By Sara Gambrill
In 2010 the FDA issued 122 warning letters to drug, device, and dietary supplement manufacturers that had not addressed observations listed by FDA representatives on Forms FDA 483 to their satisfaction. Each warning letter cited multiple violations of cGMPs. Complying with GMPs might seem a straightforward proposition, achieved by writing SOPs based on them and training employees. But, according to experts with vast experience in what GMP compliance requires, it isn’t so simple. What needs to be created at manufacturers is a GMP culture where compliance is the priority from top management to the line, training is frequent, and everyone, ultimately, is accountable for quality and avoiding 483s.
From The Top
Once a company understands which set of GMP regulations it needs to comply with—drug, device, cosmetic, or, most recently, dietary supplement—it needs to foster an environment of complete management support for complying with GMPs.
According to Carol Tousey, consultant/compliance auditor at Techceuticals, a company that offers training and solutions for pharma and nutra manufacturers, “No company is going to make GMP a lifestyle and a culture if top management doesn’t support it.”
Tousey describes management support as an all-or-nothing scenario. Every manager is going to feel the conflict between making a profit and complying with GMP at some point, but good management won’t demand that employees act in ways that are inconsistent with the company’s overall messages about the importance of GMP compliance, such as shipping product before testing it. “There are so many recalls because there are shortcuts being taken. There’s pressure being put on employees to do things they really shouldn’t be doing, and things aren’t getting done the way they’re supposed to,” Tousey says.
The Customer Isn’t Always Right
While complete management support is vital, Dennis Wogaman, COO at P.J. Noyes, a contract manufacturing and packaging company, also believes it is important to educate the customer up front. “Basically, customers want product as cheap and as fast as they can get it. Some have no comprehension of what’s involved with GMPs or some of the rigid steps you need to go through,” Wogaman says.
Educating the customer starts during the bidding process. It’s at that point Wogaman explains the testing requirements and the costs related to them, the amount of time it takes to get all the documentation taken care of before going into production, and the size of his quality staff (10 employees out of 110 total).
Wogaman adds, “There is a lot of information-sharing back and forth. Most of our customers appreciate that learning experience. But, it’s kind of hard at times, and it can get a bit emotional.”
Training Key To Engaging Employees
An important part of engaging employees is offering them proper training. In Tousey’s opinion, though, there is a lot of ineffective training in the pharma industry. “I usually see companies conducting GMP training with new employees when they’re hired and then once a year after that, and they never hear about GMP again. In my opinion, that’s not enough,” she said.
Tousey believes that when employees have to learn GMPs all at once, they get overwhelmed and don’t retain the information. Frequent, brief trainings on various parts of GMP throughout the year reinforce the initial training session and GMP culture. These can come in the form of modules that allow employees to learn at their own pace, as needed, or in the form of employee meetings. “Most people don’t even know what GMP is when they start at a manufacturing company,” she adds.
At P.J. Noyes, new employees are given an orientation involving a day or two of classroom learning with an emphasis on information-sharing on GMPs and films that support employee understanding. Production workers also are taught the many rules they must follow about how to wear their gloves, etc. and what is and isn’t allowed in production rooms. There is also a “huddle” every day at the beginning of the shift where any significant changes to SOPs are discussed.
For a GMP culture to truly be created at a manufacturing company, rules have to be enforced. Some manufacturers have a zero tolerance policy for people who violate GMPs, sending a strong message to other employees about how seriously the company takes compliance with GMPs. If such a company had a “no-jewelry” policy and discovered one of its line workers was wearing earrings, it would fire the employee immediately, thereby demonstrating that blatant disregard for rules will not be tolerated. Tousey says, “If management doesn’t deal with it head-on, it tells the other people in the company: ‘Why should we bother? Look at that guy.’”
Other manufacturers have a three-strikes-and-you’re-out policy, involving a verbal warning for the first violation, written warning for the second, and termination for the third. Still others offer retraining for employees who make mistakes and then disciplinary action for multiple infractions. Whatever method of enforcement a manufacturer chooses, it is important to maintain consistency and avoid getting 483s.
Lack Of 483s Offers Competitive Edge
While the results of internal and customer audits are not available to the public, the observations made during an inspection and listed by an FDA representative, 483s, are. Manufacturers that receive 483s can put themselves at a disadvantage when it comes to competing for business. Anyone, including competitors, can find a company’s inspection report online and use it as a marketing and sales tool at meetings with potential customers. It’s not hard to understand which manufacturer a company would prefer to have making their products when the choice is between one with 483s and one with none.
To prepare for an FDA inspection or simply to keep employees engaged and on their toes, it can be helpful to get a company audit by a private company. Regular audits can reinforce a GMP culture at the manufacturer and make checks on GMP compliance more routine rather than something that gets checked every once in a while or only when something goes wrong.
Another important way companies can create GMP culture and fend off 483s is by creating an environment where employees are unafraid to bring up problems. If employees believe they have a better chance of keeping their jobs by not telling management that something on the line seems odd to them, then they will keep these thoughts to themselves. In this case, consumers may be the first ones to tell the company about the problem.
While employees need to feel comfortable bringing up potential problems, it’s also necessary to educate them as much as possible about what constitutes a problem. “You’re walking a fine line between encouraging people to mention what needs to be mentioned in terms of problems they may see, versus crying wolf at every possible incident. That’s probably the hardest thing to get across in a GMP environment,” said Gus Fenton, a biomedical engineering consultant with 25 years of experience in many areas, including manufacturing, quality assurance, and R&D.
The sense that something isn’t right can’t be taught. In addition, though line workers may recognize a problem, they may not have the technical background to explain exactly what the problem is, perhaps making them more reluctant to bring a potential problem to management’s attention. Fenton suggests the best way to handle potential problems that line workers bring up is to walk employees through management’s evaluation process of the issue. Management should describe how the problem was evaluated, what results they saw, and why they are going to take the action they’re taking. Whether management needs to do nothing, keep an eye on the situation, or make a recall, the employees should know the decision and the reasons for it.
As far as mentioning problems, Fenton says, “Every company will tell you that’s what they encourage people to do. But, not every company has the managers who can work with the folks who are doing the assembly and allow them to feel free enough to discuss potential problems.”
We Are All Consumers
Creating a GMP culture isn’t easy. It takes a collective, consistent effort to comply with GMPs and to safeguard it against expediency, customer demands, employee indifference or anxiety, and economic pressures. GMP culture gives employees the feeling they can rely on each other to do the right thing. Perhaps there’s no better reason to have a GMP culture than the fact that we are all dependent on it. As Tousey said, “Ultimately, there’s a consumer relying on what we do. And, we’re all consumers, too. We expect that somebody was doing their job right.”
Inadequate Quality Unit (QU) Responsibilities
Lack of Adherence to Production Procedures
Inadequate Production Procedures and Validation/Verification
Insufficient Laboratory Controls
Inadequate Written Procedures for Production
Inadequate Investigations [of Complaints]
Inadequate Testing and Release
Inadequate Personnel Qualifications and Training
Inadequate Batch Record Preparation and Review
Inadequate Equipment Cleaning and Maintenance
Source: Carol Tousey via FDA