USFDA Approval Process For Drug Products & Biological Product i.e NDA Vs. BLA
Comparison of NDA and BLA application process in USA. IND, NDA, ANDA & BLA dossier submission procedure.
MARKETING AUTHORISATION, LICENSING AND QUALITY ASSESSMENT OF VACCINES IN INDI...Swapnil Fernandes
- European pharmaceutical legislation provides a comprehensive framework for the marketing authorisation of vaccines.
- In contrast to the European scenario, the Indian scenario for vaccines is relatively less regulated and follows the same process of approval as other biologics in spite of having a National Handbook for Vaccine Policy.
- Vaccine authorisation in the US, as is the case in EU, is a more straightforward process than in most other markets as the USFDA has provided vaccines with a distinct set of regulations in concerned areas of safety and quality.
MARKETING AUTHORISATION, LICENSING AND QUALITY ASSESSMENT OF VACCINES IN INDI...Swapnil Fernandes
- European pharmaceutical legislation provides a comprehensive framework for the marketing authorisation of vaccines.
- In contrast to the European scenario, the Indian scenario for vaccines is relatively less regulated and follows the same process of approval as other biologics in spite of having a National Handbook for Vaccine Policy.
- Vaccine authorisation in the US, as is the case in EU, is a more straightforward process than in most other markets as the USFDA has provided vaccines with a distinct set of regulations in concerned areas of safety and quality.
Biosimilars
A biosimilar is a biological medicine highly similar to another already approved biological medicine (the 'reference medicine'). (A medicine whose active substance is made by a living organism.)
Biologicals
Biological medicines contain active substances from a biological source, such as living cells or organisms and are often produced by cutting-edge technology.
Biological medicinal product
Biological Medicinal Products, also known as biologics or biologicals, are medicinal products that are manufactured using biotechnology processes and derived from living organisms or their products. They can include vaccines, blood products, gene therapies, monoclonal antibodies, recombinant proteins, and other complex biological substances.
Biological Investigational Medicinal Product
Refer to biological products that are being investigated in clinical trials or research studies to evaluate their safety, efficacy, or pharmacokinetic properties. These products have not yet received marketing authorization and are still in the experimental phase.
In the European Union, A biological substance is referred as the active ingredient in biological products.
A "biological substance" is defined as "a substance that is produced by or extracted from a biological source
That requires a combination of physico-chemical-biological testing, along with the production process and its control, for its characterization and the determination of its quality.“
Examples: Immunologic medicines
Medicines derived from human blood and plasma
Medicines developed by means of recombinant DNA technology
Hybridoma and mAb methods
Advanced therapy medicinal products
The requirements of the EU centralized procedure.
The approval standards for biotechnology products are the same as for chemically synthesized medicines.
Both types of products must be safe and effective and have appropriate quality.
MAA for a biotechnology product must meet the standard dossier submission requirements
MAA must generally comply with the CTD format, including with respect to
Module I (administrative information, including labelling)
Module 2 (various summaries)
Module 3 (chemical, pharmaceutical, and biological information)
Module 4 (nonclinical reports)
Module 5 (clinical study reports)
The EU has approved the highest number of biosimilars worldwide, and consequently has the most extensive experience of their use and safety.
EMA has issued scientific guidelines to help developers conform to the strict regulatory requirements for approving biosimilars.
The guidelines have evolved to keep pace with rapid advances in biotechnology and analytical sciences, and they take on board increasing experience of clinical use.
All medicines produced using biotechnology and those for specific indications must be approved in the EU through EMA
Some biosimilars may be approved at national level, such as some low-molecular weight heparins derived from porcine intestinal mucosa.
Regulatory requirnment and approval procedure of drugs in japan pptsandeep bansal
this ppt is about all the rules and regulations of drugs in Japan.this ppt contains the PMDA structure, DMF data, IND and NDA procedure, cosmetic regulations, post marketing survelliance etc.
This presentation explains concepts of Patents and Market Exclusivity. This presentation is compiled from publicly available material on the world wide web.
Biosimilars
A biosimilar is a biological medicine highly similar to another already approved biological medicine (the 'reference medicine'). (A medicine whose active substance is made by a living organism.)
Biologicals
Biological medicines contain active substances from a biological source, such as living cells or organisms and are often produced by cutting-edge technology.
Biological medicinal product
Biological Medicinal Products, also known as biologics or biologicals, are medicinal products that are manufactured using biotechnology processes and derived from living organisms or their products. They can include vaccines, blood products, gene therapies, monoclonal antibodies, recombinant proteins, and other complex biological substances.
Biological Investigational Medicinal Product
Refer to biological products that are being investigated in clinical trials or research studies to evaluate their safety, efficacy, or pharmacokinetic properties. These products have not yet received marketing authorization and are still in the experimental phase.
In the European Union, A biological substance is referred as the active ingredient in biological products.
A "biological substance" is defined as "a substance that is produced by or extracted from a biological source
That requires a combination of physico-chemical-biological testing, along with the production process and its control, for its characterization and the determination of its quality.“
Examples: Immunologic medicines
Medicines derived from human blood and plasma
Medicines developed by means of recombinant DNA technology
Hybridoma and mAb methods
Advanced therapy medicinal products
The requirements of the EU centralized procedure.
The approval standards for biotechnology products are the same as for chemically synthesized medicines.
Both types of products must be safe and effective and have appropriate quality.
MAA for a biotechnology product must meet the standard dossier submission requirements
MAA must generally comply with the CTD format, including with respect to
Module I (administrative information, including labelling)
Module 2 (various summaries)
Module 3 (chemical, pharmaceutical, and biological information)
Module 4 (nonclinical reports)
Module 5 (clinical study reports)
The EU has approved the highest number of biosimilars worldwide, and consequently has the most extensive experience of their use and safety.
EMA has issued scientific guidelines to help developers conform to the strict regulatory requirements for approving biosimilars.
The guidelines have evolved to keep pace with rapid advances in biotechnology and analytical sciences, and they take on board increasing experience of clinical use.
All medicines produced using biotechnology and those for specific indications must be approved in the EU through EMA
Some biosimilars may be approved at national level, such as some low-molecular weight heparins derived from porcine intestinal mucosa.
Regulatory requirnment and approval procedure of drugs in japan pptsandeep bansal
this ppt is about all the rules and regulations of drugs in Japan.this ppt contains the PMDA structure, DMF data, IND and NDA procedure, cosmetic regulations, post marketing survelliance etc.
This presentation explains concepts of Patents and Market Exclusivity. This presentation is compiled from publicly available material on the world wide web.
Protein and peptide drug delivery systemSagar Savale
Protein and Peptide drug delivery system are the Novel drug Delivery System. Proteins and peptides are the most abundant components of biological cells. They exist functioning such as
enzymes, hormones, structural element and immunoglobulin. The distinction between peptides and proteins is having a peptide contains less than 20 amino acids, having a molecular weight less, while a protein possesses 50 or more amino acids and its molecular weight lies above this value. The most of pharmaceutical proteins and peptides are absorbed IM, IV and Subcutaneous route of Absorption, but the oral route is more convenient for absorption of protein as compared to other. Various problems associated with administration of protein and peptide drugs are needed to overcome by different pharmaceutical approaches. Several approaches available for
maximizing pharmacokinetic and pharmacodynamics properties are chemical modification,
formulation vehicles, mucoadhesive polymeric system, use of enzyme inhibitors, absorption
enhancers, penetration enhancers etc.
Liposomes are concentric bilayered vesicles in which an aqueous core is entirely enclosed by a membranous lipid bilayer mainly composed of natural or synthetic phospholipids.
Liposomes are spherical microscopic vesicles consisting phospholipids bilayers which enclose aqueous compartments.
The size of a liposome ranges from some 20 nm up to several micrometers.
Liposomes were first produced in England in 1961 by Alec D. Bangham, who was studying phospholipids and blood clotting.
Small unilamellar vesicles (SUV), 25 to 100 nm in size that consist of a single bilayer
Large unilamellar vesicle (LUV), 100 to 500 nm in size that consist of a single bilayer
Multilamellar vesicle (MLV), 200 nm to several microns, that consist of two or more concentric bilayer
IPhVC recommendations & monitoring requirement of biosimilars, Worldwide & Iraq control of Bioproducts & biosimiliars, as well as references enlisted adverse reactions to common products used in our hospital
Lecture presented at the 31st Jan 2024 in our hospital
CDSCO Biologicals - Rules, Regulations, Guidelines and Standards for Regulato...Mohamed Fazil M
M. Pharmacy - Pharmaceutical Regulatory Affairs (MRA)
1st Semester - Regulations and Legislation for Biologics (MRA 104T)
Unit 2 - Rules, Regulations, Guidelines and Standards for Regulatory Filing of Biologicals
CDSCO Biologicals
The regulation of medicines in AustraliaTGA Australia
View this presentation for information on:
*the different categories of medicines
* registered (higher risk) medicines and how they are regulated
* listed (lower risk) medicines and how they are regulated
* accessing unauthorised medicines
* medicines advertising
* changing medicine technologies
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
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Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
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A Strategic Approach: GenAI in EducationPeter Windle
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This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
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Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
1. USFDA Approval Process
For
Drug Products & Biological Product
[NDA Vs. BLA]
By:
•
Girish A. Swami, (M.Pharm, PGDIPR, PGDDRA)
•
Mob.: +91-9881492626
•
Email- pr.girish@gmail.com
2. Outline
•
•
•
•
•
•
Overview of USFDA Framework
Biological Products
How are Biologics different?
Therapeutic Biologicals - Examples
Biologics in CBER or CDER
Regulation for Drugs & Biologics
–
–
–
–
–
–
Comparison to drugs
Inspection Team
Overview & Review Process
NDA and BLA (Similarities and Differences)
NDA/BLA Dossier content
BLA Post-approval requirement
3. Overview of Regulatory Framework
- USFDA
Introduction:
• The FDA is part of the Health and Human
services Department of the US Government.
• The FDA’s authority is based upon various laws
and statutory documents.
• The Food and Drug Administration (FDA) has
responsibility for regulation of drugs and
Biological products which are manufactured and
/ or sold in the US.
4. Organizational Structure
The FDA divided into following main Divisions or Centers.
Center for Drug Evaluation and Research (CDER)
Center for Biological Evaluation and Research (CBER)
Center for Devices and Radiological Health (CDRH)
Center for Veterinary Medicine (CVM)
Office of Regulatory Affairs (ORA)
Center for Food Safety and Applied Nutrition (CFSAN)
National Center for Toxicological Research (NCTR)
Center for Tobacco Products (CTP)
6. Center for Drug Evaluation and Research
(CDER)
The CDER is responsible for the
regulation of Chemically – derived and
most therapeutic Biological products,
both New Drugs and Generics.
7. Center for Biologics Evaluation and Research
(CBER)
The Mission of CBER is to protect and
enhance
public
health
through
the
regulation of certain therapeutic Biological
Products as well as Blood Products,
Vaccines, Tissue and Gene Therapy
Products.
8. Center for Devices and Radiological Health
(CDRH)
The
CDRH
regulation
of
is
responsible
Medical
for
Devices
Radiation Emitting products
the
and
9. Center for Veterinary Medicine
(CVM)
The
CVM
regulation
is
of
responsible
Animal
Medicinal Products
or
for
the
Veterinary
10. Office of Regulatory Affairs
(ORA)
The ORA is the lead office for all field activities of the FDA. The
duties and functions of ORA are divided between four main offices:
•
Resource Management
•
Regional Operation
•
Criminal Investigations
•
Enforcement.
ORA regions are the Pacific, Southwest, Central, Southeast and
Northeast regions of the US. Each region supports a number of local
FDA offices.
11. Office of Combination Products
(OCP)
The OCP is responsible for general oversight of the agency’s
regulation of combination products. The primary responsibilities for
regulating specific combination products remain in one of the
product centers – CDER, CBER, CDRH.
The OCP also oversees multi center reviews of combination
products,
ensures
consistent
and
appropriate
post-approval
regulation of combination products, and resolves disputes relating to
combination products.
12. Biological Product
(Biologic / Biologics / Biological)
Biological Product – a “Virus, Therapeutic
Serum, Toxin, Antitoxin, Vaccine, Blood, Blood
Component or Derivative, Allergenic product, or
Analogous product, applicable to the Prevention,
Treatment or Cure of a Disease or Condition of
human beings.”
- As per Section 351 PHS Act
13. Biologics vs. Drugs
Biologic products generally more complex
• Many innovative products.
– Virtually every new biologic is a novel product (NME)
• Demonstration of product comparability is more
difficult.
• Changes in manufacturing and scale-up can impede
(obstruct) overall approval process.
14.
15.
16. Biologics - Unique Aspects !
Source material for biologics
– Potential for transmission of adventitious agents
– Bacteria, mycoplasma, fungi, viruses, TSE agents
– Need for in-process controls, validation process validation
Heat Sensitive & susceptible to microbial contamination
– Controlled temperature during production
– Aseptic processing throughout
– Cannot terminally sterilize
Formulations
– Majority Parenteral
– Issues with concentration, Multi-use vials
17. Pharmacokinetics
– Not well established
– May not be able to measure
Potential Immunogenicity
– Desirable in vaccine strategies
– Unwanted effects in other settings (single or
chronic-dosing)
• Altered PK
• Allergic, serum-sickness reactions
• Cross reactivity to normal, essential protein
– Limitations of non-clinical studies
• Species-specific antibody development
19. Monoclonal Antibodies and related products
– Anti-EGFR (Cetuximab, Panitumumab)
– Anti-Alpha4 integrin (Natalizumab)
Fusion proteins
– TNFR linked to Fc portion of human IgG
(Etanercept)
Fab Fragments
– Anti-VEGF (Ranibizumab)
– Anti-TNFα (certolizumab pegol)
20. Oncology
– Herceptin (trastuzumab) breast cancer, ushers in new area of
highly targeted therapy
– Rituxan (rituximab) targets some lymphomas
– Zevalin (ibritumomab tiuxetan), monoclonal antibody targeted
radiotherapy
– Campath (alemtuzumab) for CML (Chronic Myeloid Leukaemia)
– Avastin (Bavacuzimab Bavacuzimab) first line metastatic
colorectal Cancer
21. CBER or CDER
An applicant must determine which division of
the FDA to submit its application, as the Center
for Biologics Evaluation and Research (CBER)
and the Center for Drug Evaluation and
Research (CDER) share responsibility for BLAs.
22. Products Regulates by CBER
•
Allergenics
Patch tests used to diagnose the causes of contact dermatitis. Extracts used to diagnose and treat rhinitis
("hay fever"), allergic sinusitis and conjunctivitis, and bee stings.
•
Blood
Blood and blood components used for transfusion, such as red blood cells, plasma, and platelets.e.g
Immunoglobuilns.
•
Devices
Medical devices and tests used to safeguard blood, blood components, and cellular products from HIV,
hepatitis, syphilis, and other infectious agents. Machines and related software used to collect blood and
blood components.
•
Gene Therapy
Gene therapy products that replace a person's faulty or missing genetic material.
•
Human Tissues and Cellular Products
Human tissues for transplantation, such as skin, tendons, ligaments, and cartilage. Cellular products, such
as human stem cells and pancreatic islets.
•
Vaccines
Vaccines used for the prevention of infectious diseases, such as mumps, measles, chicken pox,
diphtheria, tetanus, influenza, hepatitis, smallpox, and anthrax.
•
Xenotransplantation Products
Xenotransplantation products use nonhuman tissues or organs into human recipients to treat human
diseases such as liver failure, where human materials are not always available.
23. Products Regulates by CDER
Therapeutic Biological Products Transferred to CDER
•
Monoclonal antibodies for in vivo use.
•
Proteins intended for therapeutic use, including cytokines (e.g. interferons),
enzymes (e.g. thrombolytics), and other novel proteins, This category includes
therapeutic proteins derived from plants, animals, or microorganisms, and
recombinant versions of these products.
•
Immunomodulators (non-vaccine and non-allergenic products intended to treat
disease by inhibiting or modifying a pre-existing immune response).
•
Growth factors, cytokines, and monoclonal antibodies intended to mobilize,
stimulate, decrease or otherwise alter the production of hematopoietic cells in
vivo.
24. About Combination Products
Combination products are therapeutic and diagnostic products that
combine drugs, devices, and/or biological products. Combination
products involve components that would normally be regulated
under different types of regulatory authorities, and frequently by
different FDA Centers like CBER, CDER & CDRH.
(i.e.,Drug/Device, Biologic/Device, Drug/Biologic, or Drug/Device/Biologic)
Examples:
– Orthopedic implant with growth factors,
– Prefilled syringes
– Metered dose inhalers
– Transdermal patches
– Catheter with antimicrobial coating
27. Law or Act.
Drug Products fall under the Food, Drug
and Cosmetic Act.
While
Biological Products fall under the Food,
Drug and Cosmetic act,
& Public
Health Service Act.
28. Generic Equivalence
Generics : Abbreviated New Drug Application (ANDA)
A generic drug product is one that is comparable to an innovator
drug product in Dosage form, Strength, Route of administration,
Quality, Performance characteristics and Intended Use.
While
Follow-on Biologic or Biosimilar
A follow-on biologic is similar but not identical to the brandname, or
innovator, product made by the pharmaceutical or biotechnology
industry; biosimilar is the term used in the European Union.
29. Establishment Standards
General Information –
(i) Product, personnel, equipment, waste and air flow
(ii) Illustration or indication of which areas are served by each air handling unit
(iii) Air pressure differentials between adjacent areas.
Water System –
(i) General description of W/S
(ii) Validation summary
(iii) Routine w/s monitoring program.
HVAC System – (Heating, Ventilation and Air Conditioning Systems),
(i) General description
(ii) Validation summary
(iii) Routine monitoring program.
Computer Systems – The application should contain information on computer
systems which control critical manufacturing processes.
Contamination/Cross Contamination Issues – The application should contain the
following information regarding methods to prevent contamination and cross
contamination to supplement information requested in the CMC
(i) Cleaning procedures and validation
(ii) Containment features.
31. USFDA Biologics Team
The FDA team biologics was established in 1997
to assure the quality and safety of Biological
Products.
It consists of a core team of,
1.
Certified ORA investigators,
2.
CBER certified inspectors, and
3.
Specially trained compliance officers representing both ORA and
CBER
35. NDA and BLA - Similarities
There are many similarities
– Regulations
– Guidance documents
– PDUFA
36. NDA and BLA - Similarities
Specific Similarities Include
• IND regulations, Fast Track designation, Special
Protocol Assessment (SPA)
• Financial Disclosure, CTD format
• Labeling and Advertising (21CFR 201-202)
• Pediatric study requirements and waivers
• Accelerated Approval
• Orphan Exclusivity
37. Most differences are due to
Type of Product
Not due to which
FDA Center Regulates The Product
38. Unique to NDAs
• Patent Exclusivity (Generics, 505b2, & Orange Book)
• Pediatric Exclusivity (written requests)
• NDA Field Copies
• Regulations more detailed (NDA content; Filing criteria etc.)
39. Unique to BLAs
U.S. License
• Product and facility must meet “Product standards” prior to license issuance
• Review includes
–
–
–
–
•
Application review
Facility inspection (Pre-approval, review members participate)
Method validation (complete)
Compliance check
Cooperative manufacturing arrangements permitted
– Divided, Shared, Contract
FDA “official” release (21 CFR 610.2) of each product lot
(at discretion of FDA)
Container & Pkg. Label Requirements
Specific information will be required depending on the type of BLA
(e.g., Blood, Vaccines).
40. NDA & BLA Application
NDA and BLA are applications to market a new
product. NDAs are used by CDER (center for
drugs) and BLAs are used by CBER (center for
biologics)
– The BLA requires close scrutiny of the
and facilities, because of the greater
products.
manufacturing process
variability of biological
– The application will include complete reports on all studies
including patient listings, analysis according to the original
statistical analysis protocol (SAP) as well as any exploratory
analysis.
41. – Although there is no regulatory mechanism in the U.S. to approve a
generic version of a product that is marketed under a BLA, it is
possible that a generic version of a biotech product that has been
approved under an NDA could be approved.
– This confusing situation results because some biotech products are
approved under NDAs while others are approved under BLAs.
– Review and approval of an NDA or BLA are based on the
demonstration of safety and efficacy assessed from detailed reports
of the clinical trials; particularly randomized controlled studies.
– Biological products are a subset of drugs; therefore both are
regulated under provisions of the FDC Act. However, only
biological products are licensed under section 351 of the PHS Act.
(As previously noted, some therapeutic protein products are
approved under section 505 of the FDC Act, not under the PHS
Act.)
– Among other things, safety and purity assessments must consider
the storage and testing of cell substrates that are often used to
manufacture biologics. A potency assay is required due to the
complexity and heterogeneity of biologics.
42. Law
Regulation (21 CFR)
IND
FD & C Act
25, 50, 211, 312
BLA
FD & C Act. &
PHS Act.
25, 201-2, 207, 211, 600
NDA
FD & C Act.
25, 201-2, 207, 211, 314
Post BLA
FD & C Act. &
PHS Act.
201-2, 211, 600
FD & C Act.
PDUFA
25, 201-2, 207, 211, 314
POST NDA
________
Same
Same
Where,
CFR
– Code of Federal Regulations
PDUFA – Prescription Drug User Fee Act.
IND
– Investigational New Drug Application
BLA
– Biologics License Applications
NDA
– New Drug Application
PART 25 Environmental Impact Considerations
PART 50 Protection of Human Subjects
PART 201 Labeling
PART 211 Current Good Manufacturing Practice for Finished Pharmaceuticals
PART 312 Investigational New Drug Application
PART 207 Registration of producers of Drugs and listing of Drugs in Commercial Distribution
PART 600 Biological Products: General
PART 314 Applications for FDA approval to market a New Drug
43. 21 CFR PART 600
BIOLOGICAL PRODUCTS: GENERAL
Licensed biological products regulated by the Center
for Biologics Evaluation and Research (CBER)
Examples of such submissions include: Biologics
license applications (BLAs) and their amendments and
supplements, adverse experience reports, biological
product deviation reports, fatality reports, and other
correspondence.
45. 21 CFR Part 610
GENERAL BIOLOGICAL : PRODUCT STANDARDS
•
Release
– 610.1– lot release (manufacturer)
– 610.2– Samples for “Official” FDA testing and release
•
Testing
–
–
–
–
–
Potency
General Safety
Sterility
Purity (including moisture)
Mycoplasma
•
Dating Periods
•
Labeling
46. 21 CFR PART 314
Applications for FDA approval to market a New Drug
Scope of this part.
(a) This part sets forth procedures and requirements for the submission
to, and the review by, the Food and Drug Administration of
applications and abbreviated applications to market a new drug
under section 505 of the Federal Food, Drug, and Cosmetic Act, as
well as amendments, supplements, and postmarketing reports to
them.
(b) This part does not apply to drug products subject to licensing by
FDA under the Public Health Service Act (58 Stat. 632 as amended
(42 U.S.C. 201et seq. ) and subchapter F of chapter I of title 21 of
the Code of Federal Regulations.
Ref: 50 FR 7493, Feb. 22, 1985, as amended at 57 FR 17981, Apr. 28, 1992; 64 FR 401, Jan. 5, 1999
47. Current Laws
Public Health Service Act (1944)
– Section 351 - Licensure of biological establishments
and products.
FFD&C Act (1938, 1962)
– Interprets that “biological products” are also “drugs”
– The FFD&C Act. applies to a biological product,
except no application required under section 505.
48. PHS Act
The Secretary shall approve a biologics license application:
– On the basis of a demonstration that
• Product is safe, pure and potent
• The facility (ies) meet standards designed to assure that it
continues to be safe, pure, and potent
– If the applicant consents to the inspection of the facility(ies)
– Each package of biological product must bear the U.S. license
number
49. Product Standards
CFR Standards for Biologics include:
(p) “Safety” means the relative freedom from harmful effect to persons
affected, directly or indirectly, by a product when prudently administered,
taking into consideration the character of the product in relation to the
condition of the recipient at the time.
(r) “Purity” means relative freedom from extraneous matter in the finished
product, whether or not harmful to the recipient or deleterious to the
product. Purity includes but is not limited to relative freedom from residual
moisture or other volatile substances and pyrogenic substances.
(s) “Potency” is interpreted to mean the specific ability or capacity of the
product, as indicated by appropriate laboratory tests or by adequately
controlled clinical data obtained through the administration of the product in
the manner intended, to effect a given result.
- 21 CFR 600.3 and Part 610
50. ‘Approval Letter’
“This letter hereby issues Department of Health and Human
Services U.S. License No. XXXX to ___________ in accordance
with the provisions of Section 351(a) of the Public Health
Service
Act
controlling
the
manufacture
and
sale
of
biological products. This license authorizes you to introduce
or deliver for introduction into interstate commerce, those
products for which your company has demonstrated compliance
with establishment and product standards.”
51. BLA / NDA
Dossier Content
•
•
•
•
•
•
•
•
A copy of the cover letter attached to the archival copy
A completed application Form FDA 356h
A copy of the summary
A copy of the general index of the entire application
A letters of reference or authorization, if appropriate
Patent Information
Manufacturer Information
Product/Manufacturing Information (CMC)
–
–
–
–
–
–
•
•
•
Source material / raw material
Manufacturing process and controls
Formulation
Facility information
Contamination / cross-contamination information
Environment assessment or categorical exclusion
Pre-clinical Studies
Clinical Studies
Labeling
52. Application Forms
FDA 356h – Application to Market a New or Abbreviated new drug or biologic
for Human Use
FDA-3356 – Establishment Registration and listing for Human cells, Tissues,
And Cellular and Tissue based products (HCT/Ps)
FDA-3486 – Biological Product deviation report
Vaers form – Vaccine Adverse Event Reporting System
53. Patent Information
An applicant must submit information on each patent that
claims the drug or a method of using the drug that is the
subject of the BLA and with respect to which a claim of
patent infringement could reasonably be asserted.
An applicant must submit basic information about each patent,
including the following:
(i) Patent number and the date on which the patent will expire;
(ii) Type of patent;
(iii) Name of patent owner;
(iv) If the patent owner or applicant does not reside or have a place
of business within the U.S., the name of the agent of the patent
owner or applicant who resides or maintains a place of business
within the U.S. authorized to receive notice of patent certification.
54. Labeling
Label should include:
(i) The proper name of the product;
(ii) The name, address and license number of the manufacturer;
(iii) The US License number must appear on the product labeling.
(iv) The expiration date;
(v) The recommended individual dose, for multiple dose containers;
(vi) The statement “Rx only” for prescription Biologicals; and
(vii) Minimum potency of product expressed in terms of official
standard of potency or, if potency is a factor and no U.S.
standard of potency has been prescribed, the word “No U.S.
standard of potency”
55. Biologic License Application
(BLA)
Under the Public Health Services Act, the Federal Food and Drug
Administration (FDA) has been given the authority, concurrent with
its authority under the Food Drug and Cosmetic Act, to regulate
biologics. The FDA regulates a wide range of biologics, including,
but not limited to, vaccines, blood and blood by-products, certain
monoclonal antibodies, tissue and cellular products.
Within the FDA, the Center for Biologics, as well as the Center for
Drug Evaluation and Research, can be responsible for the
regulation of biologics.
56. – Biologics are evaluated for market by the FDA through the filing of a
Biologic License Application (BLA).
– A BLA, although similar to a New Drug Application (NDA), has its own
set of intricate requirements.
– Applicant has to provided the information in an acceptable format,
under the applicable regulations. However, applicants must be
cognizant that unique and specific information will be required
depending on the type of BLA (e.g., blood, vaccines).
57. Archival and Review Copies of
BLA
Federal regulations require the submission of two
copies of a BLA – Archival and Review.
Archival Copy
The archival copy is a complete copy of an application
submission and must be bound in a BLUE cover jacket.
The archival copy should include a cover letter to:
(i) confirm any agreements or understandings between the FDA and the
applicant;
(ii) identify a contact person regarding the application;
(iii) identify the reviewing division of the FDA and the HFD number; and
(iv) convey any other important information about the application.
58. Review Copy
The review copy is divided into six technical sections (“review
sections”) and should be submitted with each review section
separately bound in a specific color:
(i) Chemistry, Manufacturing and Controls (CMC) – RED;
(ii) Nonclinical Pharmacology and Toxicology – YELLOW;
(iii) Human Pharmacokinetics and Bioavailability – ORANGE;
(iv) Microbiology (if required) – WHITE;
(v) Clinical Data – LIGHT BROWN;
(vi) Statistical – GREEN.
eCTD format starting no later than two years after the
publication of the final guidance in the Federal Register,
and final guidance is likely to enforce in mid-to-late 2015
59. BLA
Post-Approval Requirements
• Required Annual Reports:
– Post Marketing Commitment (PMC) status (601.70)
• Other required submissions:
– Adverse Events (600.80)
– Distribution summary (600.81)
– Biologic Deviation Reports (600.14)
– Advertising and Promotional Labeling
• Periodic cGMP inspections
60. Changes to be Reported
(21CFR 601.12)
Manufacturing Changes
– Pre- Approval Supplements (PAS)
– 30 day Supplements (CBE30)
– Annual Reports - only if reportable changes
Labeling Changes
– Pre Approval Supplements
– Changes Being Effected (CBE) Supplements
– Annual Reports - only if reportable changes
61. Thank You
------ O -----GIRISH A. SWAMI
Asst. Manager – DRA & DQA
Serum Institute of India Ltd.