what are dietary supplements?

InstantGMP: Electronic Batch Record System for GMP Manufacturing

WHAT ARE DIETARY SUPPLEMENTS?

A PRESENTATION BY INSTANTGMP

InstantGMP: Electronic Batch Record System for GMP Manufacturing2

Topics

Dietary Supplements Dietary Ingredients GMP Manufacturing of Dietary

Supplements InstantGMP Manufacturing


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


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

http://www.fda.gov/Food/FoodDefense/Bioterrorism/FoodFacilityRegistration/default.htm


How are Dietary Supplements Supplied? Available in many forms that can be

taken by mouthCapsulesSoftgel capsulesGelcapsTabletsLiquidsPowders


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"


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"


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

http://www.gpo.gov/fdsys/pkg/FR-2007-06-25/html/07-3039.htm

http://www.gpo.gov/fdsys/pkg/FR-2007-06-25/html/07-3039.htm


Challenges of GMP Manufacturing

Good Manufacturing Practices are complexWide array of regulatory requirementsHigh time and cost to set up quality systemLong cycle times for QA review and correctionsTraining and compliance to SOPs is lengthyDocumentation coordination and data tracking is

laboriousHigh cost of compliance

InstantGMP™ is the manufacturing system that has been built from the ground up to meet these challenges


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™ - 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


Advantages InstantGMPTM enhances control, visibility,

efficiency and compliance of the regulated Life Science manufacturing process

QASponsor

Project TeamPurchasing

Manufacturing

CloudServer


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

Manufacturing

Remote Site Remote Site

ANYWHEREANY TIME


EfficiencyQC, QA, Warehouse, Purchasing, Inventory and Manufacturing activities and records are linkedSome 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


EfficiencyVendors, Tests and Methods need to be added only once


ICH Q7A Good Manufacturing Practice

International Conference on Harmonization

ICH Member Countries –European Union (EU) - 27 countriesJapanUnited StatesAustraliaCanadaNorway


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


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 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


Automated Compliance

cGMP compliance controls are built into the systemSome 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


Manufacturing Facility Compliance is Sponsor’s Responsibility

Facility and flow designed to minimize potential contamination and mix-ups

Defined areas for:ReceiptQuarantineStorageProductionPackagingWashing


Small ScaleCTM Manufacturing Facility Example

Material flow


GMP Facility Inspection is Sponsor’s Responsibility

FDA conducts facility inspections for products to be sold in the USDoesn’t include CTM facilitiesDoesn’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


Typical GMP Facilities in US and UK


MaterialsOnly QA approved materials can be used in CTM manufacturing

Excipients Containers/Closures

ComponentsWork in Process


Getting ready for manufacturing – Control of Materials

No

Vendor Qualification

API , excipients and components

identified

YesPM InitiatesProject

VendorsQualified?

ProjectDefinitionCompleted

QualityManager

ProjectManager

SpecsApproved?

Assign Part #s,tests, methods,

Specs

Select Personnel and Roles

Yes

QualityManager


Automatic Control

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

Automated rules and entries, that are based on the SOPs, are integrated in the system.


Vendors

QA shall qualify vendors for materials used in CTM

Phase 1 CTMPaper based quality survey

Phase 2 CTMEither a paper based quality survey or an on-site audit

Phase 3 CTMOn-site audit


Rooms and Equipment Room List – names of manufacturing rooms Room Log – record of activities in rooms, e.g.

CleaningMaintenanceBatch use

Equipment List – names of production equipment Shows up in drop down lists in batch records

Equipment Log – similar to Room Log


Room Log


Equipment Log


SpecificationsQA 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 InstructionsSafety and Handling


Specifications have version control to keep track of changes

Most recent specs apply, but old specs must be kept available for review

Specifications


Specifications can have Safety, Handling and Sampling instructions

Specifications


Specifications include Test, Methods and Limits that will go on Certificate of Analysis

Specifications


Process Flow – Material Management

Receipt at Warehouse Record into

I nventoryReleased

Quarantine,Test &

Release

No

Available for Bill of Materials &

ProductionYes

QualityManagerFacility

Manager


Receiving


Inventory

Once materials are received, they automatically go into inventory with aQuarantine status. Only QA can change the status.


Automated Inventory Compliance

Materials need to beIn 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


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.


Process Flow - Production

Master Production

Bill ofMaterials

ManufacturingI nstructions

Batch Production

ApproveBatch Record

QualityManager

FacilityManager

I n ProcessTests

Equipment

Sponsor


Master Production Record


Master Production RecordBill of Materials


Master Production Record –Manufacturing Instructions


Batch Production Record –Manufacturing Instructions


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


Tracking of Inventory Distribution


Security

Security Access assigned to:• Each Person• Each Role• Each Screen


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™ 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:

[email protected]

what are dietary supplements?

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