Quality Systems For Pharmaceutical Manufacturing

In September, a new FDA guidance document was released, entitled Guidance for Industry — Quality Systems Approach to Pharmaceutical Current Good Manufacturing Practice Regulations, outlining a comprehensive “Quality Systems” approach to drug manufacturing operations.

Quality Systems (QS) can be summed up as ISO 9000 meets cGMP compliance. FDA focus is shifting from compliance to a specific set of regulations and toward facilitating pharmaceutical firms adopting modern and robust quality systems that are cGMP compliant.

FDA has organized its pharmaceutical QS model into the four major sections described below:

Management Responsibilities
A firm’s leadership plays a pivotal role in the design, implementation and management of QS. Without a management commitment to develop and implement compliant operating procedures, record keeping systems and employee training programs, a firm cannot achieve cGMP compliance. Managers who only invest in compliance activities during good times will likewise never see their firm maintain compliance. Therefore, FDA recommends that management be actively involved and committed to compliance, and that they publish a Quality Policy to publicly demonstrate their long-term commitment.

FDA recommends using a risk assessment to determine the business resource levels required. Firms should evaluate how many QC Unit personnel are needed, and account for the time fillers, drivers and other personnel documenting cGMP activities spend completing documents. Included in the assessment should be the time and effort to stay abreast of constantly evolving regulatory and cGMP training requirements.

Manufacturing Operations
This includes product and manufacturing process design, packaging and labeling processes, validation, record keeping and addressing nonconformities. Key considerations are the adequacy of work instructions, ensuring product release is adequately documented, utilizing change management procedures, investigating non-conformances, and documenting critical process parameters during production. FDA recommends that manufacturers develop monitoring processes that will assist in identifying opportunities for process and system improvements.

Evaluation Activities
FDA recommends periodic reviews of manufacturing operations to evaluate compliance program robustness. FDA recommends analyzing data for trends, including production data, customer complaints and non-conformance investigations. Additional sources of review data are internal and external compliance audits, and supplier and vendor audits. Management should be involved in the review process, and these reviews should be adequately documented. Key review process outputs are preventative and corrective actions. The FDA guidance document places a significant emphasis on preventative actions.

The goal of this new FDA guidance is to ensure consistent production of safe and effective products through sustainable management and production activities. We believe this new guidance signals a transition from the current regulatory process based on perceived shortcomings in industry practices, and toward focusing responsibility for continuous improvement in cGMP systems onto pharmaceutical manufacturing firms and their management.

FDA stated that the depth of QS implementation and the maturity of a firm’s QS will be determining factors in establishing the frequency and scope of future FDA drug manufacturer site inspections. Firms with cGMP compliance programs that incorporate quality systems and have internally driven continuous improvement programs will face less FDA scrutiny of their business. This will be a powerful motivation to transition QS to the predominant industry practice in the future.

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Meet the Author
GAWDA Medical Gases Consultant J. Robert Yeoman is managing director of B&R Compliance Associates LLC in Lehigh Valley, Pennsylvania. Members can reach him at 610-837-6782 and at bob.yeoman@brcompliance.com.