Introduction

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

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

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 documentation required in an NDA is supposed to tell the drug's whole story, including what happened during the clinical tests, what the ingredients of the drug are, the results of the animal studies, how the drug behaves in the body, and how it is manufactured, processed and packaged. 

Introduction

New FDCs for approval for Marketing:1) One or more of the active ingredients is a Drug2) Active drug is approved individually but are combined for first time.3)FDCs which are already marketed , but in which it is proposed either to

change the ratio of active ingredients or to make a new therapeutic claim.

4)FDCs include those whose active ingredients have been widely used in particular indications for years their concomitant use is often necessary and no claim is proposed to be made other than convenience

Guidance Documents for NDAs

Guidance documents represent the Agency's current thinking on a particular subject.

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.  

Guidance Documents for NDAs

They also establish policies intended to achieve consistency in the Agency's regulatory approach and establish inspection and enforcement procedures.  Because guidances are not regulations or laws, they are not enforceable, either through administrative actions or through the courts.

  An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both.

The goals of the NDA are to provide enough information to permit FDA reviewer to reach the following key decisions:

Whether the drug is safe and effective in its proposed uses, and whether the benefits of the drug outweigh the risks.

Whether the drug's proposed labeling (package insert) is appropriate, and what it should contain.

Whether the methods used in manufacturing the drug and the controls used to maintain the drug's quality are adequate to preserve the drug's identity, strength, quality, and purity.

Goals of the NDA

Data required to be submitted with application for permission to market a New Drug:

1)IntroductionBrief introduction of the drug and the therapeutic class it belongs.

2) Chemical and Pharmaceutical information. Information of active ingredients eg; Generic name , INN. Physiochemical Data eg; Chemical name , structure , emperical

Formula , mol wt.Physical properties eg; Solubility , Rotation, Partition coefficient, Dissociation constant.

Analytiacal data eg;Elemental Analysis,Mass,NMR,IR,UV spectra,Polymorphic identification.

Complete Monograph Specification including eg; quantification of impurities ,Enantiomeric purity,Assay.

Dosage form and its composition. Specification of active and inactive ingredients. Outline of the method of the manufacture of the active ingredient. Stability Data.

Animal pharmacologySummarySpecific pharmacological actions.General pharmacological actions.Follow up and Supplemental safety pharmacological studiespharmaacokinetics: absorption,distribution,metabolism,excretion.

Animal ToxicologyGenral aspectsSystemic toxicity studiesMale fertility studiesfemale Reproduction and developmental studieslocal toxicityAllergenicity/Hyper sensitivityGenotoxicityCarcinogenicity

Data required to be submitted with application for permission to market a New Drug:

Human/Clinical pharmacology (Phase I)SummarySpecific Pharmacological effects.General Phamacological effectsPharmacokinetics,absorption,distribution,metabolism,excretionPharmacodynamics/early measurement of drug activity

Therapeutic exploratory trials (Phase II)SummaryStudy reports

Data required to be submitted with application for permission to market a New Drug:

Therapeutic confirmatory trials (Phase III)SummaryIndividual study reports with listing of sites and Investigators.

Special studiesSummaryBio-availability/Bio-equivalenceOther Studies eg; geriatrics,paediatrics,pregnant or nursing woman

Regulatory status in other countriesCountries where the drug ismarketedApprovedApproved as INDWithdrawn if any with reasons.Restrictions on use,if any,in countries where marketed.Free sale certificate or certificate of analysis,as appropriate.

Refernces

www.geradts.com www.law.duke.edu/journals/journalsource Regulations of Clinical Trials by Rakesh

Kumar Rishi,1st ed.