control, context, and commitment to continuous …...wcbp 2015 j.c. baker, obp/ops/cder fda control,...

WCBP 2015 J.C. Baker, OBP/OPS/CDER FDA

Control, Context, and Commitment to Continuous Improvement in Biopharmaceutical Manufacturing

1

Jeffrey C. Baker, Ph.D.

Deputy Director,

Office of Biotechnology Products, CDER

United States Food & Drug Administration

WCBP 2015, Washington, DC

WCBP 2015 J.C. Baker, OBP/OPS/CDER FDA 2

The Disclaimer

This presentation represents the views and perspectives of the speaker and should not be viewed or acted upon as FDA Policy or assumed to be an all inclusive list of FDA requirements.

For official policy and guidance, contributors are directed to http://www.fda.gov/

The speaker may be contacted at [email protected]

http://www.fda.gov/


Regulation of biological products in the US

Biological products are a subset of drugs and are therefore regulated under the Food, Drug, & Cosmetic Act.

Biological products are licensed for marketing in the United States under section 351 of the Public Health Service (PHS) Act.

The PHS Act also provides authority to immediately suspend licenses in situations where there exists a danger to public health.

http://en.wikipedia.org/wiki/File:Great_Seal_of_the_United_States_(obverse).svg


Licensure is based upon scientific, data driven assertions

The drug is safe.

The drug is pure.

The drug is potent.

The process and facilities used to manufacture safe, pure, and potent drug are very likely to

do so reproducibly and predictably.

A BLA submission is an exercise in technical, data driven advocacy of quality assurance.


“A planned set of

controls, derived

from current product

and process

understanding, that

assures process

performance and

product quality”

(ICH Q10)

Process Control Strategy

Raw Material Control

Process Monitoring

Release and Stability Testing

Training

Equipment and Facility SOPs

Inherent Material

Variability

Environmental

Stresses

Process

Capability

Critical Quality

Attributes

Quality

Assurance

Adapted from Dr. Michael Pikal, University of Connecticut


Reality gets more complicated

Raw Material Control

Process Monitoring

Release and Stability Testing

Training

Equipment and Facility SOPs

Inherent Material

Variability

Environmental

Stresses

Process

Capability Quality

Assurance

Across all sites and types of business relationships!

Across All Geographies

Across the product

portfolio!

Across the product

lifecycle with continuous

improvement and learning!

Across the process train as a whole !

Critical Quality

Attributes

Across changing business drivers!


Aspiration to technical excellence in an atmosphere of operational tension adds additional complexity and constraint.


Risk and Complexity Drive Behaviors

Immediate

Long Term

Me Us Them


Is knowledge compression risk management or a stress response?

Controlling a multivariate, probabilized, risk based design space in a Quality System that is binary: “pass’ or “fail”

Applying “Lean Principles” to management of a knowledge space leads to binary keep/drop (critical/non-critical) approach to knowledge.

Applying FMEA to communication practices compromises transparency : “there is no upside to telling them… only two things can happen: nothing and something bad. Every disclosure is a failure mode.


A good map anticipates options, paths, and outcomes and provides reproducible experiences

In order to manage residual uncertainties, an effective bioprocessing control strategy maps a performance space.

A process in control is a process that reproducibly meets expectations.

Define Demonstrate Document Maintain


A control strategy is an alarm-control system

Data is tracked and monitored

Variability is sorted as relevant or not relevant

There is a predetermined response to a signal relevant t product quality

A decision is made. The merits of an alarm-control system rest not in the number of alarms or the trigger points but in the responses to the signals.


Quality

Systems

Sound Science and Effective Engineering

Lab

Data

Pilot

Data

Site

Mfg

Data

Development

Program

Tech Transfer

Package

Validation

Master Plan

The Process Flow Document

Assurance of Predictable, High

Quality Product and Process

“Architecture of Assurance”


BLA review and the CGMP program

The original product development, process design and initial process qualification studies are evaluated as part of the BLA application review.

During a surveillance inspection investigators determine if the current manufacturing process is performing as planned and predicted.

> Is the control strategy properly targeted and working as intended?

> Is the state of control established and maintained?

> Is the identity, strength, quality, purity and potency of product on the market assured?

> How does current production compare with submitted data and predictions ?

Risk based assessment of process changes associated with continuous learning and improvement should be fully captured and accommodated by the Production Quality System.


Clear understanding and communication of purpose and intent

The BLA is an exercise in data driven technical advocacy.

This advocacy needs to be data driven, risk based, patient centered, and compelling to reviewers and inspectors.

Successful sponsors focus on effective communication of relevant science and engineering practices.

“The ability to tell a good story is a competitive advantage.”


Medicine matters.

We don’t have time to wander around the valley.

control, context, and commitment to continuous …...wcbp 2015 j.c. baker, obp/ops/cder fda control,...

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