Organization of QAcGMP compliance

BIT 230Chapters 1 and 2 (Huxsoll)

TQM

Total Quality ManagementApproach a company uses day to day7 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 goalAlso strength and qualityNew biotech lose site of quality –

develop science first, then qualityShould be done in parallel to have

less problems laterRole of QA better established in large

pharma

Quality Control (QC) within QA

QC is a testing functionDefined as fitness for useNeed to be integrated throughout

processFitness 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

QA function(pertaining to a non-clinical lab)

1. Maintain master schedule sheet2. Maintain protocol records3. Inspect each phase of study4. Submit periodic written status reports5. Ensure SOPs are followed 6. Review final study report7. 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 productionCFR 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 runmeasuring pH of a production run 3 X dailyfilling in batch recordsdeveloping batch recordsigning and dating batch recordconfirming integrity of raw materialdefining raw material to be used in

production

Routine functions of QA

Testing

Documentation

Labeling

Vendor audits

Vendor approval

Routine QA functions cont’d

Raw material receipt

Product release

Product Specifications

Training

Validation

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.mtm-laboratories.com/janusmtmportal/portal/template/Home/action/news_4.html

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 smallWhat quality systems are neededRisks of leaving out some QA functions?

New company QA

What type of productComplexity of end materialProduction methodFinancial considerationsStage 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 hidden- problem 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 validationequipment validationprocess validationvendor qualificationsraw material and product specsdocumentationQC testing

People, people, people

In-house expertise (product & quality)need for external expertise (advisory,

etc.)add staff as need arisesproper trainingother company personnel should be part

of day-to-day QA decisions and processesavoid 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

productHow 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 scientistsvery few others as administrative,

production, testing and supportoperating style develops quickly

“corporate culture” problems with this during mergers

Pre GMP company

Creative and fastlong hours for employeesgood interactionreact quickly to issues - not much red tapeless documentation - many things decided

verbally with no paper trail- can lead to problems as the company grows

costly

GMP compliant company

Large pharmaceutical companiesmany employees in production,

testing, support and administrativeequal or outnumber R & D scientistsfollow accepted, validated, approved

methodsslower to changelarge 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 plansite able to produce GMP product or must

find alternate manufacturing facilityRegulatory affairs personnel - always jobs

in this area!

Moving to GMP

Finalize planDetermine 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 variablesanalytical 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, tooincluded 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 personneltrainer content expert; experience as

instructorupper management acknowledges the

need for on-going trainingoften 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 areaExternal 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!