Related Experiment Video
Updated: Jun 14, 2025
07:25
In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
Published on: May 4, 2017
17.7K
A Risk-Based Assessment for Determining the Pharmacokinetic Comparability Requirements of Biologic-Device Combination
Mark Klitgaard Nøhr1, Shaik Rizwan Waheed2, Rasmus Juul Kildemoes3
1Regulatory Affairs, Chemistry, Manufacturing and Controls, Novo Nordisk A/S, Søborg, Denmark.
The AAPS Journal
|September 4, 2024
Summary
A new risk-based process helps assess biologic-device combination products for quality, safety, and efficacy. This method aids regulatory approval and manages manufacturing changes for parenteral medicines.
Area of Science:
- Pharmaceutical Science
- Biotechnology
- Regulatory Science
Background:
- Advancements in large molecule drug therapies and biologic-device combination products (e.g., prefilled syringes, autoinjectors) have transformed disease treatment and parenteral medicine administration.
- Ensuring product quality, safety, and efficacy is critical for regulatory approval of new combination products and for managing post-approval changes.
Purpose of the Study:
- To present a standardized, risk-based process for evaluating the impact of changes on biologic-device combination products.
- To provide a framework for determining appropriate regulatory actions related to chemistry, manufacturing, and control (CMC) changes.
Main Methods:
- A risk assessment methodology was developed, standardizing the evaluation of CMC risk factors and pharmacokinetic risk factors with weighted scoring.
- A two-dimensional risk grid was utilized to integrate CMC and pharmacokinetic risks, guiding regulatory recommendations.
- Three case studies (two clinical, one post-approval) were employed to illustrate the application and effectiveness of the risk assessment process.
Main Results:
- The proposed risk-based process provides a structured approach to assess the potential impact of CMC changes on combination product quality, safety, and efficacy.
- The methodology facilitates the determination of necessary regulatory actions, ensuring product integrity throughout its lifecycle.
- Case studies demonstrated the practical application of the risk assessment, highlighting its utility in decision-making for combination products.
Conclusions:
- The risk-based assessment framework is a valuable tool for sponsors navigating regulatory requirements for biologic-device combination products.
- This approach supports informed decision-making regarding CMC changes, ultimately contributing to patient safety and therapeutic efficacy.
- The standardized methodology enhances consistency and predictability in the regulatory review process for combination products.
Related Concept Videos
01:16Bioequivalence: Overview
949
Pharmaceutical equivalents, by definition, are drug products with the same active ingredient in the same quantities, encapsulated in identical dosage forms, and intended for the same administration routes. These pharmaceutical equivalents are deemed bioequivalent if the bioavailability of the active entity in the drug preparations is similar. Moreover, pharmaceutical equivalents demonstrating bioequivalence are also regarded as therapeutically equivalent. This means that when used as directed,...
949
01:28Biopharmaceutics and Pharmacokinetics: Overview
1.9K
Understanding drugs, drug products, and their performance in pharmaceutical science is pivotal. Drugs, whether simple molecules or complex compounds, are designed to interact with the body's biological systems to diagnose, treat, or prevent diseases. Drug products include various delivery systems such as tablets, capsules, injections, and inhalers. The performance of these drug products is gauged by their ability to deliver the active ingredient to the desired site of action at the...
1.9K
01:13Bioavailability: Overview
2.7K
Bioavailability refers to the proportion of an unaltered drug that, after administration, enters the systemic circulation and can be distributed to the desired action site. Factors such as gastrointestinal (GI) absorption and liver biotransformation influence the bioavailability of a drug when it is administered orally. When a drug is administered intravenously, it enters the systemic circulation directly; by definition, its bioavailability is assumed to be 100%. The bioavailability of an...
2.7K
01:26Pharmacokinetic Models: Comparison and Selection Criterion
50
Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
50
00:54Noncompartmental Analysis: Miscellaneous Pharmacokinetic Parameters
78
The noncompartmental approach is a widely used method in pharmacokinetics to assess drugs' behaviors in the body. It considers several factors, including clearance, bioavailability, and total volume of distribution.
One key aspect of the noncompartmental approach is determining a drug's total clearance. This can be done by dividing the drug dose by the area under the concentration-time curve from zero to infinity. The area under the concentration-time curve represents the drug's...
One key aspect of the noncompartmental approach is determining a drug's total clearance. This can be done by dividing the drug dose by the area under the concentration-time curve from zero to infinity. The area under the concentration-time curve represents the drug's...
78
01:25Routes of Drug Administration: Parenteral
1.9K
The administration of drugs via parenteral routes allows for direct drug introduction into the systemic circulation, resulting in high bioavailability because the medication bypasses the harsh conditions of the gastrointestinal tract and hepatic metabolism.
The intravenous route (IV) of drug administration can be further categorized into two types. The bolus injection administers the entire dose rapidly, while an intravenous infusion slowly delivers smaller doses steadily.
The IV route is often...
The intravenous route (IV) of drug administration can be further categorized into two types. The bolus injection administers the entire dose rapidly, while an intravenous infusion slowly delivers smaller doses steadily.
The IV route is often...
1.9K