m icro sco p ically u sin g a 300 m agn ification le n s w e a re u n ab le to detect any s ig n s of a sb e sto s f ib e r s . H ow ever, it is p o ssib le that there are asb esto s fib ers of such m inute siz e that the o rd in ary m icroscope w ill not p ick them u p . Ifp-O Z L ,/ ^0073 H earing C lerk Food and D rug A dm inistration M arch 17, 1976 Page 2 We a r e , th e r e fo r e , su b m ittin g a t ran d o m s a m p le s to a n o u tsid e laboratory for study under electron m icroscopy for the p u rp o se of determ ining w hether m inute asb esto s fib ers do or do not e x ist in our product. A s soon as the inform ation on the electron m icroscopy is av ailab le w e w ill fo rw ard co p ies of the r e s u lts to y ou . In the m eantim e, w e have in vestigated other m ethods of filtration such as those su g g ested by M illipore Corporation in volving filtration through a fib e rg la ss elem ent and su bsequ en tly through a 0.45 micron m em brane. A lthough the new system w orks equally w ell as our filtration system it, n ev erth ele ss, p resen ts the p o ssib ility of fib e rg la ss p articles existin g in the fin al p ro d u ct, w hich we feel w ould b e as detrim ental as asbestos fibers. F u rth e rm o re , w e w ould lik e to p oin t out that the p ro d u c t w h ich we m arket nationally through d istribu tors is labeled "For Intram uscular or Subcutaneous Injection O n ly". Of co u rse, w e h ave no control over a h ospital, doctor or clinic giving our product in traven ou sly. In our m inds it is extrem ely doubtful that u ltra-fin e p a rtic le s of asb esto s or fib e rg la ss w ould ev er get into the v a sc u la r system and thereby come in contact with lung tissu e . T h e r e fo r e , w e w o u ld lik e to p r o te st the above p r o p o se d r u le p a r tic u la r ly w herein it in volves the filtration of sm all volum e p a ren terals that are adm in istered in tram uscu larly or subcutan eously b e c a u se , in ou r exp er ien ce, it is extrem ely doubtful w hether any other system of filtration w ould accom plish better filtration than that w hich w e now u se . O ther p o ssib le m ethods for the filtration of such p aren terals m ight p o s sib ly in v o lv e the u se of a c id -w a sh e d (iro n fre e ) h y flo - su p e r c e l to accom plish the rem oval of m u co -p ro tein s, b u t certain ly extrem ely fine p a rtic le s of such a filter m edia w ould b e fa r m ore lik e ly to p a s s through H earing C lerk Food and D rug Adm inistration M arch 17, 1976 Page 3 either a 0.45 m icron or a 0.22 m icron m em brane than w ould asb estos fib ers or fib e rg la ss fib ers b e cau se , gen erally sp eak in g, they are sp h erical in nature w h ereas the fib e rs are longitudinal in n atu re. Your comments w ould be ap preciated . V ery truly y o u rs, ORGANICS, INC. Law rence H icks P resident LH /la DEPARTM ENT OF HEALTH, EDUCATION, AND WELFARE CROSS-REFERENCE SHEET File No. 75N-0339-C0013 See File: 75P-0261-C0073 From To Sum m ary: D ate H B W -l* (le v . 6-6M