Journal of Pharmacovigilance and Pharmacotherapeutics (ISSN: 2688-6464)

Article / review article

"Pathway for Marketing Authorization Approval of Drug Product in US"

Balamuralidhara V*, Abhishek BV, Nagendra SR

               Department of Pharmaceutics, JSS College of Pharmacy, JSS University, India

 *Corresponding author: Balamuralidhara V, Department of Pharmaceutics, JSS College of Pharmacy, JSS University, Mysore- 570 015, Karnataka, India. Tel:  +918971917777; Email: baligowda@gmail.com

 Received Date: 6 July, 2017; Accepted Date: 19 July, 2017; Published Date:  24 July, 2017

1.                   Abstract

 Developing a promising drug molecule is the main aim of the pharmaceutical company and it   takes approximately fifteen years to develop one new medicine from the earliest stages of discovery to the time it is available for treating patients. To fasten the process in bringing products to market, product development activities should be conducted in accordance with the related regulatory requirements. These requirements assist in manufacture a product that meets the regulatory standards of targeted authority. Even though information on the regulatory requirements (e.g. laws, guidance documents, international standards) for healthcare product development is readily accessible, navigating the regulatory system is not simple, and it gets even more complex when dealing with multiple authorities. To aid the drug manufacturers and to simplify the regulatory understanding that governs the product development and ensures regulatory compliance. It can be used as a starting point to assist in developing the product. Rather than serving as a compilation of regulations, the guide discusses the fundamental concepts and principles in regulatory affairs. It gives entrepreneurs a road map to follow.

 2.                   Keywords: Drug Development; Marketing Authorization; Road map; Regulations; Regulatory requirement; USFDA

1.                   Introduction

 Developing a promising drug molecule is the main aim of the pharmaceutical company and it   takes approximately fifteen years to develop one new medicine from the earliest stages of discovery to the time it is available for treating patients. To fasten the process in bringing products to market, product development activities should be conducted in accordance with the related regulatory requirements. These requirements assist in manufacture products that meet the regulatory standards of targeted authority. In order to control and regulate medicinal products, Drug regulatory authorities are being established in various countries across the globe. The regulatory body ensures in various legal and regulatory aspects of a drug.

 Regulatory authorities are in charge for enforcing the rules and regulations issuing the guidelines to regulate the drug development process, licensing, registration, manufacturing, marketing and labeling of pharmaceutical products. They also responsible to ensure safety, efficacy and quality of drugs and also provide drug information available to the public Even though information on the regulatory requirements (e.g. laws, guidance documents, international standards) for healthcare product development is readily accessible, navigating the regulatory system is not simple, and it gets even more complex when dealing with multiple authorities.

 

 In order to fasten the process of bringing the product into the market, there is a need to know where the regulatory information (Acts / Regulations / Guidance) are located on the regulatory websites. This can be obtained by the help of a “Navigation pathway” to get a regulatory approval from a targeted authority and to market the drug products that are safe and effective to provide healthcare to individuals around the world.

Steps in the Product development life cycle

Step 1: Classify the healthcare product

Step 2: Identify the healthcare claim and/or product label

Step 3: Step 3: Determine the healthcare market

Step 4: Develop the regulatory strategy

Step 5: Establish the product development plan

Step 6: Execute the product development plan

Step 7: Execute the clinical plan

Step 7a: Prepare for a pre-submission meeting to support the CTA

Step 8: Collect the data for regulatory submission

Step 8a: Prepare for a pre-submission meeting to support licensing application

Step 9: Collate the data for regulatory submission

Step 10:  Ensure post-marketing surveillance

Advantages of Navigation Pathway

Ø     Providing an applicant / regulatory expert on the website with the most descriptive path to application / regulatory information is one of the easiest ways to ensure they don't get confused while preparing a regulatory application / dossier.  

Ø     If websites are to attract application/application services, they need easy browsing experience, and then the path of navigation of the website will be the main factor in the website design and development process.

Ø     The navigation pathway not only benefits the applicant but also benefits the agency stakeholders, i.e. industry and agency.

2.                   Discussion

2.1    United States of America Factsheets

Introduction

The IND is the means through which the sponsor technically obtains this exemption from the FDA. The sponsor's primary goal is to determine if the product is reasonably safe for initial use in humans, and if the compound exhibits pharmacological activity that justifies commercial development.

Resources for Ind Submissions

The following resources include the legal requirements of an IND application, assistance from CDER to help you meet those requirements, and internal IND review principles, policies and procedures.

Guidance Documents for IND

These documents are prepared for FDA review staff and applicants/sponsors to provide guidelines to the processing, content, and evaluation/approval of applications and also to the design, production, manufacturing, and testing of regulated products.

Laws, Regulations, Policies and Procedures

The Federal Food, Drug, and Cosmetic Act is the basic food and drug law of the U.S. With numerous amendments, it is the most extensive law of its kind in the world.  The law is intended to assure consumers that foods are pure and wholesome, safe to eat, and produced under sanitary conditions; that drugs and devices are safe and effective for their intended uses; that cosmetics are safe and made from appropriate ingredients; and that all labelling and packaging is truthful, informative, and not deceptive.

Code of Federal Regulations (CFR)

The FDA's portion of the CFR interprets The Federal Food, Drug, and Cosmetic Act and related statutes. The CFR is divided into 50 titles that represent broad areas subject to Federal regulations. The following regulations apply to the IND application process:

CDER's Manual of Policies and Procedures (Ma PPs)

These documents are approved instructions for internal practices and procedures followed by CDER staff to help standardize the new drug review process and other activities

Introduction

The NDA application is the vehicle through which drug sponsors formally propose that the FDA approve a new pharmaceutical for sale and marketing in the U.S. 

The data gathered during the animal studies and human clinical trials of an Investigational New Drug (IND) become part of the NDA.

Resources for Ind Submissions

The following resources are provided in the website for understand the legal requirements of a new drug application, assistance from CDER to meet those requirements, and internal NDA review principles, policies and procedures.

Guidance Documents for NDAs:

These documents are prepared for FDA review staff and applicants/sponsors to provide guidelines to the processing, content, and evaluation/approval of applications and also to the design, production, manufacturing, and testing of regulated products.

Laws, Regulations, Policies and Procedures:

The Federal Food, Drug, and Cosmetic Act is the basic food and drug law of the U.S. With numerous amendments, it is the most extensive law of its kind in the world.  The law is intended to assure consumers that foods are pure and wholesome, safe to eat, and produced under sanitary conditions; that drugs and devices are safe and effective for their intended uses; that cosmetics are safe and made from appropriate ingredients; and that all labelling and packaging is truthful, informative, and not deceptive.

CDER's Manual of Policies and Procedures (MaPPs):

These documents are approved instructions for internal practices and procedures followed by CDER staff to help standardize the new drug review process and other activities. 

Prescription Drug User Fee Act (PDUFA):

This legislation includes authorization for FDA to continue to collect three types of user fees from applicants who submit certain new drug applications.

NDA Forms and Electronic Submissions:

This section provides information on various application forms required for submission of NDA application.

Advisory Committees:

Advisory committees provide independent advice and recommendations to the FDA on scientific and technical matters related to the development and evaluation of products regulated by the Agency.  CDER requests advice from advisory committees on a variety of matters, including various aspects of clinical investigations and applications for marketing approval of drug products. 

Guidance Documents-NDA

Introduction

An Abbreviated New Drug Application (ANDA) contains data which when submitted to FDA's Centre for Drug Evaluation and Research, Office of Generic Drugs, provides for the review and ultimate approval of a generic drug product. All approved products, both innovator and generic, are listed in FDA's Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) 

Generic drug applications are termed "abbreviated" because they are generally not required to include preclinical (animal) and clinical (human) data to establish safety and effectiveness. Using bioequivalence as the basis for approving generic copies of drug products was established by the "Drug Price Competition and Patent Term Restoration Act of 1984," also known as the Waxman-Hatch Act

Resources For And a Submissions

The following resources have been gathered to provide you with the legal requirements of an ANDA application, assistance from CDER to help you meet those requirements, and internal ANDA review principles, policies and procedures.

Guidance Documents for ANDAs:

These documents are prepared for FDA review staff and applicants/sponsors to provide guidelines to the processing, content, and evaluation/approval of applications and also to the design, production, manufacturing, and testing of regulated products.

Laws, Regulations, Policies and Procedures:

The Federal Food, Drug, And Cosmetic Act is the basic food and drug law of the U.S. With numerous amendments, it is the most extensive law of its kind in the world.  The law is intended to assure consumers that foods are pure and wholesome, safe to eat, and produced under sanitary conditions; that drugs and devices are safe and effective for their intended uses; that cosmetics are safe and made from appropriate ingredients; and that all labelling and packaging is truthful, informative, and not deceptive.

CDER's Manual of Policies and Procedures (MaPPs):

These documents are approved instructions for internal practices and procedures followed by CDER staff to help standardize the drug review process and other activities. 

ANDA Forms and Electronic Submissions:

This section provides information on various application forms required for submission of ANDA application


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Figure-3



Figure-4



Figure-5



Figure-6



Figure-7

Chemicals: IND-US

Regulatory Factsheet

Product

Drugs

Country

USA

Type of Application

IND

Life Cycle Phase

R&D

Regulatory Department

Department of Health and Human Services

Regulatory Agency

US Food and Drug Administration(FDA)

Division

Center for Drug Evaluation & Research (CDER)

Regulatory Classification

Chemicals

Table-1

 

Sl No.

CFR Part

Type of Application

1

21CFR Part 312

Investigational New Drug Application

2

21CFR Part 314

INDA and NDA Applications for FDA Approval to Market a New Drug (New Drug Approval)

3

21CFR Part 58

Good Lab Practice for Nonclinical Laboratory [Animal] Studies

Table-2

 

Guidance Documents - Ind

Sl No

Title

Issued Date

1

Safety Reporting Requirements for INDs (Investigational New Drug Applications) and BA/BE (Bioavailability/Bioequivalence) Studies Safety Reporting Requirements for INDs (Investigational New Drug Applications) and BA/BE (Bioavailability/Bioequivalence) Studies 

12/19/12

2

Current Good Manufacturing Practice for Phase 1 Investigational Drugs

07/14/08

3

Exploratory IND Studies

01/12/06

4

Content and Format of INDs for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-Derived Products. Questions and Answers

10/01/00

5

Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs - General Considerations

03/17/14

6

IND Exemptions for Studies of Lawfully Marketed Drug or Biological Products for the Treatment of Cancer 

01/15/04

7

Drug Master Files: Guidelines

09/01/89

8

FDA IND, NDA, ANDA, or Drug Master File Binders

 

9

Immunotoxicological Evaluation of Investigational New Drugs

10/01/02

10

Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well-Characterized, Therapeutic, Biotechnology-derived Products

11/01/95

11

Safety Assessment for IND Safety Reporting Guidance for Industry

12/16/15

 

 

Table-3

 

Checklist

http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/InvestigationalNewDrugINDApplication/UCM368873.pdf [2]

Reference Link

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/InvestigationalNewDrugINDApplication/default.htm [3]

Table-4

 

 

Chemicals: NDA-US

Regulatory Factsheet

Product

Drugs

Country

USA

Type of Application

NDA

Lifecycle Phase

R&D

Regulatory Department

Department of Health and Human Services

Regulatory Agency

US Food & Drugs Administration (FDA)

Division

Center for Drug Evaluation & Research (CDER)

Regulatory Classification

Drugs

Table-5

 

Sl No

Title

Issued Date

01

Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs - General Considerations

03/17/14

02

Changes to an Approved NDA or ANDA 

04/01/04

03

Changes to an Approved NDA or ANDA: Questions and Answers

01/01/01

04

Container Closure Systems for Packaging Human Drugs and Biologics

05/01/99

05

Format and Content of the Microbiology Section of an Application

01/01/90

06

Format and Content of the Clinical and Statistical Sections of an Application

07/01/88

07

Summary for New Drug and Antibiotic Applications--Format and Content of the Summary for New Drug and Antibiotic Applications

02/01/87

08

Formatting, Assembling and Submitting New Drug and Antibiotic Applications

02/01/87

09

Guideline for Submitting Supporting Documentation in Drug Applications for the Manufacture of Drug Products

 

10

NDAs: Impurities in Drug Substances 

02/01/87

11

Format and Content of the Human Pharmacokinetics and Bioavailability Section of an Application 

02/01/87

12

Format and Content of the Nonclinical Pharmacology/Toxicology Section of an Application

02/01/87

13

Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products

 

14

Drug Master Files: Guidelines

09/01/89

15

FDA IND, NDA, ANDA, or Drug Master File Binders

 

16

PET Drug Applications - Content and Format for NDAs and ANDAs_2011

08/31/11

Table-6

 

Check List

http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/UCM315023.pdf [5]

Table-7

 

Reference Link Quality Accreditation

Type of Certificate

URL website

GMP

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=211

GLP

http://www.accessdata.fda.gov/SCRIPTs/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=58&showFR=1

 

GCP

http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/GuidancesInformationSheetsandNotices/ucm219433.htm

Reference Link

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/NewDrugApplicationNDA/default.ht [6]

Table-8

 

Chemicals: ANDA-US

Regulatory Factsheet

Product

Drugs

Country

USA

Type of Application

ANDA

Lifecycle Phase

MAA

Regulatory Department

Department of Health and Human Services

Regulatory Agency

US Food & Drugs Administration (FDA)

Division

Center for Drug Evaluation & Research (CDER)

Regulatory Classification

Chemicals

Table-9

 

Sl No

Title

Issued Date

01

Microbiological Data for Systemic Antibacterial Drug Products - Development, Analysis, and Presentation

08/25/16

02

ANDA Submissions - Refuse to Receive for Lack of Justification of Impurity Limits

08/24/16

03

 Regulatory Classification of Pharmaceutical Co-Crystals

08/16/16

04

Ulcerative Colitis: Clinical Trial Endpoints Guidance for Industry 

08/05/16

05

Insanitary Conditions at Compounding Facilities Guidance for Industry 

08/03/16

06

E2C(R2) Periodic Benefit-Risk Evaluation Report (PBRER)

07/18/16

07

E2C(R2) Periodic Benefit-Risk Evaluation Report - Questions and Answers

07/18/16

08

Bacterial Vaginosis: Developing Drugs for Treatment Guidance for Industry

07/13/16

09

Updating ANDA Labeling After the Marketing Application for the Reference Listed Drug Has Been Withdrawn Guidance for Industry

07/08/16

10

Compounded Drug Products That Are Essentially Copies of a Commercially Available Drug Product Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance for Industry

07/07/16

11

Compounded Drug Products That Are Essentially Copies of Approved Drug Products Under Section 503B of the Federal Food, Drug, and Cosmetic Act Guidance for Industry

07/07/16

12

Elemental Impurities in Drug Products 

06/30/16

13

Vulvovaginal Candidiasis: Developing Drugs for Treatment

06/30/16

14

Recurrent Herpes Labials: Developing Drugs for Treatment and Prevention

06/30/16

15

Technical Specifications Document: "Quality Metrics Technical Conformance Guide, Version 1.0“ has published

06/24/16

16

Quality Attribute Considerations for Chewable Tablets Guidance for Industry

06/16/16

17

Osteoporosis: Nonclinical Evaluation of Drugs Intended for Treatment Guidance for Industry

06/13/16

18

Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance for Industry

06/09/16

19

Interim Policy on Compounding Using Bulk Drug Substances Under Section 503B of the Federal Food, Drug, and Cosmetic Ac

06/09/16

20

Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic Act Guidance

06/09/16

21

Charging for Investigational Drugs Under an IND - Qs & As 

06/02/16

22

Expanded Access to Investigational Drugs for Treatment Use - Qs & As

06/02/16

23

Individual Patient Expanded Access Applications: Form FDA 3926

06/02/16

24

E18 Genomic Sampling and Management of Genomic Data

06/02/16

25

Assessing Adhesion with Transdermal Delivery Systems and Topical Patches for ANDAs Draft Guidance for Industry

05/31/16

26

Chronic Obstructive Pulmonary Disease: Developing Drugs for Treatment 

05/19/16

27

Use of Electronic Health Record Data in Clinical Investigations Guidance for Industry

05/16/16

Table-10

 

Citation: Balamuralidhara V, Abhishek BV, Nagendra SR (2017) Pathway for Marketing Authorization Approval of Drug Product in US. J Pharmacovigil Pharm Ther: JPPT-117. DOI: 10.29011/JPPT-117. 100117