The FDA regulates dietary supplements and requires manufacturing to be in compliance with good manufacturing practices (GMPs).

1. What are Dietary
Supplements?
A Presentation by
InstantGMP
InstantGMP: Electronic Batch Record System for GMP Manufacturing

2. Topics
 Dietary Supplements
 Dietary Ingredients
 GMP Manufacturing of Dietary
Supplements
 InstantGMP Manufacturing
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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3. What are Dietary
Supplements?
 Orally ingested products that contain an
ingredient that is intended to supplement the
diet
 Dietary supplements are under the "umbrella"
of foods at the FDA
 Ingredients may be one or more of the
following:
 an amino acid
 a concentrate or extract of a plant material
 an herb or other botanical
 a mineral
 a vitamin
InstantGMP: Electronic Batch Record System for GMP Manufacturing

4. FDA Review and Approval
 Dietary supplements do not need approval
from FDA before they are marketed unless
they contain a new dietary ingredient
 FDA must conduct a pre-market review for
safety data and other information on new
dietary ingredients before marketing
 Manufacturers need to register themselves
pursuant to the Bioterrorism Act with FDA
before producing or selling supplements
InstantGMP: Electronic Batch Record System for GMP Manufacturing

5. How are Dietary Supplements
Supplied?
 Available in many forms that can be
taken by mouth
 Capsules
 Softgel capsules
 Gelcaps
 Tablets
 Liquids
 Powders
InstantGMP: Electronic Batch Record System for GMP Manufacturing

6. Purpose of Dietary
Supplements
 Ensure you have enough essential nutrients
 May help reduce the risk of some diseases
 Labeling may indicate health claims,
structure/function claims, and nutrient content
claims
 Labeling may not indicate that a dietary
supplement is for treatment, prevention or cure
for a specific disease or condition
 Only drugs can be used to "diagnose, treat,
cure or prevent a disease"
InstantGMP: Electronic Batch Record System for GMP Manufacturing

7. Who is Responsible?
 Firms that manufactures or distributes dietary
supplements must:
 make sure their products are safe
 assure that any claims made about them have adequate
evidence to show that they are not false or misleading
 register with the FDA before producing or selling
supplements according to the Bioterrorism Act
 manufacture their products in accordance with GMPs
 The FDA
 does not approve dietary supplements on the market
before 1994
 reviews and approves new dietary ingredients
 restrict a product's use or remove it from the marketplace
if they show a dietary supplement is "unsafe"
InstantGMP: Electronic Batch Record System for GMP Manufacturing

8. What is the Cost of
Compliance?
 The regulations for dietary supplement
GMP compliance estimated the cost of
compliance on small businesses
 Dietary supplement business with less
than 20 employees will bear annual
costs of about $46,000
 Business with up to 500 employees will
bear a cost of about $184,000 a year
InstantGMP: Electronic Batch Record System for GMP Manufacturing

9. Challenges of GMP Manufacturing
 Good Manufacturing Practices are complex
 Wide array of regulatory requirements
 High time and cost to set up quality system
 Long cycle times for QA review and corrections
 Training and compliance to SOPs is lengthy
 Documentation coordination and data tracking is
laborious
 High cost of compliance
InstantGMP™ is the manufacturing system that has been built
from the ground up to meet these challenges
InstantGMP: Electronic Batch Record System for GMP Manufacturing

10. InstantGMP™ - A new approach to
pharmaceutical manufacturing.
 Seamlessly incorporate everything necessary in
one place where it is visible all the time to
everyone via cloud-based application
 Provides flexibility, speed, real-time access to
information
 Uses proven quality procedures and efficient
data flow
 Accelerates startup and rapidly reacts to
changes and delays without endangering
timelines
InstantGMP: Electronic Batch Record System for GMP Manufacturing

11. InstantGMP™ - The Manufacturing
Application
 Founded on 21 CFR Part 11-compliant software
and an all-encompassing, paperless quality
system
 Electronic Batch Record system with internet-
based infrastructure
 Data is automatically visible to all decision-
makers at the same time
 Eliminates delays created by traditional linear
processes
InstantGMP: Electronic Batch Record System for GMP Manufacturing

12. Advantages
InstantGMPTM enhances control, visibility,
efficiency and compliance of the regulated Life
Science manufacturing process
Manufacturing
Purchasing Project Team
QA
Sponsor Cloud
Server
InstantGMP: Electronic Batch Record System for GMP Manufacturing

13. Visibility
 Available via the internet
 Review and sign records from any location
 Access controlled by firewall and security settings
 Manages access for employees, partners or sponsors
ANYWHERE
ANY TIME
Remote Site Remote Site
Manufacturing
InstantGMP: Electronic Batch Record System for GMP Manufacturing

14. Efficiency
QC, QA, Warehouse, Purchasing, Inventory and
Manufacturing activities and records are linked
Some of the many features:
 Standard specs, tests and vendors are reusable within the
system
 Purchase Orders automatically created
 Receiving materials and managing inventory is easy
 Automated Master and Batch Production Record copies
make documentation creating and archival a snap
 Inventory depletion as batch is being run creates less room
for error
 Documents that are transmitted electronically and signed
electronically make it simple to speed up production
InstantGMP: Electronic Batch Record System for GMP Manufacturing

15. Efficiency
Vendors, Tests and Methods need to be added only once
InstantGMP: Electronic Batch Record System for GMP Manufacturing

16. ICH Q7A Good Manufacturing
Practice
 International Conference on
Harmonization
 ICH Member Countries –
 European Union (EU) - 27 countries
 Japan
 United States
 Australia
 Canada
 Norway
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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17. Basic of GMPs according to ICH
 Instructions and procedures are clear and
unambiguous
 Manufacturing processes are clearly defined and
controlled
 Facilities designed to minimize cross-
contamination and mix-ups
 Operators are trained
 Records demonstrate that all required steps
were taken
 Distribution minimizes any risk
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18. Different approaches to GMPs
compliance depending on country
 There is a global disequilibrium – quality and
compliance are different
 A nation’s relative development dictates the level
of compliance they can afford
 ICH signatories have the best quality
 BRIC nations generally are struggling with the
cost of compliance, even while they recognize
the value for international commerce
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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19. InstantGMP starts with the Quality
System Structure
First step was design of
the quality system
structure
Next was design of
processes that link
material and process
controls together
Finally writing a
comprehensive
manufacturing solution
with compliance built-in
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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20. Automated Compliance
cGMP compliance controls are built into the system
Some of the many features:
 Limited access based on user/role security settings
 Purchasing restricted to approved materials and
vendors
 Materials quarantine/restricted until QA approval
 Specification version control
 Master and Batch Record version control
 Required signatures at specified batch record steps
 Deviations must be approved before batch is
released
 Complete automated audit trail
InstantGMP: Electronic Batch Record System for GMP Manufacturing

21. Manufacturing Facility Compliance is
Sponsor’s Responsibility
 Facility and flow designed to minimize
potential contamination and mix-ups
 Defined areas for:
 Receipt
 Quarantine
 Storage
 Production
 Packaging
 Washing
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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22. Small Scale
CTM Manufacturing Facility Example
Material flow
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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23. GMP Facility Inspection is Sponsor’s
Responsibility
 FDA conducts facility inspections for
products to be sold in the US
 Doesn’t include CTM facilities
 Doesn’t include clinical stage products
 UK and EU use UK’s “Orange Guide” to
check compliance
 China, Japan, India et al rely on local
inspectors
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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24. Typical GMP Facilities in US and UK
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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25. Materials
Only QA approved materials can be used
in CTM manufacturing
Excipients Containers/Closures
Components
Work in Process
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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26. Getting ready for manufacturing –
Control of Materials
API, excipients Assign Part #s,
and components tests, methods,
identified Specs
PM Initiates Vendors Specs
Yes Yes
Project Qualified? Approved?
Quality Quality
No Manager Manager
Project
Vendor Project
Manager Select Personnel
Qualification Definition
and Roles
Completed
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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27. Automatic Control
Automated rules and entries, that are based on the SOPs, are
integrated in the system.
Some of the many features:
 System assigns lot numbers upon receipt
 QA enters and controls raw material status based on QC
Lab input
 System issues purchase requisitions
 Production can only use approved raw materials
 Drop downs for entries in batch records ensure accuracy
 Electronic signatures allow remote, easy approvals
 Security settings limit access to only authorized personnel
InstantGMP: Electronic Batch Record System for GMP Manufacturing

28. Vendors
QA shall qualify vendors for materials
used in CTM
 Phase 1 CTM
 Paper based quality survey
 Phase 2 CTM
 Either a paper based quality survey or an on-site audit
 Phase 3 CTM
 On-site audit
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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29. Rooms and Equipment
 Room List – names of manufacturing rooms
 Room Log – record of activities in rooms, e.g.
 Cleaning
 Maintenance
 Batch use
 Equipment List – names of production
equipment
 Shows up in drop down lists in batch records
 Equipment Log – similar to Room Log
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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30. Room Log
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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31. Equipment Log
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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32. Specifications
QA shall approve specifications of
materials and components
 Test - A measurement of a quality attribute such as
potency or water content
 Method - The procedure by which the quality
attribute is measured
 Limit - The acceptable range for the attribute
 Other Requirements
 Sampling Instructions
 Safety and Handling
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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33. Specifications
Specifications have
version control to
keep track of
changes
Most recent specs
apply, but old specs
must be kept
available for review
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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34. Specifications
Specifications can have Safety, Handling
and Sampling instructions
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35. Specifications
Specifications include Test, Methods and
Limits that will go on Certificate of Analysis
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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36. Process Flow – Material Management
Receipt at Available for Bill
Warehouse Record into
Released Yes of Materials &
Inventory
Production
No
Quarantine, Quality
Facility Test & Manager
Manager Release
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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37. Receiving
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38. Inventory
Once materials are received, they automatically go into inventory with a
Quarantine status. Only QA can change the status.
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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39. Automated Inventory Compliance
Materials need to be
In an approved status to
be used in batches
Materials need to have qualified
Vendors before being used in batches
Only a Quality Manager can update a material’s status
InstantGMP: Electronic Batch Record System for GMP Manufacturing

40. Quality Testing and Release is
Sponsor’s Responsibility
InstantGMP generates form that can be sent with sample to QC.
QA can update inventory status when material is released.
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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41. Process Flow - Production
Manufacturing
Instructions
Bill of Master Batch Approve
Materials Production Production Batch Record
In Process
Equipment
Tests
Quality Facility Sponsor
Manager Manager
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42. Master Production Record
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43. Master Production Record
Bill of Materials
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44. Master Production Record –
Manufacturing Instructions
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45. Batch Production Record –
Manufacturing Instructions
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46. Testing and Release of Final Product
is Sponsor’s Responsibility
 Samples pulled from production batch
 QC will test according to methods in
specifications
 In US, QA will disposition batch after
final product in made in the US
 in the UK and Europe, QP (Qualified
Person) is used for batch release
 Finished products are entered into
inventory
InstantGMP: Electronic Batch Record System for GMP Manufacturing
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47. Tracking of Inventory Distribution
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48. Security
Security Access assigned to:
• Each Person
• Each Role
• Each Screen
InstantGMP: Electronic Batch Record System for GMP Manufacturing

49. Quick Facts
 Developed by the manufacturing and
quality experts at PharmaDirections
 Integrated internet based application
developed through “Quality by Design”
approach
 20 Core Standard Operating Procedures
built in
 21 CFR Part 11 Compliant
 System has been in use since 2004
InstantGMP: Electronic Batch Record System for GMP Manufacturing

50. InstantGMP™ Summary
 Suite of virtual GMP manufacturing systems
 Takes full advantage of cloud-based computing
 21 CFR Part 11 compliant database with hard coded SOP
requirements
 Streamlines entire process of producing GMP materials
 Simplifies the documentation and approval procedures to
reduce production lead times
 Ideally suited to making any GMP material including APIs,
drug products, OTCs, generics and dietary supplements
 For more information, contact:
JPittman@InstantGMP.com
InstantGMP: Electronic Batch Record System for GMP Manufacturing