This slide will be much helpful for the students who want to make their career path towards Bioprocess/Biotech industry.

1. Presented by SATHEESH KUMAR.SSK in Oxford
college of science.Bangalore.
(Dedicated to biotech students community.)
Contact: satheeshbiotech786@gmail.com

2. Cleanrooms/BSL/HVAC/MSDS/HEPA/OTC/NCE/
IND/NDA/ANDA/PFF/USFDA/EU/ROW/ICH/CFR
/GMP/GLP/GCP/SCADA/BIOSIMILARS/GENERI
CS/
BIOEQUIVALENCE/BIOBETTER/GRP/CAPA/large
molecule/small molecule

3.  Molecules used as active substances can be divided
into two classes – small and large molecules. They
differ not only in terms of size, but also in how
they are made, how they behave, their mode of
action in the body and their suitability for certain
drug forms.
 Small, chemically manufactured molecules (or SMOLs
for short) are the classic active substances and still
make up over 90 percent of the drugs on the market
today. By contrast, large molecules – also known as
biologics – are therapeutic proteins; they are
becoming increasingly important.
 Example for small molecule: acetylsalicylic acid (ASA)
 Example for large molecule: Insulin.

5.  Every country has its own regulatory authority, which is responsible
to enforce the rules and regulations and issue the guidelines to
regulate drug development process,licensing, registration,
manufacturing, marketing and labeling of pharmaceutical products.
USFDA(USA), MHRA(UK), TGA(Australia), CDSCO(India), HEALTH
CANADA(CANADA), MCC(South Africa),ANVISA (Brazil) , EMEA
(European Union), SFDA (China),NAFDAC(Nigeria),
MEDSAFE(Newzeland), MHLW(Japan), MCAZ(Zimbabwe),
SWISSMEDIC(Switzerland), KFDA(Korea), MoH (Sri Lanka) are the few
regulatory agencies and organizations established in respective
countries.
 World Health Organization (WHO), Pan American Health Organization
(PAHO), World Trade Organization (WTO), International Conference
on Harmonization (ICH), World Intellectual Property Organization
(WIPO) are some of the international regulatory agencies and
organizations which also play essential role in all aspects of
pharmaceutical regulations related to drug product registration,
manufacturing, distribution, price control, marketing, research and
development, and intellectual property protection.

6.  New drugs begin in the laboratory with scientists, including chemists and
pharmacologists, who identify cellular and genetic factors that play a role
in specific diseases. They search for chemical and biological substances
that target these biological markers and are likely to have drug-like
effects. Out of every 5,000 new compounds identified during the discovery
process, approximately five are considered safe for testing in human
volunteers after preclinical evaluations. After three to six years of further
clinical testing in patients, only one of these compounds on average is
ultimately approved as a marketed drug for treatment.
 Insilico and invitro analysis plays a key role in this stage of drug
development.
 An NCE is a molecule developed by the innovator company in the early
drug discovery stage, which after undergoing clinical trials could translate
into a drug that could be a cure for some disease. Synthesis of an NCE is
the first step in the process of drug development. Once the synthesis of
the NCE has been completed, companies have two options before them.
They can either go for clinical trials on their own or license the NCE to
another company.

7.  Pharmacodynamics (what the drug does to
the body)..Eg:Agonist or Antagonist.
 Pharmacokinetics (what the body does to the
drug)
 ADME studies.
 Animal testing
 a.)Institutional Animal Care and Use
Committee (IACUC)
 B.) Committee for the purpose of control and
supervision on Experimentation on
Animals.(CPCSEA)

8.  CDER is the largest of FDA's six centers, It has
responsibility for both prescription and nonprescription or
over-the-counter (OTC) drugs
 Some companies submit a investigation of new Drug (IND)
to introduce a new drug product into the market.
 IRB reviews the IND,
 CDER's Manual of Policies and Procedures (MaPPs) are
approved instructions for internal practices and procedures
followed by CDER staff to help standardize the new drug
review process and other activities. All MAPPs are available
for the public to review for a better understanding of
office policies, definitions, staff responsibilities and
procedures.
 5210.5 Review of Investigational New Drug Applications
(Bio-INDs) by the Office of Generic Drugs.
 The Applicant are allowed to file the patent once IND is
approved.

9.  There are two IND categories:
 Commercial
 Research (non-commercial)
The IND application must contain information in
three broad areas:
 Animal Pharmacology and Toxicology Studies
 Manufacturing Information
 Clinical Protocols and Investigator Information
 Once the IND is submitted, the sponsor must
wait 30 calendar days before initiating any
clinical trials.

10.  The final regulations published in the Federal
Register (daily published record of proposed
rules, final rules, meeting notices, etc.) are
collected in the Code Of Federal Regulations
(CFR). The CFR is divided into 50 titles that
represent broad areas subject to Federal
regulations. The FDA's portion of the CFR
interprets the The Federal Food, Drug, and
Cosmetic Act and related statutes. Section
21 of the CFR contains most regulations
pertaining to food and drugs. The
regulations document all actions of all drug
sponsors that are required under Federal law.

11.  21CFR Part 312 Investigational New Drug
Application/ 21CFR Part 314 INDA and NDA
Applications for FDA Approval to Market a
New Drug (New Drug Approval) 21CFR Part
316 Orphan Drugs 21CFR Part 58 Good Lab
Practice for Nonclinical Laboratory [Animal]
Studies 21CFR Part 50 Protection of Human
Subjects 21CFR Part 56 Institutional Review
Boards 21CFR Part 201 Drug Labeling 21CFR
Part 54 Financial Disclosure by Clinical
Investigators

12.  Phase-1: To evaluate safety. Ranges 20 to 80
peoples
 Phase -2: Establishing the efficacy of the
drug, usually against a placebo. Testing with
a larger group of people (100–300)
 Phase-3:Final confirmation of safety and
efficacy. Testing with large groups of people
(1,000–3,000)
 Phase-4( usually happens after PD and
marketing)

13.  Process development scientists aim to
optimise the performance of manufacturing
systems. They are responsible for identifying
and developing new processes for product
manufacture, as well as putting in place
process controls to make sure the products
are of a high quality and are manufactured in
a reproducible manner.
 Product development scientists work with
research scientists to develop new ideas and
scientific discoveries, which can be used in
the manufacture of new products. They also
develop and improve existing products.

14.  The sponsor submitted a New Drug
Application (NDA) with full information on
manufacturing specifications, stability and
bioavailablility data, method of analysis of
each of the dosage forms the sponsor intends
to market, packaging and labeling for both
physician and consumer, and the results of
any additional toxicological studies not
already submitted in the Investigational New
Drug application.

15.  New drugs, like other new products, are
frequently under patent protection during
development.
 When the patents or other periods of
exclusivity on brand-name drugs expire,
manufacturers can apply to the FDA to sell
generic versions.
 The Abbreviated New Drug Applications
(ANDA) Gives the guidance,laws and
regulation for generic drug.

16.  A Drug Master File (DMF) is a submission to the
Food and Drug Administration (FDA) that may be
used to provide confidential detailed information
about facilities, processes, or articles used in
the manufacturing, processing, packaging, and
storing of one or more human drugs. The
submission of a DMF is not required by law or
FDA regulation. A DMF is submitted solely at the
discretion of the holder. The information
contained in the DMF may be used to support an
Investigational New Drug Application (IND), a
New Drug Application (NDA), an Abbreviated New
Drug Application (ANDA),

17.  This guideline does not impose mandatory
requirements (21 CFR 10.90(b)). It does,
however, offer guidance on acceptable
approaches to meeting regulatory
requirements.
 Drug Master Files are provided for in 21 CFR
314.420

18.  There are five types of DMF's:
 Type I Manufacturing Site, Facilities,
Operating Procedures, and Personnel
 Type II Drug Substance, Drug Substance
Intermediate, and Material Used in Their
Preparation, or Drug Product
 Type III Packaging Material
 Type IV Excipient, Colorant, Flavor, Essence,
or Material Used in Their Preparation
 Type V FDA Accepted Reference Information

19.  Clean rooms:
 HVAC
 BSL Facility.
 Upstream Equipments
 Downstream Equipments
 Utilities( WFI,purified water,bioler for steam)
 Documentation as per GMP regulation
including system enteries.
 Trained man powers.

20.  Some vital examples of validation:
 Validation of clean rooms
 Validation of HVAC
 Validation of process
 Validation of cleaned container.
 Validation of equipments installed.

21.  Design qualification:
 Installation qualification:
 Operational qualification:
 Performance qualification

22.  Design Qualification is used at the stage
where a design that has been developed from
the, URS and other Health and Safety
Guidelines, is reviewed and documented by
competent persons to ensure that the
designed equipment, if built, will satisfy all
the detailed specified requirements

24.  The Installation Qualification (IQ) execution;
verifies that the equipment, and its ancillary
systems or sub-systems have been installed
in accordance with installation drawings and
or specifications. It further details a list of
all the cGMP requirements that are
applicable to this particular installation
qualification. These requirements must all be
satisfied before the IQ can be completed and
the qualification process is allowed to
progress to the execution of the Operational
Qualification (OQ).

25.  The Operational Qualification Protocol is a
collection of test cases used to verify the
proper functioning of a system. The
operational qualification test requirements
are defined in the Functional Requirements
Specification. Operational Qualification is
usually performed before the system is
released for use.

26.  Performance Qualifications are a collection of
test cases used to verify that a system performs
as expected under simulated real-world
conditions. The performance qualification tests
requirements defined in the User Requirements
Specification (or possibly the Functional
Requirements Specification).
 Performance Qualifications should be approved
before protocol execution. A copy of the
unexecuted protocol should be kept in the
validation package. The unexecuted protocol
should be approved by the System Owner and
Quality Assurance. The executed protocol should
be signed by the tester and reviewed by the
system owner and Quality.

27.  The Factory Acceptance Test (FAT) is a major
project milestone where the vendor
demonstrates that the system design and
manufacturing meets the contract specifications.
 FATs generally consist of the following:
 Review of the specification line by line while
checking the equipment for compliance with the
specification.
 Review of appropriate standards and regulations
referenced.
 Inspection for workmanship.
 Inspection for damage that can occur during
installation (lift points, accessibility, etc.).

28.  A SAT is a Site Acceptance Test the system is
tested in accordance to client approved test
plans and specifications to show the system
is installed properly and interfaces with
other systems and peripherals in its working
environment.

30.  A cleanroom or clean room is an
environment, typically used in manufacturing
or scientific research, with a low level of
environmental pollutants such as dust,
airborne microbes, aerosol particles, and
chemical vapors.

32.  CLASS A CLASS 100
 CLASS B CLASS 1000
 CLASS C CLASS 10000
 CLASS D CLASS 100000

34.  HVAC (heating, ventilating, and air
conditioning) is the technology of indoor and
vehicular environmental comfort. Its goal is
to provide thermal comfort and acceptable
indoor air quality.
 Ventilation includes both the exchange of air
to the outside as well as circulation of air
within the building. It is one of the most
important factors for maintaining acceptable
indoor air quality in buildings.

37.  Biological Safety Cabinets (BSCs), which are the primary
means of containment developed for working safely with
infectious microorganisms.
 Three kinds of biological safety cabinets, designated as
Class I, II(type A1,A2 and Type B1 and B2) and class III.
BSL types Personnel
protection
Environmen
t Protection
Product
Production
CLASS-1 Yes Yes NO
CLASS-2 Yes Yes Yes
CLASS-3 yes yes yes

38.  It is similar in terms of air movement to a
chemical fume hood,but has a HEPA filter in the
exhaust system.
 unfiltered room air is drawn in through the work
opening and across the work surface.
 minimum velocity of 75 linear feet per minute
(lfm) is maintained through the front opening.
 Used in centrifuges, harvesting equipment or
small fermenters.

40.  Air flow is drawn from the room around the
operator into the front grille of the cabinet,
which provides personnel protection. In
addition, the downward laminar flow of
HEPA-filtered air provides protection for
experimental material inside the cabinet.
Because cabinet air has passed through the
exhaust HEPA filter, it is contaminant-free,
providing environmental protection, and may
be recirculated back into the laboratory
(Class II Type A) or ducted out of the building
(Class II Type B).

41.  Due to the relative size of these two filters,
approximately 30% of the air passes through
the exhaust HEPA filter and 70% recirculates
through the supply HEPA filter back into the
work zone of the cabinet.

43.  The Class III biological safety cabinet is most
suitable for work with biohazardous agents
requiring high contain (biosafety level 3 or
4). The Class III cabinet is completely
enclosed, HEPA filter-ventilated cabinet
fitted with glove ports and decontamination
capabilities for entry and exit of material. It
offers the highest degree of personnel and
environmental protection from infectious
aerosols.

45.  PURE STEAM:
 IMPURE STEAM
 WFI ( Water for injection): Its helps to
prevent endotoxin contamination
 Purified water by MCDS
 Sterile air.

46.  Departments.
1.) Board of Directors.
2.)Human resource and admins
3.)Research and development:---
a.)Research investigators
b.)Process development
4.) Production development
5.)Quality assurance
6) Quality control
7) Storage and packing department.
9)Logistics and marketting people.
10) Technology transfer department
11)IP and IT deparrtments

47.  In the eyes of regulatory authorities, the quality issues of
biologics are definitely different from chemical drugs
because of: (1) use of living source materials to produce
the biologic, (2) increased complexity of biologic
manufacturing processes and (3) increased complexity of
the biologic molecules themselves. While chemical drugs
can become generics, biologics products are best viewed
as biosimilars, and not as bio-generics.
 Biologics are highly susceptible to adventitious agent
contamination – prions, viruses, mycoplasmas, and
bacteria/fungi microbes. Risk control procedures –
such as barriers to entry, testing to confirm absence,
and inactivation/removal – are essential. Lessons can
be learned from reported contaminations of biologic
manufacturing processes. Compared to chemical
drugs, biologics have a more complex process-related
impurity safety profile, especially due to the living
system-related impurities

48.  quality assurance is any systematic process
of checking to see whether a product or
service being developed is meeting specified
requirements. Many companies have a
separate department devoted to quality
assurance. A quality assurance system is said
to increase customer confidence and a
company's credibility, to improve work
processes and efficiency, and to enable a
company to better compete with others.

49. 1.) Wet lab work:
Working along with the team of quality
analyst and manufacturers to ensure
Quality,safety and efficacy of a product
through out the production process and to
ensure the whole process is carried out in
compliance with the standard regulatory
requirements

50. 2) Regulatory work
a.)Work with local and international
organisation to guarantee products adhere to
certain standards
b.) Prepare submission to regulatory bodies
and review submission results
c.) Resolve problems where results fail to
meet certain guidelines
d.) One can work either in a pharmaceutical
company, for an independent regulatory firm
that helps companies, or even for the
regulatory bodies themselves.

51.  Pharmaceutical companies routinely require
external audits to ensure operations are in
accordance with established guidelines
 Audit Types in Biopharmaceuticals:
 Internal audit
 A financial audit
 A compliance audit
 An operational audit,

52.  1) internal audit with accordance to ICH-
Q10(Quality management system)
a.) Plan the audit
b.)Conduct the audit
c.)Report and close the audit
d.)Follow up the audit.

53.  Compliance audit will assess level of
conformance with operating procedures as
stipulated by contractual arrangements
and/or government regulatory agencies,
including an investigation of hard-copy
prescriptions, computerized records of refills
and invoice records.

54.  An operational audit, also called a
performance or management audit, seeks to
evaluate the company's overall efficiency as
a vendor administering prescription plans for
various sponsors.
 A real time Example: GSK, a pioneer in
pharmaceuticals is presently dependent on
Kemwell biopharma(an CRO) for their
production of a X synthetic drug. So GSK
holds the right to conduct a performance
audit in kemwell to meet the quality
standards of production

56.  An example: The srikulam facility of Dr
reddys lab was inspected by USFDA On
nov.14th resulting in a form 483 with nine
observations.The observation was largely
related to Procedural and other compliances
of the plant system.
 then later company responded to the agency
with its remediation plans and avoided
further enforcement.

57.  Production: can be subdivided under two
streams namely: USP and DSP. The
equipments and operations involved differs
from product to another product.
 QA should be in full swing to prepare
BMR,checklist,SOP,EOP,STP. Etc..
 QC should be well organised with
sophisticated intruments like HPLC,GC,ASS
MS. Etc..the instrument requirement differs
according to the nature of the product

58.  QC laboratories controlling the quality of
commercial drugs that are sampled from large
repetitive batch production should comply
withall GMP requirements listed in CFR Part 210
and 211
 There involved three section of Qc analysis in
any production plant.
1) Raw material analysis.
2)in process analysis
3) Finished product anaysis
If any deviation or ooz is observed in the above
said three analysis then it should be informed to
QA where they ll try to do CAPA ( corrective and
preventive action).

59.  Quality control Stability analysis falls into 2
catagories:
 A) Real time stability analysis
 B) Facilititated stability analysis.

60.  MARKETTING is the prime and foremost focus
of any owner.
 Marketing is said to be a heart of any
business.
 Product selling and technology transfer are
the two rhythms of any biopharmaceuticals
 Technology transfer managers who are expert
in both technical aswell as management are
a key players.

61.  Postmarketing drug surveillance refers to the
monitoring of drugs once they reach the
market after clinical trials. It evaluates drugs
taken by individuals under a wide range of
circumstances over an extended period of
time. Such surveillance is much more likely
to detect previously unrecognized positive or
negative effects that may be associated with
a drug. The majority of postmarketing
surveillance concern adverse drug reactions
(ADRs) monitoring and evaluation

62.  united States Patent and Trademark Office (USPT0) is the
regulatory authority for patent management.
 Once the patent term ends, the innovating company loses
its market exclusivity privilege as generic manufactures
enter the market. There however are processes to extend
the life of a patent term through “patent term
restoration.” Additionally, the innovating company still
enjoys market exclusivity while generic manufactures
undergo their required FDA approval process.
 Another method of patent extension, due to the FDA
approval process, is under the Drug Price Competition and
Patent Term Restoration Act of 1984, also known as the
Hatch-Watchman Act. The act provides a maximum 5-year
extension, and is limited to a 14-year term from the time
of FDA approval. The calculation of extension is complex
and depends on patent prosecution and approval factors.

63.  Biosimilars, also known as follow-on biologics, are
biologic medical products whose active drug
substance is made by a living organism or derived
from a living organism by means of recombinant DNA
or controlled gene expression methods.
 Biosimilars (or follow-on biologics) are terms used to
describe officially approved subsequent versions of
innovator biopharmaceutical products made by a
different sponsor following patent and exclusivity
expiry on the innovator product.[1] Biosimilars are
also referred to as subsequent entry biologics (SEBs)
 BPCI Act
The Biologics Price Competition and Innovation Act of
2009
Code of Federal Regulations, Title 21, Part 610.10 ...
Part 210, 211(21 CFR 210, 211)

65.  The term biobetter refers to a recombinant
protein drug that is in the same class as an
existing biopharmaceutical but is not
identical; it is improved over the original.
Biobetters build on the success of existing,
approved biologics but are considered less of
a commercial risk than developing a brand
new class of biologic.
 One example is Centocor/J&J’s new anti-TNF
(tumor necrosis factor); the first was highly
immunogenic — their biobetter is humanized
to reduce this undesirable effect.

66.  Biosimilars are seen in some non-U.S. countries
as a “biologic generic.” They are intended to be
identical to the originator biologic drugs. But,
since they are manufactured using a new
process, they will have subtly different
structures and possibly different actions. For
these reasons, the United States is unlikely to
allow them as substitutes for originator biologics
without proof from expensive clinical trials. In
contrast, biobetters are not copies and will
never be considered generics. Biobetters are
new molecular entities that are related to
existing biologics by target or action, but they
are deliberately altered to improve disposition,
safety, efficacy, or manufacturing attributes.

67.  biobetters may be targeted to have improved
pharmacodynamics leading to less frequent
dosing or reduced side-effect profiles or may
have sustained or slow release formulations.

68.  Biobetters allow companies to target an
established mechanism, safety, and efficacy
profile but gain the benefit of the patent
protection and sales of a new molecular
entity. The development costs are the same
as developing a new biological product, but
the chances of successful registration are
significantly higher. This means the business
risk in developing a biobetter is significantly
reduced and the potential for return on
investment for a manufacturer is greatly
improved.

69.  1.USFDA:The mission of FDA's Center for Drug
Evaluation and Research (CDER) is to ensure that
drugs marketed in this country are safe and
effective
 CDER is the largest of FDA's six centers. It has
responsibility for both prescription and
nonprescription or over-the-counter (OTC) drugs
 ASME –BPE.
 ICH
 FFDCA(Federal Food, Drug, and Cosmetic Act)
regulatory section deals with medical device
 CMS –CENTRE FOR MEDICARE AND MEDICAID
SERVICES-havecontrols over genetic test and
diagnostic kids manufacturing.

70.  The Code of Federal Regulations (CFR) is a
codification of the general and permanent rules
published in the Federal Register by the
Executive departments and agencies of the
Federal Government.. Title 21 of the CFR is
reserved for rules of the Food and Drug
Administration. Each title (or volume) of the CFR
is revised once each calendar year. A revised
Title 21 is issued on approximately April 1st of
each year and is usually available here several
months later.
 Example : 21 CFR part 11 : contains the details
about electronic records and signatures

71.  EU provides information for companies and
individuals involved in developing and
marketing medicines for human use in the
European Union (EU).

72.  The International Conference on Harmonisation
of Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH) is unique
in bringing together the regulatory authorities
and pharmaceutical industry to discuss scientific
and technical aspects of drug registration. Since
its inception in 1990, ICH has gradually evolved,
to respond to the increasingly global face of drug
development, so that the benefits of
international harmonisation for better global
health can be realised worldwide. ICH's mission
is to achieve greater harmonisation to ensure
that safe, effective, and high quality medicines
are developed and registered in the most
resource-efficient manner.

74.  quality guidelines.(ICH Q1 to ICH Q12)
 Safety guidelines.(ICH S1 to ICH S11)
 Efficacy guidelines.(ICH E1 to ICH E18)
 Multidisciplinary quidelines.( ICH M1 to M8)

76.  ICH Q7 – GMP
 ICH Q2 – Analaytical validation
 ICH Q10- Pharmaceutical quality system.
 ICH S2-GENOTOXICITY STUDIES
 ICH S4-TOXICITY STUDIES
 ICH E6-Good clinical practice
 ICH E16- Qualification of genomic markers.

77.  Good Laboratory Practice (GLP) embodies a set
of principles that provides a framework within
which laboratory studies are planned,
performed, monitored, recorded, reported and
archived. These studies are undertaken to
generate data by which the hazards and risks to
users, consumers and third parties, including
the environment, can be assessed for
pharmaceuticals (only preclinical studies),
agrochemicals, cosmetics, food additives, feed
additives and contaminants, novel foods,
biocides, detergents etc.... GLP helps assure
regulatory authorities that the data submitted
are a true reflection of the results obtained
during the study and can therefore be relied
upon when making risk/safety assessments.

78.  Good Automated Manufacturing Practice
(GAMP) is both a technical subcommittee of
the International Society for Pharmaceutical
Engineering (ISPE) and a set of guidelines for
manufacturers and users of automated
systems in the pharmaceutical industry
 The Good Automated Manufacturing Practice
(GAMP) Guide for Validation of Automated
Systems in Pharmaceutical Manufacture
describes a set of principles and procedures
that help ensure that pharmaceutical
products have the required quality.

79. One of the core principles of GAMP is that
quality cannot be tested into a batch of
product but must be built into each stage of
the manufacturing process. As a result, GAMP
covers all aspects of production; from the
raw materials, facility and equipment to the
training and hygiene of staff. Standard
operating procedures (SOPs) are essential for
processes that can affect the quality of the
finished product.

83. Define Biotech industry????:
“we are into the business of
saving life….Mr. SS.Easwaran-(Former GM
of biozeen).

84.  Biozeen
 Biocon
 Lablink biotech
 Mr.Easwaran
 Dr. Prasad rao.
 To my father: KR.Sasidharan
 M/s.sultana.
 Thankyou one and all of you.you people played
a core role in my life. And will remain a long
lasting memory in my heart..i hope this slide will
help upcoming biotech students to learn and
know about certain basics in
biopharmaceuticals(obsolutely not all
concepts)..All the best students.

85. THANKyou.