NDA plays a very crucial role in the drug approval process. The regulation and control of new drugs in the United States has been based on this New Drug Application for decades. Since 1938, every new drug has been the subject of an approved NDA before U.S. commercialization.
Now, let's look at the key aspects of NDA, covering its definition, types, and the approval process that drives pharmaceutical progress.
What Is New Drug Application(NDA Meaning)?
New Drug Application is a vehicle through which the drug sponsors formally propose to the FDA for the approval of a new pharmaceutical for sale or market in the US. The data that is gathered during the pre-clinical and clinical trials of the IND (Investigational New Drug) will become part of NDA.
Types Of NDA In Pharma
Types of NDA or NDA classification code are mainly of 10 types.
Type 1: New Molecular Entity
Type 1 is for a drug product that has a new molecular entity ( A NME - an active ingredient which has no active moiety which was previously approved by the agency in an application submitted or marketed previously as a drug in the US).
Type 2: New Active Ingredient
Type 2 is for drug products that contain new active ingredients but not NME. (The active ingredient which is approved or marketed priorly in the US, but their ester, salt or noncovalent derivative of the unmodified parent molecule has not been approved or marketed in US)
Type 3: New Dosage Form
This type 3 of NDA is for the new dosage form of an active ingredient. Note that the active pharmaceutical ingredient has been approved or marketed in the US priorly by the same applicant or another applicant but in a different dosage form.
Type 4: New Combination
Type 4 NDA is for new drug-drug combinations of two or more active ingredients.
Type 5: New Formulation or Other Differences
A Type 5 NDA is for a product that differs from an already approved or marketed product in the U.S., but not because of a new dosage form. For e.g. new indication, new manufacturer, new applicant.
Type 6: New Indication or Claim, Same Applicant
This Type 6 of NDA was used for a drug product that duplicates a drug product which has been approved/ marketed in the US by the same applicant, an exception is that it is intended for a new indication or claim. This was used before July 27, 2009, and now replaced with Type 7 and Type 9.
Type 7: Previously Marketed but without an approved NDA
This type of NDA is for a drug product that contains an active moiety that has not been previously approved in an application but has been marketed in the US.
Type 8: Rx to OTC
This NDA form is for a drug product intended for OTC (over the counter) that contains an active ingredient that has been approved or marketed previously in the US only for dispensing with a prescription.
Type 9: New Indication or Claim, Drug not to be Marketed Under Type 9 NDA After Approval
A Type 9 NDA is for a new indication or claim for a drug already under review in another NDA. The applicant does not plan to market the drug under the Type 9 NDA after approval.
Type 10: New Indication or Claim, Drug to be Marketed Under Type 10 NDA After Approval
Type 10 NDA is intended for a drug product that is the duplicate of a drug product which is the subject of either an approved or pending NDA and the applicant aims to market the drug product pursuant to this separate Type 10 NDA after approval. This type is normally for a drug product that has a new indication or a new claim, and it may have labeling and/or a proprietary name that is different from the original NDA.
Process Of New Drug Application Submission
For an FDA NDA submission, after the Phase 3 trials, if the investigator/ drug developer has gathered enough evidence that the drug is safe and effective for its intended use, the company can choose for an application for an NDA so as to market the drug in the US.
They must include all the data from preclinical to clinical trials. After the receipt of an NDA, the FDA has 60 days to file the NDA to review it. If the FDA files the application, then the FDA assess the data thoroughly and makes appropriate decisions on to approve or reject it.
Developers must also include:
Proposed Labeling
Safety Updates
Drug Abuse Information
Patent Information
Data from the studies that have been conducted out of the US
IRB compliance Information
Directions for use
NDA must be organized in Common Technical Document (CTD) format, the standard format for submitting regulatory information to respective health authorities. Electronic Common Technical Document (eCTD) is considered as the fastest method to move the new drug application process along between the sponsor and FDA.
Pre-NDA Submission
It is the phase before applying for an NDA. To get an NDA Approval, one must make sure that the drug product is safe, efficacious, of quality and the benefit of the product outweighs the risk. This can be determined only by conducting clinical trials.
Post NDA Submission
When the FDA approves a drug product for marketing in the US, that's when the post NDA phase begins. In this phase we get to know more about the drug as it is being exposed to a wide variety of population in comparison to the clinical study done. It involves post marketing surveillance, reporting of adverse events, label updates and risk management plans.
Components Of An NDA
Meeting the clinical trial standards.
A cover letter summarizing the NDA and gives an overview of the information in the submission.
Administrative information about the sponsor of the drug, along with the company name, address, and contact information.
Pre-clinical study, laboratory and clinical study results.
Results of the Statistical analysis of the clinical trial data, along with the information about the statistical significance of these results.
Drug information, which must also include the drug’s composition, manufacturing processes, and proposed labeling.
Manufacturing information, facilities and processes utilized to manufacture the drug.
Patent information, including the patent status covering the new drug, the claims made in the patents, licensing agreements, and information about any related litigation.
Information on Institutional Review Board (IRB) compliance, information on clinical trial protocols, ethical approvals, safety of the patients, and monitoring procedures.
Directions for use, as well as the details on recommended dose, administration, storage, handling, and labeling of new drug.
Regulatory compliance between the drug manufacturer and the FDA, inclusive of the requests for additional information/ clarification.
References cited in the NDA, which also includes articles, reports, and other information sources.
Challenges For An NDA Submission
Some common NDA challenges are:
Meeting clinical trial standards.
Compliance with the standard guidelines kept forward to conduct a clinical trial.
Meeting these standards can be difficult, particularly for smaller pharmaceutical companies without extensive experience in clinical trial management.
Extensive documentation of all the data generated starting from pre-clinical and even before, if necessary.
Manufacturing of the drug in compliance with FDA regulations and provide documentation on the drug's manufacturing process, including information on raw materials, equipment, manufacturing procedures and quality control measures.
Benefits Of New Drug Application
New Drug Application is important because it gives all the relevant information for the FDA so as to decide whether:
The drug is safe and effective in its proposed use.
The benefit of the drug outweighs the risk and make sure it does.
Proposed labelling (Packaging Insert) of the drug is appropriate and describes the ingredients of the drug.
The methods used in drug manufacturing and the controls or standards used to maintain its quality are enough to preserve its identity, strength, quality and purity.
FAQs About FDA New Drug Application:
What happens if an NDA application is rejected?
If a new drug application is rejected by the FDA, they send the applicant a complete response letter (CRL) describing the reason for its decision of rejection. CDER provides the sponsor with a chance to meet with agency officials. The sponsor can ask for a hearing, correct any deficiencies, submit a new application or withdraw the application.
What are the components of a new drug application?
It is discussed under the heading, components of NDA.
What does the FDA require in a new drug application?
It is discussed under the heading, components of NDA.
How much time will it take for the approval of an NDA?
After the filing and acceptance of an NDA, the approval time typically takes no later than 10 months and 6 months for priority drugs, respectively.
Which FDA form is used for new drug application field reports?
Form FDA 3331 is used for submission of field alert reports (FARs) for CDER or CBER regulated drug products that are approved under a new drug application (NDA) or abbreviated new drug application (ANDA).
Comentários