Microbiology and Auditing. Don Singer

Transcription

1 Microbiology and Auditing Don Singer ASQ Northeast Pharmaceutical GMP/Quality Conference 2011

2 Through the eyes of a Microbiologist

3 Microbiology Audit = Inspection / Investigation

4 Systematic Auditing Planning Right People Tools Appropriate Objectives

5 Auditing approach Corporate design or policy Team Independent

6 Purpose Quality Systems Build robustness into your quality systems cgmps

7 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

8 Quality Systems Inspection Quality system Production system Laboratory controls system Materials system Packaging and labeling system Facilities and equipment system

9 Microbiological Quality Risk Dosage form Management Laboratory tests Materials management

10 Risk by route of administration High Parenteral Ophthalmic Otic Wound topicals Nebulizer solution Intranasal solution Inhaled - DPI Inhaled - MDI Low Topical cream Topical ointment Oral solutions, suspensions Liquid-filled capsules Tablet, Capsule

11 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

12 Materials risk of contamination Manufacturing process Unprocessed High Classification Animal or plant origin (e.g. lactose) Highly processed Mineral origin (e.g. Talc) Some bioburden reduction processing Semi-synthetic origin (e.g. captisol, HPM) Mineral origin (e.g. dyes, aromatics) Low Synthetic origin (e.g. povidone)

13 Audit Expertise What is a QC Microbiologist? Knowledge Base : Science Origin and Growth Control

14 Microbiological Science

15 Origin and Growth Water (H 2 O) Nutrition (CHO, CHON, CHOOH, minerals, etc.) Presence or absence of components of air

16 Other Growth Factors ph temperature osmotic conditions light

17 Microbial Origin and Survival moderate to extreme environments solid to liquid dense to dilute atmosphere, humans and other living organisms (animals - vegetation), water, soil

18 Role of a QC Microbiologist Design for microbiological control Monitor to continuously evaluate

19 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

20 Understand Thoroughly? Do you have the appropriate background and experience for microbiological investigation? If you do not, then partner with a Microbiologist

21 Tools to Assist cgmps, guidance docs, pharmacopeias Quality tools such as

22 Useful Quality Tools Assessment checklist or survey (developed by your Microbiologist colleague)

23

24 How does Risk fit Inspection decisions? High risk on-site inspection mandatory Moderate risk questionnaire assessment or on-site inspection Low risk questionnaire

25 Process flow chart Release of raw materials Fermentation Centrifugation Chromatography Bulk substance Filtration Final packaged product

26 Process analysis Excipients and Water Micronization Separation Drying Water Hydration Sterile filtration Filling

27 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

28 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

29 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

30 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

31 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)

32 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

33 Virtual Audit with a Microbiology Auditor

34 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

35 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

36 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

37 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

38 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