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Regulatory Compliance

Today's competitive market presents a fresh set of challenges to pharmaceutical companies. Good Practice consultants can assist those companies in achieving compliance by providing training on aspects of GMP for production and QC.

by Tony Gasson,Mark Stevens
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Getting There and Staying There

Today’s challenging business climate presents a number of issues that pharmaceutical companies must address if they are to remain competitive. The industry is not in the same condition it once was, as drug manufacturers are coming under increasing pressure to release new drugs in the quickest time and with the least expenditure possible. This includes identifying unsuitable compounds and products as early in the development process as possible. As a consequence, it is vital that companies ensure that they have the right staff in place with the necessary knowledge and resources to implement best practices in the research, development and manufacture of new drugs; at the same time, they must comply with the strict regulations put in place to protect public safety. However, as competition between companies to maximize profitability of new drugs increases, the ability to retain knowledge within a company becomes more of a challenge.

This article discusses the issue of achieving and maintaining Good Manufacturing Practices (GMPs) and regulatory compliance efficiently and cost-effectively. It also discusses the issues of knowledge transfer and the key challenges of retaining skilled staff.

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Achieving regulatory compliance in drug manufacturing

It is imperative that pharmaceutical companies comply with the strict rules imposed by regulatory bodies such as the U.S. Food and Drug Administration (FDA). In addition, companies must ensure that best practices, such as GMPs and Good Laboratory Practices (GLPs), are followed.

Because customers cannot deal directly with the manufacturer of a drug, regulatory authorities do this on their behalf. In addition to imposing strict quality control and testing processes, the FDA enforces controls to ensure precise batch traceability. To ensure that manufacturing procedures are compliant with regulations, they must be validated and follow written procedures each time. Batch records are key; these documents are the only records that can be relied upon when the procedures have been completed and should enable the retracing of the entire batch history. The full account of accumulated records detailing the full history of a product must be stored in the event of regulatory inspection. To ensure that this is possible, the records must be accurate at the time the procedures are carried out, which means that they must be comprehensive enough to truly represent the production and be well-organized for easy referral and cross-referencing.

The analytical laboratory should be considered a manufacturer of a GxP-compliant product, the assay result. This product needs to be produced reliably, consistently and cost-effectively and be reproducible from site to site. All QC testing associated with the development, clinical studies, regulatory approval and manufacture of the licensed product is, in effect, part of the “product” and must be treated accordingly. All persons associated with testing and storing of assay results must therefore consider this to be a GxPcompliant product for which they are responsible. It must be “fit for purpose” of the customer. This means it has to be based on sound reproducible science (i.e., validated). To achieve this requires that all procedures be well-organized in an appropriate routine that reaches the level of compliance. The manager and staff are responsible for keeping abreast of any scientific changes that can improve this “product” in accuracy and speed so that by “continuous improvement” they can maintain compliance.

It should be remembered that even unexpected results are useful if they are discussed with the Development or Production group in order to try to help everyone understand the probable causes of the result and the corrective action needed to produce what is required.

All records of validated processes are as important as the product itself. Without these records, there is no evidence to verify that the product has been manufactured and tested correctly and is therefore fit for purpose. Both the product and documents must be stored under conditions that ensure that they are of the same standard at both the beginning and end of their life. The documents should be in controlled fireproof facilities, while the product itself should be stored at a suitably controlled temperature to guarantee that it will perform its function after the permitted period of storage.

The FDA is becoming more thorough in its enforcement of regulations. Previous FDA actions against pharmaceutical companies include those against Abbott, which was fined $100 million, and Tennessee-based Wyeth-Ayerst, which paid out $30 million. FDA re-inspections can also lead to losses for companies. In 2003, Eli Lilly predicted reduced earning forecasts as a result of delayed FDA approvals.

Maintaining regulatory compliance

Once the necessary validated processes and control systems have been implemented, today’s competitive market presents a fresh set of challenges to pharmaceutical companies. The ability to achieve regulatory compliance is a significant issue, but maintaining regulatory compliance also remains a major concern.

Because of the clear challenges of complying with the often-complex FDA guidelines, many companies are still failing to implement an effective and systematic process to cope with the regulations. It is estimated that 30 to 50 percent of the 483 citations by the FDA are related to corrective and preventative actions.

What can be done to make QC testing better? There are many existing and new tools available that enable scientific, risk-managed pharmaceutical development, manufacturing and quality assurance to comply with FDA regulations. These tools offer a means of acquiring information to facilitate process understanding, develop risk-mitigation strategies and achieve continuous improvement, as well as share information and knowledge.

Process Analytical Technology (PAT) is one set of tools used to achieve compliance. PAT has been defined by the FDA as a mechanism to design, analyze and control pharmaceutical manufacturing processes through the measurement of Critical Process Parameters (CPPs) that affect Critical Quality Attributes (CQAs).3 The concept aims at understanding the processes by defining their CPPs and monitoring them in a timely manner. This ensures more efficiency in testing while at the same time reducing overprocessing, enhancing consistency and minimizing batch rejection.

Statistical Process Controls (SPCs) are another effective method of monitoring a process via control charts. Control charts in SPCs are used to determine whether a manufacturing process is under control. If the chart indicates that the process is currently under control, it can then be used with confidence to predict the future performance of the process. If the chart indicates that the process being monitored is not in control, the pattern it reveals can help determine the source of variation that needs to be eliminated in order to bring the process back into control. By continually tightening limits, it is possible to improve the overall process.

Good Practice consultants, such as GxP Consulting, can assist pharmaceutical companies in achieving compliance by providing training on aspects of GMP for production and QC. They also can act as a facilitator to develop the culture that integrates other essential activities, especially engineering and maintenance.

Retaining and growing knowledge

In order to establish and maintain a GMP and GLP culture at a company, it is vital that the correct staff be in place, armed with the right knowledge to implement the necessary processes to ensure regulatory compliance. However, retaining that knowledge is becoming more of a challenge in today’s market, as personnel often move between companies more frequently. This poses two problems that need to be dealt with: How do we retain knowledge and consistency within the company? And how do we get new members of the team working effectively as quickly as possible? The answer to both questions, though often poorly executed, is this: communication and documentation. Policies, guidelines and procedures, in whatever format, need to be current, contain an appropriate level of detail, and be owned by the right people and readily available to those who actually need the information. The purpose of the documentation is to help people understand how the organization wants them to complete a task, not just to satisfy auditors and inspectors. The manufacture and testing of a drug are the result of a combined effort by many people, teams and business functions. The value of knowledge sharing and cross-functional understanding is paramount to an organization’s ability to work efficiently and effectively. It also provides the ideal forum in which to help new members of the team understand the organization as quickly as possible and start the process of sharing knowledge and experience. These are all obvious answers, but how well does your organization manage these elements of knowledge management and sharing?

Good Practice consulting firms can rapidly deploy a team to provide interim management and/or training and coaching of new staff in order for an organization to meet its regulatory responsibilities. This provides an effective way to manage staff replacement and the transfer of necessary skills and knowledge. It also provides a smart way to support activities such as expansion and relocation of operations. For new organizations or those not familiar with regulatory requirements, these firms provide a straightforward way of introducing and implementing the controls and measures necessary to demonstrate compliance.

A consulting company is also able to provide an assessment of an organization’s current practices against the regulatory requirements. A GxP consultant will have firsthand experience identifying and implementing the standards and changes necessary to help achieve GxP compliance as quickly and efficiently as possible. This experience will have been gathered from companies of varying size and types of product. Once the assessment is complete, the consultant will work with the organization to deliver the necessary actions, such as a strategy to enable continuous improvement and to develop procedures and individual staff members.


Achieving and maintaining regulatory compliance as quickly and efficiently as possible is vital if a pharmaceutical company is to remain competitive. Failure to adhere to the strict regulations imposed by the FDA carries serious risks and can result in costly delays or even fines. The function of the QC laboratory within a GMP or GLP operation is critical to regulatory compliance. By considering the “product” of this business function as the assay result, clear definition, management and control of all testing that is associated with a drug product is possible.

A number of tools can be deployed to assist companies in their goal of achieving, maintaining and improving regulatory compliance, but a consideration of equal importance is the development of a long-term GMP culture. Effective documentation, communication, training and leadership can and do help an organization retain and share its knowledge within the organization. By doing so, there is less risk of knowledge loss, inconsistency or inefficiencies brought about by the higher turnover of staff that exists in the industry today.

Use of the correct GxP consulting services can help an organization identify what needs to be done in order to best meet its regulatory requirements; provide training, coaching and interim management; and develop pragmatic continuous improvement strategies.


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GxP Consulting provides regulatory compliance services to the highly regulated pharmaceutical and biopharmaceutical industries. For more information, call 949-725-2946, email or visit