In this soundbite from RCA Radio, Erika Porcelli, CEO of Regulatory Compliance Associates® (RCA), provides examples of how different size companies leverage the stage of business they’re in to accelerate development with outsourced staff.

 

Start ups vs Large Companies

 

Using Staff augmentation to bring in SMEs gives companies the ability to scale up and scale down quickly without taking away people from other projects.

Start-ups are typically not ready to bring on a full-time employee. In cases like these, we can bring in a subject matter expert (SME) that can help work through any regulatory, compliance, or quality problem and assist on an as-needed base.

 

Larger companies typically need help when they are performing a project such as adding a new manufacturing line into a facility. They don’t do this all of the time and only need the extra resources for this particular project. In cases like these, we will put together a team with the right skillsets that can complete the particular project. Once completed, RCA perform a hand-off with the client, and our team steps away from the project. 

 


Listen to the full episode “Outsourcing and Staff Augmentation” now!


 

All companies experience staffing support issues whether they are transient and short-lived, chronic and unplanned, or intrinsic to your business model. RCA has consultants that develop a solution to your specific needs; we can help “right-size” your team when and where you need it most.

 

Outsourcing has become an increasingly common practice in the life science industry. The quality assurance (QA) and regulatory affairs (RA) functions create extra complexity for large and small life science companies because needs may vary greatly depending on the life cycle of the organization. These companies turn to outsourcing to manage operations and tactical skills, and also help adopt best practices.

 

Successful execution comes through project monitoring, issue resolution, and risk management of the process through clear leadership. RCA’s team of experienced project management professionals organize and manage resources to ensure that projects are completed successfully, on time, and within budget.

 

RCA Outsourcing Services

 

Project Management

outsourced staffTo be successful in the field of manufacturing, you must have a proper project management plan in place. Not only do project management procedures keep your projects on time and on schedule, but they also ensure your devices’ compliance with stringent national and international regulations. RCA can help you develop an effective plan, and we can even lead these tasks so that you can run more projects at one time more efficiently.

 

Our outsourced staff capabilities for project management capabilities include:

 

  • On-site Project Leadership or Project Management Support
  • Design and Implementation of a Project Management Office
  • FDA Workshops
  • Project Assessment, Remediation, and Follow-up
  • Advanced Schedule Optimization and Management
  • Development and Implementation of Compliant Methods
    • Risk Management
    • Issues Resolution and Decision Tracking
    • Change Management
    • Performance Measurement and Tracking
  • Tool Selection for Program Portfolio and Resource Management

 

Staff Augmentation

Many companies need the assistance of a professional with specific skills and expertise when completing a project but might not have the need or resources to hire this expert as a full-time employee. Instead, you can add experienced professionals to your staff for a short- or long-term project through our medical device staffing support capabilities. RCA’s outsourcing solutions can help you manage even your most complex projects with experts trained in areas such as:

 

  • Quality Assurance
  • Regulatory Affairs
  • Validation
  • Operations
  • Product Development

 

Consulting Support

Maybe your company is struggling to complete projects on time, or perhaps you often face challenges associated with product compliance. Whatever your situation, our consultants will work with you to ensure your business’ success with consulting support services. By getting to know more about your business and goals, we’ll tailor our approach to best meet your particular needs.

 

Advantages of Outsourcing

 

When you hit a snag in your project’s development, you need to design and develop the best solution to create a timely, quality finished product. RCA’s quality assurance and regulatory affairs consultants can help you define the specific problem, generate ideas for a potential solution, and implement that solution for the utmost success in your project’s completion.

 

Our goal is to help you get your projects to completion on time and on budget — all while outsourced staff keeps superior quality at the forefront of your every task. And with a team of more than 500 pharmaceutical consultants and industry experts with an average of 25 years of experience in the life science industries, we have the extensive resources and expertise needed to meet this goal.

 

Strategic Outsourcing

 

Medical device manufacturers face the challenging task of creating top-quality products quickly with minimal personnel and growing compliance regulations to adhere to. With these increasing challenges, it’s no wonder so many local startups and Fortune 100 companies alike choose RCA for outsourced staff and strategic outsourcing services.

 

About RCA

Regulatory Compliance Associates® (RCA) provides worldwide services to the following industries for resolution of compliance and regulatory 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-and globally-regulated companies.

 

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

 

 

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

The FDA recently updated guidance for clinical trial design (2022). This update stems from an objective of the 21st Century Cures Act (Cures Act). It includes recommendations for how industry sponsors of pharmaceuticals or biologics should design and conduct clinical trials. The guidance provides a greater explanation of how biologic and oncology trial design can simultaneously evaluate more than one investigational drug.

 

FDA Guidance

 

The guidance goes into depth about the clinical research milestones of master protocol design. Data integrity considerations are also mentioned for biomarker co-development and trial statistical analysis. Traditionally, oncology clinical trials are designed to assess multiple investigational drugs at the same time. Clinical data in this type of design is analyzed across multiple cancer types during the same trial to find all sources of patient efficacy and commercial value.

 

Another primary driver is the CDMO race due to testing multiple drugs and sub-populations under the same protocol. Pharmaceutical consultants like RCA Inc. have witnessed a shortening of client commercialization timelines across the life sciences industry. This directly adds incremental pressure on project sponsors. Clinical teams are being tasked to discover late-stage drug success faster than ever before. Every trial must simultaneously ensure patient safety while producing data that satisfies the regulatory safety and effectiveness.


Need help with your Clinical Trials? Contact Us Now!


Investigational Drugs (IND FDA)

 

The FDA concisely describes this unique protocol design and clinical trial planning for IND filings and multiple sub-studies. Sub-studies may have separate goals and require aligned efforts across the data science team. For example, collaboration is needed in order to appropriately value multiple investigational drugs. Consideration should be given that therapeutic value may be in one or more disease sub-types in the clinical trial.

 

With these considerations in mind, the FDA goes on to describe the benefits of a master protocol across the study design. This provides the project sponsor design flexibility via electronic data capture (EDC) in an EDC system (e.g. shared control arm, adaptive designs, centralized data capture).

 

Clinical Trial Design

 

This new FDA guidance also provides insights on potential challenges the industry should consider when using master protocols. These unintended consequences can include greater difficulty when assigning detailed adverse events to an investigational drug if numerous products are being investigated across the clinical study.

 

Any lack of adverse event reporting clarity can impact the safety profile of an investigational drug. This directly makes the clinical analysis for FDA approval more complicated for the regulatory body. Multiple study groups can also increase the overinterpretation of study findings. For example, signs of positive product efficacy for cardiac biomarkers could be different than from cancer biomarkers. Biomarker discovery for one subpopulation could also be identified as false if based a different ad hoc patient group.

 

Basket Trials

 

Basket trial design includes assessing an investigational drug blend by including a dose-finding or safety lead-in component. The goal is to identify safe quantities of the combination early in the clinical trial before progressing with an efficacy activity-estimating factor. The FDA proposes therapeutic efficacy for sub-studies within basket trials are constructed as single-arm, activity-estimating trial. The primary endpoint would be recorded as total response rate.

 

The guidance goes on to elaborate on sub-study objectives, including study rationale for each population. A comprehensive statistical analysis plan (SAP) with reasoning for sample size and unique stopping rules based on ineffectuality should also be included in the program documentation.

 

Umbrella Trials

 

A master protocol designed to evaluate multiple drugs is commonly referred to as an umbrella trial. These umbrella trials are often administered as a single drug or as a combination product. Umbrella trials are often a randomized controlled trial to evaluate the mechanism of action of the investigational drug/drugs with a common control arm. Study design for an umbrella trial can include sub-studies based on a patient biomarker or to a separate therapeutic sub-study inside the trial.

 

Clinical Study Design

 

As the clinical study focus, the FDA provides a clear understanding of how project sponsors improve the efficiency of master protocols. For example, using a common control arm during an Umbrella Trial has proven to help evaluate multiple drugs simultaneously for a single disease state.

 

Control Arm

 

For clinical trials, the FDA now recommends a project sponsor use a common control arm when numerous drugs are evaluated simultaneously in a single illness (e.g. umbrella trials). The FDA guidance elaborates in the use of a control arm be the current standard of care (SOC) so trial results are understandable from the perspective of the biologic and oncology medical community.

 

Changes in SOC can also take place during the trial because of an FDA approval or the latest scientific data. The Statistical Analysis Plan (SAP) would need to be revised before any data analysis occurs if this is the case.

 

Novel Drugs

 

When a project sponsor uses sub-studies to assess two or more investigational drugs, the FDA advocates for providing a thorough scientific motivation for the combination. This includes the clinical trial sponsor defining the Recommended Phase 2 Dose (RP2D). Analysis should include each novel drug and ensuring the appropriate dosage has been identified for each individual drug.

 

Targeting Biomarkers

 

The FDA goes on to elaborate on digital biomarkers to help validate the patient selection and recruiting for clinical trials. Biomarkers should be clearly identified based on the intended therapeutic response.

 

For example, an oncology biomarker for tumor size can help predict the response to the investigational drug. This type of study biomarker might demonstrate how the mechanism of action succeeded or failed. There needs to be a consensus among the clinical study team on how biomarkers are justified. Understanding study measures for showing marker positivity before patients enter the trial is critical.

 

Data Monitoring

 

One final important note about the master protocol in the updated FDA guidance describes the independent radiologic review committee. This committee medical research should include blinded tumor-based assessments to provide a charter for the independent data monitoring committee (IDMC).

 

The IDMC charter would guide the committee through ad hoc trials, such as patient efficacy and drug futility. The IDMC can also recommend clinical trial protocol actions. This often includes changes in sample size or modification of a sub-study based on overwhelming futility or efficacy evidence.

 

About RCA

 

Regulatory Compliance Associates® Inc. (RCA) provides healthcare consulting services to the following industries for resolution of compliance and regulatory challenges:

 

We understand the complexities of running a life science business. Our team possesses 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-and globally-regulated companies.

 

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

 

 

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

What should you do if you are having trouble executing your protocols? 

Listen to this highlight from RCA Radio where Walter Mason explains what needs to be done if you have troubles executing your design protocols even after training.

 

 

design of protocolsListen to the entire episode where we take an in-depth look at protocols for biologics and their importance. RCA Radio Episode 13.

 

What can you do?

  • Go to the developer and let them know that it is not working for you
  • Talk through the process, go step by step
  • Look back at the FDA guidance documents
  • Get feedback
  • Implement changes in your training or to the protocol itself

 

 

 

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

The US Food and Drug Administration (FDA) recently issued final guidance (June 2021) for Biologics industry executives to help define modifications to existing products and update submission procedures.  The primary focus of the guidance is to help biologics industry employees responsible for reporting understand which type of risk category is appropriate for updated variations in chemistry, manufacturing, and controls (CMC).

 

The guidance is applicable to CMC products with an existing biologics license application (BLA) currently approved by the FDA. It’s a critical update since any Biologics company or regulatory partners must notify the FDA about every change to an approved BLA under the Code of Federal Regulations (21 CFR 601.12).


Need help adhering to the New Guidance? Contact Us Now →


FDA submission data

 

FDA Guidance

The final FDA guidance goes into detail about each post-approval change in the product, including production process, quality controls, equipment and facilities, responsible employees, and established labeling. Expanded submission data will potentially provide greater detail about the the risk profile related to the changes, and how revised changes impact the intended safety or efficacy of the product.

 

Assessing and implementing manufacturing changes is laid out in great detail in the FDA guidance. Comparability data will be used to show variations of the product pre- and post- changes. The comparability analysis is necessary to help gauge possible effects of the product changes. Data from the analysis will be represented through a variety of sources, including a combination of testing, validation studies, and non-clinical or clinical studies.

 

FDA submission procedure

 

More importantly, the guidance provides a greater amount of detail about the updated FDA submission procedure. A significant focus of the guidance acknowledges the opportunity for adverse effects and how to measure and minimize based on data about the revised formulation. The biologic submission must show reference information that considers the new identity, strength of the product, quality of the product, and purity or potency of the product.

 

The three unique types of Biologics reporting includes Prior Approval Supplement, Changes Being Effected in 30 Days/Changes Being Effected (CBE30/CBE) and an Annual Report:

 

Prior Approval Support (PAS)

  • This includes changes that have significant potential for an adverse effect on product quality. The PAS must be approved by the FDA before a Biologics company can distribute any updated BLA approved product to the market involving the changes.

 

Guidance Changes Being Effected in 30 Days/Changes Being Effected (CBE30/CBE)

  • This includes changes that have a moderate potential to have an adverse effect on product quality. The CBE30/CBE requires an applicant to report the change to the FDA in a supplement at least 30 days before distribution of the product to the market.

 

Annual Report (AR)

  • This includes changes that have a minimal potential to have an adverse effect on product quality.

 

FDA process validation

 

Assessing the impact of the change on product quality is critically important in the reporting submission.  Reporting data should include prior knowledge and findings from product development activity. Documentation surrounding process validation activities and manufacturing expertise of the approved BLA product are also requested.

 

Quality risk management activities or pre-commercial studies that provide expanded awareness of the effects of the changes can also be very valuable for FDA decision makers. Finally, a cumulative impact assessment of multiple changes on the updated BLA product can help ensure post-market surveillance activities are aligned between the FDA and Biologics company.

 

Quality Management System

 

References to a robust quality culture appear throughout the guidance, including developing of robust manufacturing processes and process controls. Innovative process validation techniques and analytical testing are listed as critical drivers Biologics companies should practice to help mitigate risks associated with manufacturing changes.

 

Having an effective quality risk management system allows Biologics industry executives to make knowledgeable choices regarding manufacturing variations. The quality system data increases the confidence of product quality and process consistency for both executives and the FDA. Formal and informal risk assessments to support of post-approval manufacturing changes increases the accuracy of a more effective assessment of the change, which can increase the speed of the FDA’s decision.

 

About RCA

pharmaceutical consultantsRegulatory Compliance Associates® (RCA) provides worldwide services to the following industries for resolution of compliance and regulatory 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-and globally-regulated companies.

 

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

 

 

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

The USA Food and Drug Administration (FDA) recently provided updated regulatory guidance for Product Lifecycle Management in the pharmaceutical industry. The guidance helps pharmaceutical companies and manufacturers better understand the administration of post-approval chemistry, manufacturing, and controls changes. The guidance provides new insights into lifecycle management concepts for both new and existing pharmaceutical products, including chemical and biologics.

 

The FDA regulatory team looked to synchronize its updated guidance more closely to ICH guidelines used with other global regulatory agencies. The benefit realized by pharmaceutical companies would be options for reducing duplicate clinical studies and increasing the standardization of safety information reporting. By revising facets of FDA marketing application submissions as well, the Agency appears to be taking a more holistic approach to improving drug development quality and pharmaceutical manufacturing strategy.


Looking for help Managing your product’s Life Cycle? Contact Us Now →


Changes include language revisions to surrounding regional legal frameworks, an expanded clarification of critical process parameters, and identifying established conditions for manufacturing processes. One important revision for regulatory affairs employees is the new recommended content of the product lifecycle management document and its location within the technical file. Clarity revisions were also made to further expand on the use of available tools described in the guideline for master files.

 

The new FDA guidance also expanded its language on post-approval chemistry, manufacturing, and controls changes. With additional tools and principles intended to improve the industry’s management of post-approval changes, FDA leadership is hoping to increase transparency between both industry employees and regulatory authorities. The benefit to pharmaceutical companies should be a deeper understanding of how product and process knowledge will contribute in the real world to post-approval changes that require a regulatory submission. By defining the level of reporting categories, industry experts should experience a deeper understanding of risk compared to product quality.

fda guidance

 

The new tools and principles are designed to improve data input into a company’s quality system. The goal is to enhance the industry’s ability to manage many chemistry, manufacturing, and controls changes that have a lower priority needed of regulatory oversight. At the same time, many at the FDA are hopeful the tools and principles could result in fewer Marketing Authorization Application submissions that increase the associated regulatory burden.

 

The guidance should increase both operational efficiency and regulatory flexibility when implemented with the proper regulatory framework and applied with widely accepted risk management principles in the pharmaceutical industry.

 

About RCA

pharmaceutical consultantsRegulatory Compliance Associates® (RCA) provides worldwide services to the following industries for resolution of compliance and regulatory 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-and globally-regulated companies.

 

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

 

 

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

The US Food and Drug Administration (FDA) has recently expanded on its clarification of a virtual audit, and how new manufacturing protocols in the COVID-19 environment will evolve. Travel constraints continue to impact the industry, especially in countries like India where a tremendous outbreak of COVID cases erupted in April 2021.

 

“This does show that indeed, we are very much interested in doing these remote interactive investigations, you know, especially the ones with video streaming technology.” said Michael Kopcha, director of the Office of Pharmaceutical Quality in the agency’s Center for Drug Evaluation and Research.


Looking for help preparing for the new guidance? Contact Us Now →


After reviewing recommendations from the European Medicines Agency (EMA) and the UK Medicines and Healthcare Regulatory products Agency (UK MHRA), the FDA continues to address the questions many pharmaceutical companies and partners have voiced during the pandemic. FDA officials commented that, due to these early learnings from other global regulatory bodies, they have recently expanded their recommendations for virtual audit best practices and new criteria of considering when to conduct a remote inspection.

 

Two of the initial primary use cases for virtual pharmaceutical inspections mentioned by the FDA include records requests and on-site inspectional work. While developing the new virtual audit process is still ongoing, one recommendation is Pharmaceutical companies should choose a proven regulatory partner to assist with the audit. Agency executives explained they will not be engaging vendors to perform virtual audits on behalf of the FDA.

virtual audit

 

One looming issue to be remedied is will virtual audits be allowed for facilities with serious good manufacturing practice (GMP) violations. FDA officials have expanded on their risk-based approach to prioritization in deciding which sites may qualify. An expanded virtual audit strategy continues to be a work-in-progress by agency officials including defining which companies qualify for an FDA virtual inspection and, more importantly, in what order the virtual audits may happen.

 

GMP violations involve either FDA warning letters or action-indicated site classifications based on the possible corrective actions needed. If the corrective actions needed for a facility can be successfully addressed remotely, it may become more likely that the number of hybrid virtual inspections authorized by the FDA will continue to grow. However, agency official commentary concluded that each facility will be examined by the FDA team on an individual basis with consideration of potential violations involved being a primary decision-making driver.

 

The good news for Pharmaceutical industry executives is it appears the FDA is willing to learn from international regulatory experiences and potentially even collaborate using technology in new ways to increase the FDA’s ability to continue operations. Global travel limitations will more than likely impact every industry for the foreseeable future in 2021 until the COVID-19 vaccine becomes more widely administered.

 

About RCA

pharmaceutical consultantsRegulatory Compliance Associates® (RCA) provides worldwide services to the following industries for resolution of compliance and regulatory 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-and globally-regulated companies.

 

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

 

 

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

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