Drug Regulatory Affairs

1. Sachin Gundecha
Regulatory Affairs Department
Gennova Biopharmaceuticals Ltd

2.  Why Regulatory is needed?
 What does Regulatory Affairs functions?
 What do they regulate?
 Why to give data to Regulatory Affairs ?
 ?
 ?

5. Regulatory affairs professionals usually
have responsibility for the following
general areas:
Role of RA To keep track of the ever-
changing legislation
Registration documents to regulatory
agencies
To give strategic and technical advice
to R&D, Production, QC dept etc. right
from the beginning of the development
of a product, making an important
contribution both commercially and
scientifically to the success of a
development programme and the
company as a whole.
They also advise on the legal and
scientific restraints and
requirements, and collect, collate and
evaluate the scientific data their
research and development colleagues
are generating.
The regulatory professional

6. The regulatory function in healthcare industries is vital in making safety
and effective healthcare products available worldwide.
Regulatory professionals are employed in industry, government and
academia and are involved with a wide range of products, including:
•pharmaceuticals
•medical devices
•in vitro diagnostics
•biologics and biotechnology
•nutritional products
•cosmetics
•veterinary products
The regulatory professional's roles and responsibilities often begin in the
research and development phases, moving into clinical trials and
extending through premarket approvals, manufacturing, labeling and
advertising and post marketing surveillance.

7. Avoiding problems
It takes anything up to 15 years to develop and launch a new
pharmaceutical product and many problems may arise in the
process of scientific development and because of a changing
regulatory environment.
Regulatory professionals help the company avoid problems
caused by badly kept records, inappropriate scientific thinking
or poor presentation of data.

8. Working internationally
Many companies operating in high-technology healthcare and related
industries operate on a multinational basis and are significant exporters.
Their regulatory affairs departments must be aware of the regulatory
requirements in all the company’s export markets.
Despite recent international efforts towards harmonization of
requirements, the regulations laid down by different governments and
their interpretation by the regulatory agencies rarely match. The
registration data prepared for one country frequently fail to meet the
requirements for another.
Therefore great care has to be taken in drawing up efficient and
economical research and development programmes whose results may
be used as widely as possible.
Regulatory professionals, with their detailed knowledge of the regulations
and guidelines, are frequently called in to advise on such matters.

9. • Pharmaceutical products are regulated in
essentially every country of the world.
• These regulations are applicable to both
the investigation and marketing of
compounds.
A Broad Scope: Regulations and Agencies

10. Regulatory Affairs Defined
• Regulatory Affairs is a specialized profession within the
pharmaceutical/biotechnology sector.
• Regulatory Affairs oversees company compliance with regulations and
laws pertaining to the manufacture, marketing and development of
regulated products.
• Regulatory Affairs acts as point of contact between the company, its
products, regulatory authorities and Marketing
• Regulatory Affairs interacts with worldwide, federal, state, and local
regulatory agencies (e.g., DCGI, Local FDA, FDA (US), EMEA
(EU), BfARM- Federal Institute for Drugs and Medical Devices
(Germany), TPD (Canada), TFDA Tanzania, BFAD Philippines etc) to
assure…
– licensing,
– registration,
– development,
– manufacturing,
– marketing and
– labeling
…….of pharmaceutical, biopharmaceutical and medical products are
conducted in compliance with all applicable rules

11. Regulatory Framework
• Development, approval for marketing, manufacturing, and ongoing
compliance of pharmaceutical/biotech products is among the most
regulated activities of any industry
• Regulations are complex systems of interrelated rules that govern
a broad range of activities
• These rules are continuously undergoing amendment and
supplementation
• Their main function is to assure that these products are safe (do
no harm) and at the same time effective ( do some good)

12. Regulatory Framework
Why do we pay so much attention to
regulation and process ??
• It takes 8 to 15 years to develop a new drug/biologic product.
• Costs up to millions of Dollar or Crores of Rupees.
• Attention to early development, successfully execution of
significant clinical studies helps to reduce number of
development failures.
• Regulatory affairs provides insight/guidance into this
development through agency wisdom collected in
guidance, previous experience, market precedence, etc.
Compliance with Regulator expectations therefore
equates with development success. Patient Protection is
of greatest importance .

13. Drug Discovery

14. You Should Know
What is Dossier ?
What is DMF ?
What is CTD / eCTD ?
What is NDA / ANDA and MAA ?
What is Biosimilar? Or
What is generic biotech?

15. What is Dossier ?
Dossier is a collection or file of
documents that contains all the technical
data of pharmaceutical product to be
approved / registered / marketed in a
country.
It is most commonly called as Registration
Dossier, In US : New Drug Application
(NDA), In EU : Marketing Authorization
Application (MAA)

16. What is DMF ?
Drug Master File (DMF)
US-USDMF: United States Drug Master File
EDMF/ASMF: European Drug Master File or Active Substance Master File
[Applicant’s Part / Open Part and Restricted part / Closed part ]
Type I – Mfg. Site, Facilities, Operating Procedures, and
Personnel (no longer applicable)
Type II - DS, Intermediate & Material Used in Their Preparation
or Drug Product
Type III - Packaging Material
Type IV - Excipient, Colorant, Flavor or Material Used in Their
Preparation
Type V - FDA Accepted Reference Information (FDA
discourages its use)

17. Types of Dossier
Eu-CTD or CTD ACTD National Format
Module 1:
Administrative
Part I:Administrative Contains all the
information but
structure varies on
country to country
basis.
Module 2: QOS Part II: QOC and CMC
Drug Substance
Drug Product
Module 3: CMC
Drug Substance
Drug Product
Part III: Preclinical
Module 4: Preclinical Part IV: Clinical
Module 5: Clinical
Eu-CTD: European Common Technical Document
ACTD: Asean Common Technical Document

19. Module 1- Administrative Documents
• Manufacturing Licence
• WHO-GMP Certificate
• Free Sale Certificate
• Site Master File
• Engineering Layout
• Equipment Drawing
• Quality policy
• Artwork
• Patient Information Leaflet
• Pack Insert
Module 1 does not only limited to above heading but it changes on
country to country basis

20. Module 2- QOS Quality Overall
Summary
Module 2 contains Quality Overall Summary for following section
 CMC information on Active Pharmaceutical Ingredient Section
 CMC information on Finished Product Section
 Pre-clinical Section
 Clinical Section
Incase of ACTD QOS is presented section Part II and then
Elaborated sections are followed.

21. Chemistry and
Manufacturing
A major part of Module 3/ Part II

22. Drug Substance
• Drug substance (Active pharmaceutical
ingredient)—
– It is the material that is exerting the pharmacological action.
– Along with other ingredients (excipients, inactives) it
subsequently it is used to formulate, the drug product.
• It can be composed of
– the desired active material,
– product-related substances,
– product—or process related impurities (subsequently removed)
• It also may contain other components, including
vehicles, or buffers.
• Biologics and biotechnology industry.
– Alternatively referred to as bulk concentrate, bulk
intermediate, or simply bulk

23. Drug Product
• Drug product (Dosage form; Finished
product)—
– one or more drug substances (active pharmaceutical
ingredients)
– usually with excipients
• Excipients
– components of a finished medicinal drug product
other than the active pharmaceutical ingredient (API).
– Included in the formulation to facilitate
manufacture, enhance stability, control release of API
from the product, assist in product identification, or
enhance other product characteristics.

24. Impurity
• Impurity—An impurity is any component
present in the excipient, drug substance, or drug
product that is not:
– the desired product,
– a product-related substance,
– or excipient, (including buffer components).
• It may be either process- or product-related.
• It may be the result of active principle
degradation during holding/processing

25. Chemistry Manufacturing &
Controls for API & FP
• Analytical Method
• Degradation Products
• Specifications
• In-process controls
• Methods Validation
• Process Validation
• (DP/DS) Characterization
• Container / Closure System
• Characterization
• Stability

26. TABLE OF CONTENTS
for
DRUG SUBSTANCE

27. 3.2.
S
Drug Substance
3.2.S.1 General Information
3.2.S.1.1 Nomenclature
3.2.S.1.2 Molecular Structure
3.2.S.1.3 General Properties
3.2.S.2 Manufacture
3.2.S.2.1
3.2.S.2.2
3.2.S.2.3
3.2.S.2.4
3.2.S.2.5
3.2.S.2.6
Manufacturer
Description of Manufacturing Process and Process Controls
Control of Materials
Control of Critical Steps
Process Validation
Manufacturing Process Development
3.2.S.3 Characterization
3.2.S.3.1 Elucidation of Structure and other characteristics
3.2.S.3.2 Impurities
3.2.S.4 Control of Drug Substance
3.2.S.4.1 Specifications
3.2.S.4.2 Analytical Procedures
3.2.S.4.3 Validation of Analytical Procedures
3.2.S.4.4 Batch Analysis
3.2.S.4.5 Justification of Specification
3.2.S.5 Reference Standards or Materials
3.2.S.6 Container Closure Systems
3.2.S.7 Stability

28.  3.2.S DRUG SUBSTANCE1 (NAME, MANUFACTURER)
 3.2.S.1 General Information (name, manufacturer)
 3.2.S.1.1 Nomenclature (name, manufacturer)
 Information on the nomenclature of the drug substance should be provided. For
example:
 Recommended International Nonproprietary Name (INN);
 Compendial name if relevant;
 Chemical name(s);
 Company or laboratory code;
 Other non-proprietary name(s), e.g., national name, United States Adopted Name
(USAN), Japanese Accepted Name (JAN); British Approved Name (BAN), and
 Chemical Abstracts Service (CAS) registry number.
 3.2.S.1.2 Structure (name, manufacturer)
 Biotech:
 The schematic amino acid sequence indicating glycosylation sites or other post-
translational modifications and relative molecular mass should be provided, as
appropriate.

29.  3.2.S.1.3 General Properties (name, manufacturer)
 A list should be provided of physicochemical and other relevant properties of
the drug substance, including biological activity for Biotech
 3.2.S.2 Manufacture (name, manufacturer)
 3.2.S.2.1 Manufacturer(s) (name, manufacturer)
 The name, address, and responsibility of each manufacturer, including
contractors, and each proposed production site or facility involved in
manufacturing and testing should be provided.
 3.2.S.2.2 Description of Manufacturing Process and Process Controls
(name, manufacturer)
 The description of the drug substance manufacturing process represents the
applicant’s commitment for the manufacture of the drug substance. Information
should be provided to adequately describe the manufacturing process and
process controls.
 Biotech:
 Information should be provided on the manufacturing process, which typically
starts with a vial(s) of the cell bank, and includes cell culture, harvest(s),
purification and modification reactions, filling, storage and shipping conditions

30.  3.2.S.2.3 Control of Materials (name, manufacturer)
 materials, solvents, reagents, catalysts) should be listed identifying where each material is used
in the process. Information on the quality and control of these materials should be provided.
Information demonstrating that materials (including biologically-sourced materials, e.g., media
components, monoclonal antibodies, enzymes) meet standards appropriate for their intended use
(including the clearance or control of adventitious agents) should be provided, as
appropriate. For biologically-sourced materials, this can include information regarding the source,
manufacture, and characterization. (Details in 3.2.A. 2 Appendices for both NCE and Biotech)
 Biotech:
 Control of Source and Starting Materials of Biological Origin
 Summaries of viral safety information for biologically-sourced materials should be provided.
(Details in 3.2.A.2.)
 Source, history, and generation of the cell substrate
 Information on the source of the cell substrate and analysis of the expression construct used to
genetically modify cells and incorporated in the initial cell clone used to develop the Master Cell
Bank should be provided as described in Q5B and Q5D.
 Cell banking system, characterization, and testing
 Information on the cell banking system, quality control activities, and cell line stability during
production and storage (including procedures used to generate the Master and Working Cell
Bank(s)) should be provided as described in Q5B and Q5D.
Reference (ICH M4Q Guideline)

31.  3.2.S.2.6 Manufacturing Process Development (name, manufacturer)
 The developmental history of the manufacturing process, as described in 3.2.S.2.2, should
be provided. The description of change(s) made to the manufacture of drug substance
batches used in support of the marketing application (e.g., nonclinical or clinical studies)
should include, for example, changes to the process or to critical equipment. The reason
for the change should be explained. Relevant information on drug substance batches
manufactured during development, such as the batch number, manufacturing scale, and
use (e.g., stability, nonclinical, reference material) in relation to the change, should be
provided.
 The significance of the change should be assessed by evaluating its potential to impact the
quality of the drug substance (and/or intermediate, if appropriate). For manufacturing
changes that are considered significant, data from comparative analytical testing on
relevant drug substance batches should be provided to determine the impact on quality of
the drug substance (see Q6B for additional guidance). A discussion of the data, including a
justification for selection of the tests and assessment of results, should be included.
 Testing used to assess the impact of manufacturing changes on the drug substance(s) and
the corresponding drug product(s) can also include nonclinical and clinical studies. Cross-
reference to the location of these studies in other modules of the submission should be
included.

32. TABLE OF CONTENTS
for
DRUG PRODUCT

33. 3.2.P Drug Product
3.2.P.1 Description and Composition of the Drug Product
3.2.P.2 Pharmaceutical Development
3.2.P.2.1 Components of the Drug Product
3.2.P.2.1.1 Drug Substance
3.2.P.2.1.2 Excipients
3.2.P.2.2 Drug Product
3.2.P.2.2.1 Formulation Development
3.2.P.2.2.2 Overages
3.2.P.2.2.3 Physicochemical and Biological
Properties
3.2.P.2.3 Manufacturing Process Development
3.2.P.2.4 Container Closure System
3.2.P.2.5 Microbiological Attributes
3.2.P.2.6 Compatibility
Continue…….

34. 3.2.P.3 Manufacture
3.2.P.3.1 Manufacturer(s)
3.2.P.3.2 Batch Formula
3.2.P.3.3 Description of Manufacturing process and Process Controls
3.2.P.3.4 Controls of Critical Steps and Intermediates
3.2.P.3.5 Process Validation and/ or Evaluation
3.2.P.4 Control of Excipients
3.2.P.4.1 Specifications
3.2.P.4.2 Analytical procedures
3.2.P.4.3 Validation of Analytical Procedures
3.2.P.4.4 Justification of Specifications
3.2.P.5 Controls of Drug Product
3.2.P.5.1 Specifications
3.2.P.5.2 Analytical Procedures
3.2.P.5.3 Validation of Analytical Procedures
3.2.P.5.4 Batch Analyses
3.2.P.5.5 Characterization of Impurities
3.2.P.5.6 Justification of Specifications
3.2.P.6 Reference Standards and Materials
3.2.P.7 Container Closure System
3.2.P.8 Stability
3.2.P.8.1 Stability Summary and Conclusion
3.2.P.8.2 Post-approval Stability Protocol and Stability Commitment
3.2.P.8.3 Stability Data

35. Part III/Module 4 Preclinical Data
Part IV/Module 5 Clinical Data
This is also a part of CTD/EuCTD/ACTD or National
Format
Contents and Applicability varies according to country.
Pre-requisite for Biotech product is
1. Viral clearance
2. Comparative clinical and preclinical study
3. PMS and or PSUR

36. Regulatory Affairs a
never ending path
…………………..

37. ?Questions please…..

38. Knowledge is already build in
guideline it is up to us
How we implicate
How we replicate
How we inflate!
Thank You !!!!!!!

39. Acknowledgment
 Dr. Rahul Kulkarni, Gajanan Deshmukh
 Entire management of Gennova
 HR team
 All of you