Operating under the oversight of the FDA and other global regulatory agencies creates a climate of transparency for regulated companies; any misstep can result in severe consequences such as product seizures, recalls, or company closure. Therefore, the way you respond to FDA Form-483 observations, warning letters, and other critical events is vital to your company's survival. Having a sound quality management system in place is critical, but when remedial action is necessary, time is of the essence. After all, you have only 15 working days from the receipt of the 483 to respond!
|The clock starts ticking the minute you receive your 483.
How to Word Your Response Letter
Crafting a timely yet strong response letter to a 483 is both a science and an art. Knowing how to provide the answers the FDA and other regulators seek will help you avoid a warning letter or further notifications. Your response must be worded in a way that is acceptable to regulators.
All too often companies respond to 483s in a casual, conversational manner and try to explain or justify what happened; this type of response is inadequate. Instead, you must use a critical thinking process to ensure that your response adequately addresses all of the issues raised by the 483 (with supporting documentation as warranted) without making promises that cannot be fulfilled or committing to unrealistic deadlines. If you over promise and under deliver (i.e., the 483s comes back), there is a good chance you’ll receive a second write up for the same violation, which almost guarantees that you’ll receive a warning letter.
Your Response Must Be Transparent and Comprehensive
Your response must be completely transparent and comprehensive; it must address not only the observation itself, but also the broader issues implicated by the observation. According to Stephen Rabe, a compliance officer in the FDA’s Cincinnati District Office, “It’s important when firms write response letters that they address the specific observations that were written down on the FDA 483. And yet the huge part that is often missing from the response letters: the company addresses individual observations, but it doesn’t really get to the solution of the problem.”(1)
Remember, regulators are not interested in a justification of “why” a particular nonconformance may have occurred but “what” corrective actions you intend to take to remedy the situation—and “when.” No remediation plan is complete unless it includes progress milestones, which outline the interim steps you intend to take toward resolution, as well as hard deadlines for completing your corrective actions. The key is to show investigators that you understand the consequences of the deviation (e.g., the deviation had such and such impact). Be sure to explain each aspect of the resolution carefully to demonstrate not only a successful resolution to the problem, but also the company’s commitment to prevent reoccurrence. Convince investigators that you are remedying the problem to satisfy not only safety and compliance issues, but also because it will make your business better. Hint: If you need help convincing senior management and other stakeholders of the importance of dealing with a 483, remind them of the damage a warning letter can do to stock prices and brand equity.
The Response is Just the Beginning
Many recipients panic when they receive a 483, but forget about it once the response letter is out the door. Constant review measurements must be implemented to assure regulators of your commitment to continuous quality improvement and compliance. In short, crafting the response letter is just the beginning: follow up is paramount to successful remediation. After you’ve sent off your response, conduct a mock audit to prepare for the FDA’s return. A gap analysis can be helpful, too. Remember, 483s are often a symptom of a much larger issue. Dig deep, uncover the root cause of the problem, and you’ll show the FDA that you are doing more than the minimum required. Chances are you’ll uncover other potential 483s or compliance problems. If you lack either the time or expertise to address the 483 in the level of detail described, consider hiring a third-party remediation partner.
Survey Says Hiring Outside Help is Beneficial during the Remediation Process
Forming an alliance with an experienced remediation partner is often the first step many regulated companies take toward restoring regulatory confidence and maintaining compliance with applicable regulations. Underwriters Laboratories (UL), a safety science company in Illinois, conducted a survey of medical device companies and how they respond to FDA enforcement actions such as Form 483s and warning letters. The results of the survey were the subject of an article published in the November/December 2013 online edition of Orthopedic Design & Technology.
According to the article, the main focus of the survey was to evaluate how often device companies enlist the help of an outside consultant to help with post-enforcement action, and what they look for in a remediation partner. The results were interesting.
Survey respondents, primarily quality, regulatory, and compliance executives from relatively small (under 1,000 employees) device firms, indicated that hiring an outside consultant proved more beneficial than relying on internal resources. Not surprisingly, the main benefit cited was “quick resolution and dedicated resources.” (2)
Ken Peterson, director of MasterControl’s quality and compliance consulting (QCC) division, which specializes in regulatory acceptance and remediation services, agrees that the need for speed and dedicated expertise is what typically drives overwhelmed and understaffed life science companies to enlist his help. “An outside remediation and regulatory compliance advisor can help you identify root causes, develop corrective and preventive action plans, and mitigate associated risks quickly and effectively—without taxing your internal resources or having to hire extra staff,” said Peterson. “This is huge, particularly for smaller companies who don’t have access to the same resources as some of the larger firms.”
However, Peterson, who has more than 20 years’ experience in consulting/organizational change, quality management, and product development, also stressed the importance of hiring the right consultant. “Industry experience is critical. If you hire a consultant who doesn’t understand your business, as well as FDA regulations, inside out, you’ll waste valuable time, energy, and money creating and following a remediation plan that isn’t right for your organization,” said Peterson. “With the 15-day post-inspection response clock ticking, you simply cannot afford to work with a remediation consultant who can’t hit the ground running.”
Most Important Criteria for Choosing a Consultant: "Proven Experience" and "FDA Reputation"
Survey respondents agreed, citing “proven experience” and “FDA reputation” as the two most important criteria for selecting a remediation partner. As the article points out, organizations, particularly smaller firms unfamiliar to FDA regulators, can often leverage their consultant’s reputation with the FDA to their advantage. In addition, consultants often bring an “outsider’s perspective” that resonates with management, which helps to secure buy in.
Roger Juneau, president of General Hearing Instruments Inc., summed up the benefits he experienced enlisting the services of an outside remediation partner, in this case MasterControl QCC, to assist with his company’s regulatory issues. “The GHI management core needed to formalize SOPs from ‘tribal’ knowledge to being truly CAPA compliant. A warning letter needed a formalized response that was on target and affordable. Our QCC consultant filled the knowledge vacuum by providing an action plan that was timely, task balanced, and affordable. We believe we are now trained and ready to manage inspections. We further believe the improved efficiencies and management oversight has taken the operation to the next level, including ISO 13485. The QMS team will continue working with MasterControl as we apply for certification,” Juneau said.
MasterControl consultants, many of whom are former FDA auditors, use a process approach and proven methodologies that enable them to provide expertise, resources, and sound project management throughout all phases of the remediation process. Outcomes, as well as timelines and objectives, are carefully established and mutually agreed upon at the onset of the project. Each aspect of the remediation is planned to include investigation and correction; systems integration of solutions; risk reduction, assessment and measurement; audit; and health authority inspection/regulation preparation and coaching. QCC also offers training workshops that teach participants how to implement and follow a best-practice system for handling 483s and other regulatory citations.
“A real remediation partner should be able to help you do it all—from drafting the response letter to getting you ready for the pre-inspection audit and everything in between,” said Peterson. “Let your consultant guide the remediation, so that you can focus on your core business initiatives.”
Have you ever engaged the assistance of a third-party remediation consultant to assist you in resolving 483s, warning letters, or other citations? What are the benefits? What do you think makes for a first-class remediation partner?
Lisa Weeks, a marketing communications specialist at MasterControl Inc., writes extensively about technology, the life sciences industry, and other regulated environments. Her two decades of marketing and advertising experience include work with McNeil Pharmaceuticals, SAP AG, SCA Mölnlycke Health Care, Crozer-Keystone Health Systems, and NovaCare Rehabilitation/Select Med.