Vedic Lifesciences Pvt Ltd Regulatory Requirements for Dietary

Vedic Lifesciences Pvt Ltd Regulatory Requirements for Dietary Supplements in USA Mansi Ahuja www. vediclifesciences. com

Health Regulators Worldwide www. vediclifesciences. com

Status of AYUSH Products in USA In INDIA q AYUSH Products q Dietary Supplements q Traditional Indian Medicine q Herbal Supplements q Food Supplements q Patent & Proprietary or Shastrokta Drugs q q Can claim disease cure / treatment Cannot claim disease cure, but only health maintenance q Only OTC Can be prescribed or OTC q Not reimbursed by insurance q www. vediclifesciences. com

Types of Health Regulations “How To Enter” Regulations (Pre-Market) “What to Submit” Regulations (Guidelines) “What To Do” Regulations (Marketing, Post-marketing) www. vediclifesciences. com

“How To Enter” Regulations Pre-Market www. vediclifesciences. com

DSHEA, 1994 q The Dietary Supplement Health and Education Act was signed into law in October, 1994. q Under DSHEA, a firm is responsible for Ø Safety of the dietary supplement Ø Claim Substantiation www. vediclifesciences. com

Definition of Dietary Supplements q “The term ‘dietary supplement’ means a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: (A) a vitamin; (B) a mineral; (C) an herb or other botanical; (D) an amino acid; (E) a dietary substance for use by man to supplement the diet by increasing the total dietary intake; or (F) a concentrate, metabolite, constituent, extract, or combination of any ingredient described in clause (A), (B), (C), (D), or (E). ” q Note: A dietary supplement is limited to products that are intended for ingestion in tablet, capsule, powder, softgel, gelcap, and liquid form www. vediclifesciences. com

Definition of Dietary Ingredient q New Dietary Ingredient (NDI): The term ‘new dietary ingredient’ means a dietary ingredient that was not marketed in the United States before October, 1994. q Old Dietary Ingredient (ODI): It means a dietary ingredient that was marketed in the United States before October, 1994. (Grandfathered Ingredients) q In case of ODI, NO PRE MARKETING APPROVAL REQUIRED from FDA. q However, pre marketing notification is required in case of NDI. www. vediclifesciences. com

Dietary Supplement ODI NDI Marketing Success OF Marketing Claims www. vediclifesciences. com Pre Market Notification

Difference between Dietary Supplement, Foods & Drugs Dietary Supplement: Supplements diet by increasing the total dietary intake Drugs: Diagnosis, Cure, Mitigation, Treatment or prevention of a disease Foods: Principal Item of a Person’s Diet www. vediclifesciences. com

“What to Submit” Regulations Guidelines www. vediclifesciences. com

Notification Requirement for NDI A pre – marketing notification is required in case of q Manufacturer who intends to market a new dietary ingredient or dietary supplement that contains a new dietary ingredient; q Distributor who intends to market a new dietary ingredient or dietary supplement that contains a new dietary ingredient. www. vediclifesciences. com

Prerequisite for NDI q In order to market Dietary Supplement containing NDI, the basic requirement is Ø pre marketing notification that must be submitted 75 days prior to entry in the market. q On September 23, 1997, FDA published in the Federal Register a final rule that established safety regulations. www. vediclifesciences. com

Submission Information q Submit an original and two (2) copies of the notification with Safety documents. q Notification should also contain the following data: Ø Your name and complete address. Ø The name of the new dietary ingredient. Ø A description of the dietary supplement or supplements that contain the NDI, including: § Amount of NDI in the dietary supplement. § Conditions of use as per Label § History of use or other evidence of safety. Ø A signature by a responsible authority from the company. www. vediclifesciences. com

Warning q Dietary Supplement with NDI can only reach the market after 75 days of notification period. www. vediclifesciences. com

“What to Do” Regulations Marketing & Post Marketing rules www. vediclifesciences. com

c. GMP Requirements as per August 24, 2007 q Regulations of c. GMP ensure the quality through out Ø Ø Ø Ø Ø q q Manufacturing operations In process Quality Control procedures Packaging & labeling Storage Cleaning Designing & Construction of Manufacturing Plants Testing methods Handling Customer Complaints Documentation As per regulations, manufacturers are required to evaluate the identity, purity, strength, and composition of their dietary supplements. Final c. GMP will effective from Ø June, 2008 for Large companies with employee strength of more than 500 Ø June, 2009 for companies with less than 500 or more than 20 employees. Ø June, 2010 for companies with less than 20 employees. www. vediclifesciences. com

c. GMP Requirements as per August 24, 2007 q Under the c. GMP rule, manufacturers are required to: Ø Employ qualified employees and supervisors; Ø Design and construct their physical plant in a manner to protect dietary ingredients and dietary supplements from becoming adulterated during manufacturing, packaging, labeling and holding; Ø Use equipment and utensils that are of appropriate design, construction, and workmanship for the intended use; Ø Establish and use master manufacturing and batch production records; Ø Establish procedures for quality control operations; Ø Proper Storage & Distribution in order to maintain efficacy & quality of product. Ø Keep a written record of each product complaint related to c. GMPs. Ø Retain records for 1 year past the shelf life date, if shelf life dating is used, or 2 years beyond the date of distribution of the last batch of dietary supplements associated with those records www. vediclifesciences. com

Claims That Can Be Made for Dietary Supplements Claims that can be used on food and dietary supplement labels fall into three categories: 1) Health claims 2) Qualified Health claims 3) Structure/Function claims q www. vediclifesciences. com

Health Claims q A "health claim" by definition has two essential components: Ø a substance (whether a food, food component, or dietary ingredient) Ø a disease or health-related condition. q A statement lacking either one of these components does not meet the regulatory definition of a health claim. q Nutrition Labeling and Education Act (NLEA), 1990 regulates the Health claim petitions. q Examples of Health Claims: Ø “Development of cancer depends on many factors. Eating a diet low in fat and high in grain products, fruits and vegetables that contain dietary fiber may reduce your risk of some cancers. ” Ø "diets high in calcium may reduce the risk of osteoporosis" www. vediclifesciences. com

Qualified Health Claims q Consumer Health Information for Better Nutrition Initiative 2003 provides for the use of qualified health claims to substantiate evidence for a relationship between a dietary supplement and reduced risk of a disease or health-related condition. q Label claim should be clear & concise to point limitation of the Evidence supporting Health Claim. q Both conventional foods and dietary supplements may use qualified health claims www. vediclifesciences. com

Structure/Function Claims q Structure/function claims describe Ø Role of a nutrient or dietary ingredient intended to affect normal structure or function in humans. Such as, "calcium builds strong bones. " Ø The means by which a nutrient or dietary ingredient acts to maintain such structure or function, Such as, "fiber maintains bowel regularity, “ Ø General well-being from consumption of a nutrient or dietary ingredient Ø Benefit related to a nutrient deficiency disease (like vitamin C and scurvy), with the prevalence of disease in US. q As Structure/Function claims are not pre-approved by FDA, manufacturers are solely responsible for Ø Claims are truthful, accurate & not misleading. Ø Notification to FDA within first 30 days for the usage of claims for the marketing of product. Ø A mandatory disclaimer statement as per law. www. vediclifesciences. com

Claims Substantiation q “Truth in Advertising” is regulated more by FTC (not FDA) q Several Penalties have been levied already q Company is responsible for expressed and implied claims (thru images, video, etc. ) q Randomized Controlled Trials (RCT) are gold standard for substantiation q Animal studies, Epidemiological studies, meta analyses may be considered. www. vediclifesciences. com

Tips for Good Clinical Trials q Follow Good Clinical Practices (ICH GCP) q Qualified, Trained and Professional Team q Scientifically Strong Protocol with a valid Statistical Plan q Maintain Audit trail q Third Party Monitoring by trained Professionals q Internal + External Audit, Quality Assurance q Central Lab for multi-centric trials q AE and SAE reporting q Compliant Data Management q High Quality Unbiased Medical Report and Manuscript Writing q Publication q Follow all available drug guidelines q Outsource / offshore the study to a CRO if required www. vediclifesciences. com

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Label Information q Required label information must appear on: Ø Principal Display Panel (PDP): It must contain § Statement of identity (name of DS)- Name of DS should Placed on label parallel to base of package and Should stand out Bold type and At least 1/2 the size of the largest print on label. § Net quantity of contents statement Ø Information Panel: It must contain § Name and address of manufacturer, packer, or distributor § Ingredient list § “Nutrition Facts” panel Ø Information Pane should be placed to the immediate right of PDP and if not, then next panel to right. www. vediclifesciences. com

www. vediclifesciences. com

Vedic Corporate Profile Vedic has so far supported over 36 clinical studies (Phase II/ III) and more than 400 preclinical across multiple therapeutic areas. Core offerings entail Preclinical Studies, Consultancy, Project Management (Phase I to IV), Clinical Data Management, Bio. Statistics, Medical Writing, Regulatory Consulting and Pharmacovigilance Services Founded in 2001, Vedic is a contract research organization that provides broad-based yet highly tailored drug development & support services to global Pharma, biotech and Lifesciences players. www. vediclifesciences. com

Vedic Services Clinic Con al s Tri ul als ta n (Phas Servic c e Ies y IV) Preclinical GAP analysis Study Consultancy Feasibility Analysis Feasibility Investigator / Evaluation Site Selection Market Regulatory Survey Study Submission & analysis & Approval Protocol CMC (IRB/EC & DCGI) Pre Cli nic al Clinic al Dat a Bio Ot Statis tic Mana Wr s ge i me t Data nt Clinical Trial Study Design/ i Validation Design Outline n g Database Design Sample Size Protocol & its Calculation Amendments Data Entry & Statistical Tracking Analysis Plans Data Coding Study Set – Analytical Site Initiation up & Audits Development & Validation Assessment Visits Experimental & Project Formulation Site Management Development & Monitoring Me d i c a l Database Access Management Data Management Reporting Informed Consent Document Regul ato ry Ser Cons v ult i an c Strategic cy SAE e regulatory collection, s planning for evaluation, specific classification countries & reporting Pre – IND meetings Medical case reviews INDs Adverse event narration & coding Planning & Patient Diary Execution of and Subject NDA and interim Emergency ADNA analysis Card Final Statistical Analysis Investigational Product Management Statistical Report Risk & Query Closeouts management Query Resolution Clinical / Statistical study Report Publication Support www. vediclifesciences. com h e r Applications for marketing license Complete Pharmacovigil ance BA/BE studies Biochemical Assays

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