Approaches to Complying with cGMP During Phase 1 Guidance for Industry INDs

FDA Guidance for Phase 1 CTM

Provide guidance for producing Phase 1 materials Covers Investigational Drugs and Biologics Establishes rules for applying quality control principles Facilitate Phase 1 trials while protecting study subjects Covers small or lab scale production
Link to FDA Guidance
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Requirements - QC Procedures
Written procedures that are well defined
Equipment that is adequately controlled Data from production, including testing, that are accurately and consistently recorded

Requirements - cGMP Documentation

Personnel and training QC plan Facility and Equipment procedures Control of Components Written Procedures for Production Change Control Laboratory Controls Container Closure and Labeling Controls Distribution Documentation
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Requirements - Record Keeping

Equipment maintenance and calibration Production records and related analytical test records Distribution records All quality control functions Component records Maintain records for 2 years after trial completed
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GMP Batches in Non-GMP Areas

InstantGMP complies with FDA guidance for Phase 1 supplies. CROs can do GMP work in same equipment/lab as development work Tox batch can be made GMP and used in Phase 1 trial Medical device developers can produce GMP finished products
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Scalable Solution
InstantGMP

From small development batches To full production batches

cGMP: Challenges of Traditional Systems

R&D contract manufacturing is a complex process.
Wide array of regulatory requirements Reality of dealing with continual changes as projects progress 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

InstantGMP is our manufacturing service that has been built from the ground up to meet these challenges
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InstantGMP - A new approach to contract 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.
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InstantGMPTM
A unique R&D contract manufacturing service that:
Allows sponsors to view and interact with manufacturing information in real time.

Can rapidly react to changes and delays without missing a deadline.

Because:
It offers flexibility, speed, proven procedures, access to real-time information and efficient data flow at all points during the manufacturing process.

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InstantGMP - The Manufacturing Application

Foundation of CFR 21 Part 11-compliant software and an all-encompassing, paperless quality system

Internet-based infrastructure
Data is automatically visible to all decisionmakers at the same time Eliminates delays created by traditional linear processes
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Comprehensive Solutions to cGMP

Specs
Purchasing

Instant GMP
Inventory Training

Production

Information is automatically updated everywhere in the system, Sponsors can access their projects from any Internet-connected computer

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Advantages
InstantGMPTM enhances control, visibility, efficiency and compliance of the regulated

Life Science manufacturing process.

Manufacturing Purchasing Project Team

Sponsor

Cloud Server

QA
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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. Can only issue approved raw materials. Reconcile Lot receipts, issues and returns. Predefined values for entries in batch records. Electronic signatures. Issues Requisitions. Limited access.

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Control
Drop down lists to ensure accuracy

Batch Production
Digital signature with date stamp

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Visibility
Available via the internet Review and sign records from any location Access controlled by firewall protection Manage access for employees, partners and sponsors

ANYWHERE ANY TIME

Remote Site Manufacturing

Remote Site

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Visibility

Review all areas of batch record via tabs: Cover Page, Approvals Page, In Process Tests, Bill of Materials Equipment List and Manufacturing Instructions Steps

Review and update manufacturing steps online

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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 Create Purchase Orders for approved vendors Receive materials and manage inventory Automated Master and Batch Production Record copies BOM created as part of record Inventory depletes as batch is being run Documents are transmitted electronically and signed electronically.
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Efficiency

Vendors, Tests and Methods need to be added only once

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QA Compliance
cGMP compliance controls are built into the system. Some of the many features: Limited access based on user/role Materials quarantine/restricted until QA approval Required signatures at specified batch record steps

Component reconciliation
Training records Specification version control Complete automated audit trail

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QA 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 materials status

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Process Flow Preparation for Manufacturing

API, excipients and components identified Assign Part #s, tests, methods, Specs

PM Initiates
Project

Vendors Qualified? Quality Manager

Yes

Yes Quality Manager

Specs Approved?

No Project Manager

Vendor Qualification

Select Personnel and Roles

Project Definition Completed

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Process Flow Material Management

Vendors In DataBase? Tests In DataBase? Materials In DataBase?

No Issue Purchase Order

No

Update DataBase

No

Specs Approved?

No

Yes

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Process Flow Material Management

Receipt at Warehouse

Record into Inventory

Released

Yes

Available for Bill of Materials & Production

No Quarantine, Test & Release Quality Manager

Facility Manager

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Process Flow - Production

Manufacturing Instructions

Bill of Materials

Master Production

Batch Production

Approve Batch Record

In Process Tests

Equipment

Quality Facility Manager Manager

Sponsor

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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 Product has been in use since 2004
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InstantGMP

Pharmaceutical Contract Manufacturing with a view

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 clinical trial materials Simplifies the documentation and approval procedures to reduce production lead times Ideally suited to the global market place - manufacturing can be done in any geographical region while all data and intellectual property is securely stored in US based servers For more information, contact: JPittman@InstantGMP.com
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