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GMP Training

Q: I am in charge of GMP training for a contract-manufacturing site with approximately 350 employees. The budget for my department was recently cut, and now I am struggling to get my employees to training. I know that this will become a potential item when my clients inspect me. Do you have any suggestions on what I can do to remedy this situation?

 

A:  This is a great question. It seems cutting the gmp training and travel budgets are the first austerity measure companies take when they are facing some budgetary difficulties. In my opinion, training should probably be one of the last areas that should have its budget cut because training is one of the key elements management can use to assure their commitment to consistently producing a high-quality product. It is also a GMP requirement.

 

The US regulations, 21 Code of Federal Regulations (CFR) 211.25, define personnel qualifications and state:

 

“Each person engaged in the manufacture, processing, packing, or holding of a drug product shall have education, training, and experience, or any combination thereof, to enable that person to perform the assigned functions. Training shall be in the particular operations that the employee performs and in current good manufacturing practice (including the current good manufacturing practice regulations in this chapter and written procedures required by these regulations) as they relate to the employee’s functions. Training in current good manufacturing practice shall be conducted by qualified individuals on a continuing basis and with sufficient frequency to assure that employees remain familiar with CGMP requirements applicable to them”.

 

cGMP Training

 

Just because your budget is cut, however, doesn’t mean you can’t make sure employees receive meaningful training. There are many organizations and companies that offer cGMP training on many webinar topics. These can range from “How to Write Effective SOPs” to “How to Perform an Effective Technology Transfer” to “Risk Management Strategies for Quality Management in the Pharmaceutical Industry.”

 

Some of these webinars are free and some require a registration fee. They are usually 90 minutes in length, and many offer an opportunity to ask the speakers questions through a chatroom feature. If you are unable to listen to the webinar live, you may have the option to purchase a recording of it and listen to it at your convenience. The recorded option offered with these webinars can be valuable for training employees who work on the second and third shifts that can often be challenging.

 

GMP Training Certification

 

In some cases, the webinar may offer continuing education credits for GMP training certification for attending. The companies offering these webinars advertise them well in advance of the event and often send out multiple reminders. The advertising for the webinars highlight who will be speaking, their qualifications, what they will cover in the training, and what you will learn as a participant.

 

In addition, they will also make recommendations on who should attend so you can determine if this is appropriate training for your employees.  This information should be printed out and used to demonstrate the appropriateness of the training during an audit.

 

FDA Training

 

FDA also offers training through the FDA Learning Portal for Students, Academia and Industry at www.fda.gov/Training/learningportal. This training, FDA reports:

 

“… provides educational resources related to FDA’s regulatory, product quality, and safety responsibilities. In each section you’ll find educational materials such as lectures and courses as well as web pages related to the particular topic.”

 

Some of the topics available include courses titled FDA 101, FDA’s Regulatory Framework, Current Initiatives, Human Drug Approval and Post-marketing. The modules also provide a course objective so you and your employees will understand what they should know after completing the training.

 

For example, there is also a module called A Tour of FDA, which, FDA states, will provide an understanding of FDA’s public health mission and how the agency is organized to carry out its mission (2). FDA also broadcasts some of its public meetings depending on the topic.

 

The agency’s public meeting regarding its Request for Quality Metrics Guidance for Industry was a great way to learn about the new guidance and what industry colleagues were thinking. This is another way employees can keep up-to-date on the current issues facing the industry.

 

GMP Training for Employees

 

Finally, for some personnel groups, GMP training for employees consists of discussions of current topics. This can include industry warning letters, 483s, or new guidance documents may be a low-cost alternative to a formal training experience. These discussions can be led by qualified company personnel and can cover not only the specifics of the issues but the rationale behind them. As with all other training, these discussions should be documented in your training system.

 

The bottom line is even though your budget has been cut there are still opportunities to get your employees the required needed training that will satisfy your customers in audits. You should sign up to receive emails from companies and organizations that offer online training, review them to determine if they are applicable to your operations, determine who should attend from your company, and make sure you document their attendance for their training record.

 

In addition, you should also monitor the FDA website for potential upcoming webcasts, past webcasts, and other public offerings that will help you and your employees receive the necessary training even with a limited budget.

 

Article Details

 

RCA

 

Pharmaceutical Technology
Vol. 40, No. 12
Pages: 66, 65

 

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CAPA Preventative Action: Getting Drug Quality Right

A well-functioning Corrective and Preventive Action (CAPA) program can make the difference between a deviation being corrected and prevented the first time. The consequence is reoccurring deviations that require reopened investigations — wasting limited resources and potentially causing product quality issues.

 

CAPA

It’s important to remember that a well-functioning CAPA program starts with a well-functioning investigations program. After you recognize you have a problem, the first step is investigating the deviation and determining the root cause. The root cause(s) will direct how, what and where the company will take corrective and preventive action.

 

Preventive Action

CAPAAs regulators note in ICH Q10, “CAPA methodology should result in product and process improvement and enhanced product development.”

 

In his book, quality consultant Phillip Crosby states, “Quality is free. It’s not a gift, but it’s free. What costs money are the ‘unquality’ things — all the actions that involve not doing jobs right the first time.”

 

QMS CAPA

To that end, setting up a CAPA quality system (QMS) must be surrounded by adequate standard operating procedure (SOP). Each SOP should monitor and include metrics to ensure nonconformances do not occur in the future. Especially when considering CAPA in pharma; this is the least costly way to deal with regulatory issues or product defect problems.

 

While the two terms in the CAPA acronym may sound similar, there are crucial differences between ‘corrective action’ and ‘preventive action’. If an FDA investigation and corresponding CAPAs are initiated, then both the corrective and preventive actions would be addressed to determine the root cause.

 

CAPA Quality Assurance

Further, impact on material or product and the direct correction to the issue (i.e., immediate correction) should be well documented. Corrective actions are taken to prevent the reoccurrence for a specific product or operation, while preventive actions prevent any occurrence for all products or operations.

 

One of the most useful strategies during a CAPA audit is to ask questions and avoid assumptions. A fishbone diagram, fault tree analysis or the ‘5 Whys Method’ are robust tools that often help determine adequate root cause.

 

CAPA Records

When conducting the investigation, companies must review multiple systems including manufacturing processes, machinery, equipment, environment, specifications, raw materials and people.

 

Deviations are not limited to these systems. Other systems should also be evaluated as necessary, but many deviations do reside within one of the listed systems.

 

CAPA Effectiveness

Another way to look at CAPA effectiveness is the metaphorical horse with blinders. Imagine the blinders are used to keep the horse focused and moving forward. This same metaphor can be used to think about the investigation and CAPA process.

 

If you go in with blinders on, just looking at the issue without reviewing other interconnected systems, important details can be missed and more costly problems may result.

 

CAPA Systems

Once all the elements of the deviation have been investigated, the narrative and its linked CAPAs should explain when and what happened. Documentation should also be included in your CAPA system for who was involved.

 

The narrative should also document the solution that was implemented to correct and prevent the reoccurrence of the issue. This includes a rationale for the root cause identified during the investigation. All these items should be well-documented within your quality system.

 

CAPA for Quality

A robust CAPA program designed to improve quality should include a well-documented system that identifies the root causes of a deviation. This includes the nonconformance, system failures, or process problems.

 

In addition, the CAPAs must address each of the root causes and identify the corrective action for remediation. Only after careful consideration about the deviation can the appropriate correction prevent the deviation from happening again.

 

CAPA Manufacturing

Qualified staff (with proper training, education, and experience) should run the CAPA program. Incorporating meaningful metrics to track the performance of overall systems can help provide early warning signals for deviations/nonconformances.

 

An appropriate Subject Matter Expert (SME) should be included in the process. Management should review potentially adverse information, oversee the overall adequacy of the CAPA program, and remediate identified deficient areas, including those that may need capital investment.

 

CAPA Quality

Once the appropriate solution for improving quality has been implemented, evaluating the solution’s effectiveness should be ongoing. There should be a process for monitoring the recurrence of the deviation and the closing out of the CAPA once the solution has been confirmed effective. All these items must be documented within the quality system.

 

The same level of depth and rigor of a CAPA for one issue may not be required for every deviation. For example, a small documentation error will likely only require a simple correction. More serious deviations, like a confirmed Out of Specification (OOS), will demand a much more robust investigation and CAPA. 

 

Deviation Meaning

The complexity of the deviation and its concomitant CAPAs not only determine the approach taken for the investigation but also inform the timeline. For example, while some standard operating procedures may call for a 30-day timeline for investigations and CAPAs, that timeline may need to be extended. Identifying the priority of the deviation helps the entire team to recognize meaning. 

 

In this case, you’d need to document the rationale for the extension and get the quality department’s approval. A critical caveat here is everything in the investigation leading to a CAPA does not need a time extension. If your company is extending a lot of investigations, then it may indicate another entirely different problem.

 

Pharmaceutical Manufacturing

The key to establishing a successful CAPA is a complete and thorough investigation focused on finding the reason the deviation occurred. This is essential in pharmaceutical manufacturing as well as many other regulated industries. 

 

Failure to identify the correct root cause will result in possible failed effectiveness checks and the dreaded reopening of the CAPA. Everything plays a part in the investigation: people, machines, materials, processes, etc.

 

CAPA Audit

Management of these players is key to identifying the deviation’s root cause. The audit process behind the investigations is crucial in addressing the issue at hand. The aim shouldn’t be to find a single root cause that management believes to be the reason for the failure but to analyze all possible root causes across all systems.

 

If an identified root cause isn’t the true reason for the failure, then the root cause can be eliminated. Each root cause eliminated narrows down the investigation. Any potential root cause that cannot be eliminated must be remediated, even if that root cause is not THE root cause of the failure.

 

Root Cause Analysis

A mistake companies make is identifying a root cause that needs remediation and stopping there. Companies should always identify all possible root causes and address them accordingly. When executed correctly, CAPAs help organizations remediate deviations/issues before they cause more technical problems and escalated costs.

 

A practical example of an investigation and CAPA process is as follows: Company X had an investigation related to the detection of nonconforming vials, which were discovered prior to packaging. The inspectors on the line found the nonconforming vials, informed the quality team, and an initial investigation ensued.

 

Quality Assurance

The quality assurance team correctly put the lot on hold while the investigation was being conducted. During the early phase of the investigation, the nonconforming vials were sent away to be analyzed by a third-party qualified laboratory. The results came back stating the discoloration was due to chemical contamination.

 

The chemical in question was not part of the formulation or the container closure system and was not on any product contact surfaces within the equipment. Company X eventually decided the contamination happened at the vial manufacturer and closed the investigation. One week after the initial observation of the discolored vials was opened and closed, the same issue arose with another product and the original investigation was reopened.

 

Forensic Investigation

The company subsequently audited the vial manufacturer, but the results were inconclusive, with no identified source of the chemical responsible for the nonconforming vials. The company continued manufacturing while the investigation was ongoing and began a 100% incoming material inspection.

 

A week later, a line operator noticed a vial exiting the depyrogenation tunnel that had a discolored blob in it. Manufacturing was stopped and the vial was sent to the contract lab for analysis. Once again, the chemical in question was the culprit.

 

Supplier Audit

The company sent a consultant to do a supplier audit of the vial manufacturer while they continued manufacturing the product. Similar to the initial for-cause audit, the external consultant could not find the source of the chemical leading to the nonconforming vials.

 

Finally, after opening the line for inspection, the company discovered that the contaminating chemical was associated with the HEPA filters. Manufacturing was finally halted on the line.

 

Corrective Action and Preventive Action

After completing a more thorough investigation, the root cause was determined to be faulty cooling valves in the depyrogenation tunnel. This was previously identified by the company as a potential root cause in the initial investigation, but was not pursued because it was classified as ‘possible but highly unlikely’ and ranked lowest on the priority list.

 

There was no alarm associated with the cooling valve which explains why the issue was not caught under routine maintenance checks. Once the problem was correctly identified, the proper and effective corrective action could be taken, including the potential costly endeavor of evaluating all products made on the line and looking at other lines with the same depyrogenation oven.

 

Cost of Poor Quality

Hypothetically, let’s say the cost of a critical deviation for Company X is a million dollars. We start by looking at the cost of poor quality (COPQ) of a defect.

 

The cost is eliminated only if the pharma company’s quality management system (QMS) is organized. This includes the QMS system being designed to detect, investigate, correct and prevent issues/deviations.

 

QMS System

If the company can prevent defects with their robust QMS, they will save money because they allocated sufficient qualified resources toward an efficient QMS — which in turn meant they didn’t have to address many defects/deviations and CAPAs. Hence the quality system pays for itself.

 

If the issue is detected within the company before anything is shipped out, the cost rises tenfold to ten million dollars. This is due to the company needing to address the now-detected issue and implement corrections (corrective action) to rectify the issue. Additionally, the team would put measures in place to ensure issues do not occur in the future (preventive action).

 

Forensic Analysis

Finally, if the company detects an issue in a drug product after it has been released by the quality department and delivered to the customer, the cost raises tenfold again. The forensic analysis must now include the cost of recalls, as well as corrective and preventive actions. The cost of quality is important to understand — for Company X, they caused themselves a $100 million mistake.

 

Company X initially thought the issue seemed small and negligible, which led to an unfortunate quick closure of the investigation. Ultimately the deviation affected twenty-eight lots of manufactured products. These lots, produced over a two-month period for several clients, were rejected due to the nonconforming vials.

 

Root Cause Strategy

Company X should have utilized a more thorough investigation and root cause strategy to follow every possible root cause. Instead, the company chose what seemed like the easiest root cause and jumped to the wrong conclusion. Then the company quickly closed this initial investigation without a complete and thorough investigation. In conclusion, this mistake created a bigger issue and a compliance and business risk.

 

It takes diligence, thoroughness and a healthy number of questions to ensure you investigate, correct, and prevent problems. But without this, the quality and efficacy of the drug product being manufactured could be jeopardized. 

 

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GMP Pharmaceutical Standards

Good Manufacturing Practice (GMP)

 

Maintaining good quality control practices throughout the entire manufacturing process requires robust GMP development, a drive toward product and process understanding, and pre-established, comprehensive written procedures that are consistently reviewed and updated.

 

Good manufacturing practice (GMP) is established by regulators to ensure that pharmaceuticals are safe and effective for the patients that rely on them.

 

21 CFR Parts 210 and 211

 

In the United States, requirements governing finished pharmaceutical quality are described in the Current Good Manufacturing Practices (CGMPs) regulations established by FDA and published in the Code of Federal Regulations (Title 21 of the CFR, parts 210–211 for most finished pharmaceuticals).

 

FDA also publishes guidance to further describe recommended practices for complying with the CGMP regulations. The agency states that “CGMPs provide for systems that assure proper design, monitoring, and control of manufacturing processes and facilities. Adherence to the CGMP regulations assures the identity, strength, quality, and purity of drug products by requiring that manufacturers of medications adequately control manufacturing operations” (1).

 

Quality Management

 

In Europe, GMPs are defined by the European Commission in EudraLex–Volume 4–Good Manufacturing Practice (GMP) guidelines (2), which were first published in 1989.

 

EudraLex states that quality management is “a system of marketing authorizations [that] ensures that all medicinal products are assessed by a competent authority to ensure compliance with contemporary requirements of safety, quality, and efficacy” (2).

 

GMP Certified 

 

To harmonize GMPs and other quality requirements worldwide, the International Council for Harmonization (ICH) works with international regulators and industry to develop common guidelines across the industry to ensure consistent quality expectations worldwide.

 

“At its core, CGMP is a science- and risk-based focus on assuring drug quality. As described in ICH Q10, Pharmaceutical Quality System, an overall attitude to drive meaningful and continuous improvements from the quality unit and other manufacturing employees is essential” (3), FDA told Pharmaceutical Technology.

 

GMP Manufacturing

 

The global nature of the pharmaceutical supply chain requires regulatory agencies to inspect and govern GMPs at manufacturing facilities. These inspections sometimes result in actions by regulators (e.g., FDA 483s, warning letters, import bans, and court actions) against companies that fail to follow GMPs.

 

Common CGMP deficiencies cited by FDA in warning letters sent to pharmaceutical companies inspected during the past year include failures to ensure product sterility, ensure data integrity, create quality control units, and develop and follow written procedures (4–7).

 

GMP Practices

 

“Companies should vigilantly encourage GMP practices that reflect the most current and robust methods of processing and control, and with a focus on providing a quality product to US consumers,” says FDA.

 

“The approach to successful CGMP is not merely a check-box approach where a single obstacle can be identified, nor is it meant to be unchanged throughout the life of a product or a CGMP facility. Using a holistic and quality risk management approach, a manufacturer can select and study specific products and processes with the goal of continual improvement of product quality and quality systems and widespread optimization.”

 

Quality Culture

 

So how do companies ensure they are “vigilantly” following GMPs and avoid the wrath of regulators? The answer appears to be found in a company’s “quality culture” and in the development, writing, and following of written procedures. Performing pharmaceutical manufacturing according to GMPs involves a dedication to quality throughout development and manufacturing processes.

 

“Corporate management plays a vital role in this endeavor by establishing a commitment to quality, which includes providing sufficient resources and oversight for manufacturing operations. There are many elements to successful implementation of CGMPs but measuring and monitoring quality indicators and managing change are key among them,” says FDA.

 

GMP Certified

 

According to Susan Schniepp, distinguished fellow at Regulatory Compliance Associates, becoming GMP certified throughout all processes and procedures involves a combination of personnel training, keeping tools and equipment updated, having a strong quality unit, and developing a quality culture at all levels of the company.

 

“How the company goes about achieving this objective is what is critical. Traditional training may not be enough. There should be constant on-the-job training and oversight on a continual basis. Upgrading tools and equipment, especially computer-driven programs, needs to involve IT departments and adhere to the current data integrity concepts,” says Schniepp.

 

“No one element will be able to sustain GMPs. All the elements work together to establish a culture where sustaining GMPs is a priority.”

 

GMP Facility

 

Chris Moreton of FinnBrit Consulting agrees. “Too often, in my experience, certain factions in an organization think that quality is someone else’s responsibility. There may be an organizational chart that shows where the quality unit sits in an organization, but ‘quality’ (including GMP) is everyone’s responsibility within an organization; from the most senior to the most junior and vice versa.”

 

Management is key in creating a quality culture, says Moreton. “If the staff see the managers taking an interest and checking on things on a daily basis, the staff will respond, and they will try harder to get things right.”

 

Regulatory

 

A commitment to staying current with regulatory expectations is a must, according to Schniepp, and she warns that complacency is the biggest obstacle to maintaining GMPs.

 

“Once a process or procedure is established and functional, there does not seem to be the impetus to update and revise it as regulatory interpretation and understanding changes. This leaves the process or procedure compliant to outdated standards,” Schnieep says.

 

GMP Audit

 

Companies must also learn from prior mistakes, according to Mark Lynch, vice-president of Strategic Compliance. “It’s best to take the lessons learned from product experience and apply them to the culture overall so those lessons only need to be learned once. Those experiences should be continuously applied on the product level, and also used to make improvements to standard operating procedures (SOPs), policies, personnel, and technology.”

 

Problem solving is another technique that must be honed, according to Lynch. “Companies must also pay continuous attention to problem identification, solution, and improvement. Refinement of problem-solving techniques contributes to organizational learning.”

 

FDA cGMP

 

Enforcing quality procedures through a policy that ties failure to follow procedures with grounds for dismissal and using internal audits to detect improper performance are options to ensuring a quality culture, according to Lynch. “It is also important that tools are a regular topic of discussion with operators to capture improvements and assure consistency.

 

Additionally, sufficient supervisory presence and oversight are key both for monitoring purposes, and to be sure operators can raise questions and get the support they need. Finally, it’s best practice to put a GMP standard reporting mechanism in place that does not require identification, so employees feel comfortable flagging an issue without fear of blame,” he says.

 

GMP Quality

 

Companies who do not consistently maintain GMPs may find themselves under additional scrutiny by regulators for repeat offenses. A variety of FDA warning letters have pointed out repeat CGMP violations at companies and/or a particular facility (8, 9).

 

FDA reports that the agency, “… strives to provide clear guidance to companies proactively and in its enforcement actions. Where repeated violations have been found at the same facility or among different facilities of the same firm, we highlight those violations so that they may be addressed adequately.

 

Corrective Action

 

A focus on a commitment to quality is essential to correcting repeated violations, as are adequate corrective actions and procedures. While we generally encourage a focus on overall quality, there are times when we encourage firms to take specific actions, which are included in our warning letters as well as in applicable guidance documents and regulations.”

 

Repeated offenses may be a failure to look at the big picture and apply solutions across all systems and/or products, according to Schniepp. “Companies think in terms of solving the individual citation but fail to take that answer for change to a global look at fixing other processes and procedures that might be susceptible to the same observation. Tunnel vision when responding to warning letters has a great potential to result in repeat observations,” says Schniepp.

 

FDA Warning Letter

 

“Some of these ‘repeat mistakes’ are found to be FDA violations of the same section of the regulations but stem from a different problem. Investigators tend to use repeat findings as a way to point to simplified trends that make one issue appear to be really bad, rather than the complex combination of issues that it truly is,” Lynch says.

 

“Some companies lack the staff, procedures, capability, and time to fully investigate and solve problems, so they pick something (e.g., a personnel error), close the investigation, and move on to release product, and the same issue reappears because it wasn’t solved.”

 

Risk Management

 

Risk management and general cost increases can be another factor to repeated offenses, according to Moreton. “Often cost and/or short-term shareholder interests are used as an excuse to avoid some measures [to long-term change] … People complain that quality costs money, but if they really want to see how expensive things can be, they should try a consent decree.”

 

SOP Procedures

 

The lack of written procedures and/or a quality unit is another frequent infraction identified in warning letters. From October 2016 through September 2017, FDA issued more than 400 FDA 483 observations for a lack of written procedures or written procedures that were not fully followed (10).

 

Quality Program

 

Written procedures are key to a robust quality program, according to FDA and industry experts. FDA believes that the “most effective quality assurance (and compliance) strategies begin with robust internal procedures to adequately design and maintain a robust operation, and that can quickly identify and correct manufacturing problems when they occur.”

 

GMP Best Practices

 

What are best practices for developing written procedures for GMPs? While the agency does not endorse one particular approach to developing written quality procedures, FDA notes that these procedures should “be written to effectively communicate to the users of the procedure.

 

FDA recommends that the style and format of procedures be accessible to users, as well as ensuring adequate coverage of its purpose. We recommend that the effectiveness of a procedural training program be evaluated to ensure that personnel learn and can follow the procedures as intended.”

 

GMP Compliance

 

The trend in a GMP compliance failure to have written procedures is disturbing, according to Schniepp. She suggests that outsourcing quality, especially for start-up companies, may add to this problem. She questions whether outsourcing companies have the processes and procedures in place to handle new products.

 

Manufacturing Operations

 

A robust sharing of information between client and contract manufacturing organization is also key, including product and process understanding. “We need to also remember that new products, particularly in the biotech segment of the industry are novel in nature so the old way of doing business may not be applicable. Whatever the reason the industry must focus effort on making sure there are GMP lab processes, procedures, and written instructions in place that support the release of product,” Schniepp stresses.

 

Having all parties involved in the GMP labeling development of written quality procedures is necessary. “Including everyone affected by the procedure and writing the procedure with their input will result in streamlined and efficient procedures, which will be easier to maintain in the long run,” says Schniepp.

 

Standard Operating Procedure

 

Standard operating procedures (SOPs) written by people not familiar with the specific operation can cause disconnects, according to Lynch. “The best way to assure adequate SOPs is to sit down with people most familiar with operations and map out the process steps and handoffs. This can be incorporated graphically using [swim lane diagrams] and similar tools like Visio (Microsoft) and include them as part of the document.”

 

“In my opinion, in order to ensure that quality procedures are effective, it is necessary to involve those who know the process or operation being documented,” Moreton agrees. “This may mean sitting down with the operator and finding out exactly what is being done and how, not what management thinks should be done and how they think the operation(s) should be carried out.”

 

Operating Process

 

According to Schniepp, procedures should be mapped out, committed to paper, reviewed periodically, and updated as necessary. “Companies need to remember that their processes and procedures are not carved in stone and need to be changed to stay compliant with the operations being performed and the current interpretation of regulations,” says Schniepp. New technologies and new product types may necessitate an update to procedures.

 

Companies should be careful to not try and fit technology or product advances into current procedures but should instead take the time to review their processes and procedures and update them appropriately in responses to these advancements, she says.

 

FDA Process Validation

 

Consistent review of GMP procedures is important, especially if a change in equipment, facility, or regulatory requirements has occurred, experts note. “Written procedures should be reviewed and updated as often as needed. However, if a process and procedure is being updated frequently then it probably wasn’t very well written in the first place,” says Schniepp.

 

“This being said, procedures that are fairly stable should be validated at least every two years to make sure they are still current and reflective of FDA regulatory expectations.” When developing written procedures, says Lynch, “each process and procedure should be tailored to its specific purpose, so they don’t include unnecessary steps that add time to the process without applicable value to the procedure at hand.”

 

SOP Documents

 

Companies often lack the documentation that will help operators understand the entire GMP process, says Lynch. “The most important concept to remember when writing procedures is to include the detailed instructions for the operation or processes being defined by that procedure and not include extra explanatory or extraneous information that has no bearing on the operation or process being defined,” agrees Schniepp.

 

cGMP Consulting

 

In warning letters, FDA commonly suggests the hiring of a third-party GMP consultant to help companies address their GMP deficiencies. Schniepp says these consultants can provide a “fresh perspective” when resolving GMP issues. “A new and fresh approach is valuable because the consulting firm has no preconceived ideas and can offer new insight to what may seem to be an old and uncorrectable problem,” says Schniepp.

 

These consultants can be helpful even when not suggested by regulators “because they are looking at the quality with eyes not steeped in the corporate culture,” according to Moreton. Consultants also have knowledge and GMP expertise the company does not have.

 

“[Consultants] can offer a variety of approaches and suggestions for remediating current problems as well as offering solutions to maintain and improving systems moving forward. One of the most important aspects to consider when hiring a consulting firm is to make sure they not only have the expertise, but they also have the time to devote to fixing the problem,” says Schniepp.

 

Manufacturing & Industrial Consultant

 

When hiring a GMP consultant, Moreton suggests companies look at the experience of the contractor as a whole as well as the qualifications of the individual consultants “to ensure there is a good fit with the contractee’s needs.”

 

Lynch warns, however, that pharmaceutical companies should not rely too much on outside help. “Consultants can help companies get back on track if companies lack the resources internally. However, eventually companies have to sustain compliance themselves. Third-parties should provide expertise in the needed area and technology and have demonstrated success.

 

Then, they should be able to teach and mentor personnel for improved behaviors and provide flexible models to fit company operations and culture. Usually, this is more than one-time training, but a program of measurement and support over time.”

 

Article Details

 

gmp pharmaceutical

 

Pharmaceutical Technology
Vol. 42, No. 7
Pages:18–23, 60

 

About RCA’s Pharmaceutical Consulting Services 

 

Regulatory Compliance Associates (RCA) has helped thousands of pharmaceutical companies meet regulatory, compliance, quality assurance, and remediation challenges. With more than 20 years of experience with FDA, Health Canada, EU and global regulatory agencies worldwide, Regulatory Compliance Associates® offers leading pharmaceutical consultants. We’re one of the few pharma consulting companies that can help you navigate the challenges associated with industry regulations.

 

Our pharmaceutical consulting firm includes over 500 seasoned FDA, Health Canada & EU compliance consultants and regulatory affairs experts who understand industry complexities. It’s a pharma consultancy founded by regulatory compliance executives from the pharmaceutical industry. Every pharmaceutical industry consultant on the Regulatory Compliance Associates team knows the unique inner workings of the regulatory process. 

 

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As your partner, we can negotiate the potential assessment minefield of regulatory compliance services with insight, hindsight, and the clear advantage of our breadth and depth of knowledge and regulatory compliance consulting. We offer the following pharma consulting regulatory affairs services for pharmaceutical companies.

 

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The regulations process surrounding pharmaceutical companies can be tricky for even the most experienced industry veteran to understand. Just one misstep could mean significant and lasting consequences for your business. At Regulatory Compliance Associates, we offer the pharma consulting experience and pharma consultants necessary to guide you through the quality compliance process.

 

  • Assessments
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  • Data Integrity

 

Quality Assurance

 

Regulatory Compliance Associates Quality consulting includes assessments, strategy, implementations, staff augmentations, and identification of quality metrics to ensure continuous improvement. Our pharma consultants understand the strategic thinking needed to align your business needs and goals. Regulatory Compliance Associates quality assurance services include quality experts with experience spanning major corporations and start-ups. Our pharmaceutical consulting firm knows firsthand how to achieve, maintain, and improve quality. Finally, our regulatory compliance services team excels in transferring continuous improvement knowledge to your organization.

 

  • 21 CFR Part 11
  • Data Integrity
  • Manufacturing Support
  • Facility Support
  • Quality Metrics

 

Remediation Services 

 

Regulatory Compliance Associates has a proven remediation services approach to managing FDA Warning Letters, Consent Decrees, Remediation and other serious regulatory situations. Our pharma consultants know how to partner with executive, legal, and communication teams. Each RCA pharma consulting Expert will develop a response that will be accepted by the regulatory agency and be realistic to execute.

 

Regulatory Compliance Associates pharma regulatory consultants will develop a comprehensive proof book of documented evidence demonstrating the corrective action taken to remediate non-compliant issues. In addition, each Regulatory Compliance Associates pharma consulting Expert understands compliance enforcement. We’ll prepare a comprehensive pharma consulting strategy to assist in your remediation efforts, drive continuous improvement, and maintain regulatory compliance with the regulations.

 

  • Regulatory Action
  • Regulatory Compliance
  • Regulatory Enforcement
  • Warning Letter
  • 483 Observation
  • Oversight Services
  • Risk Management Plan

 

About Regulatory Compliance Associates

 

gmp pharmaceuticalRegulatory Compliance Associates® (RCA) provides pharmaceutical consulting to the following industries for resolution of life science challenges:

 

 

We understand the complexities of running a life science business and possess areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. We are used to working on the front lines and thriving in the scrutiny of FDA, Health Canada, MHRA and globally-regulated companies.

 

As your partners, Regulatory Compliance Associates can negotiate the potential minefield of regulatory compliance and regulatory due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.

 

  • Founded in 2000
  • Headquartered in Wisconsin (USA)
  • Expertise backed by over 500 industry subject matter experts
  • Acquired by Sotera Health in 2021

 

About Sotera Health

 

The name Sotera Health was inspired by Soteria, the Greek goddess of safety, and reflects the Company’s unwavering commitment to its mission, Safeguarding Global Health®.

 

Sotera Health Company, along with its three best-in-class businesses – Sterigenics®, Nordion® and Nelson Labs®, is a leading global provider of mission-critical end-to-end sterilization solutions and lab testing and advisory services for the healthcare industry. With a combined tenure across our businesses of nearly 200 years and our industry-recognized scientific and technological expertise, we help to ensure the safety of over 190 million patients and healthcare practitioners around the world every year.

 

We are a trusted partner to 5,800+ customers in over 50 countries, including 40 of the top 50 medical device companies and 9 of the top 10 pharmaceutical companies.

 

Commitment to Quality

 

Our Certificate of Registration demonstrates that our Quality Management System meets the requirements of ISO 9001:2015, an internationally recognized standard of quality.

 

To begin the Regulatory Compliance Associates scoping process today, please enter your information in the blue form below and click the submit button at the bottom of the webpage. 

Quality Management System on a Managed Budget

Insights on driving value from staffing, automation and continuous improvement.

 

Developing a quality management system is the foundation for ensuring the organization’s products or services are safe, effective and controlled to deliver customer satisfaction. Throughout the organization’s lifecycle, from start-up through maturity, the quality needs of the firm, along with its budget constraints, are continually evolving. Maintaining compliance with regulations while controlling costs represents a challenging balancing act we encounter in our life science consultancy. The most successful firms apply critical assessment of their needs and gaps at present and in the future, and deploy a risk-based approach to their quality system.

 

Upfront Planning Avoids Costly Surprises

 

Before establishing a quality system, it’s critical to identify the quality standards, regulations and/or requirements surrounding the company’s products, service and business needs. The checklist in Table 1 provides some common areas to consider.

 

Gap Analysis

 

If your organization already has a quality system, perform a gap analysis against your identified standards/requirements per Table 1. If your quality team could benefit from an external assessment, consider hiring an experienced consultant or firm to provide expertise in the gap analysis.

 

ISO13485

 

If your organization is or will be manufacturing or distributing internationally, global considerations will add complexity to your quality system. For example, the following considerations can greatly impact the complexity of the quality system; European Union, ISO13485, Canadian Medical Devices Regulations, Brazilian GMP, and Japanese Ordinance #169, and others.

 

Phased Enhancements: Spread the Spend Over Time

 

quality management system

 

Maximizing Value from Staffing

 

  • Quality System Leader The organization requires a competent and knowledgeable individual as the quality system leader(s) who may implement the QMS, keep the system compliant, and maintain the design history file.
  • Based on the lifecycle of the organization, the quality system leader may be tasked with implementing the QMS or just maintaining the QMS going forward. This could be two different skill sets.
    • Tip: Early stage companies can benefit from outsourcing development of the QMS to highly experienced quality consultants and then transition maintenance of the QMS to less expensive in-house personnel.
  • Skill Assessment By analyzing the skill sets of in-house quality personnel against needs, firms can identify gaps and develop solutions. A few considerations:
    • Tip: Can current staff be trained? Training represents an upfront cost but offers long- term payoff.

 

Training Programs

 

  • Utilize assessments and audits to understand the capabilities ceiling of your existing team. If training cannot close the critical gaps, consider whether the needed skill set is temporary or long-term. Temporary gaps can be closed cost effectively through hiring of contractors or DHF consultants to provide specialized knowledge without paying for a full-time employee. Such expertise can be used for:

 

Maximizing Value from Automation

 

  • Start-up or early stage organizations can benefit from basic manual systems or hybrid systems that automate some of the more labor-intensive quality functions such as document control.
  • Mid-market organizations can benefit from increased automation through hybrid or enterprise QMS systems that address multiple quality needs such as document control, deviations control, non-conformance, equipment calibration, equipment maintenance orders, audit, CAPA, change control, training and functions that control product outputs.
  • Large organizations can benefit from enterprise QMS systems and integrating those systems with their ERP systems for even greater interoperability.

 

Maximizing Value from Continuous Improvement

 

 

  • Internal and external audits program
  • Complaints
  • Customer feedback
  • CAPA system
  • Product or process non-conformances
  • Processing data
  • Enforcement activity such as a FDA 483 or Warning Letter
  • Costs relative to the budget
  • Concerns about cybersecurity and cost

 

Budget Maximizing Tips

 

Travel:

  • Limiting travel by employees and choosing local contractors or consultants to minimize this expense.
  • For organizations with multiple locations, consider leveraging the geography of the company’s quality personnel. For example, if facility A has an out-of-state supplier located near sister facility B, then facility A might be able to tap into the facility B personnel to perform the supplier audit. The travel savings could offset the cost to quality facility B personnel on the QMS audit.

Training:

  • Delaying training can minimize this expense. Although it can be less expensive in the long run to raise the skill set of your employees in areas such as internal audits, some companies trim budgets by foregoing to deferring training.
  • Virtual cGMP training is another possibility to minimize training expense. By training all your employees at once, companies can negotiate reduced training fees and may possibly eliminate department travel by having a trainer come onsite to the company.
  • Delaying supplier audits Sometimes audits can be scheduled to the next quarter or early next year to save expense based on the acceptable risk exposure.
  • Group input: The quality team is the cornerstone of the QMS. Engaging these internal experts can identify creative opportunities to trim expenses while minimizing risk.

 

Today’s Quality leaders are responsible for managing the organization’s compliance and cost of quality, while driving customer satisfaction and maximizing their department budgets. Careful planning and judicious use of human capital and other resources are critical in deploying a risk-based strategy that delivers organizational results.

 

About RCA’s Medical Device Consulting Services

 

The regulatory compliance process surrounding the medical device industry involves a strict adherence to pre/post market information throughout a device’s life cycle. Even a single compliance issue you have can turn into a significant effect on your business. Regulatory Compliance Associates can help guide you through any stage of the medical device consulting process, with capabilities during product development through the regulatory clearance/approval of your product.

 

Our team of over 500 medical device consulting Experts — including former FDA officials and regulatory compliance leaders in the field of medical device regulation — will work with your company to create a quality assurance and regulatory compliance approach tailored to your products and regulatory needs. Regulatory Compliance Associates works with international Fortune 100 companies, venture capital start ups, and companies of all sizes and shapes. Our regulatory compliance solutions for law firms include remediation for warning letters, FDA 483’s, import bans or consent decrees. Very few regulatory compliance services have the same regulatory compliance expertise in a variety of medical fields.

 

Medical Device Cybersecurity

 

For medical device manufacturers, technology can be a double-edged sword. The innovative technologies that elevate the quality of life for patients can also be used to potentially undermine the organization using the device. The consequences can affect the device itself if Regulatory Compliance Associates medtech consultants do not implement good IoT cybersecurity and FDA cybersecurity protocols.

 

At Regulatory Compliance Associates, we offer a wide variety of services for medical devices security to help ensure that your product is protected from cyber-attacks. With a well-planned design, along with full visibility of product development and the supply chain, Regulatory Compliance Associates medical device consultant Experts can help strengthen your device’s cybersecurity. We partner with medical device companies in each phase of the design cycle. The RCA medical device consulting team understands protecting inputs from threat exposure and hardening outputs for regulatory compliance & FDA submission approval.

 

  • SaMD Consulting
  • Threat Modeling
  • Proof of Concept
  • Quality Assurance Services
  • TIR 57 & TIR 97
  • ISO 62304
  • ISO 27001

 

Regulatory Affairs

 

Regulatory affairs is Regulatory Compliance Associates® backbone. We handle more regulatory consulting submissions in a month than many manufacturers do in a lifetime. Our regulatory compliance consulting Experts have experience working with the FDA, global regulatory bodies and / or agencies, and notified bodies worldwide. Therefore, you can count on us for in-depth and up-to-date insights which increase speed-to-market.

 

As a trusted regulatory affairs consultant, our FDA veterans and regulatory consulting team represents Regulatory Compliance Associates® as one of the top medical device consulting firms. We’lll help you navigate the medical device consulting difficulties associated with new product submissions. Regulatory Compliance Associates® medical device consulting company has expertise in both the approval process and post-approval support. 

 

  • New Product Approval
  • Post-Approval Support
  • Outsourced Staffing
  • EU MDR
  • Combination Products

 

Compliance Assurance

 

Increasingly, life science companies are feeling the pressure of greater scrutiny by regulators, and responding by developing sustainable compliance strategies. Whether it’s preparing for an audit, developing a response to an FDA finding, or remediation to an adverse event, Regulatory Compliance Associates® can help.

 

Our network of over 500 medical device consultant & FDA, MHRA & EMA veterans are industry professionals offers a unique blend of expertise. This allows Regulatory Compliance Associates® to handle both simple and complex regulatory compliance challenges within medical device consulting companies.

 

  • Gap Assessments
  • Internal Audits
  • Employee Training
  • Notified Body Response
  • Data Integrity

 

Quality Assurance

 

Regulatory Compliance Associates® is globally reknown for quality assurance services, including quality system assessments, strategy, implementations, and quality metrics to ensure continuous improvement. Each Regulatory Compliance Associates® medical device consultant is a quality expert with experience spanning major corporations and start-ups. RCA’s quality assurance services experts know firsthand how to achieve, maintain, and improve quality, and we excel in transferring this knowledge to your organization.

 

In the medical devices field, quality assurance (QA) is more than merely ensuring the quality of a finished product. You need the tools to monitor and regulate every process from the design of a new product to continued quality compliance as the device is sent to market. At Regulatory Compliance Associates®, we offer you the quality assurance services you need to monitor these processes and ensure quality compliance every step of the way.

 

With more than 20 years experience working with medical device consulting companies, Regulatory Compliance Associates® trusted medical device quality assurance consultant team is fully equipped to handle your unique QA needs.

 

  • ISO13485 
  • 21 CFR 210
  • 21 CFR 211
  • Outsourced Staffing
  • MDSAP
  • Facility Validation
  • Equipment Validation
  • Quality Metrics

 

Remediation Services

 

Regulatory Compliance Associates® is widely recognized within medical device consulting companies & the life science industry for our remediation services & support. Regulatory Compliance Associates® ability to help companies successfully resolve complex regulatory challenges have a proven track record of success. Our medical device consulting services include significant experience with the development of responses to 483 Observations, Warning Letters, Untitled Letters and Consent Decrees.

 

  • Regulatory Action
  • Regulatory Compliance
  • Regulatory Enforcement
  • Warning Letter
  • 483 Observation
  • Oversight Services

 

Our value goes beyond the initial response by helping companies successfully execute their action plans, develop an improved compliance culture tailored to the needs of their business, and ultimately move beyond the regulatory action to emerge as a stronger business. We negotiate difficult demands of remediation with insight and the clear advantage of our medical device consultant expertise and experience that makes partnering with Regulatory Compliance Associates®  a competitive differentiator in the remediation space.

 

  • Quality System
  • Technical File
  • Design History File
  • Data Integrity
  • cGMP

 

Strategic Consulting

 

Whether it’s a strategy, a technical plan, or project, Regulatory Compliance Associates® medical device consultancy can help ensure a successful project. Regulatory Compliance Associates® due diligence consulting can deliver your project on time, on budget, and you’re never embroiled in a costly mistake. 

 

Our medical device consultant Experts are industry Experts are here to provide the unique insight you need before an M&A deal, through a staffing crisis and in every area of your product’s development and life cycle. As the trusted medical device manufacturing consultants of thousands of companies around the world, we have the knowledge and expertise needed to deliver exceptional results to your business — no matter your size or unique needs.

 

  • Manufacturing Optimization
  • Product Lifecycle Management
  • Mergers & Acquisitions (M&A)
  • Due Diligence
  • Device Vigilance
  • Risk Management Plan
  • Product Complaints
  • Medical Information

 

About Regulatory Compliance Associates

 

product developmentRegulatory Compliance Associates® (RCA) provides medical device consulting to the following industries for resolution of life science challenges:

 

 

We understand the complexities of running a life science business and possess areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. We are used to working on the front lines and thriving in the scrutiny of FDA, Health Canada, MHRA and globally-regulated companies.

 

As your partners, Regulatory Compliance Associates can negotiate the potential minefield of regulatory compliance and regulatory due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.

 

  • Founded in 2000
  • Headquartered in Wisconsin (USA)
  • Expertise backed by over 500 industry subject matter experts
  • Acquired by Sotera Health in 2021

 

About Sotera Health

 

The name Sotera Health was inspired by Soteria, the Greek goddess of safety, and reflects the Company’s unwavering commitment to its mission, Safeguarding Global Health®.

 

Sotera Health Company, along with its three best-in-class businesses – Sterigenics®, Nordion® and Nelson Labs®, is a leading global provider of mission-critical end-to-end sterilization solutions and lab testing and advisory services for the healthcare industry. With a combined tenure across our businesses of nearly 200 years and our industry-recognized scientific and technological expertise, we help to ensure the safety of over 190 million patients and healthcare practitioners around the world every year.

 

We are a trusted partner to more than 5,800 customers in over 50 countries, including 40 of the top 50 medical device companies and 8 of the top 10 pharmaceutical companies.

 

Commitment to Quality

 

Our Certificate of Registration demonstrates that our Quality Management System meets the requirements of ISO 9001:2015, an internationally recognized standard of quality.

 

To begin the Regulatory Compliance Associates® scoping process today, please enter your information in the blue form below and click the submit button at the bottom of the webpage. 

 

cGMP Training

Q: I saw where FDA released draft guidance on data integrity. In the guidance, the answer to question 16 says personnel should receive cGMP training to detect data integrity issues as part of a routine current good manufacturing practice (CGMP) training program. Can you give me some advice on how this topic would be addressed in the annual cGMP training?

 

cGMP trainingA: This is a great question. The draft guidance, titled Data Integrity and Compliance With cGMP was released in 2016 and is still current. In the introduction, FDA states, “The purpose of the guidance is to clarify the role of data integrity in current good manufacturing practice …” I don’t think the industry should be surprised by this guidance based on the number of recent warning letters issued with citations referencing questionable data integrity practices.

 

The guidance itself says:

 

“… FDA has increasingly observed CGMP violations involving data integrity during CGMP inspections.”

 

The guidance goes on to say:

 

“This is troubling because ensuring data integrity is an important component of industry’s responsibility to ensure the … quality of drugs, and FDA’s ability to protect the public health.”  

 

Specifically question 16 asks:

 

“Should personnel be trained in detecting data integrity as part of a routine CGMP training program?”

 

The answer in the guideline is, of course, yes and cites 21 Code of Federal Regulations (CFR) 211.25 and 212.10, which require that employees have the “education, training, and experience, or any combination thereof, to perform their assigned duties.”

 

From an industry perspective, the requirement for data integrity training seems new, but it isn’t. It is normally referred to as good documentation practices (GDP), annual GMP training, and investigations and corrective action and preventive action (CAPA) training. The question is how does one communicate to others that this training regimen relates to proper data handling, which in turn helps eliminate data integrity issues.  

 

cGMP Training

 

Annual cGMP training is integral to avoiding data integrity problems because it delineates what documents need to be maintained. If the GMPs require a document be preserved, one can assume it is a document that is subject to review and critique during an audit.

 

Focusing on the forms and records required allows one to direct their review efforts on the essential rather than on the superfluous documents that support the safety, efficacy, and quality of the products being manufactured. Once the company’s quality assurance (QA) department has identified these critical documents, the documentation group can then direct their efforts towards appropriately maintaining those documents.  

 

GDP training

 

A critical element in preserving the integrity of the information contained in these records is related to GDP training. GDP training should explain to the employees the necessity of the document in relationship to the quality of the product.

 

GDP training should focus on the importance of the data being recorded, how to correct an error, how to document the reason for the error, explain the timeliness of the signature and date of the person who performed the operation and recorded the necessary information, as well as the role of the verifier’s signature for those steps in the operation that require a witness.

 

Electronic Signature

 

GDP training should also include an explanation of the review process and what the operator’s, verifier’s, and reviewer’s signatures means. The reviewer’s signature should be regarded as complementary to the original operator’s signature. It is there to support that the recording of the data was complete, accurately reflected the function or activity being documented, and that any operational errors that occurred were investigated and corrected appropriately.

 

If you are operating with electronic signatures and data collection systems, training should include discussion on the importance of password protection and the reason and rationale for not sharing passwords and accounts so that the integrity of the electronic system is not compromised.

 

CAPA training  

 

Investigation and CAPA training should be taught to staff involved in the recording and reviewing of the documentation. It is important for these individuals to understand how deviations are investigated, if the investigation resulted in a CAPA, and what impact the investigation/CAPA results might have on the product.

 

It should also address how changes made to documentation as a result of the investigations/CAPA have been implemented in the quality management system. Documentation changes made as a result of investigation/CAPA conclusions should prompt retraining on the activity and should encompass any new documentation practices identified.  

 

Internal Audit

 

Once the employees are trained in GMP, GDP, and investigations/CAPA training, the QA group should confirm the organization’s understanding of what they were taught through the internal audit review process. This should be viewed as a confirming activity that will strengthen the records, forms, reports, and manufacturing documents that support the product’s manufacturing and release.

 

Standard Operating Procedures (SOP)

 

Issues in documentation procedures identified through the internal audit process should be responded to and tracked in a similar manner, as the company would do for an external audit by a client or a regulatory agency.  

 

The information collected during the manufacturing of the product from the receipt of the raw materials, the facility maintenance, the testing of the product up to the release of the product, and everything in between is crucial to defending the product once it has been released for patient use. It is crucial that this information be indisputable, whether it is electronic or paper.

 

Documentation

 

Bottom line, don’t over react to the guidance by sending your QA staff to criminal investigation training. Instead, utilize the cGMP training tools you already have in your quality system to reinforce the concept of data integrity throughout your training and audit processes. The best way to combat poor documentation is through the proactive inclusion of data integrity concepts, design, and implementation into your data collection systems whether they are manual or electronic in nature.  

 

Article Details

 

 

Pharmaceutical Technology

Vol. 40, No. 6
Pages: 57–58  
 
 

About RCA’s Pharmaceutical Consulting Services 

 

Regulatory Compliance Associates (RCA) has helped thousands of pharmaceutical companies meet regulatory, compliance, quality assurance, and remediation challenges. With more than 20 years of experience with FDA, Health Canada, EU and global regulatory agencies worldwide, Regulatory Compliance Associates® offers leading pharmaceutical consultants. We’re one of the few pharma consulting companies that can help you navigate the challenges associated with industry regulations.

 

Our pharmaceutical consulting firm includes over 500 seasoned FDA, Health Canada & EU compliance consultants and regulatory affairs experts who understand industry complexities. It’s a pharma consultancy founded by regulatory compliance executives from the pharmaceutical industry. Every pharmaceutical industry consultant on the Regulatory Compliance Associates team knows the unique inner workings of the regulatory process. 

 

Client Solutions

 

Whether you’re in the product planning, development or pharmaceutical lifecycle management stage or need a remediation strategy for a compliance crisis, Regulatory Compliance Associates will guide you through every pharmaceutical consulting step of the regulatory process and create a customized approach depending on your product and your pharma company’s individual needs. Our regulatory compliance clients include:

 

  • Companies new to FDA, Health Canada or EU regulations and regulatory compliance
  • Start-up organizations with novel submissions to 510(k) submissions from multi-national corporations
  • Investment firms seeking private equity due diligence for pre-acquisition and post-deal research
  • Law firms seeking pharmaceutical consulting firm expertise in the remediation of warning letters, consent decrees, 483’s or import bans

 

Regulatory Affairs

 

Regulatory affairs is Regulatory Compliance Associates backbone. We exceed other pharma consulting companies with industry experts experienced in complexities of the pharmaceutical and biopharmaceutical industries. Our pharma consulting expertise spans all facets and levels of Regulatory Affairs, from Regulatory Support for New Products to Life Cycle Management, to other services like Outsourced Regulatory Affairs, Submissions, Training, and more.

 

As your partner, we can negotiate the potential assessment minefield of regulatory compliance services with insight, hindsight, and the clear advantage of our breadth and depth of knowledge and regulatory compliance consulting. We offer the following pharma consulting regulatory affairs services for pharmaceutical companies.

 

  • New Product Support
  • Product Lifecycle
  • Other Regulatory Services
  • Combination Products

 

Compliance Assurance

 

The regulations process surrounding pharmaceutical companies can be tricky for even the most experienced industry veteran to understand. Just one misstep could mean significant and lasting consequences for your business. At Regulatory Compliance Associates, we offer the pharma consulting experience and pharma consultants necessary to guide you through the quality compliance process.

 

  • Assessments
  • Audits
  • Regulatory Agency Response
  • Preparation and Training
  • Inspection Readiness
  • Data Integrity

 

Quality Assurance

 

Regulatory Compliance Associates Quality consulting includes assessments, strategy, implementations, staff augmentations, and identification of quality metrics to ensure continuous improvement. Our pharma consultants understand the strategic thinking needed to align your business needs and goals. Regulatory Compliance Associates quality assurance services include quality experts with experience spanning major corporations and start-ups. Our pharmaceutical consulting firm knows firsthand how to achieve, maintain, and improve quality, and we excel in transferring pharma consulting knowledge to your organization.

 

  • 21 CFR Part 11
  • Data Integrity
  • Manufacturing Support
  • Facility Support
  • Quality Metrics

 

Remediation Services 

 

Regulatory Compliance Associates has a proven remediation services approach to managing FDA Warning Letters, Consent Decrees, Remediation and other serious regulatory situations. Our pharma consultants know how to partner with executive, legal, and communication teams. Each RCA pharma consulting Expert will develop a response that will be accepted by the regulatory agency and be realistic to execute.

 

Regulatory Compliance Associates pharma regulatory consultants will develop a comprehensive proof book of documented evidence demonstrating the corrective action taken to remediate non-compliant issues. In addition, each Regulatory Compliance Associates pharma consulting Expert understands compliance enforcement. We’ll prepare a comprehensive pharma consulting strategy to assist in your remediation efforts, drive continuous improvement, and maintain regulatory compliance with the regulations.

 

  • Regulatory Action
  • Regulatory Compliance
  • Regulatory Enforcement
  • Warning Letter
  • 483 Observation
  • Oversight Services
  • Risk Management Plan

 

About Regulatory Compliance Associates

 

pharmaceutical consultantsRegulatory Compliance Associates® (RCA) provides pharmaceutical consulting to the following industries for resolution of life science challenges:

 

 

We understand the complexities of running a life science business and possess areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. We are used to working on the front lines and thriving in the scrutiny of FDA, Health Canada, MHRA and globally-regulated companies.

 

As your partners, we can negotiate the potential minefield of regulatory compliance and regulatory due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.

 

  • Founded in 2000
  • Headquartered in Wisconsin (USA)
  • Expertise backed by over 500 industry subject matter experts
  • Acquired by Sotera Health in 2021

 

About Sotera Health

 

The name Sotera Health was inspired by Soteria, the Greek goddess of safety, and reflects the Company’s unwavering commitment to its mission, Safeguarding Global Health®.

 

Sotera Health Company, along with its three best-in-class businesses – Sterigenics®, Nordion® and Nelson Labs®, is a leading global provider of mission-critical end-to-end sterilization solutions and lab testing and advisory services for the healthcare industry. With a combined tenure across our businesses of nearly 200 years and our industry-recognized scientific and technological expertise, we help to ensure the safety of over 190 million patients and healthcare practitioners around the world every year.

 

We are a trusted partner to 5,800+ customers in over 50 countries, including 40 of the top 50 medical device companies and 9 of the top 10 pharmaceutical companies.

 

Commitment to Quality

 

Our Certificate of Registration demonstrates that our Quality Management System meets the requirements of ISO 9001:2015, an internationally recognized standard of quality.

 

To begin the Regulatory Compliance Associates scoping process today, please enter your information in the blue form below and click the submit button at the bottom of the webpage. 

 

International Medical Device Regulatory

Lisa L. Michels, General Counsel and regulatory affairs expert at Regulatory Compliance Associates® Inc., discusses how the global medical device regulatory landscape is impacted by international law.

 

The global medical device regulatory landscape is constantly evolving as governing bodies and/or agencies worldwide continue their efforts to harmonize and streamline rules. Over the last several years, many of these regulatory bodies have joined forces to ensure consistency in the interpretation, application, and implementation of relevant medtech regulations and globally recognized consensus standards.

 

Regulatory Submission

 

While such efforts have considerably improved the product registration process overseas, harmonization in some cases has made it difficult for some device firms to stay abreast of the planet’s evolving regulatory landscape. To remain competitive in this challenging environment, medtech companies stay ahead of the competition by proactively planning for new and/or changing global regulations. This helps agile organizations successfully launch existing, modified, or novel products in new target markets quickly. 

 

Medical Device Registration

 

Most companies want their products to be registered in as many global markets as possible, but this lofty goal introduces certain regulatory challenges. From a general business perspective, global product registration in numerous foreign markets obviously makes sense.

 

Companies possessing the legal authority to sell product(s) in certain regions where competitors are not authorized to do so often distinguishes those organizations as leaders or industry trailblazers. This approach is not always logical or practical, however.

 

Regulatory Pathway

 

Product registration should be based on a proactive strategic regulatory analysis. Understanding the available regulatory pathway options can help properly determine whether registration in a particular market. Ultimately, the team is challenges with the regions that make sense for the product and business as a whole.

 

The most common international medical device registration challenges are primarily based on the following considerations:

  • Understanding and applying country-specific medical device regulations across global markets
  • Timely implementation of country-specific medical device regulations in target markets
  • Costs associated with global product registration(s), which may include (but are not limited to) in-country agent representation, in-country product testing, and in-country collection of clinical data
  • Excessive delays and/or long lead times for regulatory reviews needed for global product registration(s) in target markets

 

Device Classification

 

These challenges are much easier to manage when they are properly assessed well before starting the product registration processes in certain global markets. Based on the device classification and type of product, there may be more (or less stringent) requirements that must be achieved in specific countries.

 

The risk level of the product and the existence of similar approved products in a particular market can complicate the product registration process in certain countries.

 

Medtech Programs

 

Many medtech companies typically tend to focus their medical device product registration efforts on seven (7) primary global markets: the United States, Canada, European Union (EU), Australia, Brazil, China, and Japan. Due to ongoing harmonization efforts, these countries are working together to streamline the registration processes and improve their consistency. 

 

Depending on the company’s overall product launch strategy, device registration in emerging markets has become common in recent years. In certain cases, product registration may be less challenging in these markets because regulations have not yet been fully developed.

 

Pre-Clinical Testing

 

The applicable medical device regulations in target markets each pose their own product registration challenges. Therefore, it is imperative that companies plan for all target market requirements early in the product development process—ideally at the idea stage.

Understanding and preparing for the hurdles associated with pre-clinical testing, clinical testing, performance testing, safety testing, labeling, and compliance with harmonized standards, can help companies overcome possible challenges with the product registration process in each potential target market.

 

regulatory compliance
 
Table: Summary Regulatory Requirements for Global Medical Device Registration in the Primary Target Markets
 
 

Regulatory Compliance

 

Achieving product registration compliance in each target market may seem like a daunting endeavor, but it’s not truly as complicated as it sounds. There are many similarities between the various regulations, as outlined in the table at right. Although the table represents only a subset of requirements, the country-specific mandates applicable to product type in each of the target markets must be carefully reviewed and assessed.

 

The most effective method to accomplish this task is to prepare a global regulatory strategy for the product(s), which may ultimately be used as a gauge to determine the likelihood of successfully launching a device in a particular market.

 

Regulatory Strategy

 

A global regulatory strategy is a documented analysis that defines the overall business objectives and requirements necessary for foreign product registration. A regulatory plan, on the other hand, is a comprehensive report based on the foundational regulatory strategy that outlines all product- and country-specific registration mandates in particular markets. 

 

The regulatory strategy and plan may be separate stand-alone documents or combined into a single global strategy and planning file. Regardless of format, however, their purpose is the same—to proactively document and plan for the implementation of applicable regulatory requirements associated with specific products in each target market.

 

Regulatory Audit

 

Keep in mind that these regulatory strategy and planning document(s) are not static. They must be updated and revised accordingly when changes are made either to the product itself or to the device’s launch strategy. A revision would be required, for example, if target markets are added or removed from the launch strategy. Any regulatory body will want to understand the risks made to existing products and regulations (particularly when new rules are introduced that can significantly affect or completely alter product registration mandates).

 

The format of the regulatory strategy and planning document ultimately depends on the company. Some organizations encourage the use of a specific format or template to document the regulatory strategy and/or plan. Other firms are more liberal about format.

 

Medical Device Regulatory

 

Fundamentally though, the setup of the regulatory strategy and planning document is not as important as the goal: To initiate and maintain robust, proactive, regulatory planning efforts as early as possible, and to effectively monitor any changes in the scope to avoid unexpected and costly delays. The key elements of a global regulatory strategy and planning document are also outlined in the table. 

 

Medical Device Global Regulatory Strategy and Planning Document

 

Detailed Product Summary

  • Detailed description of the product including its accessories, components, and software (if applicable)
  • Describe the product requirements, including technological/functional/performance/clinical requirements of the product (e.g., what the product does and how it works/mode of operation)
  • Indications for use/intended use
  • Target population
  • Labeling requirements
  • All proposed marketing claims and requirements for claim substantiation
  • Risk level/product classification/applicable product codes
  • Predicate(s) and/or similar products on the market in each target country

 

Governing Regulatory Body and/or Agency in Each Target Market

  • Planned target markets for product launch
  • Applicable laws, regulations, standards, and relevant guidance for the product
  • Analysis of harmonized requirements and standards for the product across all target markets
  • Reimbursement requirements and other country-specific considerations

 

Proposed Regulatory Pathway and Product Registration Requirements in Each Target Market

  • Regulatory submission/product registration requirements, including all applicable product testing requirements (e.g., pre-clinical testing, animal testing, clinical testing, performance testing, safety testing, etc.)
  • Timeline to obtain clearance/approval
  • Costs associated with global product registration
  • Required resources (internal/external)
  • Pre-market submission/early interaction, discussion, or consultation with governing regulatory agency or authority regarding product and proposed regulatory pathway

 

General Requirements for Product Registration in Each Target Market

  • Implementation of a Quality Management System (QMS) compliant with applicable regulations and/or standards
  • QMS audit/inspection of manufacturing facilities by the regulatory agency

 

Country-Specific Requirements for Product Registration in Each Target Market

  • Appointment of an in-country, local agent/representative/sponsor/distributor to manage the product registration on behalf of a foreign manufacturer
  • In-country product testing requirements and product samples
  • In-country clinical trial/data collection requirements
  • Product registries/databases
  • Labeling requirements
  • Language translations for labeling [e.g., instructions for use (IFU), operator or user manual, labels, etc.]

 

Other information as applicable for the specific type of product

 

Recommendations for Successful Navigation

 

The key to successfully navigating through the regulatory challenges of global product registration in the international marketplace starts and ends with diligent and proactive planning.

Product registration efforts should focus on markets where companies can leverage device submission documentation for previously approved applications. If, for example, a company has U.S. Food and Drug Administration clearance and/or CE mark approval for a product, it is often easier to register that exact device in another global market that recognizes the same (or similar) harmonized requirements and standards.

 

Companies should ensure their products are tested and comply with globally recognized consensus standards. A sampling of medical devices standards recognized in many international markets include:

 

  • EN 1041:2008—Information supplied by the manufacturer of medical devices
  • EN ISO 13485:2012—Medical devices – Quality management systems – Requirements for regulatory purposes (ISO 13485:2003)
  • EN ISO 14155:2011—Clinical investigation of medical devices for human subjects – Good clinical practice (ISO 14155:2011)
  • EN ISO 14971:2012—Medical devices – Application of risk management to medical devices (ISO 14971:2007, Corrected version 2007-10-01)
  • EN 60601-1:2006—Medical electrical equipment—Part 1: General requirements for basic safety and essential performance
  • EN 60601-1-2:2007—Medical electrical equipment—Part 1-2: General requirements for basic safety and essential performance – Collateral standard: Electromagnetic
  • EN 60601-1-6:2007—Medical electrical equipment—Part 1-6: General requirements for basic safety and essential performance – Collateral Standard: Usability
  • EN 62304:2006—Medical device software – Software life-cycle processes

 

A comprehensive global regulatory strategy and planning document must be prepared that clearly identifies all county-specific requirements necessary for successful product registration in each target market. In addition, companies should set realistic and attainable goals for timely product launches only in the markets that align with their overall global business strategy. Commercialization will only be successful if the product is a logical fit for the chosen market.

 

Perhaps most importantly, medtech firms must not register a product in a certain market simply because they can do so. Rather, they should make strategic and informed regulatory decisions about their product launch plans so they can avoid the most common regulatory challenges impacting this highly competitive industry. 

 

About RCA’s Medical Device Consulting Services

 

The regulatory compliance process surrounding the medical device industry involves a strict adherence to pre/post market information throughout a device’s life-cycle. Even a single compliance issue you have can turn into a significant effect on your business. Regulatory Compliance Associates medical device consultants can help guide you through any stage of this strategic process, with capabilities during product development through the regulatory clearance/approval of your product.

 

Our team of over 500 medical device consulting Experts — including former FDA officials and regulatory compliance leaders in the field of medical device regulation — will work with your company to create a quality assurance and regulatory compliance approach tailored to your products and regulatory needs. Regulatory Compliance Associates works with international Fortune 100 companies, venture capital start ups, and companies of all sizes and shapes. our compliance enforcement solutions for law firms include remediation for warning letters, FDA 483’s, import bans or consent decrees. Very few regulatory compliance services have the same regulatory compliance expertise in a variety of medical fields.

 

Cybersecurity

 

For medical device manufacturers, technology can be a double-edged sword. The innovative technologies that elevate the quality of life for patients can also be used to potentially undermine the organization using the device. The consequences can affect the device itself if Regulatory Compliance Associates medtech consultants do not implement good IoT cybersecurity and FDA cybersecurity protocols.

 

At Regulatory Compliance Associates, we offer a wide variety of services for medical devices security to help ensure that your product is protected from cyber-attacks. With a well-planned design, along with full visibility of product development and the supply chain, Regulatory Compliance Associates medical device consultant Experts can help strengthen your device’s cybersecurity. We partner with medical device companies in each phase of the design cycle, including protecting inputs from threat exposure and hardening outputs for regulatory compliance & FDA submission approval of your medical technology.

 

Regulatory Affairs

 

Regulatory affairs is Regulatory Compliance Associates® backbone, and we handle more submissions in a month than many manufacturers do in a lifetime. Our regulatory compliance consulting Experts have experience working with the FDA, global regulatory bodies and / or agencies, and notified bodies worldwide. Therefore, you can count on us for in-depth and up-to-date insights which increase speed-to-market.

 

As a trusted regulatory affairs consultant, our FDA veterans and industry experts represent Regulatory Compliance Associates® as one of the top medical device consulting firms. We’re here to help you navigate the difficulties associated with new product submissions. Regulatory Compliance Associates® medical device consulting company has expertise in both the approval process and post-approval support. 

 

  • New Product Approval
  • Post-Approval Support
  • Outsourced Staffing
  • EU MDR
  • Combination Products

 

Compliance Assurance

 

Increasingly, life science companies are feeling the pressure of greater scrutiny by regulators, and responding by developing sustainable compliance strategies. Whether it’s preparing for an audit, developing a response to an FDA finding, or remediation to an adverse event, Regulatory Compliance Associates® can help.

 

Our network of over 500 medical device consultant & FDA, MHRA & EMA veterans are industry professionals offers a unique blend of expertise. This allows Regulatory Compliance Associates® to handle both simple and complex regulatory compliance challenges within medical device consulting companies.

 

  • Gap Assessments
  • Internal Audits
  • Employee Training
  • Notified Body Response
  • Data Integrity

 

Quality Assurance

 

Regulatory Compliance Associates® Quality Assurance consulting includes quality system assessments, strategy, implementations, and identification of quality metrics to ensure continuous improvement, aligning with your business needs and goals. Each Regulatory Compliance Associates® medical device consultant is a quality expert with experience spanning major corporations and start-ups. We know firsthand how to achieve, maintain, and improve quality, and we excel in transferring this knowledge to your organization.

 

In the medical devices field, quality assurance (QA) is more than merely ensuring the quality of a finished product. You need the tools to monitor and regulate every process from the design of a new product to continued quality compliance as the device is sent to market. At Regulatory Compliance Associates®, we offer you the quality assurance services you need to monitor these processes and ensure quality compliance every step of the way.

 

With more than 20 years experience working with medical device consulting companies, Regulatory Compliance Associates® trusted medical device quality assurance consultant team is fully equipped to handle your unique QA needs.

 

  • ISO13485 
  • 21 CFR 210
  • 21 CFR 211
  • Outsourced Staffing
  • MDSAP
  • Facility Validation
  • Equipment Validation
  • Quality Metrics

 

Remediation Support

 

Regulatory Compliance Associates® is widely recognized within medical device consulting companies & the life science industry for remediation support. Regulatory Compliance Associates® ability to help companies successfully resolve complex regulatory challenges have a proven track record of success. Our medical device consulting services include significant experience with the development of responses to 483 Observations, Warning Letters, Untitled Letters and Consent Decrees.

 

  • Regulatory Action
  • Regulatory Compliance
  • Regulatory Enforcement
  • Warning Letter
  • 483 Observation
  • Oversight Services

 

Our value goes beyond the initial response by helping companies successfully execute their action plans, develop an improved compliance culture tailored to the needs of their business, and ultimately move beyond the regulatory action to emerge as a stronger business. We negotiate difficult demands of remediation with insight and the clear advantage of our medical device consultant expertise and experience that makes partnering with Regulatory Compliance Associates®  a competitive differentiator in the remediation space.

 

  • Quality System
  • Technical File
  • Design History File
  • Data Integrity
  • cGMP

 

Strategic Consulting

 

Whether it’s a strategy, a technical plan, or project, Regulatory Compliance Associates® medical device consultancy can help ensure a successful project. Regulatory Compliance Associates® medical device strategy consulting can deliver your project on time, on budget, and you’re never embroiled in a costly mistake.

 

Our medical device consultant Experts are industry Experts are here to provide the unique insight you need before an M&A deal, through a staffing crisis and in every area of your product’s development and life cycle. As the trusted medical device manufacturing consultants of thousands of companies around the world, we have the knowledge and expertise needed to deliver exceptional results to your business — no matter your size or unique needs.

 

  • Manufacturing Optimization
  • Product Lifecycle Management
  • Mergers & Acquisitions (M&A)
  • Due Diligence
  • Device Vigilance
  • Risk Management Plan
  • Product Complaints
  • Medical Information

 

About Regulatory Compliance Associates

 

Regulatory Compliance Associates® (RCA) provides medical device consulting to the following industries for resolution of life science challenges:

 

 

We understand the complexities of running a life science business and possess areas of expertise that include every facet of R&D, operations, regulatory affairs, quality, and manufacturing. We are used to working on the front lines and thriving in the scrutiny of FDA, Health Canada, MHRA and globally-regulated companies.

 

As your partners, we can negotiate the potential minefield of regulatory compliance and regulatory due diligence with insight, hindsight, and the clear advantage of our unique expertise and experience.

 

  • Founded in 2000
  • Headquartered in Wisconsin (USA)
  • Expertise backed by over 500 industry subject matter experts
  • Acquired by Sotera Health in 2021

 

About Sotera Health

 

The name Sotera Health was inspired by Soteria, the Greek goddess of safety, and reflects the Company’s unwavering commitment to its mission, Safeguarding Global Health®.

 

Sotera Health Company, along with its three best-in-class businesses – Sterigenics®, Nordion® and Nelson Labs®, is a leading global provider of mission-critical end-to-end sterilization solutions and lab testing and advisory services for the healthcare industry. With a combined tenure across our businesses of nearly 200 years and our industry-recognized scientific and technological expertise, we help to ensure the safety of over 190 million patients and healthcare practitioners around the world every year.

 

We are a trusted partner to more than 5,800 customers in over 50 countries, including 40 of the top 50 medical device companies and 8 of the top 10 pharmaceutical companies.

 

Commitment to Quality

 

Our Certificate of Registration demonstrates that our Quality Management System meets the requirements of ISO 9001:2015, an internationally recognized standard of quality.

 

To begin the Regulatory Compliance Associates® scoping process today, please enter your information in the blue form below and click the submit button at the bottom of the webpage.