Single-Use technologies supply materials to the biomanufacturing process that replace the need for stainless steel and traditional manufacturing processes which require extensive validation and process development.
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Quality System Expectations : Single-Use Materials
1. Quality System Expectations
Disposables (Single-Use
Materials) use in the Manufacture
of Drugs and Biologics
Bill Holden
Global Quality Leader
W. L. Gore & Associates, Inc.
Gore PharmBIO products
2. Agenda
Single-Use Technologies Movement
cGMP CFR 820 Applicable Practices
Supplier Qualifications
Material Qualifications
Minimal Quality System Standards
3. Single-Use in Pharma & Biotech
Single-Use technologies supply materials
to the biomanufacturing process that
replace the need for stainless steel and
traditional manufacturing processes which
require extensive validation and process
development.
4. What is the Movement?
Increased availability of Single-Use
materials are replacing traditional stainless
steel processes.
– Use in Single batch or limited campaigns
– Reduced process validations
– Validations allow for re-usable elements
5. Advantages
Decreased Cycle times (Batch to Batch)
Decrease Overall Captial Investment
Decreased Labor
Decreased New Product Introductions time
Increased Flexibility
Increased Potential Capacity
Decreased In Process Waste
6. Disadvantages
New Extractables/ Leachables must be determined
for product
Increased cost of consummables
Increased need for Vendor Audits
Qualified Supply Sources are limited
Increased potential for scrap of unused
components
More Solid Waste
7. The Path to Single-Use Process
Systems
Traditional Single-use
stainless BioProcess
steel Container Systems
Large capital Less capital
SIP No SIP
CIP No CIP
validation validation
9. Supplier Qualification (Expectations)
Limited Validated Suppliers
Expectations of Minimal Quality Standards
Applicable cGMP standards
ISO cGMP
21 CFR 820
Extractable CARS/
PARS
Audit
Supply Training
Robust
Control Quality
Traceability
System
10. Applicable cGMP 21 CFR 820
Applicability 820.1 (a)
– Current good manufacturing practice (CGMP)
requirements are set forth in this quality system
regulation. The requirements in this part govern the
methods used in, and the facilities and controls used
for, the design, manufacture, packaging, labeling,
storage, installation, and servicing of all finished
devices intended for human use.
– If a manufacturer engages in only some operations
subject to the requirements in this part, and not in
others, that manufacturer need only comply with those
requirements applicable to the operations in which it
is engaged.
11. Suggested Applicable Requirements
for tubing Molded Manifolds
Subpart B--Quality System Requirements
§ 820.20 - Management responsibility.
§ 820.22 - Quality audit.
§ 820.25 - Personnel.
Subpart C--Design Controls
§ 820.30 - Design controls.
Subpart D--Document Controls
§ 820.40 - Document controls.
Subpart E--Purchasing Controls
§ 820.50 - Purchasing controls.
Subpart F--Identification and Traceability
§ 820.60 - Identification.
§ 820.65 - Traceability.
Subpart G--Production and Process Controls
§ 820.70 - Production and process controls.
§ 820.72 - Inspection, measuring, and test equipment.
§ 820.75 - Process validation.
Subpart H--Acceptance Activities
§ 820.80 - Receiving, in-process, and finished device acceptance.
§ 820.86 - Acceptance status.
13. Basic Requirements (Manufacturing)
ISO 9001:2008 3rd Party certification
Demonstrable Quality System
– Responsible Quality Unit/Team
– Trained, responsible production team
members
– Appropriate Document Management System
Controlled Documents
Demonstrable Procedures, Work Instructions, etc.
14. Basic Requirements (Manufacturing)
Viable Preventative and Corrective Action
Systems
Controlled and verified suppliers
– Approved supplier list
– Verified materials (TSE/BSE Policy)
Identification and Traceability Systems
– Manual or Electronic
15. Basic Requirements (Manufacturing)
Appropriate Production Controls
– In Process Assurance of Intermediate Assembly
– In Process Traceability
– In Process Acceptance Standards
– Equipment Validations/ Calibrations/ Preventative
Maintenance
Appropriate isolation and identification of non-
conforming product
– Segregation/ labeling, and disposition
16. Basic Requirements (Manufacturing)
Organized Handling Operations
– Controlled labels and identification of parts
and components
– Assurance of packaging integrity of parts and
components
– Assurance of cleanliness of parts and
components
– Viable location traceability (manual or
electronic)
17. Basic Requirements (Manufacturing)
Records
– DMF/DHF- Batch History Record
Includes the Bill of Materials (BOM, Drawing,
additional customer specifications)
Assures traceability of part manufacture and raw
components
Assures any linkage from customer complaint can
be made.
18. Basic Requirements (Manufacturing)
Internal Audits
– Yearly Internal Evaluations
Facilities
– Clean and Organized
– Bioburden/ Particulate readings
– Appropriate environmental and disposal
controls for the parts manufactured.
– Pest control program and maintenance
19. Basic Requirements (Materials)
Sterilization method /validations (GAMMA/ STEAM, etc. )
Chemical Compatibility
Physical Properties
Extractables Test Data
Biocompatibility (USP VI Test Data)
Applicable Materials Testing
– Application specific testing
Endotoxin
Bioburden
FFU (Fitness for Use) specific testing
20. Methods of Evaluation
Desktop Audit
Supplier Visit/Audit
Data Review
Supplier Performance Data
– Delivery
– Corrective Actions
– Collaborations
