Abbreviated New Drug Application (ANDA)

This presentation gives a complete brief idea of how FDA regulates the marketing of Generic drugs. An application has to be filled out for the approval of marketing generic drugs. ANDA form has to be filled and submitted for this purpose.

1. Abbreviated New Drug Application (ANDA) Presentation by: S. Raghavigneshwari Roll.no: 19 Clinical Research Programs, Gujarat University

2. Contents What is an Abbreviated New Drug Application? What are generic drugs? Why does a generic drug look different from the brand drug? Why do generic medicines often cost less than the brand-name medicines? Abbreviated New Drug Application (ANDA) Forms and Submission Requirements Content and format of an ANDA Form. ANDA Regulatory Review Process Clinical Research Programs, Gujarat University

3. What is an Abbreviated New Drug Application? An Abbreviated New Drug Application (ANDA) is a written request to the U.S. Food and Drug Administration (FDA) to manufacture and market a “ generic drug” in the United States. Abbreviated New Drug Applications are “abbreviated” since they do not require the applicant to conduct clinical trials and require less information than a  New Drug Application . Once approved, an applicant may manufacture and market the generic drug product to provide a safe, effective, lower cost alternative to the brand-name drug it references. Clinical Research Programs, Gujarat University

4. What are generic drugs? A generic drug is a medication created to be the same as an already marketed brand-name drug in dosage form, safety, strength, route of administration, quality, performance characteristics, and intended use. These similarities help to demonstrate bioequivalence, which means that  a generic medicine works in the same way and provides the same clinical benefit as the brand-name medicine.  In other words, you can take a generic medicine as an equal substitute for its brand-name counterpart. Clinical Research Programs, Gujarat University

5. It is important to note that there will always be a slight, but not medically significant, level of expected variability—just as there is for one batch of brand-name medicine compared with the next batch of brand-name product. This variability can and does occur during manufacturing, for both brand-name and generic medicines. When a medicine, generic or brand-name, is mass produced, very small variations in purity, size, strength, and other parameters are permitted. FDA limits how much variability is acceptable . Clinical Research Programs, Gujarat University

6. Why does a generic drug look different from the brand drug? Trademark laws in the United States do not allow a generic drug to look exactly like other drugs already on the market . Generic medicines and brand-name medicines share the same active ingredient, but other characteristics, such as colors and flavorings, that do not affect the performance, safety, or effectiveness of the generic medicine, may be different. Generic drugs are approved only after a rigorous review by FDA and after a set period of time that the brand product has been on the market exclusively. This is because new drugs, like other new products, are usually protected by patents that prohibit others from making and selling copies of the same drug.  Clinical Research Programs, Gujarat University

7. Why do generic medicines often cost less than the brand-name medicines? Generic drugs tend to cost less than their brand-name counterparts because generic drug applicants do not have to repeat animal and clinical (human) studies that were required of the brand-name medicines to demonstrate safety and effectiveness. This abbreviated pathway is why the application is called an “ abbreviated  new drug application.” When multiple generic companies are approved to market a single product, more competition exists in the marketplace, which typically results in lower prices for patients. Clinical Research Programs, Gujarat University

8. When multiple generic companies are approved to market a single product, more competition exists in the marketplace, which typically results in lower prices for patients. Bringing more drug competition to the market and addressing the high cost of medicines is one of FDA’s top priorities. In 2017, FDA announced the Drug Competition Action Plan (DCAP) to further encourage robust and timely market competition for generic drugs and help bring greater efficiency and transparency to the generic drug review process, without sacrificing the scientific rigor underlying our generic drug program. Clinical Research Programs, Gujarat University

9. NDA vs ANDA Review Process Nda Requirements Chemistry Manufacturing Controls Labelling Testing Animal studies Clinical studies Bioavailability Anda requirements Chemistry Manufacturing Controls Labelling Testing 6. Bioequivalence

10. All approved products, both innovator and generic, are listed in FDA's  Approved Drug Products with Therapeutic Equivalence Evaluations   ( Orange Book ) . One way applicants demonstrate that a generic product performs in the same way as the innovator drug is to measure the time it takes the generic drug to reach the bloodstream in healthy volunteers. This demonstration of “bioequivalence” gives the rate of absorption, or bioavailability, of the generic drug, which can then be compared to that of the innovator drug. To be approved by FDA, the generic version must deliver the same amount of active ingredients into a patient's bloodstream in the same amount of time as the innovator drug.   Clinical Research Programs, Gujarat University

11. The " Drug Price Competition and Patent Term Restoration Act of 1984 ," also known as the Hatch-Waxman Amendments, established bioequivalence as the basis for approving generic copies of drug products. These Amendments permit FDA to approve applications to market generic versions of brand-name drugs without repeating costly and duplicative clinical trials to establish safety and efficacy. Clinical Research Programs, Gujarat University

12. Abbreviated New Drug Application (ANDA) Forms and Submission Requirements The ANDA is submitted to FDA's Center for Drug Evaluation and Research, Office of Generic Drugs , which provides for the review and ultimate approval of a generic drug product. In order to submit a complete ANDA, applicants should review the following forms and prepare all that are required for your specific application: Filing Review of ANDAs Manual of Policies and Procedures including filing checklist. Form FDA-356h: Application to Market a New Drug, Biologic, or Antibiotic Drug for Human Use. Instructions for using Form FDA-356h. Clinical Research Programs, Gujarat University

13. 4. Instructions for Completing Form FDA 3794 (Generic Drug user fee cover sheet) 5. Form FDA-3674: Certification of Compliance (instructions in- cluded ). 6. Drug Master Files (DMFs) Requesting a Pre-Assigned ANDA Number Applicants may request a pre-assigned ANDA number ONLY when submitting a new ANDA. If you are converting an established ANDA to eCTD (electronic- Common Technical Document), you must use the original ANDA application number. The eCTD is the standard format for electronic regulatory submissions for ANDAs. The FDA no longer accepts paper ANDA submissions. All ANDA submissions MUST be in eCTD format. Clinical Research Programs, Gujarat University

14. Question-Based Review ( QbR ) QbR is a science- and risk-based Chemistry, Manufacturing, and Controls (CMC) evaluation that focuses on critical pharmaceutical attributes essential for ensuring generic drug product quality. QbR for CMC evaluation of an abbreviated new drug application (ANDA). QbR for Sterility Assurance Evaluation (Product Quality Microbiology Review) of ANDAs. QbR for Sterility Assurance of Aseptically Processed Products. Labeling Questions for Sponsors. Clinical Research Programs, Gujarat University

15. Summary Tables - These summary tables provide a standard format for data to be in an ANDA in a concise format consistent with current recommendations. Model Bioequivalence Data Summary Tables (A detailed content and format information resource for generic drug applicants submitting ANDAs to FDA) BCS-Based Study Summary and Formulation Tables Bioequivalence Summary Tables for In Vitro Feeding Tube Testing Comparative Clinical Endpoint Bioequivalence Study Summary Tables Topical Dermatologic Corticosteroids In Vivo Bioequivalence Study Summary Tables and SAS Transport Formatted Tables for Dataset Submission Clinical Research Programs, Gujarat University

16. In Vitro Binding Bioequivalence Study Summary Tables and SAS Transport Formatted Tables for Dataset Submission Summary Tables for the Listing and Characterization of Impurities and Justification of Limits in Drug Substance and Drug Products (consistent with the recommendations described in the Guidances for Industry ANDAs: Impurities in Drug Substances and ANDAs: Impurities in Drug Products) Bioequivalence Summary Tables For Aqueous Nasal Spray Products Pharmacy Bulk Package Sterility Assurance Table Irritation/Sensitization/Adhesion Study Summary Tables Bioequivalence Summary Tables For Pressurized Metered Dose Inhaler Products Clinical Research Programs, Gujarat University

17. Content and format of an ANDA form Three copies of the ANDA are required, an archival copy , a review copy, and a field copy . Application form : The applicant must submit a completed and signed application form that contains the information- The name and address of the applicant & the date of the NDA. The NDA number if previously issued (for example, if the NDA is a resubmission or an amendment or supplement). The name of the drug product, including its established proprietary code, & chemical names. The dosage form and strength, the route of administration & the drug product's proposed indications for use. The identification numbers of all INDs that are referenced in the NDA; the identification numbers of all drug master files and other applications under this part that are referenced in the NDA. Clinical Research Programs, Gujarat University

18. A statement whether the applicant proposes to market the drug product as a prescription or an over-the-counter product. A check-list identifying what enclosures required under this section the applicant is submitting. The applicant, or the applicant's attorney, agent, or other authorized official must sign the NDA. If the person signing the NDA does not reside or have a place of business within the United States, the NDA is required to contain the name and address of, and be countersigned by, an attorney, agent, or other authorized official who resides or maintains a place of business within the United States. Clinical Research Programs, Gujarat University

19. Clinical Research Programs, Gujarat University 2) Table of contents 3) Conditions of use 4) Active ingredients r oute of administration, dosage form, & strength. 5) Bioequivalence 6) Labelling 7) Chemistry, manufacturing, and controls 8) Samples ( need not be submitted until requested by FDA) 9) Patent certification 10) Financial certification or disclosure statement

20. ANDA Regulatory Review Process

21. The ANDA process begins when an applicant submits an ANDA to the OGD (Office Generic Drugs) or CDER (Centre for Drug Evaluation and Research). The document room staff process the ANDA assigns it an ANDA number, and stamps a received date on the cover letter of the ANDA. The ANDA is then sent to a consumer safety technician, who reviews the preliminary sections of the ANDA checklist. The submitted ANDA is reviewed taking into consideration bioequivalence of the drug, chemistry and microbiology, and also the labeling. Within the first 60 days following the submission of an ANDA, a filing review is complete. Clinical Research Programs, Gujarat University

22. After the final level administrative review and individual disciplines have resolved their deficiencies, the application will either receive a full approval or a tentative approval letter. A full approval letter details the conditions of approval and allows the applicant to market the generic drug product. A tentative approval letter is issued if there are unexpired patents or exclusivities accorded to the Reference Listed Drug (RLD). ( Once a new drug is approved, the FDA provides a guaranteed period during which a generic version cannot be approved, regardless of the time remaining on the new drug's patent. This regulatory exclusivity typically runs for at least six years for new drugs ) Clinical Research Programs, Gujarat University

23. References: https://www.fda.gov/drugs/types-applications/abbreviated-new-drug-application-anda https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/requirements-and-resources-approved-andas https://www.investopedia.com/terms/a/abbreviated-new-drug-application-anda.asp https://www.law.cornell.edu/cfr/text/21/314.94#:~:text=The%20ANDA%20must%20contain%3A,referenced%20in%20the%20approved%20petition . https://www.fda.gov/media/128127/download https://www.researchgate.net/publication/325120077_Regulatory_Requirements_and_Registration_Procedure_for_Generic_Drugs_in_USA Clinical Research Programs, Gujarat University

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