In 2002, the Food and Drug Administration (FDA) announced an initiative to integrate quality systems and risk management approaches into existing regulations for pharmaceutical manufacturing.  While the FDA hasn’t changed the 21 Code of Federal Regulations (CFR) Parts 210 and/or 211 regulations, they have published industry guidance, Quality Systems Approach to Pharmaceutical CGMP Regulations.

In addition, the International Conference for Harmonization (ICH) issued the Q10 Guideline, which describes a model for the implementation of an effective quality management system for the pharmaceutical industry.  This guidance integrates key current Good Manufacturing Practice (cGMP) concepts from the pharmaceutical industry with risk management principles, and sets the stage for a systemic approach to pharmaceutical development and manufacturing.

BENEFITS OF A SYSTEMATIC PROCESS
Why should pharmaceutical companies consider implementing a systemic approach to manufacturing and quality? The 21 CFR Parts 210 and 211 regulations provide direction for specific tasks and requirements to manufacture pharmaceutical products. But these regulations do not mandate integration of the activities or documentation of the interrelationship of these key processes to each other.

The Q10 and FDA Guidance recommend you review operations as a fully integrated system.  The FDA Guidance states: “Quality should be built into the product, and testing alone cannot be relied on to ensure product quality.”  Additionally, the FDA Guidance supports the systemic approach to quality for the following reasons:

A well-designed, functioning quality system should reduce the number of (or prevent) recalls, returned, or salvaged product entering the market.

Harmonizing cGMP regulations with other quality system guidelines is desirable from good business perspectives – particularly in the face of the global economy and operations.

The FDA has determined the systems approach in conjunction with effective risk management activities facilitates more control of facilities, equipment, and process changes without negative impact on regulatory submissions.  This also facilitates more effective FDA inspections.

A robust quality system provides the necessary framework for quality by design from concept through the product lifecycle.

KEY TO AVOIDING NONCONFORMANCES AND OBSERVATIONS
I know this may seem somewhat daunting, but in reality, the implementation of the systemic approach to quality in the pharmaceutical environment is really just good business.  The key to its effectiveness is to keep it simple and not make requirements in the procedures that are unrealistic or overly complicated. Keep in mind a couple of basic business rules:

A.  K.I.S.S. – Keep it simple, silly!  Don’t make the processes more complicated than necessary.

B.  Think of the systemic approach as a ‘connect the dots’ puzzle.  You have all the pieces.  If you put them together in a specific order they reveal a picture.  This picture should reflect your business vision and commitment to quality.  At times, I have seen various departments within the pharmaceutical manufacturing operations work within individual silos, rather than integrating operations.  For example:

A company manufactures four different product lines. Each product line involves filling and packaging processes.  A deviation is identified in the fill process of one product and is documented in that operation.

Connecting the dots:  Analysis of deviations across the product lines would identify if this is a systemic issue, or something that could impact the other product lines.  This analysis is usually done through tracking and trending of deviations and/or failures, and is often product specific (silo).  Looking across the lines for similar issues could save the organization many dollars in scrap or rework of product.

Connecting the dots:  A corrective and preventive action (CAPA) system should be in place to address systemic issues across all of the product lines.

C.  Be realistic. The infrastructure processes of the integrated quality system must reflect what you actually do – not just what you want to do, or what someone says you should do.  It really doesn’t do any good to implement a procedure that is compliant to the regulations and meets the guidance expectations if it is not sustainable.  In other words, ‘say what you do and do what you say!’

Following these simple business rules will help you avoid non-conformances and/or observations during inspections.  You are probably asking ‘if the Q10 and the FDA guidance documents aren’t regulations and are not actual requirements of law, how can the FDA write 483 observations against the guidance?’  In many instances, guidance documents do become defacto law and are considered best practice as investigators issue 483s and warning letters.

PROCEDURE MUST EQUAL PRACTICE
It is no wonder that there is a lot of confusion in industry about what to expect from a systematic approach to investigations.  In many cases, I have seen companies purchase generic procedures or processes and release them into the system, without understanding the full impact on all phases of business operations.  The procedure has included requirements that have not been implemented or embraced by the organization, thus creating nonconformances and/or failures within operations.  In other words, the procedure does not reflect actual practice.

Some system procedures are written from the perspective of what someone would like to do, or has interpreted as being required, rather than documenting what is actually being done.  This is the biggest issue I see when working with companies that are implementing systems.  It is also the primary source of nonconformances and observations from the FDA.  When you think about it, integrating tasks and activities with a systemic approach is just good business.

As you start the journey to implementing a systems approach to quality, take time to define an appropriate strategy for your business by considering the following points:

• Establish a vision for the end product – what will the system look like when it is fully implemented?
• Perform a gap assessment of current procedures and practices against that vision.
• Determine the best approach to filling these gaps without turning your business upside down.
• Communicate the plans to the organization – active involvement from all employees is one key to success.
• Establish the key infrastructure support processes for the system.
• Management controls (internal audits, management review, resources, metrics/objectives) control.
• Corrective and preventive actions (CAPA).
• Document and records management.
• Design control and risk management.
• Production/operations and risk management.
• Assure these key processes fit your business needs.
• Cooperation Should Start at the Top.

You must have senior management involved and supporting this process from the beginning of the project.  Management controls are one of the key elements of a pharmaceutical quality management system.  The involvement of senior management, often referred to as management with executive responsibility (MWER) in the development, management, and oversight of the system is critical.  Executive management is responsible for the quality of the product produced, as well as compliance to regulations. Without this senior management support, there is little probability of success for the systems approach to quality.  Some specific activities to be addressed in this area are:

• Clear definition of responsibilities within the organization – this includes global, regional, and/or local, as appropriate for the business.
• Sufficient qualified resources to perform tasks and activities associated with processes and systems.
• Clear definition of information and communication flow within all levels of the organization.
• Integration of risk management into all activities, particularly design and process operations.
• Support of initiatives for continuous improvement throughout the organization.

Bio:

Christine (Chris) Park is a proven Quality Assurance professional with a wealth of experience in establishing and remediating quality systems of all sizes. As a consultant, she uses a pragmatic approach to compliance and quality assurance. Ms. Park has successfully focused on results-oriented solutions that integrate quality into the daily business activities of organizations. Her experience in R&D and general manufacturing for medical devices,

IVDs, and biotech/pharmaceuticals provides a well-balanced background for her work in compliance. She can be contacted at (678) 480-5411 or visit her website at www.qualityarchitech.com.

Note: The views expressed in this article are those of the author and do not necessarily represent those of the employer, GxP Lifeline, its editor or MasterControl Inc.  Reprinted with permission from MasterControl and GxP Lifeline.