REGULATORY REQUIREMENTS FOR THE PRODUCT

APPROVAL OF BIOLOGICS

Presented By,
Tanuja yadav
M.pharmacy
Drug Regulatory Affairs
 CONTENTS
 INTRODUCTION
 SOURCES AND TYPES OF BIOLOGICS
 DIFFERENCES BETWEEN BIOLOGICS AND CHEMICAL DRUGS
 REGULATORY AUTHORITY FOR BIOLOGICS
 DEVELOPMENT AND APPROVAL PROCESS
 BIOLOGICAL LICENSE APPLICATION (BLA)
 COMPARISON BETWEEN US AND EUROPIAN GUIDELINES
REGARDING BIOLOGICS
 CONCLUSION
 REFERENCES

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 INTRODUCTION
• WHAT ARE BIOLOGICS?
Biologics are the products manufactured, extracted from or semi synthesized from a
biological source which are regulated by FDA and are used to prevent cure and treat diseases and
medical conditions.
These are generally large, complex molecules produced through biotechnology in a living
system such as a microorganism, plant cell or animal cell.
 These could be made of sugars, proteins, nucleic acids or complex combinations of these
substances or may be living entities.
These are complex mixtures that are not easily identifiable and charcterized these tend to be
heat sensitive and susceptible to microbial contamination hence, it is necessary to use aspetic
principles from intial manufacturing process.
EXAMPLES: Botox, Herceptin, Vaccines, Enbrel

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 SOURCES AND TYPES OF BIOLOGICS

SOURCES TYPES
 Mammalian cell culture  Blood derivatives
 Bacteria  Vaccines
 Insect cell culture  Allergenic extracts
 Plant cell culture  Whole blood
 Yeast  Blood components
 Transgenics  Proteins
 Avian cell culture  Human tissues
 Humans  Cellular and gene therapies
 Xenotransplantation products

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DIFFERENCES BETWEEN BIOLOGICS AND CHEMICAL
DRUGS
PROPERTIES BIOLOGICS CHEMICAL DRUGS

SIZE Large Small

STRUCTURE Complex Simple

STABILITY Unstable Stable

MODIFICATION Many options Well defined

MANUFACTURING Impossible to ensure identical Identical copy can be made

copy

CHARCTERIZATION Impossible to charcterize Easy to charcterize

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 REGULATORY AUTHORITY FOR BIOLOGICS
 Center for biologics evalution and research (CBER) is the center within FDA that
regulates biological products for human use under applicable Federal laws including the
Public Health Services Act (PHS) and the Federal, Food, Drug and Cosmetics Act
 CBER protects and advances the public health by ensuring that biological products are
safe and effective.
 FDA's regulatory authority for the approval of biologics resides in (PHS) Act. Biologics
are subjected to regulation under Federal, Food, Drug And Cosmetics act (FD&C) Act.
 Some medical devices which are used to produce biologics are regulated by CBER
under FD&C Act's medical device amendments of 1976.
 FDA also reviews new biological products and new indications and usage for already
approved products on the market for the treatment of known diseases.
 It protects against threats of emerging infectious diseases.
 It provides the public with information to promote safe and appropriate use.
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 DEVELOPMENT AND APPROVAL PROCESS
 Advertising and Labeling
 Investigational New Drug Application (IND) or Device exemption process (IDE)
 Expanded Access
 Premarket Approval (PMA)
 Biologics License Application (BLA)
 New Drug Application Process (NDA)
 Biologics Approvals By Year

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 BIOLOGICS LICENSE APPLICATION (BLA)
 The Biologics License Application (BLA) is a request for permission introduce or deliver
for introduction a Biologic product into the market
 It is mainly regulated by 21 CFR 600-800. It is submitted by any legal person or entity
who engaged in manufacture or an applicant for a license who takes responsibilty for
compliance with product and establishment of standards.
 A Biologic License application generally applies to vaccines and other Allergenic drug
products and cellular and genetic therapies.
 Form 356h specifies the requirements for a BLA . It mainly includes the following:
1. Applicant information
2. Product / manufacturing information
3. Pre clinical studies
4. Labelling

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BIOLOGIC LICENSE
APPLICATION (BLA)
Applicants must submit the
form356h to the CBER and Await
for the review of FDA.
FDA receives the BLA and reviews
it if the manufacturers produce
inappropriate information then it
issues a letter called Refuse To File
(RTF) .
If FDA approves the BLA they will
issue a approval letter which
authorizes the manufacturer to
distribute the product.
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 UNITED STATES EUROPE

REGULATORY BODY Food And Administration (FDA) European Medicines Evaluation

FDA adopted the S6 Guidance Agency (EMEA)
CHMP has adopted ICH S6 guideline

APPROVAL STANDARD Biological Lisence Application Marketing Authorization Application

(BLA) (MAA)

PRECLINICAL STUDIES
Chimpanzee Rodent and Non Rodent species
SPECIES SELECTION
Elicit immune response Sponser should measure ADA'S
IMMUNOGENICITY
STUDY DESIGN Pharmacodynamic studies Pharmacokinetic and
Pharmacodynamic studies

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CARCINOGENICITY Inappropriate
REPRODUCTIVE AND
DEVELOPMENTAL TOXICITY May or May not be recommended
CLINICAL STUDIES Involves 3 phases(Phase I,II,III)
It must have IND in effect
Begins only when FDA approves it
Inappropriate
Fertility studies,Embryo -Fetal
development,Pre and Postnatal
development studies (PPND)
Must comply with GCP as described
in E6 Guideline which the CHMP
has adopted

PHASE I Frequently involve administration to Initial Safety, and Tolerability,PK

patients rather than healthy and PD activity
volunteers
Done for maximum tolerated dose ,
Product's metabolism,
Pharmacology,and safety at high
doses
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PHASE II Evalution of Safety and Short term Safety and Efficacy
Adverse Events

PHASE III Begin If preliminary Evidence of Therapautic confirmatory studies and

effectiveness is shown during Phase Explore the Dose Response
II Relationships

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 Conclusion

 The study introduces the legal and regulatory aspects pertaining to biologics in the united
states and european union.
 The Drug approvals in the US, Europe are the most demanding in the world .
 The main objective of the rules governing medicinal products in US , Europe is to safe
guard the public health
 It is the role of regulatory authorities to ensure that pharmaceutical companies shall
comply with regulations mentioned above .

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 REFERENCES

www.fda.gov
www.fda.gov/biologicsbloodvaccines/develepomentapprovalprocess.
www.fdagroup-com.cdn.ampproject.org.
https://www.cov.com>files>
https://www. ema.europa.eu/

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