INVESTIGATIONAL NEW DRUG APPLICATION (IND) 05-09-2011
INTRODUCTIONWhat is an IND ? An IND is a submission to the food and drug administration (FDA) requesting permission to initiate a clinical study of a new drug product. The Federal Food , Drug and Cosmetic act requires that drugs have an approved marketing application before they can be shipped in interstate commerce.
The IND application allows a company to initiate and conduct clinical studies for their new drug products. The IND application provides the FDA with the data necessary to decide whether the new drug and the proposed clinical trial pose a reasonable risk to the human subjects participating in the study.
When Do I Need An IND ? An IND is required any time I want to conduct a clinical trial of an unapproved drug. An IND would be required to conduct a clinical trail if the drug is a new chemical entity , not approved for the indication under investigation in a new dosage form. Being administered at a new dosage level. in combination with another drug and the combination is not approved.
All clinical studies where a new drug is administered to human subjects , regardless of whether the drug will be commercially developed , require an IND.
When You Don’t Need An IND An IND is not required to conduct a study if the drug : is not intended for human subjects , but is intended for in vivo testing or lab research animals (non clinical studies). is an approved drug and the study is within its approved indication for use.
CATEGORIES OF IND COMMERCIAL IND : goal is to obtain marketing approval for a new product. NON-COMMERCIAL IND : It includes INVESTIGATOR IND : In this case ,the physician is both the sponsor and investigator. EMERGENCY IND : FDA authorize immediate dispensing of a non-approved drug in a life threatening situation when no standard acceptable therapy is available. TREATMENT IND : FDA will permit investigational drug to be used to treat a serious or life threaetning disease or if there is no comparable alternative drug available.
Pre-IND Meeting A meeting between the sponsor and the fda frequently is useful in resolving questions and issues raised during the preperation of an ind. The fda encourages such meetings to the extent that They aid in the solution of scientific problems and To the extent that the fda has available resources. Most issues and questions are usually related to the Design of animal studies needed to initiate the clinical trials. The scope and design of the initial study in humans.
Meeting should be scheduled to occur within 60 days of the FDA’s receipt of the written request for the meeting. A briefing document is required at least 4 weeks prior to the meeting. The briefing document should provide summary of the information related to the product.
ESSENTIALS OF AN IND IND must present adequate information to permit the FDA to evaluate the drug’s suitability for use in the proposed clinical study. The central focus of the initial ind should be the general investigational plan and the protocol for the 1 st proposed human study. To assure that the human subjects who participate in the proposed study will not be exposed to unreasonable and significant risk.
Content And Format Of An IND Application The content and format of an initial ind is laid out in 21 CFR part 312 .1. Cover sheet – 312.23(a)(1) FDA form 15712. Table of contents – 313.23(a)(2)3. Introductory statement and general investigational plan – 312.23(a)(3)4. Investigators brochure – 312.23(a)(5)5. Clinical protocol – 312.23(a)(6)6. Chemistry , manufacturing and control data – 312.23(a)(7)
7. Pharmacological and toxicological information –312.23(a)(18)8. Previous human exposure – 312.23(a)(9)9. Additional information – 312.23(a)(10)10. Relevant information – 312.23(a)(11)
FORM FDA 15711.Name of the sponsor : He is the person who takes responsibility for and initiates a clinical investigation. May be a pharmaceutical company, a private or academic organization, or an individual.2.Date of submission : It is the date when the application is mailed to FDA.3. Address : It is the address to which written correspondence from FDA should be directed.
4. Telephone number : It is the number where the sponsor is usually available during normal working hours. A telephone number must be provided.5. Name(s) of Drug : List the generic name(s) and trade name, if available. Also, state the dosage form(s).
6. IND Number : If an emergency IND number was previously assigned by FDA, or the Form FDA 1571 is being included with an amendment to the original IND, then that IND number should be entered here; otherwise, the space should be left blank.7. Indication8. Phase of clinical investigation to be conducted9. list no.of all investigational new drug application
10. Serial no.11. Contents of application12.Name and title of the person responsible for monitoringthe conduct and progress of clinical investigation13. Is any part of the clinical study to be conducted by CRO13. Name and title of the person responsible for review andevaluation of information relevant to the safety of drug14. Name of sponsor’s authorised representative15.Signature16.Address17.Telephone no.18.Date
INTRODUCTORY STATEMENT Description of the investigational drug All active ingredients Drug’s pharmacological classification Structural formula Route of administration Summary of previous human experience Formulation of dosage forms Objective and planned duration of proposed clinical investigation.
INVESTIGATIONAL PLAN Description of clinical studies planned for the experimental drug Purpose of the study Indication to be studied Types of trials to be initiated Number of study subjects Risks involved
INVESTIGATORS BROCHURE Structural formula of drug. Summary of pharmacological , toxicological , pharmacokinetic effects in animals. Safety and efficacy Purpose of study Dose / dose frequency Monitoring procedures
CLINICAL PROTOCOL a clinical protocol describes how a particular clinical trial is to be conducted It describes the objectives of study the trial design how subjects are selected how the trial is to be carried out
It should contain the following elements: A statement of the objective and purpose of study. Name , address and qualification of each investigator participating in the study. Name and address of each clinical site. Study subject inclusion and exclusion criteria. Estimate of the number of subjects to be enrolled in the study.
Chemistry,Manufacturing and Control Data Determines the adequacy of methods used to manufature and assay investigational compound Safety concerns Describe drug substances Method of preparation Reagent and solvents Acceptable limits and analytical methods to ensure quality and purity of drug.
Pharmacological and Toxicology data : Pharmacology and drug disposition Integrated toxicology summaryPrevious human exposure : Marketed (foreign) or previouly tested in humans.
FDA REVIEW OF THE IND Once the ind is stamped as received ,it is sent to the review division within CDER. On arrival at the review division , it is critically evaluated by several reviewers of Chemisty Biopharmaceutics Medical Stastistics Microbiology Pharmacology /toxicology sections
All these areas review the data submitted with the primary purpose to ensure safety of the individual enrolled in th e study. Once an IND is submitted,the study can’t be initiated until a period of 30 days. If there are any major issues relating to the safety of the volunteers in the proposed study , the FDA can institute a clinical hold.
IND ANNUAL REPORTS Sponsors should submit an annual report that provides the FDA with a brief update on the progress of all investigations included in the IND. It should contain the following: Individual study information. Summary of the study. Listing of any significant foreign marketing developments with the drug e.g. approval in another country.