The Changing Role of Quality Assurance in the Pharmaceutical Industry

Traditional Role of the Quality Control Unit or QA

The FDA's good manufacturing practices (GMPs) state the following: Sec. 211.22 Responsibilities of quality control unit.

• (a) There shall be a quality control unit that shall have the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products, and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated.

• … .

• (c) The quality control unit shall have the responsibility for approving or rejecting all procedures or specifications impacting on the identity, strength, quality and purity of the drug product.

However, to fully understand the meaning of this statement, one must read the 1979 Preamble to the good manufacturing practices (GMPs). Some excerpts from the Preamble follow: Functions that are properly those of the engineering department or other specialized units because of their unique training and expertise should not be duplicated or usurped by the quality control unit. Where expertise is in other units, the responsibility of the quality control unit is to assure that such expertise has been utilized. In order to make clear that quality control functions may be performed by persons assigned to units outside the quality control unit, the Commissioner is replacing ‘perform’ with ‘be responsible for’. The Commissioner intends to make the quality control unit responsible for ensuring that controls are implemented during manufacturing operations which assure drug product quality, not that the quality control unit actually perform each one of the duties. The commissioner believes that, even under 211.22, management has the prerogative to organize its internal structure and assign responsibilities as it deems appropriate, as long as some identifiable person or unit has at least those responsibilities assigned by the regulations to the quality control unit. To clarify that the quality control unit could not and should not perform duties duplicative of other parts of the organization, the Commissioner has modified the definition of quality control unit in 210.3 (b). There is more of the same in the Preamble. In my experience, over the years the quality unit has taken over more and more of the quality-related tasks that correctly should be performed by other departments, especially by production and engineering. We learn from best practice in other industries that production has to take responsibility for the quality of their work, for the quality of their process, and for the quality of the output of that process, the product. ICH Q10 indicates that senior management must take responsibility for the QS. Only senior management has the power and control of resources to implement, manage, and improve the QS. If production takes responsibility for the quality control of their process and engineering for the qualification, maintenance, and control of changes of equipment, facilities, and critical systems, what is left for the quality unit or more specifically the QA unit to do? Here it is important to note that most of the work done by the quality control laboratories are controls of the production process and therefore from a process point of view are part of the production process. Ideally, these testing functions are done in production so that there is immediate feedback and control of the process. If the tests require very expensive equipment and special expertise, then they can be done in quality control laboratories. From here on we exclude these laboratory activities from our discussion.

In the past QA has periodically been described as the policeman, the controller, or even the enemy. Today, we like to think of QA as the promoter of improvement of processes, the promoter of best quality practices, and a valued ally and helper.

New Roles for QA

The traditional responsibility of QA to approve and/or reject components and products, to approve or reject procedures and specifications, to review batch records, to make sure that the QS is implemented and followed, to ensure that the factory complies with regulations, still is necessary. Much of this traditional responsibility, however, can be done by periodic, effective audits. If other departments are doing their work properly, then QA should be able to significantly reduce its checking and oversight activities. QA also needs to stop doing the work of other departments. This should free up QA personnel to perform more proactive and preventive type of activities, which would be more value-added to the organization.

ICH Q10 assigns the primary responsibility for the QS to senior management. “Senior management has the ultimate responsibility to ensure an effective pharmaceutical quality system is in place to achieve the quality objectives.” See Table I for management responsibilities.

What can QA do to help senior management fulfill its responsibilities? ICH Q10 discusses the need to use quality risk management and performance indicators, as well as to determine the root cause of problems and to do quality planning. These are all areas where QA can play a leading role. We will discuss these a little later in the article.

Manager of Quality/Organizational Excellence Certification

The American Society for Quality (ASQ) has a certification program for a quality manager. The body of knowledge required to get this certification is presented in Table II.

It is evident from this list of certification requirements that the modern quality professional needs to know much more than the GMPs. Note in section 2, Strategic Plan Development, the link to Quality Planning in ICH Q10. Note in section 4C, Measurement: Assessment and Metrics, the link to performance indicators and the use of data in ICH Q10.

In our article published in 1998 (6) we had a somewhat similar list but more focused for the pharmaceutical industry. See Table III.

There are quite a number of similarities between Tables II and III. Note in Table III the importance of QA people understanding the manufacturing process, all aspects of validation—process, equipment, cleaning, analytical methods, and so on—and especially QA personnel being master craftsmen of statistical and quality tools.

QA Today and Beyond

First, referring back to ICH Q10 and management's need for data/performance indicators in order to manage the QS, QA can perform an important role in the collection and analysis of this data. Data is needed for all the processes in the QS. Table IV lists these processes.

Most of these processes can be measured in a quantitative way. QA, in conjunction with the process owner, can determine the appropriate metrics, the best way to collect the data, analyze the data using risk analysis for prioritization and root cause analysis for focus on the real problem. Finally QA can present this data to senior management for action as part of their periodic review of the QS. If possible QA, with the help of all departments, can suggest corrective and preventive actions to senior management. Note that generally only senior management has the capability to fix root causes. Root causes are senior management problems. Besides the processes listed in Table IV, there are two other aspects of the QS that are very important, the quality culture (or the culture of the company) and the qualification of people. It is necessary and possible to measure these factors also. Culture, which is the responsibility of senior management, is frequently a root cause of problems.

Quality is achieved through the work of others. QA does not produce the quality product. QA, however, can influence the work of others who are more directly involved in the production process. QA does this by working with process improvement teams to improve the processes listed in Table IV. Of course some of these processes QA owns, such as process assessments and change control. QA has to have the expertise to work with teams (facilitation), to design good processes, and to manage change. A good process is simple, fail-safe or mistake-proofed, and user-friendly. Perhaps QA personnel need training in order to do this. Also, note that change management is listed in Table III.

QA also achieves the desired quality results by the promotion and selling of quality. Figure 1 is a diagram of the selling process.

We need to sell quality at all levels and to everyone in all departments. To do that we need to be clear on what we want to sell and why it is important. I believe telling people you must do it because it is a regulation or because the procedure says so is not very effective. Explaining the logical and scientific reason for doing a task in a specific way is more effective. All quality activities in a pharmaceutical plant should find their ultimate meaning in a benefit to the patient. Also, important to the doer is, how does doing the task this way make my life easier? The most important part of the selling process is the preparation.

The best way to promote quality is by recognizing and rewarding good practice. Good quality practices can be promoted in a variety of ways. The only limitation is our imagination. Some examples are

• During audits and in audit reports, recognize and highlight when people are doing things correctly.

• Publish in the company newsletter outstanding work by a quality process improvement team.

• Have a periodic quality day where the quality improvement teams can present their work to their colleagues.

• Have a company quality award for outstanding individual or team accomplishments.

Another way to look at the QA department is as a team of experts: experts who can help others to achieve their quality goals and to fulfill their responsibility for the quality of their work. Table V contains a partial list of expertise one may consider.

To achieve the required level of expertise will necessitate new learning, which means a lot of hard work. But that is OK.

Another idea I find intriguing which is stimulated by the lifecycle approach and the need for knowledge management. Why not have each QA person focus on one product or family of products? This person would manage the whole stream of knowledge throughout the product's lifecycle from design, qualification, through verification. This person would have also the expertise to make change control decisions, facilitate investigations of process failures, evaluate trend data, and participate in process assessments/audits. I find today's generalist approach doesn't work. The typical QA person does not have enough knowledge to be capable in all the areas encompassed in his or her work. This is increasing becoming a problem as standards/expectations are raised and technology becomes more complex.

Caveats

I have made two assumptions so far in this article: (1) the QA department is competent in fulfilling its traditional role, and (2) senior management is willing to take ownership of the QS. Of course these assumptions are not always true. It is beyond the scope of this article to discuss the first assumption, but I believe it is important to discuss the second assumption, senior management taking responsibility for the QS.

We discussed earlier that QA needs to sell quality. Let's assume that QA needs to convince senior management to take responsibility for the development, implementation and continuous improvement of the QS. I recommend three steps.

1. The QA department must have credibility. It must show a high level of competence in the areas described above, both in the traditional and new roles. It must demonstrate the power and capability to make the tough decisions required by the traditional role before it can expect to assume the new responsibilities described in this article. Furthermore, it must be seen as understanding the business dynamics, the problems of production, and other departments as contributing to improving processes as valuable and trusted members of the team, as having exceptional expertise in the areas of quality, and so forth. Without credibility it will be hard to sell anything to anyone. QA needs to be seen as a department that can help and even train senior management.

2. In my experience, given QA credibility, the best way to sell management on a more proactive and preventive approach to quality is by using quality metrics especially by measuring quality costs. We discussed earlier the role of QA in obtaining and reporting to senior management quality metrics or data. Determining the costs of quality is a powerful way to get management's attention. Traditionally, the cost of quality is categorized as appraisal costs, preventive costs, internal failure costs, and external failure costs. See Table VI for some examples.

   Typically, failure costs are very high but not quantified. Appraisal costs are also relatively high, but preventive costs are much too low. Besides being low, preventive expenditures frequently are not very effective. Examples are validation work that does not improve the process or reduce process failures, or training that does not result in improved employee performance.

   It is recommended that QA team up with finance and get good estimates of these quality costs. Having the costs and then analyzing the root causes of the failures provides QA with the ammunition they need to convince senior management that managing and improving the QS is worth their attention and time. This should result in a strategic quality improvement plan championed by senior management that focuses on improving processes, that shifts costs from failures and appraisal to prevention. In the long term this will reduce the total cost of quality. The quality improvement plan is part of and integrated with the strategic business plan or a business excellence program. Then senior management perceives improvement of the quality of the production and supporting processes as an integral part of improving business performance.

3. The third recommended step is to get outside help. As W. Edwards Deming said, a system cannot understand itself without help from outside the system (7).

For Additional Reading

• Tague, N. R. The Quality Toolbox, 2^nd ed.; ASQ Quality Press: Milwaukee, WI, 2005.

• Cartin, T. J.; Jacoby, D. J. A Review of Managing Quality and a Primer for the Certified Quality Manager Exam; ASQ Quality Press: Milwaukee, WI, 1997.

• Escoe, A. “The Practical Guide to People-Friendly Documentation, 2^nd ed.; ASQ Quality Press: Milwaukee, WI, 2001.

• Harbour, G. C.; Kieffer, R. G. Quality management team (QMT): managing the quality system. Pharm. Technol. 2000, 24 (10), 152–158.

• Harbour, G. C.; Kieffer, R. G. Quality Systems Management. In Encyclopedia of Pharmaceutical Technology, Marcel Dekker, NY, 2003.

• Nally, J.; Kieffer, R. G.; Stoker, J. From audit to process assessment—the more effective approach. Pharm. Technol. 1995, 19 (9), 128–140.

• Kieffer, R. G.; Stoker, J. R. Quality performance measurement and reporting. Pharm. Technol. 1986, 54—58.

• Magnani, J.; Vinther, A. The changing role of the quality professional\MHow do you score? PDA Letter 2013, July/August.