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A COMPARATIVE STUDY OF REGULATORY REQUIREMENTS FOR FILING GENERIC DRUG PRODUCT BETWEEN USA, INDIA, AND CHINA

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The goal of this study is to understand differences in regulatory requirements, bio-equivalence data, drug registration, approval process and, guidelines associated with the generic drug filing in the USA, India, and China and also provide enough information for the drug safety and efficacy in humans. Generic drugs are identical, indistinguishable within an acceptable bio-equivalent level for the innovator product name counterpart esteems to the "Pharmacokinetics and Pharmacodynamics" properties. A generic drug product must meet the standards, established by "United States Food and Drug Administration" in USA, "Central drugs standards control organization" in India, and "National Medical Product Administration" in China to be approved to successfully enter the pharmaceutical market. It must their bioequivalent to the branded medicine. In USA and India, in Module II there is complete information on the quality overall summary, but in China, there is complete information about a Drug substance, whereas in module III in USA and India there is complete information about Drug Substance and Drug Product, but in China, module III contains complete information about drug product only. Hence by comparing all the above differences and similarities, generic drug approval procedures and submissions become easy for registration of drugs in those countries. This compilation provides a view of harmonizing
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Yallabandi et al. World Journal of Pharmacy and Pharmaceutical Sciences
A COMPARATIVE STUDY OF REGULATORY REQUIREMENTS FOR
FILING GENERIC DRUG PRODUCT BETWEEN USA, INDIA, AND
CHINA
Sita Priya Darsini Yallabandi*1, Sujatha K1, Jaya Prakash V1, Raga Padmasri
Deepika M1, Basava Raju D2 and Ravi kumar Reddy J1
1Department of Pharmaceutical Drug Regulatory Affairs, Shri Vishnu College of Pharmacy,
Bimavaram, West Godavari, Andhra Pradesh, India-534202.
2Department of Pharmaceutical Sciences, Shri Vishnu College of Pharmacy, Bimavaram,
West Godavari, Andhra Pradesh, India-534202.
ABSTRACT
The goal of this study is to understand differences in regulatory
requirements, bio-equivalence data, drug registration, approval process
and, guidelines associated with the generic drug filing in the USA,
India, and China and also provide enough information for the drug
safety and efficacy in humans. Generic drugs are identical,
indistinguishable with-in an acceptable bio-equivalent level for the
innovator product name counterpart esteems to the "Pharmacokinetics
and Pharmacodynamics" properties. A generic drug product must meet
the standards, established by "United States Food and Drug
Administration" in USA, "Central drugs standards control organization"
in India, and "National Medical Product Administration" in China to
be approved to successfully enter the pharmaceutical market. It must
their bioequivalent to the branded medicine. In USA and India, in
Module II there is complete information on the quality overall summary, but in China, there
is complete information about a Drug substance, whereas in module III in USA and India
there is complete information about Drug Substance and Drug Product, but in China, module
III contains complete information about drug product only. Hence by comparing all the above
differences and similarities, generic drug approval procedures and submissions become easy
for registration of drugs in those countries. This compilation provides a view of harmonizing
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES
SJIF Impact Factor 7.632
Volume 9, Issue 10, 2701-2717 Research Article ISSN 2278 4357
*Corresponding Author
Sita Priya Darsini
Yallabandi
Department of
Pharmaceutical Drug
Regulatory Affairs, Shri
Vishnu College of Pharmacy,
Bimavaram, West Godavari,
Andhra Pradesh, India.
Article Received on
18 August 2020,
Revised on 08 Sept. 2020,
Accepted on 28 Sept. 2020
DOI: 10.20959/wjpps202010-17514
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the Generic Drug submissions in these three countries which may reduce the tedious work
that has to be done in altering the submission format.
KEYWORDS: Bio-equivalence, CTD, Generic Drug Submissions, USFDA, DCGI, NMPA.
INTRODUCTION
Regulatory Affairs (RA), also called Government Affairs, is a profession within regulated
industries, such as pharmaceuticals, medical devices, energy, and banking. Regulatory
Affairs also had very specific meaning within the healthcare industries (pharmaceutical,
medical devices, Biologic s, and functional foods).[1]
A generic drug (short: generics) is a drug defined as "a drug product that is comparable to
the brand/reference listed drug product in dosage form, strength, quality and performance
characteristics, and intended use." It has also been defined as a term referring to any drug
marketed under its chemical name without advertising or to the chemical makeup of a drug
rather than to the advertised brand name under which the drug is sold. Generic drugs are
therapeutically equivalent to the branded drug. Generics can only be produced after the
expiration of the branded drug’s patent (usually 20 years).[2]
Clinical data on the safety and efficacy of the drug is not required to be submitted in the case
of generic drugs because it has been already provided for the prior product. The safety and
efficacy of the original active ingredient was already proven, the bio equivalence of the
equivalent generic drug should be checked by the manufacturer.[3]
METHODOLOGY
The objective of this study is to figure out the determinants for selecting a generic application
and the regulatory aspects involved in generic drug development. Understanding the Generic
Drug Approval process in the US, India, and China is highlighting the differences between
these three Countries. Each study has some patterns and follows certain pathways to reach the
destination. Thus, the method to be followed plays an important role in determining the
outputs as well as the consequences of the study.
Types of study
The study was conducted to draw the regulatory framework for the Generic Drug Approval
process in the USA, India, and China is the mainly emphasizing on the application form,
approval timelines, and steps in sequence for generic drug approval. The literature was
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collected using numerous searches official Government websites like FDA, NMPA, and CD
SCO.
RESULTS AND DISCUSSION
Generic Drug Product Registration Requirements in the USA
1. The eCTD is mandatory for the submission of the drug applications (NDA/ANDA).
2. US FDA guidance (CFR) documents and FDA sections (e.g. 505 (b) NDA and 505(j)
ANDA) are followed for the preparation of the dossier for the drug approval applications.
3. The applications are different as follows:
a. For new drug- NDA
b. For generic drug - ANDA
c. For biological application - BLA
4. The applicant himself or a GDEA (Generic Drug Enforcement Act) certified and approved
agent may directly apply to the FDA.
5. Administrative information is different from a cover letter, forms (356h), application
information, field copy certification, debarment certification, financial certification, Patent
information, and exclusivity.
6. The paper size for the submission is Letter size (8.5x11 inches) with font size 12 in Times
New Roman format. The tables, and figures have small font size i.e. 8 to 10.
7. Package inserts are provided for drug products in labelling.
8. Proposed Labels and cartons with proper dimensions similar to that of the RLD (Reference
Listed Drugs) labels are provided.
9. The information about the clinical investigators is provided in Module 5 and the financial
disclosure Statement section of this module.
10. Request for waiver of in-vivo BE studies are provided in module 1.
11. Annotated draft labeling for labels and cartons compared with the RLD for proper
annotation is provided.
12. The EAS (Environment Assessment Statement) for categorical exclusion certification in
compliance with the law of EPA (Environment Protection Act) of the US is provided.
13. Risk management Plans section is for the post marketing surveillance and controlling the
adverse effects of the drugs by proper management. This is a part of Clinical Trial Phase IV.
14. The executed batch records for manufacturing, and packaging are provided in Module
3.2. R for only a single batch.
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15. The declaration is given for the residual solvent’s limits used or present in the drug
substance and excipients according to the USP.
16. Information on components including name and address of the supplier or manufacturer
for the raw material, package material, etc. provided in the 3.2. R format.
17. Letter of Access is not mentioned in 3.2.R.
18. Transmissible Spongiform Encephalopathy (TSE) and Bovine Spongiform
Encephalopathy (BSE) certificates are not attached in this section, whereas, submitting in
DMF.
19. Certificate of suitability certificate (CEP certificate) is not applicable.
20. Comparability protocols are not attached to both the drug substance and drug products.
21. The stability data for the accelerated studies are submitted for three months at the time of
their original submission.
22. Node extension is not allowed in the eCTD XML in software
23. SPL and STF are mandatory by the US FDA in eCTD of a drug registrations
application.[4]
ANDA Regulatory Review Process
The ANDA process begins when an applicant submits an ANDA to the OGD (Office Generic
Drugs) or CDER (Centre for Drug Evaluation and Research). The document room staff
process for ANDA assigns if it is an ANDA number, and stamps a received date on the cover
letter for the ANDA. Then ANDA is now sent to a consumer safety technician, who reviews
the preliminary sections of the ANDA checklist. The submitted ANDA is reviewed taking
into consideration the bioequivalence of the drug, chemistry, and microbiology, and also
labeling. Within the first 60 days following the submission of an ANDA, a filing review is
completed. The ANDA regulatory review process of USFDA is simplified as a flowchart
below the applicant is contacted.
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Fig 1: Anda Review Process.
Labelling Review Process
The labelling review process is to ensure that both the innovator and the generic drug have
the same labelling. After final level administrative review and individual disciplines have
resolved in their deficiencies, the application will either receive a full approval or a tentative
approval letter. A full approval letter details the conditions of approval and allows the
applicant to market the generic drug product. A tentative approval letter is issued if there are
unexpired patents or exclusivities accorded to the Reference Listed Drug (RLD).[5]
Withdraw of Approval of an ANDA
FDA may withdraw/suspend approval of an ANDA for any of the reasons listed below
When the approval of the listed drug on which the ANDA relies is either withdrawn or
suspended.
Evidence showing that the drug is unsafe for use or ineffective
The application contains any untrue statement of material fact.
If applicant is "repeatedly demonstrated a lack of ability to produce a drug, that has
introduced or attempted, such as adulterated or misbranded drug into commerce”.
Once ANDA approved, the applicant may manufacture and market generic drug products
to provide a safe, effective, low-cost alternative to the American public. FDA guidance
provides information about application contents and we ensure that a complete, high-
quality application is submitted to the FDA. FDA was previously published guidance on
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filing process, i.e, refuse-to receive standards, which should be reviewed briefly to avoid
common deficiencies in ANDA submissions.[6]
Generic Drug Product Registration Requirements in India
1. Generic drugs require Form 44 for approval in India.
2. A treasury challan of INR 15,000 is required all the active ingredients for more than one
year and INR 50,000 of the active ingredients is approved for less than one year in India.
3. Manufacturing of bulk drugs and raw materials the applicant has a manufacturing license
for bulk drugs, a copy of the same needs to be submitted.
4. Chemical and pharmaceutical information including Information on active ingredients.
a) Master manufacturing formula
b) Details of the formulation (including inactive ingredients)
c) Finished product specification
d) In-process quality control check.
e) COA including identification, pH, content uniformity, impurities, assay, etc.
f) Comparative Dissolution data in case oral dosage form as appropriate
g) Stability study evaluation as per requirements of schedule Y
5. Regulatory status of the drug including names of the company’s marketing the drug in the
country
6. Bioavailability/Bioequivalence study reports (for oral dosage forms
7. In the case of injectables formulation, sub-acute toxicity data conducted with the
applicants’ product has to be provided.
8. Prescribing information
9. Draft of labels and carton
10. Copy of License in Form-29.
The Indian generic drug Pharmaceuticals market can be divided into bulk drugs and
formulations. The bulk drug acquires 20% and formulations acquire 80% of the market with
an annual growth rate of 15%. The Indian generic drug market growing rapidly because a lot
of patents expire, major pharmaceutical companies of the world interested to invest in the
Indian market.[7]
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Fig 2: Generic drug approval process in India.
Generic Drug Product Registration Requirements in China
1. The dossier should adhere to the following standards.
The paper size should be of A4.
A complete content without any alterations should be provided.
The first page should be the directory of the application items arranged in order as per the
guidelines of “provisions for Drug Registration “(SFDA Order No.28).
The cover of the dossier should indicate the name of the drug and application item,
document item number, and the contact details of the applicant.
Foreign language materials if any, should be translated into Chinese.
2. All documents shall be sent in portfolio envelope(s), on which the application
classification, registration category, drug name, the envelope number of set X, the total
number of envelopes in the set, original or copy, the contact person, phone number and the
name of registration application agent shall be indicated.
3. Two sets of complete application dossiers (at least one set is in the original) and one set of
review documents in hard copy shall be submitted for the registration application.
4. "Import Drug Registration Application Form": the drug registration application form
submission program could be downloaded from CFDA website (www.cfda.gov.cn); the
application form shall be filled in as required, printed and saved, and shall be signed by the
overseas applicant, and signed & sealed by its domestic agent
5. When emailing or submitting the application dossiers, the electronic version of the
application form shall be sent to the following e-mail address dedicated to drug registration:
slzx@cfda.gov.cn.
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6. If data checking code on their electronic and paper application form should be the
identical.[8]
Other materials required for submission
1. The copy of the Certificate for Foreign Firm's branch permanently located in China when
the applicant's branch located in China applying; or the copy of authorization, notarization,
and the Business license of the Chinas agency.
2. The patent information and ownership certificate of the drug submitted for registration, or
of the formula and technology used in the manufacture of the drug, and the guarantee of not
constituting an infringement
3. Clinical and scientific documentation substantiating the safety and efficacy of the product
(except for generic products the originator product of which has been registered in Hong
Kong for over 5years);
4. One set of prototype sales pack (e.g. outer carton, container label, and other components
(s) comprising the sales pack) for each pack size of the product, complied fully with the
labelling requirements
5. The following document(s) to support the proposed indication(s), dosage, and ROA and
other contents of the package insert (if any): a)copy of reputable references (e.g. American
Hospital Formulary Service Drug Information, British National Formulary (BNF), Medicines
Compendium, Drug Information Handbook, Drug Facts and Comparisons, Martindale the
Complete Drug Reference or Physicians' Desk Reference); and b) documentary evidence
showing countries in section 8 (D) (g)(i);
6. Sample of the pharmaceutical substance as it sold to the purchaser or scanned image in
PDF format (scanning based on 300 dpi or higher) or photograph image in JPEG format
(pixel not less than 320×200) of the prototype sale pack or sample sale pack, including the
inner container/packaging and the unit dosage form image of the product sample showing its
contents in detail.
7. Detail and complete qualitative and quantitative composition of their finished product.
8. Specifications of the product issued by the manufacturer and document(s) showing
compliance with one or more pharmacopeia
19. Certificate of Analysis of the representative batch of the finished product, issued by
manufacturers or the company performing the analysis
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10. The BE studies should be conducted following World Health Organization guidance on
the "Multisource (generic) pharmaceutical products: guidelines on registration requirements
to establish inter changeability" or another international guideline.
Fig-3: Generic drug approval procedure in China.
5.9 Bioequivalence Testing
The Amended Regulation specifies that the generic drug shall have the same active
component, route of administration, dosage form, strength, and therapeutic effect as the
existing, approved drug. To the extent possible, bioequivalence testing is an important aspect
of the SFDA approval process for generic drug applications. Bioequivalence tests include
human tests to determine if any statistical difference in absorption and absorption speed of
the active component between the same or different dosage forms of same drugs under same
test conditions, by using the methodology of a bioavailability study with pharmacokinetic
parameters. Criteria to get acceptance of overseas BE Studies.
1. RLD should meet either one of the following criteria if RLD used in bio study is procured
either from the US/EU or Japan.
(a) MA holder & manufacturer of RLD used in bio study and MA holder & manufacturer of
China RLD should be the same.
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(b) RLD is acceptable if both the RLD’s are from the same manufacturer even though the
MA holder of RLD used in bio study is different from the MA holder of China RLD if the
parent company is the same.
(c) Manufactured by the same manufacturer but supplied by different MA holders and parent
companies also different, in this case, enough proofs should be submitted showing that the
Composition, manufacturing process, and quality of both the RLD's are the same.
2. Procuring RLD from EU has got the additional advantage as following
(d) RLD gets accepted though it is manufactured by the different manufacturers if the MA
holder is the same.
** BE study in both Fasting and Fed condition is mandatory for China filing
Table-1: BA/BE Criteria of Generic Drugs Approval in China.[9]
BE study in
both Fasting
and Fed
condition is
mandatory
for China
filing
Manufacturer
MA Holder
Remarks
Comments
a
Bio Study RLD
Same (X)
Same (X)
Acceptable
- - - - -
China RLD
b
Bio Study RLD
Same
(X)
Different
(X or Y)
The parent
company is the
same
Acceptable
China RLD
Different (Z)
c
Bio Study RLD
Same (X)
Different
(X or Y)
Parent Company
is Different
Acceptable, When
Enough Proofs should be
submitted showing that the
Composition, manu
facturing process, and quality
of both the RLD”s are the
same
China RLD
Different (Z)
Point 2 (RLD from EU) - Advantage
d
Bio Study
RLD
Different
Same (Z)
- - - - - -
Acceptable, when enough
proofs should be submitted
showing that the
Composition, manufacturing
process, and quality of both
the RLD's are the same
China RLD
Different(Y)
Same (Z)
Table 2: Comparison Study
A) Principle differences between USA, INDIA & CHINA
Requirements
USA
INDIA
CHINA
One Agency
USFDA
DCGI
NMPA
Registration Process
One Registration
Process
One Registration Process
One Registration Process
2 types:
Standard review procedure
Special review procedure
Web Address
https://www.fda.gov/
https://cdsco.gov.in/
www.nmpa.gov.cn
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Climatic Zone
Zone I and II
Zone III and IV
Climatic zone II
Language
All information should
be provided in English
All information should
be provided in English
All information should be
provided in Chinese and
original language
Braille code
Not required on label
Not required on labeling
Not required on labeling
Registration Validity Term
Lifetime
3 months
Valid for 5 years
Pharmacopeia’s
USP
IP
BP/USP/Ph.Eur
B) Administrative requirements
Requirement
USA
INDIA
CHINA
Application
ANDA
MAA
PFDA
Debarment classification
Required
Not applicable
Not applicable
No. of Copies
3
1
3
Approval timeline
~ 18 Months
~12 Months
12-18 Months
Administrative And
prescribing information
FDA form 356h
Chinese specific
application Form
Form 44
FEES
User Fee Type
FY 2021
FY 2020
ANDA
$196,868
$176,237
DMF
$69,921
$57,795
Program
Large Size
$1,542,993
$1,661,684
Medium Size
$617,197
$664,674
Small Size
$154,299
$166,168
F
A
C
I
L
I
T
Y
Domestic API
$ 41,671
$44,400
Foreign API
$56,671
$59,400
Domestic FDF
$184,022
$195,662
Foreign FDF
$199,022
$210,662
Domestic CMO
$61,341
$65,221
Foreign CMO
$76,341
$80,221
50,000
INR
Generic drugs
made in China:
318,000
Renminbi
(46,349.61USD)
Generic drugs
made outside
China:502,000
Renminbi
(73,177.85USD)
Present action
eCTD
Paper
Paper
B) Finished Product Control Requirements
Requirements
USA
INDIA
CHINA
Justification
ICH Q6A
ICH Q6A
ICH Q6A
Assay
90-100%
90-110%
95-105%
Disintegration
Not required
Required
Required
Color Identification
Not required
Required
Required
Water Content
Required
Required
Required
C) Manufacturing & Control Requirement
Requirements
USA
INDIA
CHINA
No. of Batches
3
1
3
Process validation
Required at the
time of submission
Required at the
time of submission
Required at the
time of submission
Batch size
A minimum of
1,00,000 units
Not specified
A scaled-up batch
or a full production
batch
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D) Stability Requirement
Requirements
USA
INDIA
CHINA
No. of Batches
3
01
3
Conditions
25/60 - 40/75
30/35-30/70
40/75 - 30/65
Date and time of
submission
6 Months accelerated &
6 months long-term
6 Months
accelerated & 3
months long-term
6 Months accelerated
and 6 months long
term
Container orientation
Inverted & Upright
Not specified
Not specified
Clause
21 CFR part 210 & 211
ICH Q1F
SFDA Order No. 28
QP Certification
Not required
Required
Required
Table 3: Comparison of General Parameters for the conduct of BA/BE study.[12,13]
Requirements
USA
INDIA
CHINA
Age (Years)
18 years of age or older
Adult healthy volunteers
18 to 40 years of age generally,
the same subjects not different
from 10 years of age.
BMI (Kg/m2)
18.5 24.9
Not specified
Standard weight range (within
the normal range according to
accepted normal values for BMI;
avoid high variance in subjects
body weight)
Gender,
ethnicity
Any healthy males and females.
If females used in the
bioequivalence studies should
not be pregnant
Males and/or females. The
choice of gender should be
consistent with usage and
safety criteria.
In general, if it recommended to
recruit healthy male subjects.
The study population should be
determined based on the specific
situation for each drug product;
if female subjects are recruited
they should not be pregnant
No. of subject
12
Normal 16 healthy Subjects
18-24
Genotyping or
Phenotyping
Not mentioned
Phenotyping and/ or
genotyping of subjects
should be considered for
exploratory bioavailability
studies and all studies using
parallel-group design. It
may also be considered in
the case of cross-over study
designs for safety or
pharmacokinetic reasons.
Furthermore, if a drug is
known to show an altered
pharmacokinetic profile due
to major genetic
polymorphism, studies
could be performed in
panels of subjects of known
phenotype or genotype for
the polymorphism in
question.
Consider for safety or
pharmacokinetic reasons
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Dose strength
used in the in-
vivo studies
The strength to be used
depends upon the type of
nonlinearity 1. If the non-
linearity is characterized by
greater than proportional
increases in AUC with
increasing dose, conduct the
BE studies on at least the
highest therapeutic dose 2. If
the non-linearity is
characterized by less than
proportional increases in AUC
with increasing dose and results
from saturable absorption,
conduct the in vivo studies on
the lowest strength
According to CDSCO,
single-dose studies are
generally recommended.
However, there are some
situations where the steady
study design is required
such as:
(a) Drugs with dose and
time-dependent
pharmacokinetics.
(b) Some modified-release
products.
(c) When there was a
problem for sensitivity in
plasma concentration
measurements since after
the single-dose
administration.
(d) If the intra-individual
variability is reduced at a
steady-state (CDSCO,
2005).
should be performed on the
highest strength, unless reasons
of safety justify the use of a
lower strength
Diet and Fluid
Requirements
No food should be allowed for
at least 4 hours post-dose
Subjects should start the
recommended meal 30 minutes
before the administration of the
drug product. Study subjects
should eat this meal in 30
minutes or less; however, the
drug product should be
administered 30 minutes after
the start of the meal.
Standardized meals are
scheduled at the same time in
each period of the study.
Total energy from the meal:
800-1000 cal (US FDA BA/BE,
2003)
Following an overnight fast of
at least 10h, subjects should be
administered the drug product
with 240mL (8 fluid ounces) of
water. No food should be
allowed for at least 4h post-
dose. Water can allowed as
desired except for one hour
before and after drug
administration. Subjects should
be receive standardized meals
CDSCO recommends on
standardization of the fluid
intake in all studies.
Total energy from meals
950-1000 Kcals
Overnight fasting of 10
hours with subsequent
fasting of 4 hours post-dose
It follows the guidance's and
specifications proposed by
guidance " Multisource (generic
pharmaceutical products:
guidelines on registration
requirements to establish inter
changeability
At least 8 hours before the
administration of the products. If
the Summary of Product
Characteristics of the reference
product contains specific
recommendations concerning
food intake related to food
interaction effects the study
should be designed.
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scheduled at the same time in
each period for the study.
Highly variable
drugs
· An RSABE approach may be
applied to AUC and C max
(55). A summary of the study
design and acceptance criteria
is as follows:
· The reference product should
be administered at least twice
to determine within-subject
variability
· Either a 3- or 4-period
replicate design study is
acceptable; The AUC and C
max GMRs in the study should
fall within 0.80 to 1.25
· BE limits are scaled to the
within-subject variability of the
reference product, but not until
the within-subject standard
deviation of the reference
product (SWR) is ≥ 0.294; and
A 95% upper confidence bound
for (μT-μR) 2 −θsWR2 must be
≤0, where μT=test product
mean μR=reference product
means
· Non compartmental analysis
to determine PK parameters
B Not specified
No information was given the
BE guidance
A) Acceptance criteria for Bioequivalence for Solid oral dosage form
Country
90% confidence Interval on log-transformed data
C max%
AUC0-t%
AUC0-t
USA
80-125
80-125
80-125
INDIA
80-125
80-125
80-125
CHINA
80-125
80-125
80-125
B) Acceptance criteria for Narrow Therapeutic Index for Solid oral dosage form
Country
Narrow therapeutic index drugs 90% confidence interval
Log transformed data
C max
AUC0-t
USA
80-125%
80-125%
INDIA
Acceptance criteria not defined
Acceptance criteria not defined
CHINA
Acceptance level may need to
be tightened
Acceptance level may need to
be tightened
ACKNOWLEDGEMENT Authors express their sincere thanks to Shri Vishnu College of
Pharmacy for providing the facilities and support for carrying out this work.
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Yallabandi et al. World Journal of Pharmacy and Pharmaceutical Sciences
CONCLUSION
In this study, the differences between Regulatory requirements Registration and Approval
process of Generic drug filing in the most stringent regulated market in the USA, domestic
market India and most stringent emerging market China were discussed. The key factor in the
generic drug filing is that the drug product must meet all the necessary criteria to be
therapeutically equivalent to the innovator drug product. The generic drug filing in the United
States, India & China are the most demanding, because these two countries are holding the
first, second, and third positions in the Pharmaceutical market in the world. Generic drug
filing comparison has shown various similarities and differences between these specified
countries that include differences in the
Registration process
Procedures
Fees structure
Applications
Approval timeline
Manufacturing & Control Requirement
Finished Product Control Requirements
Stability Requirements
General Parameters for the conduct of BA/BE study
Hence by comparing all these above, generic drug approval procedures and submissions
become easy for registration of drugs in those countries. It also significantly reduces the time
and resources need to compile an application for registration, easy in the preparation of
electronic submission, simplifies the regulatory information between regulatory authorities,
and playing field good for the export market.
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Article
Full-text available
Abstract: Branded drugs play an important role in medications, but generics are their cost effective alternatives. Generics are similar to branded drugs in terms of purity, efficacy and are perceived to be safer as compared to new drug molecules, as they tend to be older and time tested. Indian pharmaceutical market of generic drugs is increasing day by day. The availability of generic medication is an important issue in the ASEAN region. The regulatory requirements of various countries vary from each other. Therefore it is challenging for the companies to develop a single drug which can be simultaneously submitted in various countries for approval. The role of regulatory authorities is to ensure the quality, safety, and efficacy of all medicines in circulation in their country. It not only includes the process of regulating and monitoring the drugs but also the process of manufacturing, distribution, and promotion. The regulatory environment has similar characteristics but drug registration requirements and processes differ among the countries. One of the primary challenges for regulatory is to ensure that the pharmaceutical products are developed as per the regulatory requirement of that country. This process involves the assessment of critical parameters during product development. Regulatory requirements and generic drug registration for USA and ASEAN regions is made at the end of the section. In ASEAN region documentation can be filed in the ACTD format. In US region documentation can be filled in the CTD/eCTD format.
Article
Full-text available
Most countries are facing escalating health-care expenditures. A recent trend to control these staggering increases in costs is to encourage the use of generic medicines. Physicians are at the centerpiece of the medication use process as they are the dominant prescribers in all clinical settings. It is therefore prudent to examine what they perceive about generic medicines. The current study attempts to identify and review the literature on physicians' perceptions and practices on the use of generic medicines. Using subject-related keywords, an extensive literature search was undertaken through indexing services available in the authors' institution's library. Full text papers written in English language between 1980 and 2008 were retrieved and reviewed. Fourteen studies, majority (n = 5) from the United States were reviewed and included. Most of the studies used quantitative methodology. Generally, physicians were neutral to slightly supportive on the use of generic medications. Most of the studies reviewed highlighted the factors that can influence physicians' views as policy-related issues, patient-related variables, drug characteristics and physician-related variables. Although physicians accept generic substitution under policy and economic pressures, they still have concerns about the overall quality and reliability of generic drugs as well as generic interchange of certain drug categories.
Comparative Study of Generic Drug Approval Process in EU
  • P Sindhuja
  • M V Pooja Rajan
  • Brahmaiah Nagabhushanam
  • D Bonthagarala
  • G Reddy
  • Ramakrishna
P. Sindhuja, Pooja Rajan, M. V. Nagabhushanam, Brahmaiah Bonthagarala, D. Nagarjuna Reddy, G. Ramakrishna, Comparative Study of Generic Drug Approval Process in EU, USA and China Volume 7, Issue 9, 316-331 -A Review, Available from http://www.wjpps.com/download/article/1535715250.pdf
Regulatory process involved in the generic drug approval process in the USA
  • R Suthakaran
Suthakaran R. Regulatory process involved in the generic drug approval process in the USA, Europe, and India. Indo Am J Pharm Res., 2013; 3: 1451-6. Available from: https://www.ejmanager.com/mnstemps/36/36-1393404044.pdf
International guidelines for bioequivalence of systemically available orally administered generic drug products: a
  • B Davit
  • A C Braddy
  • D P Conner
  • X Y Lawrence
Davit B, Braddy AC, Conner DP, Lawrence XY. International guidelines for bioequivalence of systemically available orally administered generic drug products: a