The U.S. Food and Drug Administration (FDA) is authorized to perform random inspections and audits, and these inspections can lead to FDA warning letters and FDA Form 483 observations. Quality managers must take several proactive steps to reduce the risk of warning letters, but what exactly should be done, besides the obvious, which is to be in compliance with defined regulations?  

First, let’s define and understand the meaning of warning letters and Form 483 observations.  Warning letters are considered to be informal and advisory by the FDA.  Nevertheless, organizations are expected to voluntarily comply with the law and to take corrective actions.  The FDA Form 483 provides support for the alleged violation and communicates the concerns discovered during the inspection.

Organizations are given an opportunity to voluntarily and promptly respond in writing and include a corrective action plan.  However, if issues highlighted by the FDA are not addressed and communicated in a timely manner, the FDA will initiate an enforcement action, and these actions can include product recalls, fines, penalties, and, of course, your reputation is at stake.

Here are some tips on how to avoid a warning letter and  form 483 observation:

1. Be inspection ready

Have a QMS in place that meets your operational needs and compliance requirements, conduct your own internal audits on a regular basis, identify audit team members and assign tasks, provide a schedule of meetings, identify confidentiality requirements, and involve senior management.  Inform your employees about audits, provide resources needed, and appoint staff to accompany auditors when they do arrive.

1. Clearly Written Standard Operating Procedures

The Standard Operating Procedures (SOPs) need to be clearly and concisely written, but also maintained by getting them modified when necessary. Make sure you document any changes and that only the most recent version is available to your team and to inspectors.  

1. Proper Document Control

An automated document control system provides proper version control of your documents, including SOPs.  Your document control should eliminate the possibility of human errors and provide standardization to your version control, revision history, and approval process.  Establish proper permissions to prevent unauthorized access and changes to your documents.

1. Develop a compliance culture

Make quality and compliance a cornerstone of your culture.  A corporate culture is often driven by the organization’s CEO.  You need your CEO and executive team to be on board, and to understand and communicate the importance of compliance and quality to the entire organization.  One way to ensure senior management involvement is to actively involve them in the initial meeting of an audit, during the audit process, and in the final meeting.  Make sure to keep senior management involved with all subsequent communications with the FDA.

1. Correct observations real-time

Take every effort possible to correct observations while the FDA investigator is still onsite and express that remaining issues are in the process of being addressed, ideally with a stated timeline.  It’s important to communicate these changes or planned changes before or during a close-out meeting, and before the FDA inspection report is completed. Remain professional, provide proof whenever possible, and keep copies of signed-off documents.

1. A hyper-adaptive Quality Management Software

QMS software has evolved from customizable solutions that are typically expensive, time consuming, and with limited configurability capabilities to quality automation software that empower users with tremendous flexibility and at a lower total cost of ownership.  A modern and hyper-adaptive quality automation solution will ensure compliance today and into the future as you can easily address new business and regulatory changes.

If you want to own your own quality and compliance experience, learn more about Intellect’s comprehensive, integrated and hyper-adaptive eQMS software suite and automation platform.

Things change very fast in the world of mobile apps. Besides the mobile phone manufacturers adding better cameras, processors, accelerometers, and gyroscopes; mobile app developers are following those upgrades up with new and improved apps. When talking about mobile medical apps, you probably wondered if the FDA regulates them. The answer has been changing, and we will present some of the latest rules brought by the FDA to make the picture somewhat more transparent.

Groups of Apps Regulated by the FDA

Before you conduct a regulatory assessment, you should determine whether your mobile app is affected by FDA's regulations. The FDA has been evident in their mobile medical app guidance that they intend to use a risk-based approach when applying their rules. Mobile medical apps that could pose a risk to a patient’s safety or health are the only ones the FDA regulates. There are four possible groups of apps, following the FDA’s way of sorting them:

1. The app is not a medical device,
2. Even if it is a medical device, the FDA has said that they will not regulate it,
3. The FDA will regulate because they said that it is an app, and
4. None of the above.

Apps that fall into groups 1 and two are not regulated by the FDA, while apps from the fourth group are those without analogs in any known examples. Apps from the group 4 are likely to be controlled. It is explained in the FDA’s “Guidance for Industry and Food & Drug Administration Staff” guidance document.

More Challenges with Proving FDA Compliance

The surge of mobile healthcare apps is the surge behind FDA’s regulatory updates and changes in medical app development. According to the Mobile Medical Applications Guidance for Industry and Food & Drug Administration Staff guidance, a medical app is considered to be an app that works as an accessory to transform a mobile medical platform for a form of medical use or augment, supplement, or support an existing medical device. To ensure the effectiveness and safety of medical apps, the FDA will use the same risk-based approach that it uses for other medical devices.

The Emergence of the De Novo Pathway Trend

PMA (Premarket Approval and 510(k) pathways for putting a product on the market have been more popular than De Novo pathway, but this is changing. It is happening because the FDA is streamlining the application process without requiring a 510(k) anymore. What De Novo method provides is a way to classify new medical devices as Class I or II when there’s no predicate device. If a person believes that their medical device is appropriate for classification into these two Classes, they can submit a de novo request without preceding NSE and 510(k). The De Novo pathway is highly risk-based, which means that you can get a product on the market without a lengthy premarket approval application (PMA.) It is only if your new technology isn’t considered high risk and you’re able to demonstrate how all known risks can be mitigated.

New and innovative ways for health improvement and better health care delivery are being opened with the widespread use and adoption of mobile technologies. The FDA is there to encourage mobile medical app development and has a responsibility to oversee their effectiveness and safety. If you’re conducting a digital transformation to be FDA compliant with all new regulations and laws, involve your compliance team to ensure alignment from the beginning.

We had the pleasure to work with one of the largest food safety and quality services providers in the world. The company is known for working with clients as a trusted partner to promote public health through analysis, consulting, auditing, training, contract research, and sensory analysis services, through a network of global laboratories.

The Challenge

The multilingual global company needed a way to address and improve non-conformance response, customer complaint response, and compliance which included approvals, and documentation with Oracle CRM. The solution has to be multilingual to accommodate all their labs worldwide.

The company needed an effective solution to capture, track and maintain accurate, auditable non-conformance records through a centralized database. They wanted to streamline the process for identifying, evaluating, reviewing, and handling nonconforming parts, materials, and products and view any aspect of their workflow for complete transparency and reporting.

They also wanted to streamline customer complaints management to improve product quality and safety, decreases audit time, lower risk, and ensure FDA and ISO compliance.

The Solution

To address non-conformance, the company used Intellect’s NCM solution to create, track, and maintain accurate, auditable conformance records to ensure compliance with all management records. The “Quality Tools” app for non-conformance, customer complaints and corrective and preventive actions (CAPA) was configured to meet their exact business processes in 3 months. Employees are now assigned and notified of follow-up tasks to ensure accountability, automated email notifications and reminders.

In addition, Intellect managed their customer complaints by tracking the intake of customer complaints through investigations and CAPAs which enables continued improvement. The easy-to-use solution works on any device. Record incidents were centralized to facilitate investigations, report results better, and close cases. With Intellect’s Complaints Management, they improved communications with customers by acknowledging, tracking, and implementing any requirements that resulted in improved product quality and reduction in product recalls, ensuring compliance.

The solution met their multilingual requirements and was available to users in 8 languages, English, French, Spanish, Italian, Polish, Portuguese, Turkish and Mandarin.

The Results

The results were improved visibility to common issues for better resolution. Response time to customers on issues was improved. Internal audit tracking was overhauled resulting in reduced audits by 25%. ROI was achieved in less than 6 months. Overall, shared knowledge across the company was increased which ultimately provided considerable annual savings.

Why do people cringe at the very thought of compliance and change? Perhaps it’s because compliance means having to behave according to someone else’s command, and it’s our natural reflex to be resistant to being controlled, and skeptical of change.

But what if our reluctance to change was causing our organizations to lose massive amounts of money due to inadequacies caused by outdated processes?

The loss of revenue that occurs when document control systems are inefficient can be significant, and can cost manufacturers millions of dollars. These inefficiencies can be traced to the use of paper/hybrid-electronic systems which partially involve a manual approach or the combination of both digital and paper files. As with any manual approach, this was prone to error which resulted in delays.

And for this reason, FDA-regulated and ISO-certified companies mandated with a document change control system have shifted to automated digitized solutions which eliminate the laborious and time-consuming manual management of documents.

Here are the main benefits of an automated digitized solution for document control and how it helps ensure companies meet ISO and FDA regulations:

Easy Creation of Various Types of Documents

An automated digitized solution simplifies document creation. Different document types mean handling each document differently and may consist of separate approvers and workflows. An automated solution simplifies the creation and approval of documents, assigning the correct workflow based on each document's unique routing.

Faster Review and Approval

It’s up to the system to route documents to be reviewed by the relevant employees, ensuring final approval is received on all documents before they are used and distributed. Automated digitized solutions

have intelligent business rules that make room for deviations in the process when necessary.

Employee Training Integration

When the Training Management system is integrated with a document control system, companies can easily define which employee needs training on each document. The systems updates training records, allows self-training, and automatically updates employee status when training has been completed.

Promotes Collaboration Through Visible Reporting

When the reporting system is integrated with good document control, employees can quickly and effectively look at data to run the necessary reports. Visibility allows employees to look at data and keep business processes consistent and controlled.

Keep Data Secure Through Intuitive Filtering

A centralized system doesn’t mean that all users should be granted access. For security reasons, employees should only have the appropriate access to documents needed for them to approve, review, and make any necessary changes. A document control system allows you to filter and secure data thus limiting visibility data to only what is relevant to each user.

In conclusion, document control systems are put in place to ensure manufacturers are building products that are reliable and safe. ISO and FDA regulations are enforced to ensure that both process and documentation follow pre-approved methods.

For a company to thrive, it needs to recognize that compliance is a necessary tool that will give it a competitive edge. Achieving and maintaining compliance ultimately leads to efficiency and better output. Having an automated digitized solution helps you achieve all that by eliminating manual processes that are prone to error, giving your ability to filter access, automate redundant processes, and ensuring the correct routing and workflows.

Operating a business in a government-regulated environment carries a high expectation of compliance and strict adherence to guidelines and policies. For companies that operate in the hyper-regulated scope of the Food and Drug Administration, software compliance is a top priority that must meet rigorously enforced standards.

There is no room for error in either medical or pharmaceutical software applications. The greatest concerns in each area focus on electronic recordkeeping and signatures (ERES) as mandated by Title 21 Part 11 of the Code of Federal Regulations.

WHO MUST COMPLY

Part 11 compliance applies primarily to medical device manufacturers and pharmaceutical companies. However, business operating in any of a number of life science product related industries must also ensure software compliance:

● Biotech and nanoscience companies

● Biologic and other drug developers

● Some cosmetic company applications

● Contract research organizations

There are few exceptions, but generally speaking, any company involved in the research, development, manufacture, or distribution of an FDA regulated product must be operating ERES software that complies with Part 11 guidelines.

FOCUSED ON RELIABILITY

Prior to cloud origination, digital conversion, and full-software integration, FDA regulated companies stored and submitted records in paper form. Hard-copy records carried a certain degree of reliability and trustworthiness necessary in the closely watched industry of medical and pharmaceutical development.

As technology advances, so have storage solutions and records. It is no longer efficient or economical to maintain volumes of paper when digital storage and filing are industry-wide norms. Twenty years ago, the FDA implemented Part 11 as part of an effort to standardize and regulate the quality, reliability, and trustworthiness of non-paper records, signatures, and filings with the agency.

Since the implementation of Part 11, software regulations have become an integral part of compliance issues and guidelines. When any company generates reports and signs off electronically, and submits digital documents to the FDA, it must comply with Part 11 regulations. Any software application used in the process must meet strict requirements.

SOFTWARE REQUIREMENTS

The FDA mandates a wide-range of complex and technical software requirements that individual companies must meet to comply with Part 11 rules. Since the accuracy and reliability of ERES data is the key focus of FDA concerns, software must include:

● Some validation process to ensure accuracy and identify altered or invalid records

● The ability to generate complete copies in various forms

● Security controls to limit access to authorized users

● Long-term storage and retrieval

● Appropriate training and tracking of electronic signature use

● Time and date stamped audit trails

In addition to these compliance requirements, companies must also have written policies regarding the use, control, and authorization of ERES systems among other strictly applied security and authenticity issues.

As technologies change and become obsolete more quickly, companies experience regular software issues and compliance questions. When evaluating software compliance, a good rule of thumb is for companies to exercise Part 11 software practices in any instance where records meet Part 11 definitions.

If your company’s software is out of date, lacks security and verification assurances, or has other compliance issues, it is time to find a solution. Ensure your company’s systems meet the latest Part 11 iterations and do not risk FDA sanctions because of a failed software audit.

Managing workflow in any business or industry can be like trying to tame an octopus with its many tentacles, especially in today’s tech-centric production lines. However, effective workflow management and planning can do more than lead to efficiency and cost savings. It can also increase the success of data gathering and analysis in across the board quality management systems including CAPA and Document Control.

By keeping the right people in the loop and informed though a transition to digital workflow, your management team can improve information sharing and communication. Effective workflow management stems from a variety of practices and technological inclusions that replace older practices not designed to keep up with today’s rapidly changing business environments.

Get Back On Track Quickly

No business functions without quality and improvement. Systems like CAPA and Document Control benefit from improved workflow because information is disseminated, returned, and processed more quickly and accurately. When CAPA practices detect a regulatory anomaly on a pharmaceutical or medical device production line, efficient workflow enables a rapid correction to ensure a near instantaneous return to compliance.

Efficient workflow management reduces communication discrepancies and lags that may lead to production disruptions. When companies increase the reliability of delivered information and corrective planning and action, they reduce down time and the traditional non-digital evaluation period between a business process interruption and return to service.

Communicate Effectively with Team Members

One obstacle facing production businesses, especially those operating in remote and multiple sites, is ensuring that all team members have the latest and most accurate information regarding a company goal, directive, case management, or other time-sensitive communication. Information delivery provides feedback that leads to productivity, solutions, and drives quality control and customer satisfaction. A lack of shared information results in policy and procedural breakdowns that impair quality output and other business processes.

With employees working off-site, separate from management and quality control teams, the simultaneous delivery of information and management decisions ensures that your entire team functions as a unit. Some examples of synchronized information delivery accomplished through increased workflow management include:

• Regulatory issues and updates
• Workload assignments
• Customer feedback
• Task notices and deadlines adjustments

When every member of your team receives the same information, it eliminates the occasional system-wide hiccups that interrupt quality management, production, and output. Synchronized digital delivery eliminates the redundancy of paper copies and the need to file documents at a number of locations and offices when a single cloud-based alternative serves multiple recipients.

Keep Teams on the Same Digital Page

When a business relies on compliance and regulatory issues — such as FDA directives codified at the ubiquitous 21 CFR — every member of the quality control team needs the same up-to-date information at their fingertips. Communication among management personnel relies on integrated and autonomous workflow that includes delivery to key personnel who are aware of assigned tasks and problem solving procedures.

Effective business process management demands on-the-fly delivery, communication, and tasking. When a quality issue arises, you cannot afford to have team members thumbing through outdated manuals and regulations or not knowing their position in the QMS flow.

For businesses focused on strict regulatory compliance to critical standards, workflow management assures heightened responsiveness and effective quality performance. Eliminate lag times, outdated documents, and interactive missteps with an out-of-the-box QMS solution that incorporates workflow in both CAPA and Document Control modules. Should you wish to develop your workflow by customizing these modules or creating new ones, this is an ideal solution for your business.