Organization of QA
cGMP compliance
BIT 230
Chapters 1 and 2 (Huxsoll)
TQM
Total Quality Management
Approach a company uses day to day
7 strategies
Leadership
Information and analysis
Strategic planning
Human resource development and
management
TQM
Strategies continued
Process quality management
Quality and operational results
Customer focus and satisfaction
• Often focus is on the customer – so last but
not least- customer driven success
Quality Assurance
A unit that is part of the whole
US CFR – United States Code of Federal
Regulations- defines the quality unit’s job
Approve or reject all materials associated
production of any product – includes
containers, components, labels, other
packaging materials
Quality
Ensure purity- # 1 goal
Also strength and quality
New biotech lose site of quality – develop
science first, then quality
Should be done in parallel to have less
problems later
Role of QA better established in large
pharma
Quality Control (QC) within
QA
QC is a testing function
Defined as fitness for use
Need to be integrated throughout process
Fitness for use divided into several
components - next slide; these 4 major
components subdivided into further
categories - THESE important regardless
of product
Manage from the top down
Upper management sets tone for
company style and compliance
Biopharm products complex- therefore
need “quality of manufacture”
CFR definition of QA unit - 7 points
(pertaining to a nonclinical lab)
1. Maintain master schedule sheet
2. Maintain protocol records
3. Inspect each phase of study
4. Submit periodic written status reports
5. Ensure SOPs are followed
6. Review final study report
7. Prepare a signed statement (with
inspection dates, etc. for final study).
QA vs. QC
Will discuss more later, but major point of
confusion
QC function limited - testing methods
“Controls the product” in production
CFR does not clearly define QC- more of a
QA definition
Product production
QA defines systems and methods to
ensure quality of a product- QC tests
various aspects of a product as it is being
developed
Which function: QA or QC?
SOP for measuring pH of a production run
measuring pH of a production run 3 X
daily
filling in batch records
developing batch record
signing and dating batch record
confirming integrity of raw material
defining raw material to be used in
production
Routine functions of QA
Testing
Documentation
Labeling
Vendor audits
Routine QA functions
cont’d
Raw material receipt
Product release
Product Specifications
Training
Other QA Functions
1. Company awareness
long and short term goals
QA part of business involvement team
if QA operates as a separate group company
not as successful
upper management must commit to QA
sometimes overlooked in biotech
Other QA Functions cont’d
2. Product knowledge
without it failure is likely
know the product, process used to develop
it, support systems, and product use (e.g.
target population- FOSAMAX example - older
population, people with arthritis, people with
difficulty sitting up)
AGAIN, product defined by systems
established to assure its consistency
Other QA Functions cont’d
3. Facility knowledge
function of equipment
function of local environment of production
facility
need personnel expertise in these areas proper training, etc.
don’t work in a vacuum
Other QA Functions cont’d
4. Networking through outside
organizations
regulatory agencies
other companies with similar product line
conferences
understand industry and regulatory
standards
Other QA Functions cont’d
5. Risk analysis/decision making
analyze situations
make recommendations- if so, assure proper
modification of SOP
risk/benefit ratio to modification of SOP
Page 8 - quality systems functions and
percentage at various companies
http://www.mtmlaboratories.com/janusmtmportal/portal/temp
Establishing QA
Define the function of QA (chicken and
egg problem)
Should start before production of material
to be used in Phase 1 clinical trials
Start when biotech company is small
What quality systems are needed
Risks of leaving out some QA functions?
New company QA
What type of product
Complexity of end material
Production method
Financial considerations
Stage of development
is product in-licensed?
is there some parameters for product
development already determined?
Factors to achieve Quality
Page 9-10 (points 1-12)
Key points:
Quality indicators discussed not hiddenproblem in other sectors of company, not just
quality (e.g. Vioxx, was everything
transparent?)
resource allocation
good exchange of dialogue
accept responsibility (e.g., Tylenol case)
QA functions
Assay development and validation
equipment validation
process validation
vendor qualifications
raw material and product specs
documentation
QC testing
People, people, people
In-house expertise (product & quality)
need for external expertise (advisory, etc.)
add staff as need arises
proper training
other company personnel should be part
of day-to-day QA decisions and processes
avoid attitude that QA is not needed
QA organization
Figure 1.3, Page 11
Compares organization at various stages
of a company
Large pharma has a separate QA
department with significant staff
Day-to-day goals
Setting standards
sets standards for goals for both QA group
and entire company
written
especially important for process deviations
based on expectations and outcomes for
product
How is the experience gained with a
product?
Day-to-day cont’d
Implement training
can’t really do it here in class- need to be on
the job; but learn the basics here (e.g.,
microbiological procedures - sterile technique)
ongoing training needed
make time for training (can easily be cast
aside)
make training a goal (objective) of the
employee’s yearly plan- reward built in
Day-to-day cont’d
Feedback
constructive
realistic
communication key
support time commitments and constraints
What is your time back up plan?
Coming into cGMP
compliance
Chapter 2
How does a company look
pre-GMP?
Small company- few to a few dozen
employees
mostly research scientists
very few others as administrative,
production, testing and support
operating style develops quickly
“corporate culture”
problems with this during mergers
Pre GMP company
Creative and fast
long hours for employees
good interaction
react quickly to issues - not much red
tape
less documentation - many things decided
verbally with no paper trail- can lead to
problems as the company grows
costly
GMP compliant company
Large pharmaceutical companies
many employees in production, testing,
support and administrative
equal or outnumber R & D scientists
follow accepted, validated, approved
methods
slower to change
large volume of documentation
Moving from Pre- to GMP
Company has identified product to
produce; plan needed to develop product
under GMP
Be part of company master plan
site able to produce GMP product or must
find alternate manufacturing facility
Regulatory affairs personnel - always jobs
in this area!
Moving to GMP
Finalize plan
Determine budget (may be when a
company goes public)
START the project
I’ll say it again: documentation!
How is the documentation used?
GMP required documents
Process variables
analytical methods used to determine
quality of intermediate and final products
functioning of support systems
facility is functional and suitable
clean and functional equipment
reproducibility
Remember Flu
Vaccine
problem this
past Fall??
Clinical production
Need GMP here, too
included to document:
raw materials
labeling
batch records
equipment/building preventative
maintenance
Yields
Figure 2.1, page 19
GMP training
On-the-job training necessary
“validation” of personnel
trainer content expert; experience as
instructor
upper management acknowledges the
need for on-going training
often external trainers brought in
(certified)
GMP training
Audits - internal and follow same GMP
guidelines as external audit
written and well organized
follow approved procedures
auditors trained and from outside immediate
work area
External audits include review of internal
audits, although not FDA’s current policy
Documents for auditing
Master schedule
generated up to 2 years in advance
may be included in SOP
internal audits not surprise
but, not a time to do everything at last
minute; must perform duties regularly
hold post-audit meeting
have corrective action and back-up plans
There’s never time
to do it right, but
always time to do
it over!