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AABBBBRREEVVIIAATTEEDD NNEEWW DDRRUUGG 
AAPPPPLLIICCAATTIIOONN ((AANNDDAA)) 
DR ANTHONY MELVIN CRASTO 
2014
TThhiiss iiss aa vvaasstt ttooppiicc aanndd aa sshhoorrtt 
oovveerrvviieeww iiss ggiivveenn 
aanndd 
iinn nnoo wwaayy ccoommpplleettee jjuussttiiccee ccaann bbee 
ddoonnee ffoorr tthhiiss
Dedicated ttoo mmyy ssoonn LLiioonneell CCrraassttoo,, 
He was only in first standard in school (dec2007) when 
I was Paralysed head to toe. 
His smiling face sees me through day in and day out. 
Vast readership from academia and industry motivates me, and keeps me going. 
I am helping millions with free websites and has 7 million hits on google 
Thanks for helping me to keep lionel smiling
READ MY ARTICLE AT 
http://www.allfordrugs.com/abbreviated-new-drug-application- 
anda/
TTOOPPIICCSS:: 
1. Introduction 
2. History of ANDA 
3. Guidelines available for ANDA 
4. Filling of ANDA 
5. Manufacturing and control requirements of the ANDA 
6. 180 days exclusitivity under Hatch Waxman amendment 
7. Concept of Paragraph I to IV 
8. Substantially complete ANDA 
9. House keeping regulation 
10. Patent expiration regulation 
11. Triggering period 
12. Waivers of exclusitivity 
13. 505(b)(2) application 
14. Supplemental new drug applications 
15. Case studies 
16. List of ANDA approved 
17. 2006 pending ANDA 
18. ANDA filed by or with Indian Pharmaceutical company 
19. List of references
11.. IInnttrroodduuccttiioonn 
ANDA contains data submitted to FDA's Center for Drug evaluation and 
Research, Office of Generic Drugs, for review and ultimate approval of a 
generic drug product. 
Once ANDA is approved, an applicant may manufacture and market the 
generic drug product to provide a safe, effective, low cost alternative to the 
American public. 
A generic drug product is the one that is comparable to an innovator drug 
product in dosage form, strength, route of administration, quality, 
performance characteristics and intended use.
All approved products, both innovator and generic, are 
listed in FDA's Approved Drug Products with Therapeutic 
Equivalence Evaluations (Orange Book). 
Generic drug applications are termed "abbreviated" 
Use of bioequivalence as the base for approving generic 
drug products was established by the "Drug Price 
Competition and Patent Term Restoration Act of 1984," 
also known as the WAXMAN-HATCH ACT.
22.. HHIISSTTOORRYY OOFF AANNDDAA:: 
In 1938, proof of safety 
In 1962, “THE KEFAUVER HARIS AMENDMENTS” 
“THE KEFAUVER HARIS AMENDMENTS” led to “DRUG 
EFFICACY STUDY IMPLEMENTATION (DESI)”. 
FDA’s realization 
Mid 1966 notice in federal Register 
DESI review ultimately led to evolution of ANDA concept.
On April 24th 1970, the ANDA policy was published with 
exception of DESI pending list drugs and exempt as per 
court order 
In November 1984, The Drug Price Competition and 
Patent Term Restoration Act. 
Title 1: ANDA regardless of time before or after 1962 
Title 2: Patent extension for life lost 
Title 3: Textile and wood products 
In April, 1992 FDA finalized the regulations outlining the 
requirements for ANDAs.
On November 21, 1997 Modernization Act was 
signed. 
Section 506A-Changes for approved ANDA/NDA 
Hatch-Waxman Amendments
33.. GGUUIIDDEELLIINNEESS AAVVAAIILLAABBLLEE FFOORR 
AANNDDAA:: 
Guidelines describe format & content for 
the following sections. 
– Application summary 
– Chemistry, Manufacturing and controls section 
– Non clinical pharmacology and toxicology section 
– Human pharmacokinetics & bioavailability section 
– Clinical and statically section 
– Microbiology section
Guidelines available for ANDA includes: 
Organization of ANDA 
Electronic submission of data for ANDA 
Submission of archival copy of application in Microfiche 
Guideline for impurities in drug substances 
Guideline for submitting supporting documentation for the Manufacture of 
Drug substance. 
Guideline for submitting supporting documentation for the Manufacture of 
finished dosage forms.
Guideline for submitting supporting documentation for stability 
studies of Human drugs and Biologics. 
Guideline for packaging 
Guidelines for changes in approved ANDA and NDA 
Variations in Drug Products that may be included in a single ANDA 
180 days exclusivity under Hatch Waxman amendment 
Guidelines for alternate source of API in pending ANDAs 
Post marketing reporting of Adverse Drug reactions 
Guidelines for changes in approved ANDA and NDA
44.. FFIILLIINNGG OOFF AANNDDAA::
Proper organization 
Proper format, clear table of contents, correct 
folders (jackets), correct tabulation and pagination 
Detail’s under 21 CFR 314.50, 21 CFR 314.94 
and 21 CFR 314.440 
OGD’s recommendation of bioequivalence, 
chemistry and labeling portions of an application
PPaappeerr bbaasseedd ffiilliinngg ooff AANNDDAA:: 
I. Application copies and general format: 
Submit Archival (reference, retained and official 
approved copy) and filed copy (duplicate, used by 
FDA investigators) in english 
Translation copy with original reference copy
Review copy (duplicate, FDA viewer, destroyed) 
in 2 sets of binders (jackets) 
In first binder CMC 
In another BE data 
Remaining data (table of contents, labeling) in 
both 
Consistency in color coding binders, volume size 
and specifications, size and quality of paper
II. Cover letter: 
– Purpose of submission 
– Type of submission (ANDA, amendment, supplement, annual report, or 
resubmission of a previously withdrawn application) 
– Name, title, address and signature of applicant 
– Proprietary name (if any) and name of drug product 
– Number of volumes submitted 
– Commitment to resolution of any issues identified in the methods validation 
process after approval 
– Statement that the application or a portion of the submission is in electronic 
process after approval 
– Clearly identify submissions that contain sterility assurance data
III. Table of content{(21 CFR 314509B)}:
IV. Tabs: 
Contents Section Tabs 
E.g. Section VI - Bioavailability/Bioequivalence) 
V. Pagination: 
Centre bottom of the page. 
VI. Field copy -additional information: 
Foreign applicants should submit the field copy to the Office 
of Generic Drugs
EElleeccttrroonniicc ssuubbmmiissssiioonn:: 
ADVANTAGES: 
Consistent submission 
Rapid review 
Reduction in archiving and storage space 
Establishment of structured database of technical information 
associated with generic drug applications. 
OGD archiving capability no guidelines 
OGD has process for some in hard and some in soft copy.
Electronic submissions separated into 2 parts: 
To address bioequivalence information 
To address information related to chemistry, 
manufacturing, and controls (CMC) 
Applicant may choose to submit either or both 
parts 
Each part consist three electronic files: 
– An electronic submission document (ESD) 
– A set of data files 
– A companion document.
Key element for entering information in electronic 
submission - Entry and Validation Application 
(EVA). 
First step in submission –getting unique 3 digit 
number 
Electronic submission along with hard copy to 
OGD 
30 days 
Cover letter-CMC and/or bioequivalence ESD will be 
submitted as electronic version as new correspondence within 
30 days.
DDiiffffeerreennccee bbeettwweeeenn ssuubbmmiissssiioonn ooff NNDDAA 
aanndd AANNDDAA:: 
NDA requirements ANDA requirements 
Well-controlled clinical studies to 
demonstrate effectiveness 
Detailed descriptions of the components 
Preclinical and clinical data to show 
safety 
Manufacturing, controls, packaging, and 
labeling data sufficient to assure the 
bioavailability or bioequivalence of the 
drug to be marketed. 
Detailed descriptions of manufacturing 
and packaging procedures 
Proposed annotated labeling referencing 
all studies from which statement s 
contained in the package insert has been 
derived.
55.. MMAANNUUFFAACCTTUURRIINNGG AANNDD CCOONNTTRROOLL 
RREEQQUUIIRREEMMEENNTTSS OOFF TTHHEE AANNDDAA::-- 
Very important 
From 1977-1992, 105 Non approval letter 
issued by FDA
FDA Manufacturing and Controls guidelines:- 
• Guideline for the format and content of an application summary. 
• Guideline for the format and content of the chemistry, manufacturing, and 
controls section of an application. 
• Guideline for stability studies for Human drugs and Biologics 
• Guideline for packaging of Human Drugs and Biologics. 
• Guideline for submitting supporting documentations in drug applications 
for the manufacture of drug substances. 
• Guideline for submitting supporting documentation for the manufacture of 
finished dosage forms. 
• Guidelines for drug master files.
Requirements for Drug substances sources: 
Copy of potential supplier’s most recent establishment 
inspection repot describing FDA’s findings 
Supplier should have a DMF available at FDA for 
reference purposes 
Specifications for drug substances:- 
Assay methodology is not specified into the monograph 
for older drugs or method described is not specific –FOIs 
requests to FDA-copy of pertinent assay 
Check impurity peaks
-Drug product requirements:- 
Validation studies - to verify the accuracy, precision, specificity, 
recovery and sensitivity of the method (s) conducted by the sponsor’s 
product with those obtained with the original brand name product 
using the same methodology. 
-ANDA expiration dates:- 
Tentative approval of two year expiration date for a product if 
satisfactory data reflecting at least three months storage under 
accelerated conditions 
Final approval for the expiration date is obtained when acceptable 
shelf life data for two years on more than one production lot is made 
available
6. 180-Day Generic DDrruugg EExxcclluussiivviittyy uunnddeerr tthhee 
HHaattcchh--WWaaxxmmaann AAmmeennddmmeennttss ttoo tthhee FFeeddeerraall FFoooodd,, 
DDrruugg,, aanndd CCoossmmeettiicc AAcctt 
WAXMAN HATCH AMENMENTS BENIFITS 
TO INOVATOR’S COMPANIES TO GENERIC DRUG COMPANIES 
IF SUIT 
180 DAY EXCLUSIVITY PERIOD 
TO CHALLEGE PATENT DRUG 
45 DAY TO CLAIM 
NOT SUIT 
DELAYED FOR 30 MONTHS
After Hatch-WWaaxxmmaann AAmmeennddmmeenntt 
rreessuulltteedd iinnttoo 
Increased availability of generics: 
1984: 12% prescription were generics 
2000: 44% 
2003: 51% 
10,357 FDA approved branded drugs vs. 7,602 
generic counterparts 
Savings of $ 8 – 10 billions every year 
Average saving per prescription: approximately 53 $ 
1% rise in Generic prescription = $ 1.3 billions saving
10,357 FDA approved branded drugs 
vs. 7,602 generic counterparts 
Savings of $ 8 – 10 billions every year 
Average saving per prescription: 
approximately 53 $ 
1% rise in Generic prescription = $ 1.3 
billions saving
GGeenneerriicc PPhhaarrmmaacceeuuttiiccaallss:: 
FFaaccttss && FFiigguurreess aatt aa ggllaannccee
GGeenneerriicc PPhhaarrmmaacceeuuttiiccaallss:: 
FFaaccttss && FFiigguurreess aatt aa ggllaannccee ((ccoonnttdd..))
7. Concept ooff ppaarraaggrraapphh II ttoo IIVV:: 
For filing ANDA, generic company must include a 
patent certification as per section 505(j) (2) (A) (vii) of 
the Hatch Waxman Act. 
The certificate has to make one of the following 
statements: 
I. No patent information on the drug product that is the subject 
of the ANDA has been submitted to FDA 
II. That such patent has expired 
III. The date on which such patent expires 
IV. That such patent is invalid or will not be infringed by the 
manufacture, use, or sale of the drug product which the 
ANDA is submitted.
The first three paragraphs (I, II, III) results in no generic drug 
being sold during the term of the innovator’s patent 
protection. 
In case paragraph IV certification generic drugs can be sold 
during the term of the innovator’s patent protection. with rule 
of 45days suit and 30 months ban. 
Bann approved unless: 
The court decides that such patent is invalid or not infringed. In this case ANDA 
approval is made effective on the date of the court decision 
The court decides that such patent has been infringed and sets a date for approval of 
the ANDA as provided. 
The court grants a preliminary injuction prohibiting the ANDA applicant from 
engaging in the commercial manufacture or sale of the drug until the court decides 
the issues of patent validity and infringement.
88.. SSUUBBSSTTAANNTTIIAALLLLYY CCOOMMPPLLEETTEE AANNDDAA:: 
“Substantially complete” means application with all required 
information like bioequivalence, etc. 
If a new bioequivalence study required for ANDA approval- not 
substantially complete and the applicant would not be eligible for 
exclusivity. 
Withdrawal of paragraph IV certification – voluntarily/ settlement/ 
defeat in patent litigation by first applicant-looses exclusitivity. 
Again first applicant submit paragraph IV certificate for 180 days 
exclusivity and there are no subsequent applicants then first applicant 
would be eligible for exclusivity.
99.. HHOOUUSSEE KKEEEEPPIINNGG RREEGGUULLAATTIIOONNSS 
First generic loses patent litigation Para IV to III 
(loses exclusivity) 
Same day submission first applicant 
Happens if patent expires on that day or generic wants to 
challenge innovator’s ANDA for 5 years exclusivity and 
submits at end of 4 year 
For 6 months pediatric exclusitivity happens if patent expires on 
that day or generic wants to challenge innovator’s ANDA for 
5(1/2) years exclusivity and submits at end of 4(1/2) year
1100.. PPAATTEENNTT EEXXPPIIRRAATTIIOONN 
RREEGGUULLAATTIIOONN 
Patent for which Para IV filed expires first generic loses exclusitivity 
Subsequent generics gets 
exclusitivity
1111.. TTRRIIGGGGEERR PPEERRIIOODD 
Unnecessary delay or settlement Trigger period concept 
Commencement of the 180-day exclusivity period for the first applicant is 
either the first commercial marketing of the first applicant’s product, or a 
decision of a court holding the patent invalid, not infringed, or unenforceable, 
whichever is earlier. 
For exercising exclusitivity 180-day ‘triggering period’ 
court decision regarding the patent favorable to the first applicant or the first 
applicant must begin commercial marketing of its product 
if not first generic would lose its eligibility for exclusivity and subsequent 
generic filers for ANDA would be eligible for immediate approval.
There is new ‘triggering period’ which is separate 
and distinct from the 180-day ‘exclusivity period.’ 
The triggering period would begin upon the : 
Tentative approval of a subsequent ANDA with a paragraph iv 
certification for the same drug product 
Expiration of a 30 month stay of ANDA approval due to patent 
litigation 
Expiration of a preliminary injunction prohibiting marketing of an 
ANDA product 
Expiration of the statutorily described exclusivity periods for the listed 
drug
Delay of ANDA into market 
Mean while subsequent generics gets tentative approval 
FDA proposes 60 days trigger period for first generic to launch 
product into the market else lose exclusitivity
First generic sued Para IV certification and is facing 
patent litigation by innovator 
Triggering period would not begin at least until the 30 month 
period has lapsed 
At the end of the 30 month period, the triggering period 
would begin on the date a subsequent applicant receives 
tentative approval, or if a subsequent applicant had 
previously received tentative approval then on the date the 
30 month period expired.
1122.. WWAAIIVVEERR OOFF EEXXCCLLUUSSIIVVIITTYY 
No regulations 
Can waive to all subsequent and not single 
generic applicant
1133.. 550055((bb))((22)) AAPPPPLLIICCAATTIIOONN::-- 
Section 505 of the FD&C Act describes 3 types of new drug 
application : 
An application that contains full reports of investigations of safety 
and effectiveness (Section 505 (b)(1)) 
An application that contains full reports of investigations of safety 
and effectiveness but where at least some of the information 
required for approval comes from studies not conducted by or for 
the applicant and for which the applicant has not obtained a right of 
reference (Section 505(b)(2)) 
An application that contains information to show that the proposed 
product is identical in active ingredient, dosage form, strength, route 
of administration, labeling, quality, performance characteristics, and 
intended use, among other things, to a previously approved product 
(Section 505(j))
What kkiinndd ooff iinnffoorrmmaattiioonn ccaann bbee 
uusseedd ffoorr 550055((bb)) ((22)) aapppplliiccaattiioonn?? 
Published literature 
The FDA’s findings of safety and efficacy for 
a previously approved drug product without 
requiring the sponsor to obtain a right of 
reference from the original applicant.
What kind of aapppplliiccaattiioonn ccaann bbee ssuubbmmiitttteedd 
aass aa 550055((bb)) ((22)) aapppplliiccaattiioonn?? 
• New chemical entity (NCE)/new 
molecular entity (NME) 
• Changes to previously approved drugs
SSOOMMEE EEXXAAMMPPLLEESS OOFF 550055((BB)) ((22)) 
AAPPPPLLIICCAATTIIOONNSS 
Change in dosage form 
Change in route of administration 
Change in strength 
Change in dosage regimen 
Change in formulation (excipient) 
Change in active ingredient like use of different salt of same drug 
New molecular entity i.e. is prodrug of previously approved drug product 
Substitution of an active ingredient in a combination product 
Combination product: An application for a new combination product in 
which the active ingredients have been previously approved individually. 
Rx/OTC switch 
OTC monograph. 
Naturally derived or recombinant active ingredient. 
Bioinequivalence:
WWHHAATT CCAANN''TT BBEE SSUUBBMMIITTTTEEDD AASS 
550055((BB)) ((22)) AAPPPPLLIICCAATTIIOONNSS?? 
• An application that is a duplicate of a listed drug and eligible for 
approval under section 505(j). 
• An application in which the only difference from the reference 
listed drug is that the extent to which the active ingredient(s) is 
absorbed or otherwise made available to the site of action is less 
than the listed drug. 
• An application in which the only difference from the reference 
listed drug is that the rate at which its active ingredient(s) is 
absorbed or otherwise made available to the site of action is 
unintentionally less than that of the listed drug
typ What typee ooff ppaatteenntt aanndd//oorr eexxcclluussiivviittyy 
pprrootteeccttiioonn iiss aa 550055((bb)) ((22)) aapppplliiccaattiioonn 
eelliiggiibbllee ffoorr?? 
• Granted 3 years of Waxman-Hatch exclusivity if one or more of the 
clinical investigations other than BA/BE studies was essential to 
approval of the application and was conducted or sponsored by the 
applicant (21 CFR 314.50(j); 314.108(b)(4) and (5)). 
• Granted 5 years of exclusivity if it is for a new chemical entity (21 
CFR 314.50(j); 314.108(b) (2)). 
• Eligible for orphan drug exclusivity (21 CFR 314.20-316.36) or 
pediatric exclusivity (section 505A of the Act).
BENEFIT OOFF 550055((bb)) ((22)) AAPPPPLLIICCAATTIIOONN:: 
• Filing of ANDA in form of NDA 
• 3 or 5 years of Hatch-Waxman marketing 
exclusivity . 
• An approved 505(b) (2) product, may 
receive an “AB” substitutability rating in 
the Orange Book.
CCUURRRREENNTT CCHHAALLLLEENNGGEE TTOO TTHHEE 550055((bb)) 
((22)) MMEECCHHAANNIISSMM:: 
505(b)(2) does to not allow FDA to 
unauthorizing rely on or use of an Innovator’s 
proprietary data to approve 505(b)(2) NDAs or 
to give rating “A” in orange book. 
A petition was filed with the FDA on behalf of two 
pharmaceutical industry giants (Pfizer/Pharmacia) to 
curtail the FDA’s approval of 505(b) (2) applications. 
The Pfizer/Pharmacia petition requested the FDA to 
Cease approval of all 505(b)(2) NDAs 
Refuse to grant “A” substitutability ratings to such products in orange 
book...
1144.. SSUUPPPPLLEEMMEENNTTAALL NNEEWW DDRRUUGG 
AAPPPPLLIICCAATTIIOONNSS 
• Once an ANDA as an NDA has been approved, 
any significant changes in the conditions 
described in the application must first be approved 
via a supplemental NDA/ANDA. 
• Any substantive modifications proposed for the 
formulation may require the submission of 
additional data assuring the bioavailability of the 
drug. 
• Certain minor changes, however, as permitted by 
specific regulations, may be made without the 
filing of supplemental applications.
• Supplemental application I is filed for any 
the changes occurs in chemistry, 
manufacture of drug, use, labeling, safety, 
effectiveness, identity, strength, quality or 
purity of the drug or the adequacy of the 
manufacturing methods, facilitation, and 
controls to preserve these elements.
SSuupppplleemmeennttss ttoo nneeww ddrruugg aapppplliiccaattiioonnss rreeqquuiirriinngg 
FFDDAA aapppprroovvaall bbeeffoorree tthhee cchhaannggee iiss mmaaddee ffoorr tthhee 
ddrruugg ssuubbssttaannccee.. 
Relaxation of specification limits 
The establishment of new regulatory limits 
The deletion of a specification or analytical method. 
A revision in the method of synthesis, including the use of different 
solvents or alterations in the approved route. 
The use of different facility or establishment for the drug substances 
manufacture, where the process used to produce the drug substance differs 
materially from that approved in the NDA/ANDA and/or the facility has 
not received a current satisfactory, good manufacturing practice inspection 
within the last two years covering the manufacturing process.
Supplements ttoo nneeww ddrruugg aapppplliiccaattiioonnss rreeqquuiirriinngg FFDDAA 
aapppprroovvaall bbeeffoorree tthhee cchhaannggee iiss mmaaddee ffoorr tthhee ddrruugg 
pprroodduucctt.. 
• The addition or deletion of an ingredient or alteration of the composition 
(except for deletion of colorant.) 
• The relaxation of specification limits. 
• The establishment of a new regulations analytical method. 
• The deletion of a specification as regulatory analytical method. 
• A revision in the method of manufacture, including changing or relaxing 
and in process control. 
• The use of a different facility or establishment, including a different of 
contract, laboratory, on labels, to manufacture, process, test, or pack the 
drug. 
• The use of new container/closure system or a revision of a relevant 
specification (s) and regulatory analytical method(s). 
• A change in container size ( except for solid forms) 
• An extension of the expiration date based on data obtained using a new or 
an unapproved revised stability testing protocol. 
• The establishment of a new processing procedure for batches failing to 
meet quality assurance specifications. 
• All labeling changes except for those specifically exempted.
Supplements ffoorr cchhaannggeess tthhaatt mmaayy bbee mmaaddee 
bbeeffoorree FFDDAA aapppprroovvaall 
Full explanation of the basis for the such changes is required 
The cover letter and the supplement should be plainly marked, “ Special 
supplement changes being effected. 
Includes for: 
The addition of a new specification (s) or test method. 
Revisions in methods, facilities( Except for a new facility or controls to 
provide increase assurance of product, identity, quality, purity, and strength). 
Revisions in labeling to add or strengthen: 
– A contraindication, warning, precaution or adverse reaction. 
– An instruction about dosage and administration to further assure the safe use of the 
product. 
– A statement about drug abuse, dependence, or over dosage. 
– Revisions in labeling to delete false, misleading , or unsupported indications of use 
or claims for effectiveness. 
– Use of a different facilities or establishment to manufacture the drug substance, 
where the method of manufacture does not differ materially form that in the former 
facility and the new facility has received a satisfactory cGMP inspection within 
the last two year.
Changes ddeessccrriibbeedd iinn tthhee AAnnnnuuaall rreeppoorrtt 
• Revisions made to comply with an official compendium e.g. 
USP,NF. 
• Revisions in the package insert concerning the description section, 
or the how supplied section, that do not involve a change in dosage 
strength and / or form, or minor editorial changes in these and/or 
other sections. 
• Deletion of a colorant from the drug product. 
• Extension of expiration dating based on data obtained using a 
protocol approved in the application. 
• A switch to another container/closure system, where the material (s) 
used is the same general type as previously approved.(e.g. a change 
from one high-density polyethylene to another). 
• In the case of solid dosage forms a change in container size without 
a change in the container/closure system. 
• The deletion or addition of an alternate analytical method.
Supplemental nneeww ddrruugg aapppplliiccaattiioonn 
cchheecckklliisstt:: 
• Make all submissions in duplicate, including cover letters. 
• Include a brief description in the cover letter of what the supplement contains, 
including its objective and the headings , “supplemental expedited review 
requested” or “ special supplement changes being effected” when appropriate. 
• Whenever possible make a side by side comparison of current versus proposed 
conditions. 
• Use reference numbers for the NDA and the supplement if it is an additional 
submission. 
• Describe in detail all aspects of the change 
• Use dates when referring to previous submissions of FDA letters, particularly if 
the correspondence goes back more than several years. 
• When submitting photocopies make sure that all copies are clear and legible. 
• To assure legibility also type the name of the person signing the document. 
• When referring to drug master files (DMFs), confirm that they are up-to-date. 
Any changes submitted to a DMF must be relevant to the application (s) they 
affect. 
• Address all submissions concerning supplemental NDAs to the appropriate 
office and division of the FDA.
1155.. CCAASSEE SSTTUUDDIIEESS:: 
A. Patent of PAXIL (Paroxetine HCL hemihydrate) 
• SmithKline Backhem (SKB) obtained patent of Paxil as 
NDA. 
• In 1998 Apotex filed Para IV certificate for getting ANDA 
• SKB filed legal suit for patent infringement 
• 30-months stay on Apotex approval 
• SKB filed patent extension 1: for use as liquid oral 
• 3 more patents in 1999 & 2000 for anhydrous form 
• 5th patent for Paroxetine methanosulfate in 2000 
• Serial Patent submission tactics, with newer 30-month stay 
every time 
• Result: The patent of litigation expired, but Apotex could 
not enter due to the newer (later) patents
1199.. LLiisstt ooff rreeffeerreenncceess:: 
1. www.fda.gov 
2. www.phorum.com 
3. www.morganfinnegan.com 
4. www.drugdeliverytech.com 
5. Richard A., Guarino M. D., “New drug 
approval process” second edition, Marcel 
dekker, 56, 325-356/427-446.
To take full advantage of Chemical Web content, it is essential 
to use several Software:Winzip,Chemscape Chime, Shockwave, 
Adobe Acrobat, Cosmo Player, Web Lab Viewer, 
Paint Shop Pro, Rasmol, ChemOffice, Quick Time,etc
TTHHAANNKK YYOOUU!! 
DR ANTHONY CRASTO 
amcrasto@gmail.com 
http://newdrugapprovals.org/

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ABBREVIATED NEW DRUG APPLICATION (ANDA) by Anthony crasto

  • 1. AABBBBRREEVVIIAATTEEDD NNEEWW DDRRUUGG AAPPPPLLIICCAATTIIOONN ((AANNDDAA)) DR ANTHONY MELVIN CRASTO 2014
  • 2. TThhiiss iiss aa vvaasstt ttooppiicc aanndd aa sshhoorrtt oovveerrvviieeww iiss ggiivveenn aanndd iinn nnoo wwaayy ccoommpplleettee jjuussttiiccee ccaann bbee ddoonnee ffoorr tthhiiss
  • 3. Dedicated ttoo mmyy ssoonn LLiioonneell CCrraassttoo,, He was only in first standard in school (dec2007) when I was Paralysed head to toe. His smiling face sees me through day in and day out. Vast readership from academia and industry motivates me, and keeps me going. I am helping millions with free websites and has 7 million hits on google Thanks for helping me to keep lionel smiling
  • 4. READ MY ARTICLE AT http://www.allfordrugs.com/abbreviated-new-drug-application- anda/
  • 5. TTOOPPIICCSS:: 1. Introduction 2. History of ANDA 3. Guidelines available for ANDA 4. Filling of ANDA 5. Manufacturing and control requirements of the ANDA 6. 180 days exclusitivity under Hatch Waxman amendment 7. Concept of Paragraph I to IV 8. Substantially complete ANDA 9. House keeping regulation 10. Patent expiration regulation 11. Triggering period 12. Waivers of exclusitivity 13. 505(b)(2) application 14. Supplemental new drug applications 15. Case studies 16. List of ANDA approved 17. 2006 pending ANDA 18. ANDA filed by or with Indian Pharmaceutical company 19. List of references
  • 6. 11.. IInnttrroodduuccttiioonn ANDA contains data submitted to FDA's Center for Drug evaluation and Research, Office of Generic Drugs, for review and ultimate approval of a generic drug product. Once ANDA is approved, an applicant may manufacture and market the generic drug product to provide a safe, effective, low cost alternative to the American public. A generic drug product is the one that is comparable to an innovator drug product in dosage form, strength, route of administration, quality, performance characteristics and intended use.
  • 7. All approved products, both innovator and generic, are listed in FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book). Generic drug applications are termed "abbreviated" Use of bioequivalence as the base for approving generic drug products was established by the "Drug Price Competition and Patent Term Restoration Act of 1984," also known as the WAXMAN-HATCH ACT.
  • 8. 22.. HHIISSTTOORRYY OOFF AANNDDAA:: In 1938, proof of safety In 1962, “THE KEFAUVER HARIS AMENDMENTS” “THE KEFAUVER HARIS AMENDMENTS” led to “DRUG EFFICACY STUDY IMPLEMENTATION (DESI)”. FDA’s realization Mid 1966 notice in federal Register DESI review ultimately led to evolution of ANDA concept.
  • 9. On April 24th 1970, the ANDA policy was published with exception of DESI pending list drugs and exempt as per court order In November 1984, The Drug Price Competition and Patent Term Restoration Act. Title 1: ANDA regardless of time before or after 1962 Title 2: Patent extension for life lost Title 3: Textile and wood products In April, 1992 FDA finalized the regulations outlining the requirements for ANDAs.
  • 10. On November 21, 1997 Modernization Act was signed. Section 506A-Changes for approved ANDA/NDA Hatch-Waxman Amendments
  • 11. 33.. GGUUIIDDEELLIINNEESS AAVVAAIILLAABBLLEE FFOORR AANNDDAA:: Guidelines describe format & content for the following sections. – Application summary – Chemistry, Manufacturing and controls section – Non clinical pharmacology and toxicology section – Human pharmacokinetics & bioavailability section – Clinical and statically section – Microbiology section
  • 12. Guidelines available for ANDA includes: Organization of ANDA Electronic submission of data for ANDA Submission of archival copy of application in Microfiche Guideline for impurities in drug substances Guideline for submitting supporting documentation for the Manufacture of Drug substance. Guideline for submitting supporting documentation for the Manufacture of finished dosage forms.
  • 13. Guideline for submitting supporting documentation for stability studies of Human drugs and Biologics. Guideline for packaging Guidelines for changes in approved ANDA and NDA Variations in Drug Products that may be included in a single ANDA 180 days exclusivity under Hatch Waxman amendment Guidelines for alternate source of API in pending ANDAs Post marketing reporting of Adverse Drug reactions Guidelines for changes in approved ANDA and NDA
  • 15. Proper organization Proper format, clear table of contents, correct folders (jackets), correct tabulation and pagination Detail’s under 21 CFR 314.50, 21 CFR 314.94 and 21 CFR 314.440 OGD’s recommendation of bioequivalence, chemistry and labeling portions of an application
  • 16. PPaappeerr bbaasseedd ffiilliinngg ooff AANNDDAA:: I. Application copies and general format: Submit Archival (reference, retained and official approved copy) and filed copy (duplicate, used by FDA investigators) in english Translation copy with original reference copy
  • 17. Review copy (duplicate, FDA viewer, destroyed) in 2 sets of binders (jackets) In first binder CMC In another BE data Remaining data (table of contents, labeling) in both Consistency in color coding binders, volume size and specifications, size and quality of paper
  • 18.
  • 19.
  • 20. II. Cover letter: – Purpose of submission – Type of submission (ANDA, amendment, supplement, annual report, or resubmission of a previously withdrawn application) – Name, title, address and signature of applicant – Proprietary name (if any) and name of drug product – Number of volumes submitted – Commitment to resolution of any issues identified in the methods validation process after approval – Statement that the application or a portion of the submission is in electronic process after approval – Clearly identify submissions that contain sterility assurance data
  • 21. III. Table of content{(21 CFR 314509B)}:
  • 22.
  • 23.
  • 24.
  • 25.
  • 26. IV. Tabs: Contents Section Tabs E.g. Section VI - Bioavailability/Bioequivalence) V. Pagination: Centre bottom of the page. VI. Field copy -additional information: Foreign applicants should submit the field copy to the Office of Generic Drugs
  • 27. EElleeccttrroonniicc ssuubbmmiissssiioonn:: ADVANTAGES: Consistent submission Rapid review Reduction in archiving and storage space Establishment of structured database of technical information associated with generic drug applications. OGD archiving capability no guidelines OGD has process for some in hard and some in soft copy.
  • 28. Electronic submissions separated into 2 parts: To address bioequivalence information To address information related to chemistry, manufacturing, and controls (CMC) Applicant may choose to submit either or both parts Each part consist three electronic files: – An electronic submission document (ESD) – A set of data files – A companion document.
  • 29. Key element for entering information in electronic submission - Entry and Validation Application (EVA). First step in submission –getting unique 3 digit number Electronic submission along with hard copy to OGD 30 days Cover letter-CMC and/or bioequivalence ESD will be submitted as electronic version as new correspondence within 30 days.
  • 30. DDiiffffeerreennccee bbeettwweeeenn ssuubbmmiissssiioonn ooff NNDDAA aanndd AANNDDAA:: NDA requirements ANDA requirements Well-controlled clinical studies to demonstrate effectiveness Detailed descriptions of the components Preclinical and clinical data to show safety Manufacturing, controls, packaging, and labeling data sufficient to assure the bioavailability or bioequivalence of the drug to be marketed. Detailed descriptions of manufacturing and packaging procedures Proposed annotated labeling referencing all studies from which statement s contained in the package insert has been derived.
  • 31. 55.. MMAANNUUFFAACCTTUURRIINNGG AANNDD CCOONNTTRROOLL RREEQQUUIIRREEMMEENNTTSS OOFF TTHHEE AANNDDAA::-- Very important From 1977-1992, 105 Non approval letter issued by FDA
  • 32. FDA Manufacturing and Controls guidelines:- • Guideline for the format and content of an application summary. • Guideline for the format and content of the chemistry, manufacturing, and controls section of an application. • Guideline for stability studies for Human drugs and Biologics • Guideline for packaging of Human Drugs and Biologics. • Guideline for submitting supporting documentations in drug applications for the manufacture of drug substances. • Guideline for submitting supporting documentation for the manufacture of finished dosage forms. • Guidelines for drug master files.
  • 33. Requirements for Drug substances sources: Copy of potential supplier’s most recent establishment inspection repot describing FDA’s findings Supplier should have a DMF available at FDA for reference purposes Specifications for drug substances:- Assay methodology is not specified into the monograph for older drugs or method described is not specific –FOIs requests to FDA-copy of pertinent assay Check impurity peaks
  • 34. -Drug product requirements:- Validation studies - to verify the accuracy, precision, specificity, recovery and sensitivity of the method (s) conducted by the sponsor’s product with those obtained with the original brand name product using the same methodology. -ANDA expiration dates:- Tentative approval of two year expiration date for a product if satisfactory data reflecting at least three months storage under accelerated conditions Final approval for the expiration date is obtained when acceptable shelf life data for two years on more than one production lot is made available
  • 35. 6. 180-Day Generic DDrruugg EExxcclluussiivviittyy uunnddeerr tthhee HHaattcchh--WWaaxxmmaann AAmmeennddmmeennttss ttoo tthhee FFeeddeerraall FFoooodd,, DDrruugg,, aanndd CCoossmmeettiicc AAcctt WAXMAN HATCH AMENMENTS BENIFITS TO INOVATOR’S COMPANIES TO GENERIC DRUG COMPANIES IF SUIT 180 DAY EXCLUSIVITY PERIOD TO CHALLEGE PATENT DRUG 45 DAY TO CLAIM NOT SUIT DELAYED FOR 30 MONTHS
  • 36. After Hatch-WWaaxxmmaann AAmmeennddmmeenntt rreessuulltteedd iinnttoo Increased availability of generics: 1984: 12% prescription were generics 2000: 44% 2003: 51% 10,357 FDA approved branded drugs vs. 7,602 generic counterparts Savings of $ 8 – 10 billions every year Average saving per prescription: approximately 53 $ 1% rise in Generic prescription = $ 1.3 billions saving
  • 37. 10,357 FDA approved branded drugs vs. 7,602 generic counterparts Savings of $ 8 – 10 billions every year Average saving per prescription: approximately 53 $ 1% rise in Generic prescription = $ 1.3 billions saving
  • 38. GGeenneerriicc PPhhaarrmmaacceeuuttiiccaallss:: FFaaccttss && FFiigguurreess aatt aa ggllaannccee
  • 39. GGeenneerriicc PPhhaarrmmaacceeuuttiiccaallss:: FFaaccttss && FFiigguurreess aatt aa ggllaannccee ((ccoonnttdd..))
  • 40.
  • 41. 7. Concept ooff ppaarraaggrraapphh II ttoo IIVV:: For filing ANDA, generic company must include a patent certification as per section 505(j) (2) (A) (vii) of the Hatch Waxman Act. The certificate has to make one of the following statements: I. No patent information on the drug product that is the subject of the ANDA has been submitted to FDA II. That such patent has expired III. The date on which such patent expires IV. That such patent is invalid or will not be infringed by the manufacture, use, or sale of the drug product which the ANDA is submitted.
  • 42. The first three paragraphs (I, II, III) results in no generic drug being sold during the term of the innovator’s patent protection. In case paragraph IV certification generic drugs can be sold during the term of the innovator’s patent protection. with rule of 45days suit and 30 months ban. Bann approved unless: The court decides that such patent is invalid or not infringed. In this case ANDA approval is made effective on the date of the court decision The court decides that such patent has been infringed and sets a date for approval of the ANDA as provided. The court grants a preliminary injuction prohibiting the ANDA applicant from engaging in the commercial manufacture or sale of the drug until the court decides the issues of patent validity and infringement.
  • 43. 88.. SSUUBBSSTTAANNTTIIAALLLLYY CCOOMMPPLLEETTEE AANNDDAA:: “Substantially complete” means application with all required information like bioequivalence, etc. If a new bioequivalence study required for ANDA approval- not substantially complete and the applicant would not be eligible for exclusivity. Withdrawal of paragraph IV certification – voluntarily/ settlement/ defeat in patent litigation by first applicant-looses exclusitivity. Again first applicant submit paragraph IV certificate for 180 days exclusivity and there are no subsequent applicants then first applicant would be eligible for exclusivity.
  • 44. 99.. HHOOUUSSEE KKEEEEPPIINNGG RREEGGUULLAATTIIOONNSS First generic loses patent litigation Para IV to III (loses exclusivity) Same day submission first applicant Happens if patent expires on that day or generic wants to challenge innovator’s ANDA for 5 years exclusivity and submits at end of 4 year For 6 months pediatric exclusitivity happens if patent expires on that day or generic wants to challenge innovator’s ANDA for 5(1/2) years exclusivity and submits at end of 4(1/2) year
  • 45. 1100.. PPAATTEENNTT EEXXPPIIRRAATTIIOONN RREEGGUULLAATTIIOONN Patent for which Para IV filed expires first generic loses exclusitivity Subsequent generics gets exclusitivity
  • 46. 1111.. TTRRIIGGGGEERR PPEERRIIOODD Unnecessary delay or settlement Trigger period concept Commencement of the 180-day exclusivity period for the first applicant is either the first commercial marketing of the first applicant’s product, or a decision of a court holding the patent invalid, not infringed, or unenforceable, whichever is earlier. For exercising exclusitivity 180-day ‘triggering period’ court decision regarding the patent favorable to the first applicant or the first applicant must begin commercial marketing of its product if not first generic would lose its eligibility for exclusivity and subsequent generic filers for ANDA would be eligible for immediate approval.
  • 47. There is new ‘triggering period’ which is separate and distinct from the 180-day ‘exclusivity period.’ The triggering period would begin upon the : Tentative approval of a subsequent ANDA with a paragraph iv certification for the same drug product Expiration of a 30 month stay of ANDA approval due to patent litigation Expiration of a preliminary injunction prohibiting marketing of an ANDA product Expiration of the statutorily described exclusivity periods for the listed drug
  • 48. Delay of ANDA into market Mean while subsequent generics gets tentative approval FDA proposes 60 days trigger period for first generic to launch product into the market else lose exclusitivity
  • 49. First generic sued Para IV certification and is facing patent litigation by innovator Triggering period would not begin at least until the 30 month period has lapsed At the end of the 30 month period, the triggering period would begin on the date a subsequent applicant receives tentative approval, or if a subsequent applicant had previously received tentative approval then on the date the 30 month period expired.
  • 50. 1122.. WWAAIIVVEERR OOFF EEXXCCLLUUSSIIVVIITTYY No regulations Can waive to all subsequent and not single generic applicant
  • 51. 1133.. 550055((bb))((22)) AAPPPPLLIICCAATTIIOONN::-- Section 505 of the FD&C Act describes 3 types of new drug application : An application that contains full reports of investigations of safety and effectiveness (Section 505 (b)(1)) An application that contains full reports of investigations of safety and effectiveness but where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference (Section 505(b)(2)) An application that contains information to show that the proposed product is identical in active ingredient, dosage form, strength, route of administration, labeling, quality, performance characteristics, and intended use, among other things, to a previously approved product (Section 505(j))
  • 52. What kkiinndd ooff iinnffoorrmmaattiioonn ccaann bbee uusseedd ffoorr 550055((bb)) ((22)) aapppplliiccaattiioonn?? Published literature The FDA’s findings of safety and efficacy for a previously approved drug product without requiring the sponsor to obtain a right of reference from the original applicant.
  • 53. What kind of aapppplliiccaattiioonn ccaann bbee ssuubbmmiitttteedd aass aa 550055((bb)) ((22)) aapppplliiccaattiioonn?? • New chemical entity (NCE)/new molecular entity (NME) • Changes to previously approved drugs
  • 54. SSOOMMEE EEXXAAMMPPLLEESS OOFF 550055((BB)) ((22)) AAPPPPLLIICCAATTIIOONNSS Change in dosage form Change in route of administration Change in strength Change in dosage regimen Change in formulation (excipient) Change in active ingredient like use of different salt of same drug New molecular entity i.e. is prodrug of previously approved drug product Substitution of an active ingredient in a combination product Combination product: An application for a new combination product in which the active ingredients have been previously approved individually. Rx/OTC switch OTC monograph. Naturally derived or recombinant active ingredient. Bioinequivalence:
  • 55. WWHHAATT CCAANN''TT BBEE SSUUBBMMIITTTTEEDD AASS 550055((BB)) ((22)) AAPPPPLLIICCAATTIIOONNSS?? • An application that is a duplicate of a listed drug and eligible for approval under section 505(j). • An application in which the only difference from the reference listed drug is that the extent to which the active ingredient(s) is absorbed or otherwise made available to the site of action is less than the listed drug. • An application in which the only difference from the reference listed drug is that the rate at which its active ingredient(s) is absorbed or otherwise made available to the site of action is unintentionally less than that of the listed drug
  • 56. typ What typee ooff ppaatteenntt aanndd//oorr eexxcclluussiivviittyy pprrootteeccttiioonn iiss aa 550055((bb)) ((22)) aapppplliiccaattiioonn eelliiggiibbllee ffoorr?? • Granted 3 years of Waxman-Hatch exclusivity if one or more of the clinical investigations other than BA/BE studies was essential to approval of the application and was conducted or sponsored by the applicant (21 CFR 314.50(j); 314.108(b)(4) and (5)). • Granted 5 years of exclusivity if it is for a new chemical entity (21 CFR 314.50(j); 314.108(b) (2)). • Eligible for orphan drug exclusivity (21 CFR 314.20-316.36) or pediatric exclusivity (section 505A of the Act).
  • 57. BENEFIT OOFF 550055((bb)) ((22)) AAPPPPLLIICCAATTIIOONN:: • Filing of ANDA in form of NDA • 3 or 5 years of Hatch-Waxman marketing exclusivity . • An approved 505(b) (2) product, may receive an “AB” substitutability rating in the Orange Book.
  • 58. CCUURRRREENNTT CCHHAALLLLEENNGGEE TTOO TTHHEE 550055((bb)) ((22)) MMEECCHHAANNIISSMM:: 505(b)(2) does to not allow FDA to unauthorizing rely on or use of an Innovator’s proprietary data to approve 505(b)(2) NDAs or to give rating “A” in orange book. A petition was filed with the FDA on behalf of two pharmaceutical industry giants (Pfizer/Pharmacia) to curtail the FDA’s approval of 505(b) (2) applications. The Pfizer/Pharmacia petition requested the FDA to Cease approval of all 505(b)(2) NDAs Refuse to grant “A” substitutability ratings to such products in orange book...
  • 59. 1144.. SSUUPPPPLLEEMMEENNTTAALL NNEEWW DDRRUUGG AAPPPPLLIICCAATTIIOONNSS • Once an ANDA as an NDA has been approved, any significant changes in the conditions described in the application must first be approved via a supplemental NDA/ANDA. • Any substantive modifications proposed for the formulation may require the submission of additional data assuring the bioavailability of the drug. • Certain minor changes, however, as permitted by specific regulations, may be made without the filing of supplemental applications.
  • 60. • Supplemental application I is filed for any the changes occurs in chemistry, manufacture of drug, use, labeling, safety, effectiveness, identity, strength, quality or purity of the drug or the adequacy of the manufacturing methods, facilitation, and controls to preserve these elements.
  • 61. SSuupppplleemmeennttss ttoo nneeww ddrruugg aapppplliiccaattiioonnss rreeqquuiirriinngg FFDDAA aapppprroovvaall bbeeffoorree tthhee cchhaannggee iiss mmaaddee ffoorr tthhee ddrruugg ssuubbssttaannccee.. Relaxation of specification limits The establishment of new regulatory limits The deletion of a specification or analytical method. A revision in the method of synthesis, including the use of different solvents or alterations in the approved route. The use of different facility or establishment for the drug substances manufacture, where the process used to produce the drug substance differs materially from that approved in the NDA/ANDA and/or the facility has not received a current satisfactory, good manufacturing practice inspection within the last two years covering the manufacturing process.
  • 62. Supplements ttoo nneeww ddrruugg aapppplliiccaattiioonnss rreeqquuiirriinngg FFDDAA aapppprroovvaall bbeeffoorree tthhee cchhaannggee iiss mmaaddee ffoorr tthhee ddrruugg pprroodduucctt.. • The addition or deletion of an ingredient or alteration of the composition (except for deletion of colorant.) • The relaxation of specification limits. • The establishment of a new regulations analytical method. • The deletion of a specification as regulatory analytical method. • A revision in the method of manufacture, including changing or relaxing and in process control. • The use of a different facility or establishment, including a different of contract, laboratory, on labels, to manufacture, process, test, or pack the drug. • The use of new container/closure system or a revision of a relevant specification (s) and regulatory analytical method(s). • A change in container size ( except for solid forms) • An extension of the expiration date based on data obtained using a new or an unapproved revised stability testing protocol. • The establishment of a new processing procedure for batches failing to meet quality assurance specifications. • All labeling changes except for those specifically exempted.
  • 63. Supplements ffoorr cchhaannggeess tthhaatt mmaayy bbee mmaaddee bbeeffoorree FFDDAA aapppprroovvaall Full explanation of the basis for the such changes is required The cover letter and the supplement should be plainly marked, “ Special supplement changes being effected. Includes for: The addition of a new specification (s) or test method. Revisions in methods, facilities( Except for a new facility or controls to provide increase assurance of product, identity, quality, purity, and strength). Revisions in labeling to add or strengthen: – A contraindication, warning, precaution or adverse reaction. – An instruction about dosage and administration to further assure the safe use of the product. – A statement about drug abuse, dependence, or over dosage. – Revisions in labeling to delete false, misleading , or unsupported indications of use or claims for effectiveness. – Use of a different facilities or establishment to manufacture the drug substance, where the method of manufacture does not differ materially form that in the former facility and the new facility has received a satisfactory cGMP inspection within the last two year.
  • 64. Changes ddeessccrriibbeedd iinn tthhee AAnnnnuuaall rreeppoorrtt • Revisions made to comply with an official compendium e.g. USP,NF. • Revisions in the package insert concerning the description section, or the how supplied section, that do not involve a change in dosage strength and / or form, or minor editorial changes in these and/or other sections. • Deletion of a colorant from the drug product. • Extension of expiration dating based on data obtained using a protocol approved in the application. • A switch to another container/closure system, where the material (s) used is the same general type as previously approved.(e.g. a change from one high-density polyethylene to another). • In the case of solid dosage forms a change in container size without a change in the container/closure system. • The deletion or addition of an alternate analytical method.
  • 65. Supplemental nneeww ddrruugg aapppplliiccaattiioonn cchheecckklliisstt:: • Make all submissions in duplicate, including cover letters. • Include a brief description in the cover letter of what the supplement contains, including its objective and the headings , “supplemental expedited review requested” or “ special supplement changes being effected” when appropriate. • Whenever possible make a side by side comparison of current versus proposed conditions. • Use reference numbers for the NDA and the supplement if it is an additional submission. • Describe in detail all aspects of the change • Use dates when referring to previous submissions of FDA letters, particularly if the correspondence goes back more than several years. • When submitting photocopies make sure that all copies are clear and legible. • To assure legibility also type the name of the person signing the document. • When referring to drug master files (DMFs), confirm that they are up-to-date. Any changes submitted to a DMF must be relevant to the application (s) they affect. • Address all submissions concerning supplemental NDAs to the appropriate office and division of the FDA.
  • 66. 1155.. CCAASSEE SSTTUUDDIIEESS:: A. Patent of PAXIL (Paroxetine HCL hemihydrate) • SmithKline Backhem (SKB) obtained patent of Paxil as NDA. • In 1998 Apotex filed Para IV certificate for getting ANDA • SKB filed legal suit for patent infringement • 30-months stay on Apotex approval • SKB filed patent extension 1: for use as liquid oral • 3 more patents in 1999 & 2000 for anhydrous form • 5th patent for Paroxetine methanosulfate in 2000 • Serial Patent submission tactics, with newer 30-month stay every time • Result: The patent of litigation expired, but Apotex could not enter due to the newer (later) patents
  • 67. 1199.. LLiisstt ooff rreeffeerreenncceess:: 1. www.fda.gov 2. www.phorum.com 3. www.morganfinnegan.com 4. www.drugdeliverytech.com 5. Richard A., Guarino M. D., “New drug approval process” second edition, Marcel dekker, 56, 325-356/427-446.
  • 68. To take full advantage of Chemical Web content, it is essential to use several Software:Winzip,Chemscape Chime, Shockwave, Adobe Acrobat, Cosmo Player, Web Lab Viewer, Paint Shop Pro, Rasmol, ChemOffice, Quick Time,etc
  • 69. TTHHAANNKK YYOOUU!! DR ANTHONY CRASTO amcrasto@gmail.com http://newdrugapprovals.org/