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 contains a new molecular entity (NME - an active ingredient that contains no active moiety that has been previously approved by the agency in an application submitted under section 505 of the act 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 of NDA is for a new dosage form of an active ingredient that has been approved or marketed in the US 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 was used for a drug product that duplicates a drug product that has already been approved or marketed in the US by the same applicant, except that it is intended for a new indication or a claim. This was used prior to July 27, 2009, and now this has been 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: This NDA is for a new indication or claim. The drug will not be marketed under this 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: This NDA is for a new indication or claim for a drug, with the intention to market the drug under this NDA after approval.
It is for a drug product that is the duplicate of a drug product that is the subject of either an approved or pending NDA and the applicant intends to market this drug duct under the separate Type 10 NDA after approval. This type is normally for a drug product that has a new indication or claim, and it may have labeling and/or a proprietary name that is distinct 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 apply for an NDA to market the drug in the US.
They must include all the data from preclinical to clinical trials. After an NDA is received the FDA has 60 days to file the NDA so as to review it. If FDA files the NDA, then the FDA will review the data thoroughly and make decisions on to approve or reject it.
Developers must also include:
Proposed Labeling
Safety Updates
Drug Abuse Information
Patent Information
Any data from the studies that may have been conducted outside US
IRB compliance Information
Directions for use
NDA must be organized in CTD (Common Technical Document) format, which is the standard format for submitting regulatory information to respective health authorities. eCTD (Electronic Common Technical Document) is regarded as the fastest delivery method to move the new drug application process along between the sponsor and FDA.
Pre-NDA Submission
This is the period before applying for an NDA. To get to NDA, 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 a drug product has gained FDA approval for marketing in the US, that's when the post NDA phase starts. In this phase we get to know more about the drug as it is being exposed to a variety of populations compared to the clinical study done. It consists of post marketing surveillance, reporting of adverse events, label updates and risk management plans.
Components Of An NDA
A cover letter that summarizes the NDA and provides an overview of the information contained 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.
Statistical analysis results of the clinical trial data, including information about the statistical significance of the results.
Drug information, including the drug’s composition, manufacturing processes, and proposed labeling.
Manufacturing information, including the facilities and processes used to manufacture the drug.
Patent information, including the status of patents covering the new drug, the claims made in the patents, licensing agreements, and information on any related litigation.
Institutional Review Board (IRB) compliance information, including information on clinical trial protocols, ethical approvals, patient safety, and monitoring procedures.
Directions for use, including details on the recommended dose, administration, storage, handling, and labeling of the new drug.
Regulatory correspondence between the drug manufacturer and the FDA, including requests for additional information or clarification.
References cited in the NDA, including 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 manufacturing the drug and the controls used to maintain its quality are adequate 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 gives the sponsor 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.
How long does a new drug application approval take?
After filing for an NDA and once it is accepted, the approval typically takes no later than 10 months and 6 months for priority drugs, respectively.
Which form of FDA is used for new drug application field reports?
Form FDA 3331 is used to submit a field alert report (FARs) for CDER or CBER regulated drug products approved under a new drug application (NDA) or abbreviated new drug application (ANDA).
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