Chasing Quality
Quality control must keep pace with an evolving regulatory world.
Mark Crawford
Plenty of variables come into play when dealing with quality—a tougher U.S. Food and Drug Administration (FDA), new recall requirements, changing timelines, revisions to the FDA’s 510(k) clearance process—not to mention all the advanced tools and methods available for collecting data in real time and improving quality throughout the supply chain.
According to a recent FDA survey of medical device makers, the top five most important quality issues in 2010 are risk management, design control, supplier quality, quality system regulation (QSR) compliance and post-market surveillance.
Of course, there are two bottom lines for manufacturers—1) satisfying customers and end-users with safe medical products and superior patient outcomes, and 2) complying with FDA expectations.
“For manufacturers, the easy answer is simply to follow the regulations,” said Dan O’Leary, regulatory compliance expert and president of Ombu Enterprises LLC in Swanzey, N.H. “I routinely review device warning letters and the number of times the phrase ‘failure to establish the procedures required by …’ or ‘failure to follow your procedure for …’ appears is amazing. While warning letters can raise some obscure issues, in nearly all cases a 483 or a warning letter can be avoided by simple adherence to the regulations. The regulations in QSR are not complex, nor do they require manufacturers to do things outside good business practices.”
That is often easier said than done, especially for manufacturers who are hurting financially, lack dedicated quality/compliance officers, outsource heavily, or don’t keep up with changing regulations, especially now that the FDA expects things to be done differently than they used to be.
“The FDA has added inspectors and the new commissioner [Dr. Margaret A. Hamburg] is very enforcement-oriented,” cautioned Edwin Bills, principal consultant with Bilanx Consulting in Sumter, S.C. “She’s coming down harder on manufacturers and more quickly. Because of recent recalls related to the supply chain, the FDA has a great deal of interest in the supplier-manufacturer relationship. Medical device manufacturers are increasingly being held accountable for their supply chains and what kinds of verifications are in place.”
Unless medical device manufacturers have professional staff dedicated to regulatory compliance, it can be hard to keep pace with evolving policy. “We are seeing more manufacturers and suppliers reach out for assistance with quality and regulatory issues/projects,” said Brent Noblitt of Noblitt & Rueland, a consulting firm in Irvine, Calif. “Many of our clients who are progressive but lean on resources find that consulting with outside experts is a cost-effective way to help their current employees who are already fully utilized and unable to take on new or ongoing projects.”
Start with the Supply Chain
Customers and end users are demanding attention to critical requirements, validated and repeatable manufacturing processes and quality that is built into the design of the product. They also want a comprehensive review of the processes and procedures that go into the manufacturing, packaging and testing of each product.
“A strong design control process must be in place and clear product specifications must be established and mutually agreed upon before moving forward with any product,” said Tom Black, vice president of OEM sales and marketing for B. Braun Medical Inc. in Bethlehem, Pa. “In essence, they are demanding the same from their suppliers that they demand from themselves.”
OEMs are demanding perfection from their suppliers all along the supply chain. “Over the years, there has been a shift in expectations,” O’Leary said. “There was a time we measured quality as percent nonconforming; in today’s world, customers expect parts-per-million quality levels.”
Each company in the supply chain must understand and meet the customer’s requirements for quality and also understand the critical control points of their process. The greater the distance along the supply chain, the more difficult the communication issues become; the same direct relationship exists in the customer direction. Risk increases with distance, where distance is measured in terms of links along the supply chain or geographic distance.
“The second- and third-tier suppliers are most vulnerable,” Black noted. “This requires a clear understanding of the OEM’s requirements by the first-tier outsourcing partner. It is imperative for the second- and possibly third-tier partners to have an understanding of the critical requirements of the product, along with an understanding of how their components fit into the finished product, as well as how the finished product is being used. The old ‘you’re only as good as your weakest link’ saying fits perfectly here. Any miscommunication can lead to quality issues with the finished assembly, or the end user. It is the responsibility of the first-tier outsourcing partner to manage the customer’s requirements through the entire supply chain.”
The distance problem really is one of communication. It always is preferred to have a familiar working relationship with your major suppliers, but if they are located offshore that can be expensive.
“Video conferencing is a cost-effective way to have frequent face-to-face communication,” O’Leary advised. “Regular phone calls are fine, too. The problem is that distance often has an inverse relationship with communication frequency and effectiveness.”
Noblitt agreed, adding that “systematic communication is critical” in today’s medical device manufacturing environment.
“Suppliers need to be able to reliably contact their manufacturer when something changes with the part, service or assembly they are providing,” he said. “The communications process and expectations should be spelled out clearly in the purchasing agreement between the two parties.”
The risk along the supply chain can be mitigated with well-thought-out supplier quality agreements, especially for essential components. Consider, for example, a manufacturer who purchases a sterilized component from a supplier. The supplier is one step away and the supplier’s contract sterilizer is two steps away.
“You could have an agreement that defines the quality aspects of your relationship with your supplier,” O’Leary said. “This could include a requirement that your supplier have an agreement with the sterilizer, and that you are ‘named’ as a party in the agreement.”
Speed to Market
In order to speed up time to market, manufacturers need to continually reassess how they look at quality. “Quality cannot be inspected into a product,” said Kimberly Paris, director of quality for B. Braun Medical Inc. “Quality needs to be fully integrated into each step of design, development and manufacture of a product, both by the finished device manufacturer as well as by suppliers. These activities need to focus on providing value to the end customer. Ensuring quality is integrated into these activities will increase speed to market.”
As important as speed to market is, it also is critical for all partners to understand that quality should not be compromised by speed to market. If an outsourcing partner overlooks one area of quality, it only will make the project time line much longer, and result in higher costs.
“That is why our manufacturing representatives, along with the various disciplines closely tied to manufacturing (quality, regulatory, testing, sterilization, validation) are all involved from the beginning of a project,” Black pointed out. “Leaving out any area of expertise at the initial review stage will only be asking for issues down the road.”
This is where an effective Lean manufacturing approach can help. Running a Kaizen for the product being developed for manufacturing in the initial stages will maximize speed without compromising quality. Six Sigma methods also are designed to improve processes and sustain the improvement. Many companies find the initial costs high but, if successful, Six Sigma results in lower long-term costs. The sustainability often is driven by the reduction in cost—as quality improves, and the process produces fewer problems, cost will decrease. Careful monitoring of both the process controls and cost will hold the gains.
“All operations’ disciplines must be involved up front with a project in order for quality and speed to keep a similar pace,” Black emphasized. “Experience with various manufacturing capabilities also provides an advantage in this area.”
Many manufacturers keep supplier scorecards and measure both on-time delivery and incoming quality, often weighing them as equals. “The speed problem, however, does show up in inventory levels,” O’Leary explained. “In the current economic climate, inventory levels tend to drop, creating a potential inability to satisfy demand. This could have an impact along the supply chain.”
Regulatory Issues
As more companies outsource and others become virtual manufacturers, the FDA has heightened its concerns regarding these relationships, leading to an increase in purchasing controls compliance issues.
“Medical device software continues to get heavy scrutiny from the FDA, due in a large part to the number of product recalls as a result of software issues,” said Noblitt. “Some of the other non-compliances that can be found in the warning letters repeatedly are design control issues, management controls, training, corrective and preventive action (CAPA), process validation, etc.”
O’Leary indicated that the new leadership at FDA seems to think the agency has done an inferior job in the past and getting back to the basics. “For example,” he said, “the agency has not kept up with the required inspection frequency for device manufacturers in the U.S., let alone foreign device manufacturers. The agency is now hiring additional domestic inspectors and more firms will be inspected more frequently.”
The FDA also has not been able to keep up with the increasing volume of medical device reports.
“The eMDR (electronic medical device reporting) initiative will change this, since the agency will not have to rekey as many MDRs,” said O’Leary. “Presumably this will lead to increased review and action.”The agency also has increased its enforcement stance. It changed the process to issue warning letters, so they can be issued faster. In addition, there is a greater expectation of holding company officials responsible for problems.
Released in 2008, the Global Harmonization Task Force’s Document GHTF/SG3/N17:2008, “Guidance on the Control of Products and Services Obtained from Suppliers,” is a guideline for purchasing controls for the supplier-manufacturer relationship. The FDA expects medical device manufacturers to follow these recommendations and impose them throughout their supply chains (this will be emphasized in an upcoming revision of the Quality System Inspection Techniques guidance for inspectors).
“One of the main things the FDA wants to see documented in contracts with suppliers is that the products can’t be changed without the approval of the buyer,” said Bills. Any change must be reviewed and approved by the purchaser or medical device manufacturer. This is really a big deal to the FDA because of previous high-impact recalls that were triggered by components that failed (such as Heparin’s falsified ingredient from a plant in China that led to the deaths of more than 80 people). If such an agreement cannot be secured, then manufacturers must apply sufficient controls to ensure the procured product is of the required quality.
Maximizing Quality
Over the last several years finished-device manufacturers have looked to their suppliers to enhance their process controls in order to assure consistency of their quality output. As a result of these increased expectations on suppliers, finished-device manufacturers further have partnered with suppliers to integrate their inspection methods, measurement techniques and process control expertise to ensure their expectations are met with each lot of product produced. Before installing any technologically advanced inspection methods and techniques, medical device manufacturers first need to determine the metrics that need to be measured, based on critical product requirements specific to the device as determined through their design process. Once this is understood, then appropriate methods can be defined.
“In order to maintain streamlined processes and provide real time feedback,” says Paris, “integrated or online inspection methods can be leveraged. Depending on the level of process automation, these inspection methods can be tied in to the manufacturing process to provide closed-loop feedback for process monitoring and control.”
One of the most important processes for the prevention and solution of regulatory and quality issues is proper training of personnel. Unfortunately, with the uncertain economy and healthcare legislation, manufacturers have let training investments dwindle in order to save costs. “Many manufacturers are behind in their training of personnel and need to catch up before their next FDA inspection,” Noblitt said.
Educating suppliers is not an easy task, especially when each supplier is providing a different material or service with different applications. “There is no ‘one-size-fits-all’ solution,” Paris told MPO. “An assessment regarding their knowledge of product applications and process controls must first be made to determine where the education process begins and how it should be approached to be effective.”
The ability to communicate clearly the requirements and expectations needed from the supplier is critical. Successful communication typically does not happen on a one-to-one basis (between the quality and purchasing departments, for example) and must be nurtured. “Cross-functional team efforts, including technical personnel, are needed to ensure suppliers understand the full requirements,” Paris added. “Having these requirements documented through specifications, drawings, quality agreements and supply agreements is also essential for maintaining product quality.”
Controlling Costs
The cost of quality, in terms of inspections and testing, varies dramatically by product and company. For the most part, however, the overall cost of operating a compliant quality system is based on the number of staff involved in maintaining that system.
“One of the problems with headcount is that many tasks are collateral duties,” O’Leary said. “For example, few companies have full-time quality auditors. Usually the auditors have another full-time job and do auditing in a part-time role. Consequently, it is hard to lay off an auditor. One loses auditing skills because layoffs occur for other reasons. The costs are hidden, since a company may need to train a new auditor to meet the schedule.”
Training is one of the most cost-effective methods of maximizing quality and minimizing the risk of regulatory, quality and product liability issues. An in-house training course in which entire teams, departments or even the entire company is trained on certain aspects of quality and the quality system can pay dividends financially, due to both product quality improvements and higher employee morale in understanding their co-workers’ needs.
“Identifying the proper people that can benefit from a particular training session is important and will depend on the topic being trained, such as quality system, design control, risk management, software, auditing and complaint handling,” Noblitt said. “Interdepartmental training also provides an understanding between departments, which leads to less bickering and more cooperativeness in getting a job done quickly and thoroughly.”
Maintaining Quality Overseas
For medical devices, the international quality gold standard is ISO 13485, issued by the International Organization for Standardization, or ISO. QSR and ISO 13485 are essentially the same, both being versions of ISO 9001. Many companies have one quality management system that satisfies both standards at the same time.
ISO 13485, according to the organization “specifies requirements for a quality management system where an organization needs to demonstrate its ability to provide medical devices and related services that consistently meet customer requirements and regulatory requirements applicable to medical devices and related services.”
The primary objective of ISO 13485 is to facilitate harmonized medical device regulatory requirements for quality management systems. As a result, it includes some particular requirements for medical devices and excludes some of the requirements of ISO 9001 that are not appropriate as regulatory requirements.
The major differences between ISO 13485 and QSR are the audit frequency and severity of action. “For ISO 13485, notified bodies audit every six or 12 months on an established schedule,” O’Leary said. “The FDA shows up about every five years.”
Accredited third-party firms can conduct FDA inspections and report the results to the FDA. The hope was that notified bodies would become accredited and manufacturers would have their regular FDA inspection conducted in conjunction with ISO 13485, the European Union’s Medical Device Directives, and Canadian Medical Device Regulation inspection. “Very few manufacturers participated,” noted O’Leary.
For medical device manufacturers, international quality standards (especially ISO 13485) are increasingly important because international marketplaces are developing into opportunities for growth that might exceed the U.S. in sales volumes. “Although notified bodies have become more rigorous in their audits, making standard compliance and certification more meaningful, the FDA quality system regulation is still the yardstick by which U.S. manufacturers are measured,” said Noblitt.
Alternatively, suppliers to medical device manufacturers have found that ISO 13485 certification is very helpful in obtaining consideration and recognition by medical device manufacturers that are searching for a particular vendor. Not only is it an effective marketing tool to attract manufacturers, it also has the ability to reduce the number and/or length of supplier audits performed by individual manufacturers during the year.
Many U.S. companies offer the same product in multiple markets around the world, most frequently in the United States, Canada and the European Union. The regulatory systems are different but not contradictory, which adds cost and delays to the approval process. To counter these effects, the Global Harmonization Task Force issues guidance documents aimed at harmonizing device regulations around the world. The FDA is an active participant, but the Center for Devices and Radiological Health within FDA has not adopted GHTF guidance documents.
However, on the pharmaceutical side, there is a corresponding organization called the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. The FDA also is an active participant in this group and the FDA’s Center for Drug Evaluation and Research has adopted their guidance documents.
“I expect to see CDRH start to utilize the GHTF documents,” predicted O’Leary. “This will create an ‘international’ view that may require some new methods or approaches.”
An area of change for medical device companies is the Harmonized Standards in the European Union. New standards come into effect every year, but the transition period is long so companies can meet the standards. Even so, companies often procrastinate. “One good example is the new revisions to MDD,” said O’Leary. “Even though there was ample notice, many companies were scrambling in February and March to meet the deadline.”
Customers and medical device manufacturers demand the best from their suppliers. Meeting quality standards such as ISO 13485 and ISO 9001 helps suppliers understand quality systems and what it takes to implement them—this, of course, gives the OEM a level of comfort that someone else (an ISO registrar) has looked at the supplier’s quality system and found it to be acceptable.
“However,” cautioned Noblitt, “manufacturers also need to be wary that ISO certification does not guarantee that quality products will always be received from all their vendors. It is still important to monitor quality levels and perform supplier audits, especially on high-risk suppliers who deliver and use non-compliant parts or assemblies that may result in a substantial safety, regulatory, legal or financial risk.”