Why Your Biotech, Pharmaceutical or Medical Device Organization Needs an Independent Consultant
Navigating the regulatory complexities and laboratory hurdles often hindering the development journey is daunting. This is where independent consultants, such as Metis Consulting Services, play a crucial role in unlocking the full potential of your products and achieving regulatory success.
Written by Li-Anne Rowswell Mufson
In today's complex regulatory landscape, biotech, pharmaceutical, and medical device organizations face numerous challenges in bringing products to market while ensuring compliance with evolving standards. Navigating the regulatory complexities and laboratory hurdles often hindering the development journey is daunting. This is where independent consultants, such as Metis Consulting Services, play a crucial role in unlocking the full potential of your products and achieving regulatory success. Consultants offer fresh eyes that pick up on potential pain points that the team may not see on the inside.
R&D Laboratory
Metis Consulting Services offers comprehensive R&D laboratory support, including but not limited to small molecule development, biologics development services, and cross-functional expertise. With their specialized knowledge and experience, they provide valuable insights and guidance to streamline your development processes and overcome technical challenges. For more, Listen to Queens of Quality Podcast “A Journey through the Pharmaceutical Regulation and Quality Design S2:E7
Audits/Inspection Readiness
Preparing for audits and inspections is critical to maintaining regulatory compliance. Independent consultants assist your organization in conducting thorough audits, ensuring inspection readiness, and implementing corrective actions to address any identified issues, ultimately helping to maintain good standing with regulatory authorities.Ffor more listen to Queens of Quality Podcast A Comprehensive Guide to Audits and Compliance in Pharmaceuticals | S2:E2
Clinical Data Management
Effective clinical data management is essential for demonstrating the safety and efficacy of pharmaceutical and medical device products. Independent consultants offer expertise in clinical data management and ensure that your data is collected, processed, and analyzed in compliance with regulatory requirements. For more listen to Queens of Quality Podcast Unlocking Ethical AI in Life Sciences: Insights with Steve Thompson and Emily Barker PT3
| S2:BONUS 3
Corporate Training
Continuous training and development are vital for keeping your team updated with the latest regulatory standards and industry best practices. Independent consultants provide tailored corporate training programs to enhance your staff's regulatory knowledge and skills, ultimately contributing to improved compliance and operational efficiency. For more listen to: Queens of Quality Podcast A Comprehensive Guide to Audits and Compliance in Pharmaceuticals| S2:E2
Regulatory Strategy Advising
Navigating the complex regulatory landscape requires a strategic approach. Independent consultants advise regulatory strategy, helping your organization develop and execute robust regulatory strategies that align with your business objectives and ensure timely product approvals.For more listen to Queens of Quality Podcast” A Comprehensive Guide to Audits and Compliance in Pharmaceuticals” S2:E2
Pharmacovigilance
Ensuring the safety of pharmaceutical products throughout their lifecycle is a vital concern. Independent consultants support your organization in establishing and maintaining effective pharmacovigilance systems, including adverse event reporting, risk management, and regulatory compliance.
Listen to the Queens of Quality Podcast S1 E5 “Pharmacovigilance”
Quality Management Services
Maintaining high-quality standards across all aspects of your operations is essential for regulatory compliance and product integrity. Independent consultants offer quality management services, including quality system assessments, process improvements, and compliance monitoring, to help you achieve and sustain a culture of quality within your organization. Listen to the Queens of Quality Podcast S2 E8, “Embracing Evolution and Growth in Quality.”
REMS/RMPs
Risk Evaluation and Mitigation Strategies (REMS) and Risk Management Plans (RMPs) are mandatory programs for post-market activities for designated products. REMS and RMPs (in the 2EU) are designed to manage known or potential risks associated with certain products. Independent consultants with expertise in REMS/RMPs guide these strategies' development, implementation, and evaluation to ensure the safe and effective use of pharmaceutical products. Listen to the Queens of Quality Podcast S2 E6, “Revolutionizing the REMS Industry with Sherice Mills.”
Consulting
The expertise and support independent consultants provide can significantly benefit pharmaceutical and medical device organizations, particularly in navigating regulatory challenges, enhancing operational capabilities, and ensuring compliance with the highest standards. Pharmaceutical consulting provides a bridge between laboratory research and patient care. An alliance of scientific rigor and strategic acumen turns therapeutic concepts into accessible treatments. What are the benefits of using pharmaceutical consultants? They guide your organization's journey from bench to bedside in the biotech, pharmaceutical, and medical device industry. Pharmaceutical consultants don the hat of strategists, advisors, and analysts to steer drug developers through the complex maze of bringing a new drug to market. They are the catalysts for innovation, ensuring that groundbreaking treatments see the light of day and reach the right patients at the right time. If your organization is striving for regulatory success and seeking to maximize the potential of its products, engaging an independent consultant such as Metis Consulting Services is an excellent strategic decision with far-reaching benefits, ultimately leading to the primary goal for all involved: enhanced patient outcomes. FDA Guidance on REMS from May 2024 here
Metis Consulting Services offers a complete and customizable suite of services, including but not limited to
1. Audits/ Inspection Readiness-
3. Corporate Training-
4. REMS-RMP
5. Regulatory Strategy Advising-
7. Quality Management Services-
8. R&D Laboratory Services-
9. Ethical AI
With our support, biotech, pharmaceutical, and device manufacturers can confidently navigate the complex landscape of regulatory requirements and industry best practices, ensuring their products' safety, efficacy, and quality.
Welcome Back to the Metis Blog
In this Blog Space, we discuss topics of interest to people in our industry and what is happening here at our company. At Metis, we offer services in
Audits/Inspection Readiness, Consulting Services,*Corporate Training,*Data Management,*Pharmacovigilance,*Quality Management, and REMS.
We aim to help organizations keep up with regulatory conditions and industry best practices to ensure patient safety and access to effective therapies.
Written by Li-Anne Roswell Mufson
We've been on Hiatus for a few months, generally having a "Make-Over." We have been doing some fixing up and growing within our company, looking at the blog as well, and at last, we are back!
We now have a title for this Blog Space.
We are calling it...Drum Roll, please, "The Guard Rail." TADA
Why?
In this Blog Space, we discuss topics of interest to people in our industry and what is happening here at our company. At Metis, we offer services in
*Audits/Inspection Readiness, *Consulting Services,*Corporate Training,*Data Management,*Pharmacovigilance,*Quality Management, and *REMS.*
We aim to help organizations keep up with regulatory conditions and industry best practices to ensure patient safety and access to effective therapies.
Metis has passionate, experienced consultants who do this work because we care about keeping the focus on the patients. Our goal is to keep them safe and get them access to effective therapies. We have the most significant impact by helping organizations keep up with global regulatory conditions, Risk Mitigation, and industry best practices. And we see the most crucial part of our mission as keeping the patient first, for us and for our clients.
In other words, we work on the industry Guard Rails.
Our industry needs guard rails. Nowhere is this more evident than in the recent surge of AI use in Life Sciences, which, not so coincidentally, is our topic for today.
We say "new" in quotes because AI is not new; the concept has been around since the 50s, but with the eruption of ChatGpt and generative AI, the use of AI in Life Sciences is exploding.
Today, we want to discuss the intersection of artificial intelligence (AI) and life sciences. While AI is not a new concept, the recent eruption of generative AI and ChatGpt has led to explosive growth in the use of AI in life sciences. This growth is exciting but raises concerns about ethical considerations and responsible deployment.
The ethical deployment of AI is crucial to ensure patient safety and to uphold the highest ethical standards in the pharmaceutical industry. We need to balance technological advancements with ethical considerations. AI has tremendous potential to optimize treatments and unlock profound insights from complex datasets. However, it also poses unique challenges, including data privacy, algorithmic biases, and responsible use of patient information. As Steve Thompson put it so well when he was Metis CEO Michelleanne Bradley's guest on the Queens of Quality Podcast Bonus episode S2.5 E1, "Although this is exciting, we have to act ethically, responsibly…with a multidisciplinary approach..it all sounds really good and fascinating.. but (Michelleanne), you mentioned Guard Rails; we have got to put these things in place to ensure we are applying this technology ethically and responsibly."
In that episode and the others in this bonus series, Michelleanne clearly agrees. AI may be the "shiniest tool in the shed," but that doesn't mean we should leap into using it everywhere without putting guard rails in place. We aim to help organizations keep up with regulatory conditions and industry best practices to ensure patient safety and access to effective therapies.
Check out Queens of Quality podcast episode S2.5E1QoQ
To ensure the ethical deployment of AI in life sciences, we must commit to continuous improvement, transparent model development, and the mitigation of biases. A diverse team of multidisciplinary experts, including scientists, ethicists, data analysts, industry professionals, and more, should work collaboratively to align technological advancements with ethical principles.
The ethical implications of relying on AI for critical decision-making demand meticulous attention and algorithm oversight. Fairness, transparency, accountability, and privacy principles should be non-negotiable in every facet of AI development, deployment, and regulation. Michelleanne quoted Michael Crichton to remind us in Jurassic Park by way of his character Dr. Ian Malcolm, played by Jeff Goldblum, in the movie, "Your scientists were so preoccupied with whether they could, they didn't stop to think if they should." We need to ask ourselves this question.
We can only harness AI's potential to improve patient outcomes and drive innovation by embracing an ethically conscious approach. However, we must uphold the highest ethical standards in the pharmaceutical industry.
In today's fast-evolving landscape, the convergence of Artificial Intelligence (AI) and Life Sciences heralds immense possibilities and intricate ethical quandaries. Understanding the interplay between AI and ethical considerations is essential for professionals entrenched in the Regulatory, Life Sciences, and Pharmaceutical industries. This understanding will steer this transformative journey.
The Current State and Future of AI in Life Sciences
AI is a beacon of innovation in the Life Sciences domain. Its capabilities span from streamlining drug discovery processes to enhancing patient care through predictive analytics. The current landscape paints a promising future where AI optimizes treatments and unlocks profound insights from complex datasets. It is vital to be watchful with our Data Management Systems. Link to DMS
Ethical Dilemmas in AI
However, ethical dilemmas accompany this rapid advancement. Issues such as data privacy, algorithmic biases, and the responsible use of patient information cast a critical spotlight on the ethical deployment of AI in the pharmaceutical realm. We know that patients will suffer if we remove the human element from the equation altogether OR if we don't work to ferret out the human biases inherent in human-provided data and other challenges. Our industry will suffer, too, and we may be throttled to a stop or even move backward before we can move forward.
The Importance of Continuous Improvement in AI
Continuous improvement lies at the core of ethical AI deployment. It needs ongoing algorithm refinement, transparent model development, and bias mitigation. A commitment to oversight ensures that AI systems evolve to become more accurate, fair, and reliable. Nobody can move forward if we do things as we have always done. Check out this episode of Queens of Quality podcast: QoQ 2.5E2
Challenges of Creating Synthetic Patients
Developing synthetic patients and digital replicas of actual patients for research and analysis poses unique challenges. Ensuring these models accurately represent diverse demographics and medical conditions while avoiding biases demands collaborative efforts and stringent ethical considerations. Unaided by AI, humans have done some very unkind things to one another in the name of science while perpetuating harmful biases. The 1932 Tuskegee Airmen syphilis study and the New Zealand 1966 cervical cancer study, to name two, have provided models of unethical practice for a generation of researchers. We need to be sure we don't exacerbate those biases by plugging them into AI.
The Role of AI in Risk Management
AI serves a pivotal role in risk management within the Pharmaceutical industry. Its applications span from early detection of health risks to optimizing clinical trials and facilitating regulatory compliance. However, the ethical implications of relying on AI for critical decision-making demand meticulous attention.
Importance of Multidisciplinary Teams in AI
The ethical deployment of AI in Life Sciences necessitates collaborative efforts by people with diverse expertise. Multidisciplinary teams, comprising scientists, ethicists, data analysts, and industry professionals, bring varied perspectives essential for aligning technological advancements with ethical principles. By our very nature, none of us can "see" our own biases. Michelleanne likens our job to an almost anthropological approach here. The more diverse Multidisciplinary Teams we have working on this, the less likely those biases will slip through to the algorithms unchallenged.
Ethical Considerations in AI
Above all, ethical considerations are the guiding compass for AI integration in the Pharmaceutical industry. Fairness, transparency, accountability, and privacy principles should be non-negotiable in every facet of AI development, deployment, and regulation. We need algorithm oversight, and the FDA will require industry experts to advise on this.
The synergy between AI and Life Sciences presents unparalleled opportunities for the Pharmaceutical industry. However, this convergence demands a delicate equilibrium between innovation and ethics. Balancing technological advancements with ethical considerations is not just a choice but a responsibility that shapes the future of healthcare. Only by embracing an ethically conscious approach can the potential of AI be harnessed to improve patient outcomes, drive innovation, and uphold the highest ethical standards in the Pharmaceutical industry.
So how can we do this? What is the mechanism for maintaining this balance?
We need people from all the diverse specialties, Data people, Clinical people, etc., to get involved now. We also need an Algorithm Review Board, like the IRB, to get engaged before we find ourselves dealing with a catastrophe that causes a reactive regulatory response.
Let's put out the fires before they start.
If you want to become part of this solution, contact us at hello@Metisconsultingservices.com to join the conversation.
RIC, REMS, and the REMarkable Dr. Frances Oldham Kelsey
Frances Oldham Kelsey was a Canadian-born physician who fought big pharma companies and a tremendous amount of pressure to do her job. In the process, she saved lives and heartbreak for thousands of Americans.
Dr Francis Oldham Kelsey - image from Library of Congress
Written by Li-Anne Rowsell Mufson
METIS' CEO and Founder Michelleanne is finishing up with the SQA Conference and is headed to the REMSIndustry Consortium (RIC) to Convene on March 22nd and 23rd.
The promised second half of our blog on REMS and The history of Thalidomide is below. I wound up becoming even more fascinated with Dr. Frances Oldham Kelsey and her heroism, and it is particularly appropriate to celebrate her during Women's History Month. If you want to hear more about REMS, listen to Ep. 6 Of the "Queens of Quality Podcast."
if you'd like to know more about how our consultants can help your company with REMS programs, drop us a line at Hello@metisconsultingservices.com
Frances Kelsey: A Woman Who Made a REMarkable Difference in the World of Medicine
Who is Dr. Frances Oldham Kelsey?
Frances Oldham Kelsey was a Canadian-born physician who fought big pharma companies and a tremendous amount of pressure to do her job. In the process, she saved lives and heartbreak for thousands of Americans. She was born in 1914 and received her bachelor of science and master of science degrees from McGill University, Montreal, in 1934 and 1935. In 1938 she earned her Ph.D. from the University of Chicago and married and had two children while teaching and earning her medical degree there. She began her career at the Food and Drug Administration (FDA) in 1960 at the age of 46. At the FDA, Kelsey worked in the Division of New Drugs and was responsible for reviewing and approving new drugs for the American market. During her time at the FDA, Kelsey became a vocal advocate for rigorous testing and regulation of new drugs. She also believed in ensuring the safety and efficacy of new medicines before they were approved for sale.
What did Frances Kelsey do that was so remarkable?
In 1961, during her first month at the FDA, Kelsey began her very first significant project, reviewing a new drug called Thalidomide. It was a sedative being marketed as a safe and effective treatment for morning sickness in pregnant women, among other sedative uses. As other countries began approving the drug for sale, Kelsey was skeptical about its safety. Dr. Kelsey knew that drugs could cross the placental barrier and harm an unborn baby. So she asked for evidence of trials on pregnant animals and requested that the company submit more data about its safety and efficacy, but they were reluctant to do so. These were never provided.
In fact, that company resubmitted the NDA several times without ever providing the information she sought. Dr. Kelsey's insistence on more testing and regulation saved thousands of lives. When other countries began approving the drug for sale, thousands of babies were born with congenital disabilities. However, the drug was never approved for sale in the United States due to Kelsey's diligence and attention to detail. Despite all her efforts, and even though the drug was not approved in the United States, as many as 20,000 Americans were given Thalidomide in the 1950s and 1960s. These individuals were part of two clinical trials operated by the American drug makers Richardson-Merrell and Smith, Kline & French. The Sales manuals even assured doctors that the new drug had been "shown to be absolutely harmless" in pregnant women and children.
And if not for Dr. Kelsey, that number would have grown exponentially.
She was eventually awarded the President's Award for Distinguished Federal Civilian Service by John F. Kennedy for her efforts to ensure the safety of drugs prescribed to pregnant women.
How did Kelsey's work impact the regulatory landscape?
Kelsey's story has been told in films, books, and documentaries. She is a powerful symbol of achievement through dedication, hard work, and determination. Her story highlights the importance of rigorous testing and regulation in the world of medicine. The FDA strengthened and improved its regulations due to Kelsey's work. The 1962 Kefauver-Harris Amendment required more data to be collected about the safety and efficacy of new drugs before they were approved for sale. The amendment also allowed the FDA to issue sanctions against pharmaceutical companies that did not comply with the regulations.
Kelsey's work also had a global impact. Organizations like the World Health Organization (WHO) and the International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use were formed to coordinate and facilitate the regulation and testing of drugs among different countries. And the FDA would never have created the REMS program.
What’s REMS again?
As we have mentioned, REMS (Risk Evaluation and Mitigation Strategy) is a drug safety program that the U.S. Food and Drug Administration (FDA) has implemented for medications to help ensure the benefits of the medication outweigh the risks. The key participants in the Risk Evaluation and Mitigation Strategy (REMS)are patients, healthcare providers, pharmacists, and healthcare settings that dispense or administer the drug. There are four pieces to REMS:
Risk piece-there are serious risks identified
Evaluation- through trials, analysis, etc.
Mitigation piece- what can be done to reduce that risk
Strategy piece - how that mitigation is done
When was REMS started?
Risk Evaluation and Mitigation Strategies (REMS) are programs instituted by the FDA to monitor medications with a high potential for serious adverse effects. REMS applies only to specific prescription drugs but can apply to brand-name or generic drugs. The REMS program was formalized in 2007. REMS programs are designed to reinforce medication use behaviors and actions that support the safe use of that medication. While all medications have labeling that informs healthcare stakeholders about medication risks, only certain medications require a REMS. REMS are not designed to mitigate all the adverse events of a medication; Rather, REMS focus on preventing, monitoring, and/or managing specific serious risks by informing, educating, and reinforcing actions to reduce the frequency and/or severity of the event.
According to the FDA's website, there are three major components to the strategy for each REMS.
Communication to Patients-REMS may require the drug manufacturer to develop materials for patients like medication guides(these would be in addition to the medication guides all drugs must include.) These handouts contain FDA-approved information in patient-friendly language that can help inform patients about the safest way to use the medication.
Communication to Health Care Providers, Pharmacists, and Health Care Settings-
The REMS may include communicating directly to health care providers, pharmacists, nurses, or other participants involved in the delivery of these medications. In some cases, the communications may also target medical professional societies or state licensing boards to inform them of the REMS' particular safety concerns and/or to support conveying this information to their members. They may provide information about a specific risk and steps to take to reduce it.
3. Required Activities or Clinical Intervention-Sometimes these activities are referred to as "elements to assure safe use (ETASU)."
Sometimes, participants are required to conduct activities that support the safe use of the medication. These activities must be undertaken before the drug can be prescribed, dispensed, or received.
The storied history of Thalidomide was one of the critical elements in the regulations that eventually led to the institution of the REMS programs.
Dr. Frances Kelsey's story can be an inspiration to us all. She was a woman who rose to prominence during a time when women were not taken seriously in the world of medicine. Despite this, she was determined to ensure that the drugs on the market were safe and effective. Kelsey's story highlights the importance of Quality assurance and regulatory oversight in the pharmaceutical and medical device world. Dr. Kelsey's story is also a reminder that change is possible. By questioning the status quo and challenging the accepted standard, she brought about positive change in how drugs are regulated and tested.
Her story should remind us all of the importance of insisting on evidence, putting patient health first, doing the work, and, of course, standing up for what is right.
Cited research
The Story of Thalidomide in the U.S., Told Through Documents. https://www.nytimes.com/2020/03/23/health/thalidomide-fda-documents.html
What's in a REMS? | FDA. https://www.fda.gov/drugs/risk-evaluation-and-mitigation-strategies-rems/whats-rems
Risk Evaluation and Mitigation Strategies | REMS | FDA. https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems
What is this Alphabet Soup?
Although it is reasonably well understood conceptually, the REMS program is relatively new - it started in 2007- and is still in the process of being operationally understood.
What is this alphabet soup?
Written by Li-Anne Rowswell Mufson
REMS- RISK EVALUATION AND MITIGATION STRATEGY.
RIC- REMS Industry Consortium
Although it is reasonably well understood conceptually, the REMS program is relatively new - it started in 2007- and is still in the process of being operationally understood. The reality of multiple Sponsor and Vendor organizations sharing a REMS program can lead to breakdowns in Communication, Collaboration, and Consensus among the different organizations and even the departments within those organizations. With help from Metis' Consultants and with the tools provided by RIC, organizations can work to identify potential issues before they start and prevent communication siloing along departmental and organizational lines; by fostering collaboration and consensus with shared REMS sponsors and vendors.
Evaluation within the REMS program is used to mitigate risks, and the strategy for the Mitigation piece is presented to the FDA. The FDA evaluates for both tactics and strategies.
Because of all the complexities and even some unnecessary complications, staying current and having specialists in this manner is essential. That is the reason the RIC was started.
The REMS Industry Consortium provides education and learning tools to help and standardize the successful execution of an REMS program. Metis is a very enthusiastic supporter of the Consortium as it kicks off.
What is RIC?
The REMS Industry Consortium, Inc. (RIC) is a nonprofit organization made up of industry experts. According to the RIC website, it " brings together the perspectives of organizations that sell—or anticipate selling—prescription drugs or biologics subject to Risk Evaluation and Mitigation Strategies (REMS).”
The RIC seeks to:
Foster and encourage two-way communication between manufacturers/REMS sponsors and FDA
Discuss and clarify challenges faced by industry sponsors and the FDA
identify best practices for REMS throughout the development, review, and management lifecycle
Provide the FDA with a "sounding board" to solicit feedback on REMS
collectively explore vendor participation and capabilities in REMS."
The emphasis is mine. In these areas, in particular, having knowledgeable and experienced consultants from Metis will be invaluable to pharmaceutical manufacturers subject to REMS.
What is REMS?
The U.S. Food and Drug Administration (FDA) introduced the Risk Evaluation and Mitigation Strategies (REMS) program in 2007 to ensure that the benefits of particular drugs outweigh their risks. REMS is a comprehensive strategy pharmaceutical manufacturers must develop and implement to manage known or potential serious risks associated with a specific drug while ensuring continued patient access to the medication.
One key aspect of REMS is the Risk Identification and Analysis (RIA) process, which involves identifying potential risks associated with a drug and analyzing the likelihood and severity of those risks. Based on the RIA, pharmaceutical manufacturers develop a REMS program that includes various strategies to manage and mitigate the identified risks.
REMS programs typically include a combination of elements such as medication guides, communication plans, training and certification programs for healthcare providers, patient registries, and restricted distribution programs. These elements aim to ensure that healthcare providers and patients have access to the information they need to make informed decisions about the pharmaceutical's use and minimize the risks associated with its use.
Pharmaceutical manufacturers must submit a proposed REMS program to the FDA for review and approval before marketing the drug. The FDA reviews the proposed REMS program to ensure that it includes appropriate risk management strategies and is feasible to implement.
Once the REMS program is approved, pharmaceutical manufacturers must implement and maintain the program as authorized. The FDA monitors the implementation and effectiveness of REMS programs through various means such as inspections, audits, and assessments.
Pharmaceutical manufacturers must understand and comply with REMS requirements to ensure that their drugs are safe and effective for patient use. Failure to comply with REMS requirements can result in enforcement action by the FDA, including fines, product seizures, and injunctions.
In summary, REMS is a critical program that pharmaceutical manufacturers must comply with to ensure the safe use of their drugs. REMS requires manufacturers to identify and mitigate potential risks associated with their drugs and implement various risk management strategies to minimize those risks. Pharmaceutical manufacturers should work closely with the FDA throughout the REMS process to ensure that their REMS programs meet regulatory requirements and effectively protect patient safety.
Coming up
In our next blog post, we will discuss the history of thalidomide, the heroic work of Frances Kelsey, and how that eventually led to the institution of REMS.
Metis' CEO, Michelleanne Bradley, has been involved with REMS programs since they began in 2007. For more information about RIC and REMS, listen to Episode 6 of the "Queens of Quality" Podcast. You can also drop us a line at Hello@metisconsultingservices.com or check us out on LinkedIn.
Audit & Inspection Readiness
Inspections and audits allow the pharmaceutical sponsor to improve its processes and demonstrate continual improvement in every department and phase of the process.
Written by Li-Anne Rowswell Mufson
This month we will discuss Audit and Inspection Readiness
Last month, we talked a little bit about People’s perception of Quality teams, inspectors, auditors, and “the police” and how that isn’t what our goals should be with Internal and External Audits. This month we are going to talk about how to get the most out of “mock Inspections” Practice Interviews and how to be ready for Audits and Inspections
Why are inspections and audits important?
Inspections and audits allow the pharmaceutical sponsor to improve its processes and demonstrate continual improvement in every department and phase of the process.
While Inspectors may come in with a stated focus—for example, they may focus on GCP—depending on what they discover, they may “Pivot” and talk extensively with another department. For example, the organization may expect them to stay in manufacturing, but they wind up focusing on Pharmacovigilance.
So the organization needs to plan ahead so all departments are ready.
Steps in Performing an Audit
First step you need an Audit Calendar
Internal, Vendors, Suppliers, and Partners: This should not necessarily be every year, but there should be training and audits on the calendar every year. Determined by the Quality Department. This Ensures compliance with regulations and objectives and shows how good you are at what you do.
Doing actual run-throughs of interviews and inspections
Identifying the right “Key people”
Performing the due diligence and auditing your vendors actually ensures that they are qualified to do the job they are contracted to do. The Sponsor is the responsible party.
Don’t just check the box.
Identifying the Right Key People
Identifying the Right Key People—Who will be selected to be in front of an inspector? It is very important to choose key people to represent for a “mock” inspection. The same personnel who are chosen need to present for a “mock” inspection as well. If folks cannot answer questions in their immediate remit, they shouldn’t be there. But staff should understand that this is an opportunity to show how good you are at your job.
Key people from every department who know the documents and systems of their department. Choose people who will answer all questions honestly and directly without guessing or speculating. They should refer any questions that can't be answered to someone who can. Regulatory agencies expect employees to be trained to do this. Don't "hide the truth" because it will make you look bad. Don't state your opinion, don't volunteer information that was not asked for. "Shine"
Such a person might be asked, “Do you know what problems exist?”
If that person can say, “Yes, and this is how we are working on it,” you’re golden.
If the auditor has to tell you what the problem is, you are in trouble. It is an uncomfortable conversation. A 483 because the health authority had to tell you what the problem is means that communication within the organization is probably an issue as well.
An Internal Audit should be used to identify and address problems or concerns that exist in the systems. Again, you don't want the Health Authority to be the one to let you know about any issues.
Communication issues—Listen to your team Members if they tell you about an issue. Put it on a project plan so you’ve at least acknowledged a difficulty and put it on the “to-do List.” Sometimes, the people on the ground who are doing the work may request to have issues included in an internal audit. It may serve to open communication with the folks at the top.
The Sponsors Responsibilities
The Sponsor is the ultimate responsible party for all activity related to their product. Often, a client will say, “My vendor does that.” And while that may be true, the Sponsor can’t abdicate that responsibility. This is when having an external body to do those kinds of audits can be really beneficial. It promotes the relationship between the functional area or contract owner and the Quality Organization. Because the Quality Organization is now supporting the function in the preparation. An objective 3rd party doesn’t share the organization’s bias.
Regulatory agencies prefer independent third-party audits so that the potential for conflict of interest can be eliminated. When you use the in-house team for auditing a vendor, it is like having the fox watch the hen house. If you use the same company as the vendor, you are essentially outsourcing the bias. We do need to trust the vendors and have a collaborative attitude, BUT the oversight is also the responsibility of the Sponsor. So bringing in a 3rd party to audit vendors and even internally. This means you have a neutral Auditor. And your Quality team can be even more helpful to you. In preparation and response.
Avoid common 483 observations like "FIRM FAILED TO FOLLOW ITS OWN SOP." Don’t let this happen in your organization. Train everyone to be familiar with all SOPs and documents relevant to the department's work. Get revisions done in a timely manner.
Get your Documentation in order
List all Documents relating to the audit. Batch manufacturing records Master formula records, SOP's Method of Analysis deviations, change controls testing data, etc..
Qualification Documents for equipment, water systems, Instruments for Quality control, Instruments for production, process validation, method validation, etc., must be reviewed before the audit.
Check for correctness, overwriting, and updating. Include supporting data, analytical data, and data generated from production and warehouse equipment.
Do not throw away our original data. Print Clearly in logs and fill out all documents completely. Record data directly in the appropriate form or notebook (no napkins, scrap paper, etc.. and then transfer. if you do accidently record your data on a piece of scrap you need to staple it to the notebook or form because THAT scrap is original data. Always attach labels or printouts where indicated. Record all requested info and fill in all the blanks, If it isn't documented, it doesn't exist.
Use black indelible ink and write corrections clearly above or beside the line-through with an initial and date.
NEVER average OUT-OF-SPEC results to obtain a passing result. Don't continue testing samples until you get enough that pass. (See Barr Case?)
Have another person perform double checks where indicated in the batch record. These are required for critical steps, such as adding and weighing raw materials, which are historically problematic points in the process.
Record ID, part, lot, document, revision, and other control numbers. If something should go wrong these numbers permit traceability.
NEVER Backdate or falsify records.
Check for Calibration on Equipment
Avoid the most Common errors
If you are a supervisor or manager, report mistakes and encourage people to report them. Then, figure out how to correct and prevent the issue.
Wear your Protective gear
Know where safety "Stop" buttons, First aid kits, eye wash, and other
Read your MSDS- Safety Data Sheets
Be especially careful around Breaks when tired or when someone interrupts you. Be vigilant
Wear appropriate clothing, sterile gowns, lab coats, hair coverings, shoe coverings, etc...
Don't wear a lab coat or uniform while outside the building i.e. smoking
Keep it clean
Use validated procedures on Surfaces and equipment, keep tags, and logbook current
WASH YOUR HANDS
Report illnesses
Check expirations on materials
Remove, segregate and destroy all expired materials
Record ID, part, lot, document, revision, and other control numbers. If something should go wrong these numbers permit traceability.
DO NOT bring food, drinks, gum, tobacco, or house plants into production and lab areas
Check Pest Control Devices frequently
Keep shipping and receiving and any other doors closed. Check the bottoms of outside doors for gaps. Rodents only need a 1/4-inch gap to get in.
Quality organizations are starting to become more collaborative in style rather than adversarial. So that the opportunity to outsource the audit to help the internal quality organization. It is possible to have “practice Interviews as well. You can work through the interview piece together without the intensity of a “mock Inspection” Coaching the interviewees is another valuable tool that an outside consultant.
Risks vs. Non-compliance of outsourcing: They may be able to demonstrate compliance, but the risks are still there.
The biggest Risk is “You don’t know what you don’t know”
Listen to team members
Audit calendar—Internal, Vendors, Suppliers, and Partners. Not necessarily every year, but there should be training and audits on the Calendar every year. Determined by the Quality Department. This is to ensure compliance with regulations and objectives and to show them how good you are at what you do.
Importance of having an audit plan or program
[11:28] Why an external audit is important
[17:19] New trends in auditing and inspection
[20:02] Things you should not say in an audit interview
[23:16] How do you perform an audit of your vendors?
[24:49] Risk vs non-compliances