Biopharmaceutical Quality

Cynthia H Sarnoski PhD28th June 2012

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What is Quality?

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Quality

Quality is never an accident;

it is always the result of high intention,

sincere effort, intelligent direction and skillful

execution;it represents the wise choice of many alternatives.

~ William A. Foster ~

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Basis for Quality Requirements

Customer expectationsGood Business PracticeGood Science PracticeRegulatory conformance

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Regulatory Agencies

FDA (Food and Drug Administration)To promote/protect public health by helping safe/effective products reach the market in a timely way.

EMEA (European Agency for the Evaluation of Medicinal Products)To protect public health thru evaluation and supervision of

medicines

Other National Agencies (MHRA, IMB, ANVISA, etc.)

To ensure medicines sold/supplied to other countries are safe, efficacious and meet required quality.

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Requirements within the Code of Federal Regulations 21CFR 211.22 for the Quality Unit

Role of GQO

According to US regulations,

the Quality Unit

must act independently

of production/manufacturing

in executing it’s responsibilities.

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Current Good Manufacturing Practices 21CFR 211

Establish requirements for the manufacture of safe, effective, potent, pure and stable products.These include:Facilities, Equipment, Process, and Materials are appropriate for intended purpose.Appropriately skilled personnelManagement ControlsDocumented evidence

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Typical Quality Unit

Quality Control +Quality Assurance__________________Quality Unit

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Quality Unit Responsibilities

Approve or reject all Production MaterialsReview and approve allProcedures and SpecificationsValidation/Qualification documentsChange ControlsRegulatory SubmissionsEnsure systems/programs are established and maintained for:Adequate inspection, sampling, and testingIdentification of deviations, investigations and corrective actions/preventative actionsMany, many more . . . . .

Role of GQO

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Quality is maintained throughout the product life cycle…

Cell BanksRaw

MaterialsComponents

Cell Culture PurificationActive

SubstanceFinal

Product

<<<<<<<Quality Assurance + Quality Control >>>>>>>>

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Key Quality Processes

Quality Control

Product Disposition

Marketed Product Support

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Quality Control Sampling and Testing

● Raw Materials● Media● Components● Process materials● Water● Environment● In-Process● Cell banks● Bulk drug substance● Finished Product

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Laboratory Controls

Sample chain of custodyCompendial standardsValidated methodsReagent controlReference standardsEquipment ValidationEquipment CalibrationDocumentation

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Testing Requirements

Adventitious agent contamination controlViral, microbialPotencyPurityProcessStabilityCharacterizationIdentitySafetyComposition: excipientsForensics

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Drug Product Testing

E n v iro n m e n ta lM o n ito ring

E xc ip ie n ts

E n v irn m en ta lM o n ito ring

R a wM a te ria ls

E n v irn m en ta lM o n ito ring

R a wM a te ria ls

M e d iaC o m p o ne n ts

E n v iro n m e n ta lM o n io to ring

M e d iaC o m p o ne n ts

E n v iro n m e n ta lM o n io to ring

M e d iaC o m p o ne n ts

C e llB a nk

In p roce ssT e s ts

P ro du c tionC e lls

In P roce ssT e s ts

P ro ce ssM a te ria ls

F e rm e n ta tionIn te rm ed ia te

In P roce ssT e s ts

P ro ce ssM a te ria ls

P u rif ica tionIn te rm ed ia te

In P roce ssT e s ts

R e s in s P ro ce ssM a te ria ls

A c tiveS u bs tan ce

C o n ta in erC lo su res

In P roce ssT e s ts

D ru g P ro d u ct

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Product Disposition

Batch Record ReviewTest Record ReviewInvestigationsChange Controls

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Product Disposition continued

Key responsibilities at Product DispositionMarketing authorizationCompliance with cGMP’sUnderstanding impact of deviations --

quality, safety, efficacy

Engagement in quality systems supportingproduct manufacture and control

Understanding those deviations requiring regulatory action

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Marketed Product Support

● Stability●Cell banks●Active Substance●Final Drug Product●Annual Product ReviewsField Alerts & Biological Products Deviation Report (BPDRs) Product QualityInquiriesComplaintsAdverse Events

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Marketed Product Support continued

Inquiries A non-medical comment, question or request for

information such as product availability, temperature/stability, product expiry dating, dosing, product formulations/ingredients, chemical composition of componentry, etc.

Complaints A report regarding an alleged defect associated

with physical, chemical, microbiological, or other aspect of a product, component, or package.

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Marketed Product Support continued

Adverse Events

Any untoward, undesired or unplanned eventin the form of signs, symptoms, disease or

laboratoryor physiological observations occurring in a

personadministered a product

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Quality Personnel Competencies

Good science practicesProblem solvingGood analytical practicesGood documentation practicesEffective communication skillsVerbal and writtenDecision makingPursuit of “WHY?”

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Questions?