Cleaning ValidationDoes your prospective CMO have what it
takes to protect your molecule?
Tyler JohnsonValidation Section Manager
16th Annual Global Bioproduction Summit
December 12, 2016
San Diego
Meet The Speaker
• 12+ years in pharmaceutical industry
• Process validation and cleaning validation
‒ Technology transfer - Lifecycle
‒ Customer support - Audits
• Equipment, facilities and utilities
Tyler Johnson
Validation Section Manager
Bringing the Best of
Together
Pfizer’s McPherson, Kansas, site
Pfizer’s busiest contract
manufacturing site
• 40+ biopharma companies
‒ Biologics
‒ Small molecule
‒ Lyo
• 35-40 inspections/year
Cleaning Validation:
The 5 Critical Questions to Determine...
CMO’s fitness for risk-based decision-making
CMO’s ability to meet regulations around the globe
Are you a good fit? Compliance is a spectrum
Fitness for risk-based decision-making
• ICH Q9 (Quality Risk Management) Principles (11/2005)
‒ The evaluation of the risk to quality should be based on scientific knowledge
and ultimately, link to the protection of the patient.
‒ The level of effort, formality, and documentation of the quality risk management
process should be commensurate with the level of risk.
Q1: How does your site implement ICH Q9 re: cleaning validation
and monitoring (verification)?
Worst-CaseAutomated/
Manual
Specific/Non
-Specific# of RunsCPP/CQA
Dirty/Clean
Hold Times
Routine
Monitoring
Fitness for risk-based decision-making
• Rather the Maximum Allowable Carryover (MAC) should be no greater
than 10ppm.
• In this manner of calculation, the intermediate value of ARL can be
compared directly to the default criterion of NMT 10 ppm to determine
which value will be used to calculate the MAC and subsequently the
residual carryover limit (RCL; in µg/swabs or µg/mL).
Q2: What is your default criterion and how do you calculate it?
10ppm
Ability to meet cleaning validation regulations around
the globe
• FDA’s Process Validation: General Principles and Practices (01/2011)
‒ Process Design / Qualification / Verification
• EU’s GMP Annex 15 (10/2015)
‒ Carryover limits based on a toxicological evaluation
‒ Equipment grouping
‒ Dirty and “un-clean” hold times
Q3a: How has your site implemented recent guidance from
(insert guidance here)?
Ability to meet cleaning validation regulations around
the globe
• World Health Organization: Technical Report Series 937 (2006)
‒ Visually clean
‒ No more than 10ppm
‒ No more than 0.1%
Q3b: What about countries regulated by WHO (Canada, Brazil
and Australia)?
Compliance is a spectrum: Are you a good fit?
• Quality Agreement
‒ Defines roles and responsibilities
‒ Methods of contact
‒ Compliance requirements
‒ General quality system
Q4: What happens when our quality systems disagree?
Your
requirementsCMO
GAP
Continuous Improvement: Is it important to you?
• cGMPs for the 21st Century Guidance (09/2004)
‒ Encourage the early adoption of new technological advances by the
pharmaceutical industry.
• Quality By Design
‒ A systematic evaluation, understanding, and refining of the process.
• PAT
‒ Implementation of on-, in-, and/or at-line measurement.
Q5: What is the most recent continuous improvement initiative
you have implemented re: cleaning validation?
Questions?