Tag: biotech consulting

Cell and Gene Therapy Development

Posted on by Brandon Miller

 

Cell and Gene Therapies also known as (ETMPs) have continued to evolve in recent years. Over the last 15 years the industry and regulatory bodies have continued to learn more about them and in recent year there have been more and more guidance documents released outlining what the regulating bodies want the manufacturers and developers of these different biologic products to look for and adhere to during development.

 

Cell and Gene Therapies are Personalized medicine meaning, one patient, one drug. These types of drugs are not produced in large scale or in batches like the standard biologics or drugs we have been used to manufacturing up to this point. They are made in very small batches that are produced in laboratory setting but require the same environmental controls as your typical aseptic processing but a much smaller scale.

 

Issues with Approval

The issues companies face when manufacturing cell and gene is that they are introducing variability right away in the process in terms of the active ingredient. In this type of manufacturing, the active ingredient is the specific patient’s genome. With the variable ingredient, manufacturers do not know what they are working with upfront which makes the process difficult. It is a non-tradition way of thinking that makes validating a process that has that kind of variability hard on cell and gene companies without experience in this area.

 

The Non-traditional Approach

This approach to drug approval is based on an individualized patient’s genetic makeup and requires the developers to make a constant process of taking the patient’s genetic material and producing the cell and gene therapy dose at the end. Developers have to be able to categorize the variable, walk it through the process, and then categorize it again at the end making sure it is safe and effective for the patient even though it is based on their cell and gene genetic material.

 

 

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FDA Guidance: GASK

Posted on by Brandon Miller

fda guidanceThe pharmaceutical and biologics industry recently received updated FDA guidance on the use of Generally Accepted Scientific Knowledge (GASK) in regulatory submissions.

 

The FDA guidance provides new examples of when it is applicable to leverage GASK data to meet safety requirements required in a new drug application. Clinical information in the drug discovery data that supports the nonclinical safety of a drug can contain GASK citations. Additionally, the citations would be based on existing clinical studies that have been validated by FDA in approved products on the market.

 

What is GASK?

 

Generally Accepted Scientific Knowledge refers to information and methods widely considered as accepted by life science industry experts. It can include established scientific principles, published papers, and best practices that have passed the regulatory scrutiny of drug development. GASK is most often utilized during the evaluation of safety and efficacy data of regulated products.

 

FDA Approval

 

The FDA guidance elaborates on the process of FDA regulators and how new drug applications are evaluated. Further, the FDA often requires life science companies to provide a significant amount of regulatory data to support safety and efficacy claims.

 

This regulatory clinical research often comes from clinical trials, preclinical studies, and other types of scientific data sources. However, in scenarios where there may be limited clinical trial data conducted, GASK can be used to provide supporting documentation for regulatory compliance. 

 

Drug Development

 

Life science companies are required to offer nonclinical information to support regulatory approval of a New Drug Application (NDA) or Biologics License Application (BLA). Additionally, the FDA guidance elaborates on how nonclinical information helps the Agency focus on important matters, such as:

 

  • Identifying pharmacological effects, including the mechanism of action of the drug in vitro and/or in vivo
  • Identifying absorption, distribution, metabolism, and excretion of the drug in vitro and/or in animals
  • Identifying possible consequences of exposure duration (e.g., chronic)
  • Identifying risks for special populations (e.g., pediatrics)

 

Regulation Examples

 

The FDA guidance goes on to describe unique conditions in which sponsors have successfully used GASK in their product development program. Each sponsor cited these GASK resources to meet FDA’s regulatory approval requirements instead of conducting certain nonclinical studies:

 

  • Products containing a substance that naturally occurs in the body. Sponsors submitted GASK regarding that substance and the known effects on biological processes.
  • Demonstrated drug impact on a particular biological pathway. Sponsors submitted GASK regarding the impact and FDA regulators concluded specific nonclinical studies were not necessary to support drug approval and drug labeling.

 

Active Ingredient

 

The FDA guidance continues by listing examples of substances that are typically present in a healthy human body. For example, endogenous substances where the drug replaces a substance that should naturally be present but, for pathological reasons, a patient may lack sufficient amounts. The FDA approved drug may enable and help accelerate the proper functioning of the human body.

 

Pharmacological

 

Additionally, a key driver of using GASK for FDA approval is the patient who has been prescribed a drug & the pharmacological impact experienced. Existing human pharmacokinetic studies and toxicology studies are recommended and may support the approval of the regulatory application. Specifically, regulators wil look to examine if the drug helps increase the level of the endogenous substance to the level of a healthy individual.  

 

Diet

 

Further, exogenous substances that are already present in a patient’s diet may help expedite U.S. Food and Drug Administration approval. This scenario includes a patient’s exposure to an unmodified food substance that doesn’t exceed typical levels of dietary exposure when the drug is taken orally. The FDA guidance also states that certain nonclinical studies may be unnecessary based on the relevance of the exogenous substance to the clinical research submitted. 

 

New Drug Application

 

If an FDA sponsor utilizes GASK information in their new product application, they must submit justification in the appropriate regulatory submission filing (e.g. BLA submission, 510(k) submission, etc.). The FDA guidance recommends as early as possible in product development to the assigned FDA regulator.

 

Finally, food and drug regulation feedback would be provided to the sponsor for the proposed regulatory strategy for approval. The FDA submission should incorporate evidence for the use of GASK, including textbook excerpts and/or non-product-specific published literature.

 

 

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FDA Publishes Updated Biologics Guidance

Posted on by Brandon Miller

The US Food and Drug Administration (FDA) recently issued final guidance 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’s Biologics & Biotech Consulting Services

Regulatory Compliance Associates® can assist you in ensuring the quality of your biologics or biosimilar product during its entire lifecycle. From pre-market to post-market reviews, inspection, and compliance, our Biotech consulting experts can shepherd your biologics through design, labeling, promotion, production, and testing. Our Biologics consultants & consulting services include:

 

Regulatory Affairs

 

Regulatory affairs is Regulatory Compliance Associates®  backbone and we fully understand the complexities of the biologics industry. Our biotech consulting expertise spans all facets and levels of Regulatory Affairs, from early phase & bioanalytical sciences through late phase and post approval.

 

  • Preclinical & CMC Consulting
    • FDA Meetings & Briefing Package Assistance
    • Clinical Trial Applications
    • Marketing Applications
    • Medical Writing
  • Lifecycle Management
  • Submission Planning & Strategic Support
    • eCTD Publishing & Submissions
  • Strategic Consulting & Intelligence
  • US Agent
  • Project Management Support
  • Clinical Development Support
    • Clinical Research Organization (CRO) Sourcing
  • Analytical Development Support
    • Bioassay Design & Validation
    • Immunoassay Support
    • Statistical Analysis & Specification Setting

 

Compliance Assurance

 

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

 

  • Assessments
    • Current Good Manufacturing Practice (cGMP)
    • Corrective & Preventive Action (CAPA), Investigations & Deviations
    • Facility & Maintenance 
    • Data Integrity
    • Quality System Gap Assessment
  • Audits
    • Supplier Audits
    • CRO Audits
    • cGMP Compliance Audits: Manufacturing, Pilot Plant, Laboratory
    • cGLP Audits
    • Good Clinical Practices
  • Preparation, Training & Inspection Readiness
    • cGMP Fundamentals (Annual Training Required by Regulations)
    • Quality System Regulation
    • Risk Management
    • Investigations, Deviations & CAPA & Root Cause Analysis
    • Validation & Technology Transfer
    • Purchasing Controls & Supplier Management
    • Document Management & Change Control
    • Audit Readiness
    • Quality Culture & Management Responsibility
    • Data Integrity & Good Documentation Practices (GDP) Centered on How the Data is Recorded, How to Correct an Error, and How to Document the Reason(s) for the Error

 

Quality Assurance

 

Regulatory Compliance Associates® Quality consulting services include assessments, strategy, implementations, staff augmentations, and identification of quality metrics. Our biologics consultants goal is to ensure continuous improvement, aligning with your business needs and goals. Our biotech consulting subject matter experts have 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.

 

  • Quality Management System Implementation
  • SOP Development
  • Document Control Systems
  • Change Control
  • Laboratory Operations & Control

 

Remediation Services

 

Regulatory Compliance Associates® is widely recognized within the life science industry and global regulatory agencies for its ability to help companies successfully resolve complex remediation services challenges. With a proven track record of success, Regulatory Compliance Associates® biologics consultants have significant experience with the development of responses to 483 Observations, Warning Letters, Untitled Letters and Consent Decrees.

 

  • Regulatory Action
    • 483 Response & Remediation
    • Warning Letter Response & Remediation
    • Consent Decree Response & Remediation
    • Oversight Services
  • Consulting
    • Comprehensive Audits
    • Remediation Plan Development & Implementation
  • Manufacturing Support
    • Re-validation of Existing Equipment & Processes
    • Remediation of System Deficiencies Related to, Manufacturing Process, Equipment, or Facility 
    • Facility Improvements (Aging Facilities) 

 

Strategic Consulting

 

Whether it’s a corporate needs analysis, corporate growth / transformation strategy or due diligence / acquisition, Regulatory Compliance Associates®  worldwide biotech consulting experience can help ensure a successful mix of top-notch advice and people so your engagement is on time, on budget, and you’re never embroiled in a costly mistake.

 

  • Portfolio Management
  • Mergers & Acquisitions / Due Diligence
  • Staffing Support

 

About RCA

 

fda guidanceRegulatory Compliance Associates® (RCA) provides biologics consulting & biotech 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.

 

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.