Dmf & distribution records seminor

drug master file

1. Drug Mas t er File And Distribution record Presented by- Mr. OMKAR SASANE M. Pharm. Sem-I (Dept . Of Pharmaceutics) Under the Guidance of- Mrs. VINITA PAWAR Mr. KRISHNAKUMAR LONE (Dept . Of Pharmaceutics) JSPM’S RAJARSHI SHAHU COLLEGE OF PHARMACY AND RESEARCH PUNE- 33 1

2. I n t r oduct i on A Drug M a s t er F i l e (DMF ) is a subm i ssion t o the F o o d a n d D rug A dmin i s t r a t io n (F D A ) that m a y b e u s ed t o p r o v i d e c onfi d ent i a l d e tailed i n f orma t io n abou t f a c i l iti e s, p r ocesses, or ar t ic le s us e d in th e manu f a c t u r i n g , p r o c ess i ng , p a cka g i n g, a n d stori n g of one or mo r e human drugs. The subm i ssion of a D M F is not r e q u i r ed b y l a w o r F D A r eg u l a t i o n a n d a D MF is s u b m i t t e d sole l y a t th e d i sc r e t i o n o f th e holder ( a perso n w ho o wn s a D MF ) . The i n f orm a t i on c o nt a i n ed in the D M F m a y b e u s ed t o s u p p or t an I n v esti g a t i o n al New D rug Applica t ion (IND), a New D rug Applica t ion (N D A) , an A b b r e v i at e d New D r u g A ppl i c a tio n (AN D A) , ano t h e r D M F , a n Export Applica t ion, or ame n dments a n d supplem e nt s t o a n y of th e se. Bu t a D M F is N O T a substi tu t e f or an IN D , N D A , AN D A , or Exp o rt Applica t ion. 2

3. T ypes o f Dru g ma st er f i le T ype I: M anufacturing Si te, Fa c i l it i es, Oper a ting Pr o c edur es , and Per s onnel T ype I I: Dru g Subst a n c e, Dru g Su b st a nce In t er m ediate, a n d Mater i a l used in their prepa r ation o r Dru g Product T ype III : Packag ing Material T ype I V : E xcip i ent s , C olorant, Flavo r , Essence or Mat e r i al u s ed in the i r pre pa r ation T ype V : F D A Accep t ed Re f ere nce Infor m at ion 3

4. T ype I:Man u f acturing Si t e , F acilities, Ope r a ting P r ocedu r es , a nd P e r sonnel 4 N O T MOR E APPLICAB L E. (WITHD R A W N B Y F D A) A T ype I DMF is r e c ommende d fo r a p e rso n outsid e o f t h e Uni t ed Sta t es t o assis t F D A i n condu c t i n g on si t e in spections of the i r manu f ac t uri n g f acil i t i es. The DMF sh o ul d descr ib e the manu f ac t uri n g si t e, equip m e n t ca pabili t ies, a n d ope r a t ion a l l a y o u t . The d escript i on of th e s i t e sh o ul d in cl ude a ctual si t e a dd r ess, a nd a ma p sh o wi n g it s lo c a t ion w i t h r espect t o th e n e a r est cit y . An a e ria l p h o t og r ap h a n d a d ia g r a m of th e s i t e m a y b e helpful. A d ia g r a m of majo r p r od u ction a n d p r ocessi n g a r e a s is helpful f or unde r sta nd in g th e ope r a t ion a l l a y o u t .

5. T y p e I I: Dru g Su b s t ance, Dru g Su b s t ance I nt erm e di a t e & M a t eria l used in t h eir p r epa r a ti o n O R Dru g P r oduct: (1 ) Dr u g Substanc e In t erm e dia t es, Dr u g Substanc es, and Ma t erial use d in thei r p r e p a r ation. Su mmarize al l signi f ica n t s t eps in th e ma n u f ac t uri n g a n d cont r ols of th e drug in t erm edia t e or su b sta nce. (2 ) Dr u g P r od uct Ma n u f ac t uri n g p r ocedu r es a n d cont r ols f or f i n i shed dosage f orms sh o ul d o r din ar i l y b e su b mit t ed in a n IN D , N D A , AN D A , or Export App l ication. I f t h is in f or m a tion cannot b e s u b m it t ed in a n I N D , N D A , A N D A , or Expor t App l ica t ion, it sh o ul d b e su b mit t ed in a DM F . 5

6. T y p e I I: Dru g Su b s t ance, Dru g Su b s t ance I nt erm e di a t e & M a t eria l used in t h eir p r epa r a ti o n O R Dru g P r oduct: F OL L O WIN G GEN E R A L P OIN T S IN C L UDE D IN TY P E II DM F s. Ma n u f ac t uri n g Sect i on Qual i t y Con t r ols I n put s ( R a w / P kg . M a t eri als) I n t e r medi a t es & I n - p r ocess Finish e d Drug Subst a n ce V al idat ions St a bili t y data Imp uri t ie s Pkg. & Labeli n g 6

7. 1 . Manu f acturi n g Sect i on Data of i npu ts (R a w Ma t erials/ P acka g in g Ma t erial s ) & S ou r c es List al l RM s & PMs with so u r ces Id e n t i f y K e y St a rtin g Ma ter i al s ( K SMs) If K SM s a r e co m pl e x m o lecul es, e x t e n s i v e data a r e r equi r ed If co m pl e x K SM s a r e o u tsou r ced, F D A can as k : Deta iled m f g. P r ocess Qual i t y data (including imp uri t ie s & r es i dual so lv e n t l e v els ) ; J u sti f icati o n / E v ide n ce o n h o w c a rr yo v er o f i mpurities f r om K SMs t o f i n i shed API i s cont r ol l ed 7

8. 2 . Qua l ity Co n t r o l Sect i on Ob j ect i v e: T o ensu r e qu a l i ty a t e v ery stage o f p r o c ess: Input s ( R a w/P k g . Ma t er i als) In term edia t es & I n - p r oc e ss Fin i shed Dr u g Su b sta nce G r adua l in c r e a se in c h ec k s a s t he p r ocess p r og r ess e s specifications & T est m eth o ds f or al l ab ov e Com p le t e An a l yt i cal Data of stu d y ba t c h es (Cer t i f i c a t es of A n a l y ses) Sampling P r ocedu r es a dop t ed A n a l ytical R e f e r e n ce St a nd a r d (A R S) : (P r epa r a t ion, Puri fica t i o n & Qualif i cation wi t h P h armaco p oeial Standa r d) I f Non - Pha r maco p oei a l : Ex t e n s i v e t es t in g T est ba t c h es v s. A R S: IR/U V /NMR/ X RD 8

9. 3. Ana l yti c al V ali d a ti ons Done a cc o r dan c e t o R efe r en c e Gu i d e line s : IC H Q 2 A & B V a l i d ation of P ’ c opoe i al meth o ds is als o e xpect e d t o a ssess su i t a b i l i ty As s a y/Impuri t i es ’ d e t er m in a t i o n / O VI estima t ion F o r c ed D e g r adatio n St u d i es (H y d r o l ytic, Oxid a t i v e, A cidic, Al k a l i , phot o - deg r ad a t i on e t c.): Es t a b l ish s t a b i l i ty i n dicati n g metho d s T h r ee c ons e cut i v e c om m e r c i a l sca l e ba t ches A cc ele r a t ed st u d i es (4 ° C / 75 % R H ): 3 m onth s satisfa c t or y data. Long t erm st u d i es (2 5 ° C / 6 % R H ): Mus t c o ntinu e t o c o nfir m she l f - l i f e S t a b i l i ty s t u d y s a mpl e s m u s t be pac k ed in simu l a t e d ma r k et c o nt a i n e r s. S t u d y sha l l inc l u d e a l l s u s c e p tib l e pa r ame t ers (e . g. impu r iti e s, pote n cy e t c.), i . e . O VI, B D e t c. c a n b e omitt e d Label un i d e nti fi e d i m p ur i t ie s , if i n c r easing signific a n t l y 9

10. 4. I mpur i ties Sect i on O b ject i v e : T o p r o v e t h a t q u a lit y obtaine d is b y d e sign of p r o cess, not b y chan c e E x pla i n : H o w carr y o v er o f i m p urities i n - p r ocess st a g e t o AP I is co n t r olled H o w r es i dual so lv e n t s a r e th r o w n a w a y i n v a r ious sta g e s of p r oc e ss J u st i f i cat ions f or limi t s a ppli e d . 10

11. 5. P acki n g & Labe l li ng Detai le d description o f co m ple t e packin g configu r a tion List ou t prima r y & secondary p k g. Ma t erials F o od-g r ade cer t i f ica t ion o f inner - m o st p k g. Ma ter i a l S t abili t y sample packi n g m u st b e ide ntica l Specifica t i o ns & T est me t h o d s f or al l packi n g ma t erials Specime n labe l m u st be submit t ed Cle a r mention o f r e c omme n ded s t o r a g e conditions ( t empe r a t u r e, l ig h t p r o t e ct i on e t c. ) N e v er s wi t c h - o v er t o al t er n a t e packi n g , unles s sta bili t y es t ablishe d & app r o v ed 11

12. T ype III: P ac k aging M a t erial S h ould b e i d e n t i fi e d b y t h e i n t e nde d use , comp o n e n ts, con t r ols f or its r e l e a s e . c o m p o s it i o n , a n d The n ames o f the su p pl i e r s or f a br ic a t o rs o f the com p o n e nt s use d i n p r e p ar i ng the p a c k ag i n g ma t e r i a l a n d the ac c e p t a nc e specifi c at i o n s sh o ul d a l s o b e g i v e n . D a t a s u pport i n g the ac c ep t a b i l i ty o f the p a c k ag i n g m a t e r i al f or i ts i n t en ded use shou l d a l so b e subm i t t ed a s o u t l i n e d i n the "Gu i del i n e f or S u b mi t ti n g D o c um e nt a ti o n f or P acka g i n g f or Human D rugs a n d Biologic s . " T o xi c o l o g i c a l da t a on th e se ma t e r i a l s w o u l d b e i n cl u ded u nde r t h is type o f D M F , i f no t o t h e rw i se a v ai l a b l e b y c r oss r e f e r e n ce t o a no t h e r d o cumen t . 12

13. T y p e I V E x cipie n ts, Colo r a n t, Fl a v ou r , Essence, or M a t eria l Used in their P r epa r a tion Ea c h a d d i t i v e shou l d b e id e n t i fi e d a n d c h a r a c t e r i zed b y its met h od of manu f a c t u r e , r e l e a se spec i fica ti o ns , an d te s t i n g m e tho d s. T o xi c o l o g i c a l da t a on th e se ma t e r i a l s w o u l d b e i n cl u ded u nde r t h is type o f D M F , i f no t o t h e rw i se a v ai l a b l e b y c r oss r e f e r e n ce t o a no t h e r d o cumen t . Usual l y , the o f fici a l c o mpend i a a n d F D A r egulatio n s f or C o lou r ad d it i v es ( 2 1 CFR P arts 7 th r ough 82 ), D i r ect f o o d ad d it i v es ( 2 1 CFR P arts 17 th r ou g h 173 ), Indi r ect f o o d ad d it i v es ( 2 1 CFR P arts 17 4 th r ou g h 178 ), F o od subs t a n ces ( 2 1 C F R P a r ts 18 1 th r o u g h 186 ) m a y b e use d a s s o u r ces f or r e l ease t e s t s, specificati o ns , a n d s a f et y . Gu i de l i n e s s u g g est e d f o r a T ype I I D M F m a y b e h e l p f u l f or p r e p a r i n g a T ype IV D M F . 13

14. Ty p e V : FDA A c cepte d Re f erenc e Information F D A disc o u r a g es th e us e o f T ype V DM F 's f or miscellan eous in f o rmat i o n , dup l ica te in f orma tion, o r i nf orm a t i on tha t sh o ul d be in cl uded i n one o f th e other t y pe s o f DM F ' s . If a n y h o lde r w ishes t o sub m it in fo rmati o n an d supporting data in a DMF tha t i s no t c o v e r e d b y T y pe s I th r o ug h I V , a h o lde r m u st f i rst su b mit a le t t er of in t e n t t o th e Drug Mas ter File St a f f. F D A w i l l t h en c ontact th e h o lde r t o disc u ss th e p r o p osed su b mission. 14

15. Submissions t o D r ug M a s t e r F i les Ea c h D M F s u b mission s h ould co n ta i n a t r a n s m i t ta l l e t t e r , a d mi n i s t r at iv e i n f o r m a t i on a bo u t t he su b miss i on, an d t he spec i fic i n f or m a ti o n t o b e i n cl u ded i n the D M F a s descri b ed i n th i s sectio n . The D M F m u st b e i n the En g l i sh l a n g u ag e . Whe n e v er a subm i s s i o n c o n t a i ns i n f o r mat i on i n a no th e r l an g u age , a n accu r a t e ce r t i fi e d E n g l ish t r a n s l a ti o n m u s t a ls o b e i n cluded. Ea c h p age o f each co p y of the D M F sh o u l d b e d a t ed an d co nsecu t i v e l y num b e r ed . A n upd a t e d tab l e of c o n t ents s ho u l d b e i n cluded w i th e ach s u bm i ssio n . 15

16. Transmitta l Let t ers Origina l Submissi o ns Id e ntificat ion o f su bmissio n : O r ig inal, the classi f ie d i n Sect i on III, and it s su b jec t . Id e ntificat ion o f th e applica t ions, i f k n o wn, t y pe o f DMF as tha t th e DMF is in te nd e d t o suppor t , in cl u din g th e n a me and add r ess o f e a ch sponso r , applica n t , or h o lde r , and al l r el e v a n t doc u ment num ber s . Sign a tu r e o f th e h o lde r o r th e auth o rized r ep r ese n t a t i v e . 16

17. Amendments Id e n ti f ic a t ion of su bmissio n : Ame n dme n t , th e DMF n um be r , t y p e o f DM F , and th e su b jec t o f th e ame n dmen t . A descr ipti o n o f th e p u rpose o f su bmi s sion, e . g . , u p da t es, r e v i s e d f orm u la , o r r e vis e d p r ocess . Si g na tu r e o f th e holder o r th e authoriz e d r ep r es e n t a t i v e. 17

18. Administrative Informati on Origina l Submissi o ns Names a n d add r ess e s of th e f ol l o wi n g: DMF h o lde r : P erson w ho o wn s a DMF Corpo r a t e headq u ar t ers. Ma n u f ac t uri n g/p r ocessi n g f acil i t y . Con tac t f or F D A cor r espond e nce. Ag e n t(s ) , if a n y: A P erson w ho is appoin t ed b y a D M F ho l der t o ser v e a s th e cont a ct f or th e holde r . The speci f ic r espons ibili t ie s of e a ch perso n lis t ed i n a n y of the ca t egori e s in Sect i on a. Sta t ement of co m mitmen t . A s ig n ed sta t eme n t b y th e h o lde r cer t i f yin g tha t th e DMF is c ur r e n t a n d tha t th e D M F h o lde r w i l l c o m p l y wi t h th e s t a t eme n ts mad e in i t . 18

19. Amendme n ts Name o f DMF h o lde r . DMF num be r . Name and add r ess f or cor r espond e nc e . A f f ec t ed sect i on a n d/or pag e num bers o f th e DM F . The nam e and add r ess o f each person w h o s e IN D , N D A , AN D A, DM F , o r Expor t Appl i ca t i on r eli es o n t he su bjec t o f the ame n dment f or sup por t . 19

20. Au t hor i z a ti o n T o R e f e r T o A Drug Ma s t e r F ile L e t t er of A ut h orizatio n t o F D A Be f o r e F D A can r e v i e w DMF in f o rmat i o n i n supp o rt o f an applica t ion, th e DMF h o lde r m u st submit i n d u p lica te t o th e DMF a let t er o f auth o riza t i on permitt i n g F D A t o r e f e r ence th e D M F . If th e h o l d er c r oss r e f e r e n ces it s o w n DM F , th e h o ld e r sh o uld supp l y i n a le t te r o f a uthorizatio n th e i nf o r mat i on designa t ed by i t ems 3 , 5 , 6 , 7 , a n d 8 o f this section . The h o lde r does no t need to se n d a t r a n smitt a l le t t er wi t h it s le t t er o f authoriz at i o n . 20

21. The le t t er o f authoriz at i on sh o ul d in cl ude th e f ol l o wi n g : The da t e . Name o f D M F h o lde r . DMF num be r . Name o f person s a u thoriz e d t o in corp o r a t e i nf orma ti o n i n the DMF b y r e f e r e n c e . S p eci f ic p r od u cts c o v e r ed b y th e D M F . Su bmission da t es o f 5 , ab o v e . Sect i on num bers a n d/or pag e num bers t o b e r e f e r enced . Sta t ement o f com m it m ent tha t t he D M F is c u r r ent an d tha t the DMF h o lde r wil l co m p l y wi t h th e sta t eme n t s made i n i t . Sig n a t u r e o f authoriz i n g of f ic ia l . T yped n a me and t i tl e o f of f ic ia l authoriz i n g r e f e r e n ce t o th e DM F . 21

22. A hol d er w ho wi s hes t o close a DMF should submit a r equest to th e D rug Mas t er F i l e Sta f f stating th e r eason f or th e closu r e. The r equest should include a sta t ement tha t the holder ' s obli g ations. The Age n cy m a y close a D M F tha t does not con t ai n a n a n nua l upda t e of per sons authorized to incorpo r a t e in f ormation i n th e DMF b y r e f e r ence an d a li s t o f chan g es mad e s i nc e the p r e vious an n ua l r epor t . The holder wil l be n o tified of F D A 's in t ent to close th e DM F . CLOSURE OF A DRUG MASTER FILE: 22

23. Distribution 1. Dis t ribu t io n : T he divi sion a n d t he m o ve me n t of pharmaceuticals products from the premises of the manufacturer to the end user or to an intermediate point by means of various transport methods. 2. Distribution records : Are written data related to distribution of drug products from manufacturer to the distributor. 23

24. Distr i bution p r ocedu r e It shall include the following:- A procedure whereby the oldest approved stock of a drug product is distributed first. Deviation from this requirement is permitted if such deviation is temporary and appropriate. A system by which the distribution of each lot of drug product can be readily determined to facilitate its recall if necessary. 24

25. Continued…. It must be constructed and procedures established to facilitate recall of defective product. The manufacturer must maintain records of all distribution transactions involving in process or finished goods. A variety of distribution recording system must be utilized. Computerized tracking systems are most common but paper systems such as recording the lot or control number on the retained copies of the shipping invoices or recording the dates on which each lot commenced distribution also use. 25

26. Cold Chai n Distribution. It is the example of distribution. It can be defined as the channels of distribution, handling and storage of a temperature sensitive product. For temperature sensitive products such as vaccines, biologics and some parenteral solutions. It has become a practice that assures the product strength, purity, potency and efficacy for the end user. 26

27. Distribution Records Are written data related to distribution of drug products from manufacturer to the distributor. These records should be maintained in such a way that batches of drug products are easily available. It is important that information should be readily available so that product recall is efficient in case there is complaint or adverse reaction due to use of the drug product. 27

28. Continued…. E v ery di str i b utor is al s o o bl i ged to ma intain a co m plete a nd ac c urate record of further di stri butio n . A distribution register may be m ainta i ned for detailed info r m at i o n ab o ut di stri bution of each batch of drug prod uc t . 28

29. Distributio n r ecords shoul d contain : - Na m e St r eng t h of th e p r o d uct Na m e and add r ess of con sig nee Dat e and q u anti t y s hip ped Cont r ol n u m ber of drug p r o d uct 29

30. R e f e r ences ww w . f da.g o v w w w . f da.g o v / cder/guidan c e/dmf.html w w w .emea.eu.int/htm s / v et 30

31. 31