Regulatory Requirements for Dietary Supplements in USA

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Regulatory Requirements for Dietary Supplements
in USA
Vedic Lifesciences Pvt Ltd

• Mansi Ahuja

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Health Regulators Worldwide
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Status of AYUSH Products in USA

• In INDIA
• AYUSH Products
• Traditional Indian Medicine
• Patent Proprietary or Shastrokta Drugs
• Can claim disease cure / treatment
• Can be prescribed or OTC

• In USA
• Dietary Supplements
• Herbal Supplements
• Food Supplements
• Cannot claim disease cure, but only health
  maintenance
• Only OTC
• Not reimbursed by insurance

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Types of Health Regulations
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How To Enter Regulations

• Pre-Market

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DSHEA,1994

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

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Definition of Dietary Supplements

• 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).
• Note A dietary supplement is limited to products
  that are intended for ingestion in tablet,
  capsule, powder, softgel, gelcap, and liquid form

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Definition of Dietary Ingredient

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

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Dietary Supplement
ODI
NDI
Pre Market Notification
Marketing
Success OF Marketing
Claims
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Difference between Dietary Supplement, Foods
Drugs
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What to Submit Regulations

• Guidelines

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Notification Requirement for NDI

• A pre marketing notification is required in
  case of
• Manufacturer who intends to market a new dietary
  ingredient or dietary supplement that contains a
  new dietary ingredient
• Distributor who intends to market a new dietary
  ingredient or dietary supplement that contains a
  new dietary ingredient.

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Prerequisite for NDI

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

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Submission Information

• Submit an original and two (2) copies of the
  notification with Safety documents.
• Notification should also contain the following
  data-
• Your name and complete address.
• The name of the new dietary ingredient.
• 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.
• A signature by a responsible authority from the
  company.

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Warning

• Dietary Supplement with NDI can only reach the
  market after 75 days of notification period.

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What to Do Regulations

• Marketing Post Marketing rules

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cGMP Requirements as per August 24, 2007

• Regulations of cGMP ensure the quality through
  out
• 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 cGMP will effective from
• June, 2008 for Large companies with employee
  strength of more than 500
• June, 2009 for companies with less than 500 or
  more than 20 employees.
• June, 2010 for companies with less than 20
  employees.

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cGMP Requirements as per August 24, 2007

• Under the cGMP rule, manufacturers are required
  to
• Employ qualified employees and supervisors
• 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
• Use equipment and utensils that are of
  appropriate design, construction, and workmanship
  for the intended use
• Establish and use master manufacturing and batch
  production records
• Establish procedures for quality control
  operations
• Proper Storage Distribution in order to
  maintain efficacy quality of product.
• Keep a written record of each product complaint
  related to cGMPs.
• 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

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Claims That Can Be Made for Dietary Supplements

• Claims that can be used on food and dietary
  supplement labels fall into three categories
• Health claims
• Qualified Health claims
• Structure/Function claims

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Health Claims

• A "health claim" by definition has two essential
  components
• a substance (whether a food, food component, or
  dietary ingredient)
• a disease or health-related condition.
• A statement lacking either one of these
  components does not meet the regulatory
  definition of a health claim.
• Nutrition Labeling and Education Act (NLEA), 1990
  regulates the Health claim petitions.
• Examples of Health Claims
• 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.
• "diets high in calcium may reduce the risk of
  osteoporosis"

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Qualified Health Claims

• 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.
• Label claim should be clear concise to point
  limitation of the Evidence supporting Health
  Claim.
• Both conventional foods and dietary supplements
  may use qualified health claims

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Structure/Function Claims

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

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Claims Substantiation

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

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Tips for Good Clinical Trials

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

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Label Information

• Required label information must appear on
• 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
• Information Panel It must contain
• Name and address of manufacturer, packer, or
  distributor
• Ingredient list
• Nutrition Facts panel
• Information Pane should be placed to the
  immediate right of PDP and if not, then next
  panel to right.

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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.

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Vedic Services
Pre Clinical Services
Consultancy
Clinical Trials (Phase I-IV)
Clinical Data Management
Bio Statistics
Medical Writing
Regulatory Consultancy
Other Services

• Preclinical Consultancy
• Feasibility Evaluation
• Study analysis Protocol
• Study Set up Audits
• Experimental Project Management

• GAP analysis
• Feasibility
• Market Survey
• CMC
• Analytical Development Validation
• Formulation Development

• Study Feasibility Analysis
• Investigator / Site Selection
• Regulatory Submission Approval (IRB/EC DCGI)
• Site Initiation
• Assessment Visits
• Site Management Monitoring
• Investigational Product Management
• Closeouts
• Query Resolution

• Data Validation
• Database Design
• Data Entry Tracking
• Data Coding
• Database Access Management
• Data Management Reporting
• Risk Query management

• Clinical Trial Design
• Sample Size Calculation
• Statistical Analysis Plans
• Planning Execution of interim analysis
• Final Statistical Analysis
• Statistical Report

• Study Design/ Outline
• Protocol its Amendments
• Informed Consent Document
• Patient Diary and Subject Emergency Card
• Clinical / Statistical study Report
• Publication Support

• Strategic regulatory planning for specific
  countries
• Pre IND meetings
• INDs
• NDA and ADNA
• Applications for marketing license

• SAE collection, evaluation, classification
  reporting
• Medical case reviews
• Adverse event narration coding
• Complete Pharmacovigilance
• BA/BE studies
• Biochemical Assays

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Thank You
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act Us at vedic_at_vediclifesciences.com Phone
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