Download “Cold Chain” and Why it Matters Putting the Whole Package/Process

• What Regulations Apply to Me and Why?
• What is “Cold Chain” and Why it Matters
• Putting the Whole Package/Process
together within Your Industry
Pharmaceuticals and
The Regulated
Environment WE Live In
21 CFR 11
• Electronic Signatures and Records
21 CFR 210
• cGMPs For Manufacturing, Processing,
Packing, or Holding Drugs
21 CFR 211
• cGMPs For Finished Pharmaceuticals
21 CFR 600
• Biological Products
21 CFR 606
• cGMPs For Blood and Blood Components
21 CFR 800
• Medical Devices
Data
Distribution
Equipment
Facilities
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Personnel
Utilities
Warehousing
Etc…
What are
the goals of
all of these
regulations?
• Safety and Efficacy
of the Product
How does
one meet
these goals?
• State of Control
Document
Control
• The management of documents
within an organization promoting
continuity of lifecycle. Accomplished
through the use of a standardized
quality system.
Formalization
of Processes
• The documentation of procedures to
ensure repeatability and audit ability.
Document
Format
Auditing
Corrective/
Preventative
Actions
Approval
Process
Documentation
Standards
Deviations
Training
Standard Operating
Procedure (SOP) document
format should be
determined PRIOR to
implementing the
document control program.
The Approval Process for any controlled
document should be routed through the
individuals that are most appropriate for the
document.
The review/approval process should involve an
appropriate number of individuals to put a
critical eye to the process.
Must be complete
• No empty fields
Corrections must be
done in GMP format
• Initial, date of correction,
single line through
incorrect information
Must be free of
obliterations, erasures,
and correction fluid
Signatures should be
dated when they are
made
Basic cGMP Training
Overall Job Orientation
SOP Specific Training
Training Records
Re-Training
Measurement
Deviations
• Documentation of instances that SOP’s were
not followed.
CAPAs
• Plans to correct a situation causing a
deviation or to proactively address a situation
that may cause a deviation in the future.
Internal
Auditing
• Ensuring Compliance
With Existing
Procedures
Vendor
Qualification
External
Audits
• Ensuring Vendors Meet
The Regulatory Needs
• Investigations Into Your
Existing Quality System
By Regulatory
Organization or
Potential
Customers/Partners
Helps Maintain Validated State of Equipment
Manages Change Through Documentation and Evaluation
• Changes should be proposed before being made.
• Proposed changes should be evaluated by an experienced person/panel.
• Evaluation should include a conclusive argument as to the re-validation of
the equipment.
• Once signed off, documents should be filed with validation lifecycle
documents.
SOPs should fit your operation
The SOPs should be developed using a risk based approach.
• What are your critical processes?
Electronic means should augment your paper based system
• 21 CFR Part 11 should be followed for critical systems
Processes that have a direct
impact on the product should
all be formalized.
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Receipt
Shipping
Storage
Maintenance
Pest Control
Security
Calibration
Validation
Formalization of
Processes Need
to Address All
Aspects of the
Mission
Gaps in
Integration
Create
Chances to
Adulterate
Product
• Are You Willing To Take Them?
SOPs Need to Cover
Not Only the Process,
But Also All of the
Critical Pieces of
Equipment/Processes
Used Within and
Outside the Process.
Design Document Control System
Develop Quality System
Take Risk Based Approach Toward Your Equipment/Processes
Decide Which Are Critical to Your Mission
Formalize the Processes
Audit ALL of the Processes
Improve Them as They Evolve
“Cold Chain”
Management in the
Pharmaceutical
Industry
• Starts Upon Acceptance and Ends When Product Administered or Destroyed
• Not Always “Cold”
• Label Approved via the FDA
• Label is Benchmark of Proper Stewardship
• Data Can Ensure the Safe Use of Product After Excursion
• Law Puts Responsibility on Possessor
• Responsible for Safety and Efficacy of Product
• WHO Study - 50% of Products Compromised
• Ensure Product Via Proactive Use of Materials Management Tools and Data
Generated
• Data is Essential to Proving Compliance
• Proving Compliance with Standards and Regulations is Challenge
Equipment
Product Efficacy
Regulatory Compliance
Real Time Management
• Multiple Sites and Building
• Many Brands and Generations
• Various Equipment
• Validation
• Preventive Maintenance
• Equipment Files
• Calibration
• Label Requirements
• Data Records
• Liability / Risk management
• Patient is more educated than before
• FDA / JCAHO
• Birth to Death records
• Guilty until proven otherwise
• QC /QA
• Eliminate moving target – define your system
• Subcontractor Meets Standards?
• Alarm notification
• Data retention / vaults
• Reporting
• Support team
Process and Practices Highly Fragmented
In Most Cases Employs Low-Tech Solutions
Low Quality Controls
Significant Failure Rates
• “ An estimated 17% to 37% of providers expose vaccines to improper
storage temperatures. Refrigerator temperatures are more commonly
kept too cold than too warm. Out-of-range temperature readings require
IMMEDIATE action. It is estimated that more than $100 million worth of
vaccine is exposed to freezing temperatures each year in the United
States”.
• Is Automated Better Than Manual or Does it Matter?
• Can I Meet the Requirements Without A System or Process?
• What Do the Regulators Say
• Medication Refrigerator Temperature Logs
Q: Are we required to maintain temperature logs for medication storage refrigerators and freezers?
A: Joint Commission does not specifically require temperature logs for refrigerators and freezers used
for medication storage. Standard MM.2.20 requires that medications be stored under necessary
conditions to ensure stability. EC.6.10 additionally requires that you describe and implement
processes to maintain and monitor equipment performance. If your organization chooses to use
temperature monitoring to achieve this, the monitoring method must track temperature in an
ongoing fashion to indicate whether or not internal temperature has deviated from the required
ranges for all drugs stored. In addition, the organization should have a defined process outlining
disposition of medication from a refrigerator or freezer which has deviated from the recommended
temperature range
“The United States Pharmacopoeia (USP) is an official compendium which defines various terms relative to the proper management
of time, temperature, sensitive medications and prescription products. Although the USP is not “the law” it is used by the Food and
Drug Administration, state authorities and the courts to establish standards of practice.”
Freezer
• A place in which the temperature is maintained thermostatically between -20C and
-10C (-4F and 14F).
Cold
• Any temperature not exceeding 8C (46F). A refrigerator is a cold place in which the
temperature is maintained thermostatically between 2C and 8C (36F and 46F).
Cool
• Any temperature between 8C and 15C (46F and 59F). An article for which storage
in a cool place is directed may, alternatively, be stored in a refrigerator, unless
otherwise specified by the individual monograph.
Room Temperature
Controlled Room
Temperature
• The temperature prevailing in a work area.
• A temperature maintained thermostatically that encompasses the usual and
customary working environment of 20C to 25C (68F to 77F); that results in a mean
kinetic temperature calculated to be not more than 25C; and that allows for
excursions between 15C and 30C (59F and 86F) that are experienced in
pharmacies, hospitals and warehouses. An article for which storage at Controlled
Room Temperature is directed may, alternatively be stored in a Cool Place, unless
otherwise specified in the individual monograph or on the label.
• System Should Have Real Time Product Support, Oversight and Data
Management
• Provide Continuous Monitoring of Critical Alarm Parameters
• Established Contact Procedures for Designated Emergency Contacts
• Powerful & Economical System Based Cold Chain Management Tool
• Continuous Witness Providing 24/7 Oversight of Your Critical
Systems
• Monitoring Possibilities
• 90% of Applications are Temperature
• Computers, Flood, Power Outage, Open Doors
• Application Should be Continuously Upgraded and Applied Process
Improvements Implemented
• 100% Scalable to Customer Needs