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?