Investigational New Drug Application Process (IND) - As a Tool for Drug Discovery

Pratik Dash*, Satyajit Behera and Dillip Kumar Mohapatra

Department of P.A. and Q.A., Gayatri College of Pharmacy, Gayatri Vihar, Jamadarpali, Sambalpur. India

INTRODUCTION:

The investigational new drug application is the result of a successful preclinical development programme. The IND is also the vehicle through which a sponsor advances to the next stage of drug development known as clinical trials (Human trials). After a successful preclinical developmental stage of drug. Sponsor focuses on collecting the data and information on limited human studies^{1, 2}.

OBJECTIVE:

Ø To focus FDA’s attention during early phase of clinical research on assuring the safety of human test subjects.

Ø To provide sponsors with a greater measure of flexibility in conducting Phase-1 trial.

Ø To facilitate consultation between FDA and sponsors, especially after there is an indication that the new drug is safe and efficacious in humans.

METHODOLOGY:

Generalization of IND approval process

For decades, the regulation and control of new drugs in the United States has been based on the New Drug application (NDA). Since 1938, every new drug has been the subject of an approved NDA before U.S. commercialization. The data gathered during the animal studies and human clinical trials of an Investigational New Drug (IND) become part of the NDA. The NDA has evolved considerably during its history. When the Food, Drug and Cosmetic Act (FD&C Act) was passed in 1938. NDAs were only required to contain information pertaining to the investigational drug’s safety. The NDA was again the subject of change in 1985. When the FDA completed a comprehensive revision of the regulations pertaining to NDAs. While this revision commonly called the NDA Rewrite, modified content requirements, it was mainly intended to restructure the ways in which information and data are organized and presented in the NDA to expedite FDA reviews^{3, 4}.

FUNDAMENTALS OF NDA Submission^5-8

As outlined in Forms FDA-356h. Application to Market a New Drug for Human Use or As an Antibiotic Drug for Human Use. NDAs can consist of as many as 15 different sections.

Ø Index

Ø Summary

Ø Chemistry, Manufacturing, and Control

Ø Samples, Methods Validation Package, and Labeling

Ø Nonclinical Pharmacology and Toxicology

Ø Human Pharmacokinetics and Bioavailability

Ø Microbiology (for anti-microbial drugs only)

Ø Clinical Data

Ø Safety Update Report (typically submitted 120 days after NDA’s submission)

Ø Statistical

Ø Case Report Tabulations

Ø Case Report Forms

Ø Patent Information

Ø Patent Certification and

Ø Other information

NDA CONTENT AND FORMAT REQUIREMENTS^{9, 10}

Although the exact requirements are a function of the nature of a specific drug, the NDA must provide all relevant data and information that a sponsor has collected during the products research and development. The FDA has numerous guidelines that relate to NDA content and format issues. These guide lines can be obtained from CDER’s Drug Information Branch (DIB).

NDA CLASSIFICATIONS

CDER classifies new drug applications with a code that reflects both the type of drug bring submitted and it’s intended uses. The numbers 1 through 7 are used to describe the type of drug^{17, 18}.

Ø New Molecular Entity

Ø New Salt of Previously Approved Drug (not a new molecular entity)

Ø New Formulation of Previously Approved Drug (not a new salt OR a new molecular entity)

Ø New Combination of Two or More Drugs

Ø Already Marketed Drug Product – Duplication (i.e., new manufacturer)

Ø New indication (claim) for Already Marketed Drug (includes switch in marketing status from prescription to OTC)

Ø Already Marketed Drug Product – No Previously Approved NDA.

GENERAL REQUIREMENTS

Ø The new (present) NDA regulations require that an application be submitted in two copies.

Ø An archival copy that serves as a permanent record of the submission are.

Ø A review copy is made up of a number of separate technical volumes each tailored to the needs of the disciplines involved in the review.

Ø Both the archival and review copies are submitted in hard copy the regulations permit an application to submit the archival copy as microfiche.

ANDA (ABBREVIATED NEW DRUG APLLICATION)

Ø An applicant may manufacture and market the generic drug product to provide a safe effective, low cost alternative to the American public.

Ø A generic drug product is one that is comparable to an innovator drug product

Ø 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.

Ø Instead, generic applicants must scientifically demonstrate that their product is bioequivalent.

GENERIC DRUG

Ø Generic drug is a copy that is the same as a brand-name of drug in dosage, safety, administration, purpose and performance.

GENERIC DRUG REQUIREMENT

Ø Affordable price

Ø Equivalent to branded drugs in all aspects, but with less cost

Ø Reduce health-care costs for consumers

Ø Lower spending by insurance companies and employers

Ø Bring drug price competition and benefit consumers.

GENERIC DRUG EXPENSES

Ø No huge development costs that were initially incurred by innovators

Ø No extensive safety/efficacy testing required (animal, clinical studies etc. already established and proved in market.

Ø All initial costs on research, development, marketing, promotion were already made by innovators.

GENERIC DRUG V/S BRANDED DRUG

Ø Contain same active ingredient

Ø Are identical in strength, dosage from and route of administration

Ø Have the same indications, dosing and labeling

Ø Are bioequivalent

Ø Meet the same batch-to-batch requirements for strength, purity and quality

Ø Are manufactured under the same strict GMP regulations as the branded drugs

Ø Undergo review, scrutiny and inspection by US FDA with same stringent standard as the branded counter-parts.

HATCH-WAXMAN ACT 1984¹⁵

Ø One of the most successful legislations ever passed

Ø Mother of generic drug industry

Ø Created the regulatory framework for timely entry of generic drugs

Ø Opened up generic drug business

RESULTS AND DISCUSSION:

The investigational new drug application is the result of a successful preclinical development programme. NDAs were only required to contain information pertaining to the investigational drug’s safety. 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.

CONCLUSION:

Hence it is high time that new drug application as well as its derivatives is becoming advanced with the development of science and technology.

REFERENCES:

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2. Indian Council of medical Research (ICMR), New Delhi, 2000, Ethical Guidelines for Biomedical Research on human subjects, 11-68.

3. Indian Council of medical research (ICMR), New Delhi, 1994, Guidelines on responsibility for clinical trials of contraceptives conducted in India, 12-15.

4. Indian Journal of Pharmacology, 1998, 24-27.

5. A handbook of Federal Drug Law, 1996, 7-9.

6. ICH Guidelines for Good Clinical Practice, 1997.

7. Bankowski Z., Howard- Jones, N.Eds. Human Experimentation and Medical Ethic, Council for International Organization of Medical sciences, 1982, 135.

8. Simon R., Optimal two-stage designs for Phase-II Clinical Trial, 1989, 10, 1-10.

9. Good Clinical Practice: www.altavista.com.

10. Clinical Trials, www.scirus.com.

11. Ethics in Clinical Research, www.pharmacology. indiaserver.com.

12. Good Clinical Practice, www.elsevier.com.

13. Clinical Quest, Vol-I, No.6, July 2003, www.catalystc linicalservices.com.

14. Clark Kathie "DIA Update: News from the FDA". The eCTD summit. June 30, 2009,468.

15. Strom Shannon "IND in eCTD Format: Considerations". The eCTD summit. January 25, 2010, 664.

16. Krieger Lisa M. "Study Targets Stalemate over Medicinal Use of Marijuana “San Jose Mercury News, July 19, 1998.

17. Troetel W.M. Achieving a Successful US IND Filing (1) The Regulatory Affairs Journal 6, January 1995, 22-28.

18. Troetel W.M.: Achieving a Successful US IND Filing (2) The Regulatory Affairs Journal 6, February 1995, 104-108.

Received on 26.01.2010

Accepted on 12.02.2010

Research J. Science and Tech. 2(3): May –June. 2010: 47-50