ChemOn Inc

Test Area

About Chemon’s advantages

Typically, the drug development process is divided into three major steps: discovery, nonclinical development, and clinical trial. As one of the leading CROs in Korea, we provide a full range of nonclinical services for the pharmaceutical, biotechnology, and medical device industries. Chemon is also expanding our services into overseas markets.

Investigational New Drug (IND) approval is the first step towards being able to begin clinical trials. For IND-enabling nonclinical services, we offer the best quality and affordable pricepoint for companies looking to develop new synthetic medicines and biologics.

By following USFDA’s IND submission checklist, companies file INDs to obtain marketing approval for a new drug. However, the requirements for an IND submission are complicated and can be hard to understand. Based on contract research and consulting by experts and more than 200 people in the field of regulatory toxicology and pharmacology, Chemon will help you navigate the IND application process and meet the stringent requirements, especially for the following components in USFDA’s IND submission checklist.

GLP Compliance Certification
Pharmacology and Drug Distribution
Toxicology: Integrated Summary
Toxicology - Full Data Tabulation using SEND system
Additional Information
Other FDA-Requested Information

Investigational New Drug (IND) Submission checklist

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Investigational New Drug (IND) Submission checklist

Investigational New Drug (IND) Submission checklist
	1. Cover Sheet
	2. Submit completed Form FDA 1571 as instructed by FDA Refer to www.fda.gov/cder/forms/1571-1572-help.html Note: If a study conduct obligations have been contracted to a CRO, indicate that a CRO is contracted rather than listing individual obligations. Note: If an investigation involves an exception from informed consent for emergency research, state on the Cover Sheet.
	3. Table of Contents Provide a detailed Table of Contents Page
	4. Introductory Statement and General Investigational Plan A brief overview of the general investigational plan for the study. This information is repeated later in the IND, in a concise detail. First section: must include the name of drug, active ingredients, its pharmacological class, structural formula (if known), formulation of the dosage form(s) to be used, route of administration, and broad objectives and expected duration of the study. Second section: must include a summary of previous human experience, reference to other INDs, if relevant, and investigational and marketing experience in other countries, if applicable. Third section: indicate if the drug has been withdrawn from investigation or marketing for any safety or effectiveness reasons, including where and why. Last section: provide a summarize plans for investigating the drug within the next 12 months, including rationale for the study, indications(s) to be studied, general plan for evaluating the drug, kind of studies planned for the first year (specify if these plans are not yet complete), expected number of patients to be enrolled and anticipated risks based on animal toxicology data.
	5. Investigator Brochure Include a copy of the Investigator’s Brochure where applicable
	6. Protocol(s) Submit a protocol for each planned study. Submit an Form FDA 1572 for each Investigator participating in the study Note: Protocols not submitted with the original IND must be submitted in an IND Protocol Amendment.
	7. Referencing Other Sources If utilizing a drug that is currently subject to a manufacturer’s IND, or marketing application, refer to that IND or application or Drug Master File (if appropriate) to prevent duplicating information that are already available to FDA. Include a Letter of Authorization from the other sponsor permitting FDA to use their information for this IND. The Sponsor also must file a copy of the letter to its own FDA file. Available information in a published scientific literature may be referenced, if appropriate. Include a copy of each of the copyrighted items with the IND submission. Material copyrighted by others must be included in a bibliography section, not in the body of the IND. May utilize references of the current edition of the United States Pharmacopoeia – National Formulary, if appropriate, to satisfy some of the requirements in the Drug Substance and Drug Product sections.
	8. Introduction The Introduction should state whether any information in regards to the chemistry of the drug substance, drug product, or the manufacture of either might suggest any possible human risks. If so, document all possible human risks and indicate how these safety issues will be monitored, or why the risks can be dismissed. Ensure to describe any differences between the drug product planned for use in clinical studies and that used in animal toxicology studies. Does the differences in the drug product affect the safety profile, and how it is affected. If not, please clarify.
	9. Drug Substance Include a summary of the following elements: A brief description of the drug substance, including its physical, chemical, or biological characteristics, and some evidence to support its proposed chemical structure. The name and address of its manufacturer. A brief description of the general method of preparation of the drug substance, including a list of the reagents, solvents, and catalysts used. A detailed flow diagram is suggested as the most effective presentation. More information may be needed to assess the safety of biotechnology-derived drugs or drugs extracted from human or animal sources. The acceptable limits and analytical methods used to ensure the identity, strength, quality, and purity of the drug substance, with a brief description of the test methods used, (e.g., IR spectrum to prove the identity, and HPLC chromatograms to support the purity level and impurities). Submission of certificates of analysis is also suggested. A brief description of the stability study and the test methods used to monitor the stability of the drug substance during the toxicological studies should be submitted. Preliminary tabular data based on representative material may be submitted. Neither detailed stability data nor the stability protocol should be submitted. Note: Validation data and established specifications ordinarily need not be submitted at the initial stage of drug development. However, for some well-characterized, therapeutic biotechnology-derived products, preliminary specifications and additional validation data may be needed in certain circumstances to ensure safety in Phase 1.
	10. Drug Product Include a summary of the following elements: A list of all components, which may include reasonable alternatives for inactive compounds, used in the manufacture of the investigational drug product, including both those components intended to appear in the drug product and those which may not appear, but which are used in the manufacturing process. A list of one or two pages should be submitted. The quality (e.g., National Formulary, American Chemical Society) of the inactive ingredients should be cited. For novel excipients, additional manufacturing information may be necessary. Where applicable, a brief summary of the quantitative composition of the investigational new drug product, including any reasonable variations that may be expected during the investigational stage. The name and address of the clinical study drug product manufacturer. A brief, general description of the method of manufacturing and packaging procedures as appropriate for the product. A detailed flow diagram and a brief written description of the manufacturing process should be submitted, including sterilization process for sterile products. A brief description of the acceptable limits and analytical methods used to ensure the identity, strength, quality, and purity of the drug product. For example, for sterile products, sterility and pyrogenicity tests should be submitted. Submitting a copy of the certificate of analysis of the clinical batch is suggested. A brief description of the stability study and the test methods used to monitor the stability of the drug product to be used in clinical studies (packaged in the proposed container/closure system and under expected storage conditions), should be provided. Preliminary tabular data based on representative material may be submitted, but not detailed stability data nor the stability protocol. Note: Validation data and established specifications need not be submitted at the initial stage of drug development. For well-characterized, therapeutic, biotechnology-derived products, a detailed assessment of bioactivity and preliminary specifications should be available.
	11. Placebo Provide a brief, general description of the composition, manufacture, and control of any placebo (if any) to be used in the proposed clinical studies.
	12. Labeling Provide a copy of all labels and labeling for the investigational product. A mock-up or printed representation of the proposed labeling that will be provided to investigator(s) is acceptable. Investigational labels must carry a "caution" statement that reads: "Caution: New Drug - Limited by Federal (or United States) law to investigational use."
	13. Environmental Impact If applicable, must make a claim for categorical exclusion from submission of an environmental assessment. If the product meets the exclusion requirements, state “I claim categorical exclusion under 21 CFR 25.31(e) for the study/studies under this IND. To my knowledge, no extraordinary circumstances exist.”
	14. Pharmacology and Toxicology Information There are three parts in this section. FDA provides guidelines on conducting these assessments. The review division should be contacted or the FDA website can be searched for these documents. The first IND submission should capture all current pharmacology and toxicology information upon which the decision to proceed to study the product in humans was based, up through what is known when the IND is ready for submission. As additional information is gathered and the studies progress, submit informational amendments to keep the IND current.
	15. Responsible Person(s) The IND must provide identification and qualifications of individual(s) who evaluated the animal safety data and have concluded as reasonably safe to begin the proposed human study. This person(s) should sign the summary attesting that the written summary accurately reflects the animal toxicology data from the various completed studies. The submission must state where the animal studies were conducted and where the records of the studies are available for inspection.
	16. GLP Compliance Certification GLP compliance is required for in vitro and in vivo, in order to assess product safety. Regulations ensure that the data are obtained and reported to FDA appropriately. A declaration to conduct the study in full compliance with GLP must be documented. If not in compliance, a statement of reasons for noncompliance and sponsor's view on how such non-compliance might affect the interpretations of the findings must be provided.
	17. Pharmacology and Drug Distribution A description of the pharmacological effects and mechanism(s) of actions of the drug in animals Information on the absorption, distribution, metabolism, and excretions of the drug. A summary report of up to 5 pages should be submitted.
	18. Toxicology: Integrated Summary An Integrated Summary is only used for drugs and well-characterized, therapeutic biotechnology-derived products. For novel biotechnology-derived products, the review division should be consulted first. Need for studies depend on the nature of the drug and the phase of human investigation, including acute, sub-acute and chronic toxicity tests, tests on reproduction and fetal effects, any special toxicity tests unique to the product’s use (e.g., dermal, inhalation, etc.) and any necessary in vitro tests. When species specificity, immunogenicity, or other considerations appear to make many or all of the toxicological models irrelevant, consult the review division. If final quality-assured individual study reports are not available at the time of IND submission, an integrated summary report of toxicological findings based on unaudited draft reports is acceptable. Unaudited draft reports might undergo minor modifications during final review and quality assurance auditing. Full toxicology department individual study reports should be available to FDA, upon request. In addition, individual study reports should be available to FDA, upon request, as final, fully quality-assured documents within 120 days after the start of the human study for which the animal study formed part of the safety conclusion basis. These final reports should state in the introduction any changes from those reported in the integrated summary. If there are no changes, that should be also be stated clearly in the introduction of the final, fully quality-assured report. If the integrated summary is based upon unaudited draft reports, sponsors should submit an update to their integrated summary by 120 days after the start of the human study (s) identifying any differences found in the preparation of the final fully quality-assured study reports and the information submitted in the initial integrated summary. If there were no differences found, that should be stated in the integrated summary update. FDA believes 10 to 15 pages of text with additional tables (as needed) should suffice for the integrated summary. FDA also encourages the use of visual data displays (e.g., box plots, stem and leaf displays, histograms or distributions of lab results over time). The integrated summary should contain the following: Describe the design of the studies and any deviations from that design that occurred. Include the dates when the studies were performed. Reference to the study protocol and protocol amendments may suffice for some of this information. Present the animal toxicology and toxicokinetic findings systematically (a "systems review" perspective, e.g., CNS, cardiovascular, pulmonary, etc.). Those findings that an informed and experienced expert would reasonably consider as possible signals of human risk should be highlighted. If a product's effects on a particular body system have not been assessed, that should be noted. If any well-documented toxicological "signal" is not considered evidence of human risk, the reason should be given. In addition, the sponsor should note whether these findings are discussed in the investigator's brochure.
	19. Toxicology - Full Data Tabulation Submit for each animal toxicology study that supports the safety of the proposed clinical investigation (a full tabulation of data suitable for detailed review). This should consist of line listings of the individual data points, including laboratory data points for each animal in these trials, along with summary tabulations of these data points. To allow interpretation of the line listings, ensure the line listings should be either: Or A copy of the study protocol and amendments.
	20. Previous Human Experience Include relevant information about previous investigations or marketing in the United States and other countries, including published material relevant to the product’s safety and/or effectiveness. List other countries where the product has been marketed and whether it was withdrawn from any of those markets (and why), or state that there has been no previous human experience. Previous human experience may be presented in an integrated summary report.
	21. Additional Information When referencing any previously submitted information, refer to it by name, reference number, and volume and page number to assist FDA in finding the reference(s). Examples of other information that can be included: discussion about drug dependency or abuse potential and radioactive dissymmetry information.
	22. Other FDA-Requested Information FDA may require other additional information be included in the IND
	23. Material in a Foreign Language Material in a language other than English (including scientific literature published in a foreign journal) must be included in the IND with a certified accurate and complete English translation.
	24. Format Jackets: FDA has detailed specifications about the binders, called Jackets, which must be used for the IND. Refer to www.fda.gov/cder/ddms/binders.htm and follow the specifications. Specific Jacket colors are required: • Red: Original (for the FDA archive) • Green: Copy (for the FDA CMC reviewer) • Orange: Copy (for other applicable FDA reviewers) Tabs: tab and clearly label each part within a Jacket, including sub-sections. Submit original and two copies of the IND to the appropriate FDA Center (Refer to Form FDA 1571)

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About Chemon’s advantages

Investigational New Drug (IND) Submission checklist

ChemOn Inc
ChemOn Inc