The FDA’s current focus on measuring, incentivizing and rewarding the development of a Quality Culture across all levels of a manufacturing organization was emphasized in Janet Woodcock’s plenary speech last year at the ISPE Annual Meeting. In 2014, with increased emphasis under the new legal statutes GDUFA (Generic Drug User Fee Amendment) and FDASIA (FDA Safety and Innovation Act), this new FDA focus is expected to have a significant impact on CMO partners who form a key part of the global supply chain for many blue-chip life science companies.

There has always been an understanding between CMO partners and their pharmaceutical and medical device customers: the CMO is expected to deliver a quality product, with fairly minimal oversight by the life science partner, unless a quality issue arises. That is not to say that regular audits are not conducted, but a pre-contract review of quality procedures and training may be limited to a conference room discussion, or perhaps a review of PowerPoint trainings used to educate the CMO workforce on cGMP. Perhaps, in some instances, a manufacturing superintendent is posted on the day shift, to ease interaction between the two companies.

However, with this new emphasis on building a quality culture “from the shop floor to the boardroom,” as Janet Woodcock said in her address to industry last year, CMOs will undoubtedly be experiencing real and increased oversight by FDA. Dr. Woodcock emphasized overseas FDA audits as well.

CMOs also have a real opportunity to use quality culture to set themselves apart from the competition. If a CMO partner can show, and even showcase, its quality culture to a potential pharma or medical device partner, that could be a differentiator. Even in existing relationships, it may be to the CMO’s commercial advantage to highlight its quality programs, when re-negotiating a contract. If the quality program can be quantified and shown to be consistent, the CMO may be able to negotiate more favorable terms the next time around.

One way to quantify a quality program is to institute shop-floor operator training inside the organization. CMOs will find a real advantage in the marketplace if an operator education program is visible, measurable and consistent. In addition, FDA will look favorably upon the early adopters of expanding quality culture vertically — down to the shop floor. However, this sort of training should go beyond simply understanding Standard Operating Procedures (SOPs), to more comprehensive understanding of how and why they are performing functions in a certain way. Current Good Manufacturing Practices are present, but training should go deeper and explore the “whys” of cGMP.

Think about it. Intuitively, we know that the leading causes of quality problems are boredom and repetition. Very rarely does an operator cause a problem intentionally. But, SOPs, even today, found in manufacturing areas as paper instructions, encased in plastic and attached to tanks with key rings, are performed by rote, with little understanding of why certain tasks are to be performed in a particular way.

Explaining the “whys” can make a huge difference in execution of the daily routine on the manufacturing floor. Simple explanations on where medicines are used, and by whom, are important. For example, explaining the full life cycle of a drug, showing the ultimate patient experience, ties a humdrum packaging task into a more personal experience, allowing operators to connect their tasks with patients, as part of a family of grandchildren, parents, spouses and selves.

Showing the science behind cGMPs also can help tremendously. Explaining the chemistry of the process, if it is a drug, or the biology if it is cell culture, can go a long way towards helping those that handle the process understand the critical nature of measurement, cleanroom handling, and the risks of not adhering to SOPs. Even equipment science — how various valves protect backflow, or monitor the amount of flow — can be explained. Equipment vendors welcome the opportunity to visit on a regular basis and conduct training. The side benefit is recognition by the manufacturing crew that they are valued, that training is important to the organization and that they, in turn, are important pieces of the system that delivers safe medicine to the public (FDA’s core mission).

It is important that this type of effort not just be for show. It has to be scheduled, and demonstrable, both to potential clients and to the FDA. This means a regular schedule of training, as well as demonstrated log-in, sign-up and participation record, by operators on all shifts, across all areas of a site, and even more importantly in our global economy, consistently across all geographies. Thus, training should be available in multiple languages, if your sites cover different geographies.

And this brings up another interesting consideration: does your CMO organization promote a culture that makes it OK to ask questions, to probe, to bring to the surface perceived quality problems? Once training programs commence, there will most certainly be more awareness and more questions. Which is just what you want, isn’t it? Be prepared, with a system of escalation already in place and clearly explained (perhaps at the end of every shift or training session) that not only allows but encourages quality issues to be raised, without penalty.

Recognizing cultural differences about challenging authority and asking questions is also important to consider, particularly when you move below the managerial level and onto the shop floor. Manufacturing workforces in Eastern cultures may emphasize deference to superiors, and the importance of status within an organization. ‘Losing face’ can be considered worse than staying quiet on a perceived quality issue, unless the training emphasizes that patients are our families, and encourages raising quality issues as part of protection of families. In addition, understanding the “real science,” the “whys” of cGMP, lessens the cultural taboos against bringing problems to the attention of superiors, because the operator understands he is questioning the science and the data, not questioning an individual or his supervisor.

Western cultures may not view voicing quality observations as a negative, but newer operators might, for example, defer to experienced ones or to the loudest voice in the room, However, experience has shown that younger operators, simply because they experience less of the “rote” behavior discussed earlier, are more likely to voice an important question, particularly if operators have undergone training that reveals why a particular task is being performed in a particular way.

It may seem intuitive that understanding why certain manufacturing practices make safer medicine would lead to higher quality products, but a specific example makes it even easier:

Injectables — How They Work
Teaching manufacturing operators and technicians the simple science behind the SOPs comes alive when you talk about injectable products. Students are taught that injections bypass all the body’s defense mechanisms because the drug goes directly into the bloodstream. Creams, ointments and tablets, on the other hand, benefit from many of the body’s own defense fortress, with its natural filters such as the skin, stomach, liver, etc., before entering the bloodstream. With injectables, there is no such natural defense; the drug goes directly into the bloodstream. Learning the science behind the Injectable Manufacturing SOPs makes routine procedures come alive.

Cleanroom in Slow(er) Motion
Educating operators to move slowly and deliberately inside a cleanroom is another example of teaching the “whys” of cGMP. The airflow inside a cleanroom is designed for calm, methodical handling, not for quick motion and movement, or excited hand-waving while an operator shares the latest football scores. Disruption of the airflow too dramatically can be detrimental to the safety and efficacy of the products, by increasing the potential risk of contamination. Again, explaining why and how the walls and filters that surround an operator were designed will make following the “rules” more intuitive.

How Do You Train Across Geographies?
If your organization decides to embark on an operator training program, then consider this. It is critical for quality training to be consistent across geographic borders and between a company’s multiple sites. With 90% of the medicines we ingest produced generically and 70% of those medicines also produced overseas1, make sure the training you provide is consistent across your global organization, and is available in multiple languages. Again, this sounds obvious, but your competitive advantage is lost if the GMP education is only available in English. A CMO that can show a web-based training program for its operators across its global organization with access to multiple languages will gain a competitive advantage in the marketplace.

Training Delivery Methods
The learning industry has migrated from a classroom environment to an online environment, with content delivered in smaller, bite-sized pieces over a longer period of time. This is perfect for the manufacturing workforce; operators and technicians will value the ability to learn at their own pace using on-line learning.

Video training, shown in short clips at the beginning or end of a shift, is an excellent way to begin your quality culture implementation. The training could also be done in a classroom setting, by shift, once a week or even once a month.

Consider the following when evaluating quality training for your operators:

1. Look for learning programs that focus on the “Whys” not simply the “Whats”
2. Look for video learning that can be delivered in small five to 10 minute segments. (This allows for a more realistic schedule of daily interaction than longer courses.)
3. Make sure the learning package chosen can grow with your company — multiple local language capability is key
4. Ask for easy customization for medical device or biotech or pharmaceutical — if you have a particular need, ask about the time and cost to customize.
5. Ensure that the Support function is available across time zones, 24/7
6. Look for the ability to track students’ participation — this is the proof of your quality culture implementation!
7. Simple reporting functions are key for CMOs who will want to want to showcase training results for use in marketing
8. Look for training packages that allow operators to learn at their own pace, but allow managers to track and see their progress.

The best learning is one that encourages the application of knowledge and a curriculum that encourages written responses that display acquired knowledge, rather than standardized multiple choice testing. The idea is to encourage learning about the quality process; engagement/writing/instructor interaction is far better at achieving true learning than requirements to fulfill a certain grade on a multiple choice test.

CMOs are not Immune
CMOs will feel increased levels of scrutiny inside their organizations and Dr. Woodcock at FDA stated that she is dedicating higher levels of funding to the effort of audits, and is increasing staff.²

However, FDA is also quite clearly on a path to conduct more risk-based audits, as it has been mandated to do under FDASIA. There have been multiple meetings with industry to define the quality metrics necessary for consistent measurement of a risk-based approach to measuring an organization’s quality culture. While there is an ongoing debate on how to define a consistent measurement of company risk profiles, there seems little doubt that more frequent audits will be the result for those who have the poorest quality rankings. If a quality culture can be clearly demonstrated, at all levels of an organization, there will be fewer audits and the savings can be considerable; for example, the cost difference between bi-annual audits and annual or multi-annual FDA audits alone is substantial.

In addition, higher quality can mean commanding a better price in the market for a CMO’s services. For a CMO going back to re-negotiate a contract with a client, there is no question that its bargaining position will be stronger if the CMO has taken a proactive role in continuous quality improvement: developing, measuring and communicating its quality culture with its pool of potential clients. At the ISPE annual meeting last year, one of the technical presentations by a well-known Big Pharma quantified a 15% cost saving from increasing product quality. So, while it may take investment up front, there are excellent commercial, market and operational reasons to consider investment in quality improvement and culture across all levels of the manufacturing organization.

Operator training is certainly not the only answer to enhancing an existing quality culture. You can’t simply flip a quality switch to build a quality culture across a global CMO base. However companies shouldn’t “let the perfect become the enemy of the good” when looking to implement this FDA driven initiative — commercially, there are clear reasons to become an early adopter and invest in operator learning sooner, rather than later. 

References

1. Food Safety News, Obama Administration Seeks FDA Funding Increase for FSMA Implementation by Helena Bottemiller, April 11, 2013
2. Janet Woodcock plenary speech, ISPE Annual Meeting, Washington DC, November 2013.

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Gerry Creaner has more than 30 years of experience in the Life Sciences Manufacturing industry across a range of technical, managerial and business roles. A chemical engineer by profession, he established a very successful engineering consultancy prior to founding GetReskilled, an online education and learning business focussed on the manufacture of safe and effective medicines for the public, with particular emphasis on developing these competencies within the operator and technician groups across the global supply chain. For more information, contact gerard.creaner@getreskilled.com