Qualification of Ancillary Reagents and Materials: An

16 Pages·2008·0.55 MB·English

Qualification of Ancillary Reagents and Materials:
An Industry Approach
Gary C. du Moulin, Ph.D., M.P.H.
Senior Director, Quality Compliance
Genzyme Biosurgery
Qualification of Ancillary Reagents and Raw materials is a Critical Part
of the Modern Pharmaceutical Quality System (PQS)
ICH Q10; Section 3.1.3 (commercial manufacturing)
“The pharmaceutical quality system should
assure that the desired product quality is
routinely met, suitable process performance is
achieved, the set of controls is appropriate,
improvement opportunities are identified
and evaluated, and the body of knowledge
is continually expanded.”
The PQS is the foundation for each of the drug
manufacturing systems
§ Production System
§ Facilities and equipment system
§ Laboratory control system
§ Materials system
§ Packaging and Labeling systems
Assuring the Pharmaceutical Ingredient Supply Chain
§ Most pharmaceutical ingredient safety problems have
been due to a lack of good supply chain controls
throughout the entire distribution chain from the
manufacturer to the user
§ History of product poisoning –Late 2006
contamination of cough syrups and antihistamines
with diethylene glycol –dozens die
§ How does it happen?
§ Similar organoleptic properties between similar materials
§ A long and questionable supply chain
§ Alteration/adulteration of documents throughout the supply
chain
§ Lack of analytical testing/verification of contents
Prevent Use of Substandard Ancillary reagents by Implementing a
comprehensive approach to monitoring ingredient supply chain integrity
§ Only do business with trustworthy sources
§ Establish a robust supplier qualification program (e.g. vendor
audits, quality agreements, appropriate ongoing QC of incoming
lots)
§ Verify each ingredient shipment comes from approved
suppliers/manufacturers
§ Verify shipments came through expected routes and were not
diverted
§ Thoroughly examine containers upon receipt for damage and
evidence of tampering
§ Insist of original certificate of analysis (COAs); fax is not
acceptable –original papers with actual test results signed by QA
(ICH Q7A)
Genzyme’sMaterial Qualification Program: A Team
Approach
§ Quality assurance: manages the program, auditing,
documentation, metrics, management review,
investigations
§ Quality control: in process and lot release testing, raw
material testing
§ Manufacturing: metrics, deviations and investigations
§ Manufacturing Technical Services: Validation and new
material assessment
§ Regulatory Affairs: communication with regulatory
authorities
§ Materials Management: purchasing, inventory control
Building a Raw Materials Program
§ Issuance and control of part numbers
§ 5 digit number where the first 2 digits indicate the category ofan item
and the last 3 digits indicate the order in which they were assigned,
ex. 21XXX; 2-purchased biochemicals, 1-prepared media, solutions,
enzymes
§ Includes steps for requesting, revising, controlling and obsoleting
part numbers for materials, labeling, etc
§ Determining inspection classification
§ Building a raw material qualification program
§ Materials Management organization
§ Compliance Development: a weekly meeting where class
assignment, criticality, and other material issues are discussed
§ Change Control
§ Vendor qualification
§ Raw materials validation
§ Metrics and management review
Inspection Classes
§ Inspection Class I: Items that do not require disposition by
Quality Systems, ex. Pasteur pipettes, heat sealable pouches
§ Inspection Class II: Materials that require inspection by Quality
Control against a Material Specification and a Certificate of
Analysis received with each vendor lot, ex. Tissue culture flasks
§ Inspection Class III: Materials that require inspection by Quality
Control against a Materials Specification and acceptance testing
upon receipt, ex. Insulin solution
§ Inspection Class IV: Materials that require inspection by Quality
Control against a Material Specification, a Certificate of Analysis
with each vendor lot and prequalification testing on samples of
each vendor lot., ex. Fetal bovine serum, cholera enterotoxin
Definition: Critical Materials
§ Definition: A material in contact with cells which could alter
either the growth characteristics of the cells or the ability ofthe
cell culture to meet lot release specifications.
§ All Critical Materials are classified “Inspection Class II”or higher
§ Any critical material must be adequately described by the
manufacturer through records detailing the formulation or by the
provision of the data in the form of a Drug Master File (DMF)
§ Critical materials include materials of animal origin, primary or
secondary labels, final packaging materials, product insert or
instructions for use, and immediate product container or closure
systems
§ A checklist is completed to insure determination of “critical
material”is appropriate.
§ Vendor must be qualified
§ Full documentation in QA
Material Specifications Developed for each Class II-IV Raw
Materials
§ Approval
§ Description
§ Classification
§ Sampling Plan
§ Specifications
§ Other Requirements
§ Storage/transportation conditions
§ Control/Expiry
§ Safety
§ MSDS