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Microbiology and Auditing

The document discusses considerations for auditing microbiological controls in pharmaceutical manufacturing, including evaluating quality systems, production processes, laboratory controls, materials management, and risk factors. It provides examples of criteria to assess for manufacturing, laboratory, and API/excipient audits, such as process flow, cleaning validation, water systems, and microbial limits. The purpose of the audits is to ensure robust microbiological quality systems are in place.

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Pravin Prabhakar
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338 views38 pages

Microbiology and Auditing

The document discusses considerations for auditing microbiological controls in pharmaceutical manufacturing, including evaluating quality systems, production processes, laboratory controls, materials management, and risk factors. It provides examples of criteria to assess for manufacturing, laboratory, and API/excipient audits, such as process flow, cleaning validation, water systems, and microbial limits. The purpose of the audits is to ensure robust microbiological quality systems are in place.

Uploaded by

Pravin Prabhakar
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PDF, TXT or read online on Scribd
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Microbiology and Auditing

Don Singer

ASQ Northeast Pharmaceutical GMP/Quality Conference 2011


Through the eyes of a
Microbiologist
Microbiology Audit = Inspection / Investigation
Systematic Auditing
• Planning
• Right People
• Tools
• Appropriate Objectives
Auditing approach
Corporate design or policy

• Team

• Independent
Purpose
Quality Systems

Build robustness into your quality systems

cGMPs
Types of audits with Evaluation of
Microbiological control
• Contract manufacture
• Contract microbiology laboratory
• Excipient manufacturer
• Active ingredient manufacturer
• Combination of any of the above

• Internal manufacture or laboratory


Quality Systems Inspection
Quality system
Production system
Laboratory controls system
Materials system
Packaging and labeling system
Facilities and equipment system
Microbiological Quality Risk
Management
• Dosage form

• Laboratory tests

• Materials management
Risk by route of administration
High
Parenteral
Ophthalmic
Otic
Wound topicals
Nebulizer solution
Intranasal solution
Inhaled - DPI
Inhaled - MDI

Topical cream
Topical ointment
Oral solutions, suspensions
Liquid-filled capsules
Tablet,
Capsule
Low
Lab tests risk from impact of results
High
Sterility Test
Bacterial endotoxin test

Antimicrobial Preservatives
Effectiveness Test
Biological assays

Microbial enumeration and


Specified microorganisms tests
Microbial identification

Media growth promotion

Low
Materials risk of contamination
Manufacturing process Classification
High
Animal or plant origin (e.g. lactose)
Unprocessed

Highly processed
Mineral origin (e.g. Talc)

Semi-synthetic origin (e.g. captisol, HPM)


Some bioburden reduction Mineral origin (e.g. dyes, aromatics)
processing

Synthetic origin (e.g. povidone)


Low
Audit Expertise
What is a QC Microbiologist?

Knowledge Base :
Science
Origin and Growth
Control
Microbiological Science
Origin and Growth
• Water (H2O)

• Nutrition (CHO, CHON, CHOOH, minerals, etc.)

• Presence or absence of components of air


Other Growth Factors
• pH
• temperature
• osmotic conditions
• light
Microbial Origin and Survival
• moderate to extreme environments
• solid to liquid
• dense to dilute
• atmosphere, humans and other living
organisms (animals - vegetation), water, soil
Role of a QC Microbiologist

Design for microbiological control

Monitor to continuously evaluate


Control
How to manipulate the environment

• Understand microbial growth limitations

• Determine how to reduce or eliminate


microbial growth

• Understand dynamics of environment and


microbiological growth / survival
Understand Thoroughly?

Do you have the appropriate


background and experience for
microbiological investigation?

If you do not, then partner with a Microbiologist


Tools to Assist
• cGMPs, guidance docs, pharmacopeias

• Quality tools such as


Useful Quality Tools
• Assessment checklist or survey (developed by
your Microbiologist colleague)
How does Risk fit Inspection decisions?
• High risk – on-site inspection mandatory
• Moderate risk – questionnaire assessment or
on-site inspection
• Low risk – questionnaire
Process flow chart

Release of raw materials

Fermentation

Centrifugation
Chromatography

Bulk substance

Filtration

Final packaged product


Process analysis
Excipients and Water

Micronization

Separation

Drying

Water
Hydration

Sterile filtration

Filling
Details of Process with Controls
• HACCP plan
• Perform a virtual HACCP analysis using tour,
procedures and assessment survey

• Amount of detail depends on level of risk


Audit Findings Template
• Same document format as Lead auditor
Or
• Modified document for notes during audit

For efficiency and clarity.


• Agreed on format with Lead auditor
Objectives
I perform an audit with these intended goals:

1. Determine quality systems in place for


microbiological control
2. Determine level of knowledge and
capabilities of audited site
3. Determine if continuous improvement is part
of culture
Objectives (cont.)
4. Determine if culture matches ours
5. Share knowledge and perspective with client
where adds value
6. Develop a relationship based on respect,
shared learning, communications
Right People Participants
To ensure that adequate and timely information
is generated during an audit
Questions should be directed to the
Microbiologist who has accountability and
responsibility, and possibly to their staff

Additionally, communicate with operators, or


validation scientists, if appropriate
(e.g. for sterile operations)
Success or Failure
The results from an audit depend on the
accuracy of information

A non-microbiologist should have effective


access to someone who is educated in
pharmaceutical microbiology
Virtual Audit with a Microbiology
Auditor
Criteria to Consider for Manufacturing
Audits
Excipient control – C of A, specs, QC testing,
material storage, weighing
Process flow –containment, gowning
Process equipment – validation, cleaning,
sterilization, microbial monitoring
Process areas – cleaning, sanitization, access
control, gowning, gloves, microbial monitoring,
‘classification’ qualification
Source of water, water system control and
monitoring
Criteria to Consider for Manufacturing
Audits
Formulation – excipient and component handling,
bulk material handling, in-process sampling, hold
time qualifications
Dosage dependent manufacture controls (e.g.
mixing, drying, milling, compaction)
Finish/fill operations – sampling, cleaning,
operator technique/intervention, controls (e.g.
filtration, sterilization, closure control), process
qualification
Finished product QC testing, stability testing
Criteria to Consider for Laboratory
Audits
Organization and reporting structure
Laboratory layout
Sample tracking, storage
Media control, made or purchased
Supplies, reagents control
Instrument control – calib., PM
Lab and instrument cleaning, disinfection
Criteria to Consider for Laboratory
Audits
Lab monitoring
SOPs and their control
Microbial identification process
Exceeded limit or atypical result procedure
Quality improvement program, measures
Proficiency testing
Test methodology
Method suitability procedures
Criteria to Consider for API or Excipient
Manufacture Audit
Process flow and contributing factors (e.g.
intended use of compound, parenteral vs.
non-sterile)
Monitoring of process
Origin and control of raw ingredients
Water system control and monitoring
Microbial monitoring of ‘product’

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