A Systems Based Approach to Process Deviation and Failure Investigation Audits

Michael G. Kovalycsik Assistant Vice President Wyeth Pharmaceuticals Vaccines Research, Quality Assurance ASQ February 24th, 2009

Presentation Goals
Present

a systems and risk based approach to auditing investigation and deviation processes and systems. Identify several cGMP required elements of these systems which are likely to be reviewed during regulatory inspections. Review audit approaches covering critical aspects of these systems which may point to compliance gaps.

Systems Based Approach to Process Deviation and Failure Investigation Audits

What

is a System ?

Websters

Definition - Interdependent group of items forming a unified whole.

Systems Based Approach to Process Deviation and Failure Investigation Audits

Auditing

Systems Clearly identify 5 items about the system:

What

is the system? What is the system supposed to do and how is it done? Does the system do it? How does the system interact with other key systems? How is the system controlled and measured?

One Point to Take Home Today

Just

as no man is an island, no cGMP system stands alone, on its own.

The

Process Deviation and Failure Investigation System will interact with all other cGMP systems!!!

What is the System?

Process

Deviation and Failure Investigations

Examples
Roles

of some critical Failure Investigation and Deviation system components:

and responsibilities of management Communications and documentation Deviation and Failure Investigation Tracking and Trending Training Computer systems Others.

What is the System Supposed to do?

Failure
cGMP

and Deviation Investigation Objectives

objective is to generate a result or outcome which is supported by either data, documents, records, or reports which will assure the product being produced meets the requirements of safety, identity, strength, purity and quality and is acceptable from a regulatory compliance standpoint.

Systems Based Approach to Deviation and Failure Investigation Audits

Key

Questions:

Are

the investigations and deviation reports being initiated/conducted/written/reviewed/approved/reported and analyzed appropriately? Are timing commitments appropriate and are they being met? Are the true root causes being correctly identified and corrected?

How Does the System do it?

cGMP

Expectations include:

SOPs

or other controlled documentation must be in place describing operations and documentation of performance of these operations.
Procedures

must be appropriately reviewed and approved. Should adequately describe who, what, when, and how for: micro-aspects (individual reports) macro-aspects (root causes, tracking and trending)
Responsible

individuals must be identified for all key tasks. Time commitments are identified.

How Does the System Interact with other Key Systems?

Must

identify all other areas that support the system or are impacted by the system. Verify adequacy of scope of involvement of these areas
Other

departments, analyses, batches, equipment, etc.

Is

the required involvement of other areas being achieved? How is this documented? Are appropriate responses (based on adequate impact and risk assessments) being taken as a result of system output? How is this documented? Are the responses adequate and timely?

How is the System Measured and Controlled?

Is

there a mechanism to capture the systems performance and if so is it adequate?

Timing? System Risk

specific performance parameters?

If

system changes are needed are they under appropriate review and approval
Change

Control? Timing? How is this documented?

Systems Based Approach to Deviation and Failure Investigation Audits

Review
What

of 5 Key Questions:

is the system? What is the system supposed to do and how is it done? Does the system do it? How does the system interact with other key systems? How is the system controlled and measured?

Auditing Deviation and Failure Investigation Systems

Audit
As

Timing

a Scheduled Audit

Include

in scheduled QC Laboratory Audits, Manufacturing Audits, Clinical Supply and Development Audits, QA Audits or as stand alone audit. Recommend to always include as part of a Rehearsal PAI
Be

sure to include investigations and deviations from relevant clinical trial, development, and validation activities

As an Unannounced Audit An audit necessitated by significant issues such as: New cGMP Expectations or Regulatory Requirements, Recurrent Manufacturing Problems, QA or Corporate Request, or others.

Auditing Deviation and Failure Investigation Systems

Audit

Strategies - Macro-Aspects Goal - Overall assessment of the system for compliance with internal procedures and regulatory expectations. Good Starting Point - SOPs describing the system
Acceptable

and up to date from a regulatory (BPDR) and cGMP standpoint NOTE: Relationship between laboratory failure investigations and manufacturing investigations is critical.

Auditing Deviation and Failure Investigation Systems

Audit

Strategies - Macro -Aspects

Responsible Individuals, QA involvement of Failure Investigations and Deviations
the individuals appropriately trained and qualified?

Identify
Are

Records

Recommend

review of at least last 2 years worth to identify those individual reports to explore further. Look for repeat problems Specific products, areas, lab methods, equipment, procedures, individuals, etc. Always review any reports dealing with critical impact areas Sterility and Sterility Assurance !!!

Auditing Deviation and Failure Investigation Systems

Audit

Strategies - Macro -Aspects Overall System Performance

Numbers

of Investigations and Deviations - Are they reasonable wrt. batches produced, tests performed, etc.? Trending and Reporting of Trending
What How Are

trends are being looked for and how?

Equipment, Facility,Individual, Analytical Method?

Product,

are these reported and to whom?

Quality Committee, Senior Management ?

QA,

true root causes being identified and corrected? Risk to patient?

Auditing Deviation and Failure Investigation Systems

Audit

Strategies - Macro-Aspects

Individual

report tracking and reconciliation procedures

Performance

metrics for timely initiation, reconciliation and completion of reports

Verification of Corrective Action Completion Is there a written requirement? Who is responsible? QA? Audits? What happens if a corrective action commitment is not met?

Auditing of Deviation and Failure Investigation Systems

Audit

Strategies - Micro-Aspects

Audits

of individual deviation and investigation reports Compliance with SOPs Scope of the reports
Appropriate

impact assessment and involvement of other departments, analyses, batches, samples, equipment, etc. progress updates, completion of reports

Timeliness
Initiation,

Auditing Deviation and Failure Investigation Systems

Audit

Strategies - Micro-Aspects
of the reports
Required

Completeness

relevant information included or attached Check references as needed. Are all the boxes checked?
Appropriate
QA,

review and approvals

Area Management, Regulatory, Senior Management? What do the review and the approval signify?
Notification

of management and regulatory authorities

(BPDR) Risk to Patient??

Auditing Deviation and Failure Investigation Systems

Audits

of Related Systems

Again ... The relationship between laboratory failure investigations and manufacturing investigations is critical.

Deviation and Failure Investigation audits can and will likely, lead down any other cGMP audit path. Common other areas include: QA Facilities Engineering and Maintenance Laboratories Customer Complaints Product Recalls many, many more.

Auditing Deviation and Failure Investigation Systems

The

Most Important Questions One Should Always Ask Themselves at the End of an Audit:
Do

I understand the area/item/procedure/system I just completed auditing? Does the area/item/procedure/system I just completed reviewing make sense from a cGMP standpoint and is it in compliance?

Presentation Goals
Present

a systems and risk based approach to auditing investigation and deviation systems. Identify several cGMP required elements of these systems which are likely to be reviewed during regulatory inspections. Review audit approaches covering critical aspects of Deviation and Failure Investigation systems which may point to compliance gaps.

Auditing Deviation and Failure Investigation Systems

Thank You Very Much!!! Michael G. Kovalycsik (845)-602-4754 Kovalym@Wyeth.com