Key Operational Challenges Hindering the Successful Market Launch of Topical Transdermal Formulations

Medium Screening:

Previously, alcohols, acetonitrile, and tetrahydrofuran were commonly selected as receptor media for in vitro release testing (IVRT) studies. However, the latest guidelines explicitly specify the use of a biphasic system comprising water and alcohol, with strict control of the aqueous phase pH at 7, while also simulating the skin’s pH environment of 5–7.

Consistency of Experimental Methods:

In the early-stage method design for in vitro release testing (IVRT), the aqueous medium should be standardized to ensure consistency in both the manufacturing process and release profiles, prior to conducting in vitro permeation testing (IVPT) experiments, thereby reducing the complexity of the IVPT procedure.

Consider comprehensive factors:

Since manufacturers submit applications based on statistical data generated by SAS software, attention must be paid to data manipulation and the quality of statistical data. In addition to improvements in experimental design methods, the selection of transdermal diffusion apparatus and skin models is equally important.

Clinical Strategy Development:

Currently, the primary methods for evaluating bioequivalence of marketed transdermal products both domestically and internationally include PK-BE, PD-BE, and confirmatory clinical studies. In addition, adhesion testing and skin irritation testing are required.

Clinical Trial SOP:

The development of Standard Operating Procedures (SOPs) is critical to the quality and reliability of clinical trials. By standardizing procedures, clarifying responsibilities, ensuring necessary conditions, and guaranteeing quality, SOPs can effectively enhance the efficiency and quality of clinical trials, thereby ensuring reliable research outcomes. SOPs include the following content:

Subject Factors:Physiological factors of the subjects, including age, sex, lifestyle habits, and living environment, must be taken into consideration, and the integrity of the administration site must be assessed. Standard Operating Procedures (SOPs) should be established and tailored to different clinical trials to ensure the integrity of drug administration.

Medication Administration Completeness:Taking semi-solid formulations as an example, the subject’s posture affects both uniformity and adhesion. The uniformity of application, the area covered, and the consistency of application thickness all influence the transdermal permeation rate.

Environmental Factors:Season, humidity, temperature, and light exposure significantly influence blood drug concentrations. We strictly controlled environmental temperature and humidity, as well as subject conditions, to minimize bias in trial data.

Human Factors:Subject compliance and investigator proficiency significantly impact experimental outcomes. It is essential to minimize experimental bias and enhance the accuracy of clinical trials through repeated simulations and pilot tests, as well as comprehensive standard operating procedures (SOPs).

Temperature Control:

Hot-melt adhesive formulations have stringent temperature control requirements, necessitating the use of calculus and proportional control techniques to enhance temperature accuracy and stability during the heating process. Laboratory-scale production typically involves small volumes and limited material quantities, employing bulk heating methods; although this approach results in significant temperature drift, it facilitates experimental adjustments. In contrast, large-scale production benefits from external circulation heating systems to ensure consistent and sustained thermal stability.

Excipient Selection:

Currently, the industry typically opts for hot-melt adhesives with high softening points to enhance heat resistance and anti-aging properties. However, the softening point alone cannot directly predict the heat resistance of hot-melt adhesives; precise temperature control is the key to achieving optimal performance.

Flowability Compatibility of Mixing Equipment:

Considering the differences in flowability between chemical drugs and traditional Chinese medicine formulations, mixing equipment must exhibit excellent compatibility with varying flow characteristics. Furthermore, coating equipment for large-scale production should ideally be equipped with a measurement and control system to ensure coating uniformity and rapid response.

Homogeneity of Mixing:

In production and experimentation, the amount of gelatin must be added proportionally according to different dosage forms, and different stirring methods and impellers should be employed to achieve a uniform mixing state. Meanwhile, appropriate feeding techniques should be selected to prevent splashing of powders and liquids, thereby ensuring mixing homogeneity.

The training program featured hands-on sessions focused on two key areas: laboratory and production. Participants engaged in in-depth practical operation of R&D and production-related instruments and equipment, including semi-solid IVRT and IVPT testing, patch IVRT and IVPT testing, and IVPT skinIntegrity Testing, hands-on operation of large-scale production equipment for gel patches, hands-on operation of large-scale production equipment for hot-melt adhesive patches, etc.;

Invite experts with extensive practical experience and profound insights in the field of transdermal drug delivery systems, as well as leading manufacturers of advanced instruments and equipment used in R&D and production, to address the challenges and pain points in practical R&D and manufacturing processes. This includes refining method validation, defining critical quality attributes, and evaluating key quality aspects such as the selection of active ingredients, excipients, solvents, and processing techniques during development.

Assist the R&D team in project initiation, formulation development, and process design by fully considering potential issues during the R&D and production phases, as well as specific manufacturing processes. Help R&D and quality personnel improve and optimize equipment, rationally layout production lines to achieve efficient large-scale production, further reduce production costs, and accelerate the commercialization of the pipeline.

Topic 1: Clinical Development Strategies for Generic Topical Patch Products

Section 1: Basic Introduction to Topical Patches

Section 2: Regulatory Basis for the Clinical Development of Topical Patches

Section 3: Clinical Development Strategies for Topical Patches

Section 4: Key Considerations for PKBE of Topical Patches

Section 5: Key Considerations for Bioequivalence Studies with Clinical Endpoints for Topical Patches

Topic 2: Breakthrough New Technologies in Clinical Trials of Topical Transdermal Preparations—OFM Microdialysis

Section 1: Introduction to the Principles of OFM Microperfusion Technology

Section 2: One Application Case of OFM -Acyclovir CreamEvaluation of BE in Dermal Interstitial Fluid

Section 3: Characteristics and Development Prospects of OFM Microperfusion

Topic 3: IVPT Data Requirements and Data Processing & SAS Software Practical Demonstration

Section 1: Introduction to SAS Software

1.1 Introduction to SAS

1.2 Introduction to SAS Software and Component DEMO

Section 2: IVPT Data Requirements

2.1 Completeness Requirements

2.2 Accuracy Requirements

2.3 Repeatability Requirements

2.4 Normativity

Section 3: Statistical Analysis and Calculation of IVPT Data

3.1 IVPT Endpoints – AMT Calculation

3.2 IVPT Endpoints – Calculation of Jmax

3.3 Calculation of Drug Retention (ar) in the Skin (or Permeation Barrier)

3.4 Statistical Analysis Demonstration Using SAS Software

Topic 4: Discussion on CDE Guidelines for In Vitro Release Testing (IVRT) and In Vitro Permeation Testing (IVPT) of Transdermal Drug Delivery Systems

Section 1: Summary of Differences Between IVRT and IVPT in USP <1724>, FDA Guidance, and NMPA CDE Guidelines

1.1 Skin Model Requirements

1.2 Skin Processing and Preservation

1.3 Experimental Design

1.4 Experimental Conditions

Section 2: Causes of IVRT/IVPT Failure and Solutions

2.1 Causes of IVRT Failure and Solutions

(1) Formulation Factors

(2) Release medium factors

(3) Factors Related to Experimental Apparatus

2.2 Causes of IVPT Failure and Solutions

(1) Skin Barrier Factors

(2) Factors in Formulation-Skin Interactions

(3) Factors Related to Experimental Setup

Section 3: Analysis of Reasons for Deficiency Letters Regarding IVRT and IVPT in Submission Materials

3.1 Analysis of Reasons for Deficiency Letters Regarding IVRT/IVPT Submissions

(1) Reasons Related to Trial Design

(2) Causes Related to Trial Conditions

(3) Reasons Related to Data Recording and Processing

(4) Reasons Related to Method Validation

(5) Reasons Related to In Vitro-In Vivo Correlation

3.2 Case Analysis of IVPT Deficiency Letters

Topic 5: Key Points in the Development and Manufacturing of Transdermal Patches

Section 1: A Historical Review of Transdermal Drug Delivery

Section 2: Development History of Transdermal Patches

Section 3: Classification of Transdermal Patches

3.1 Acrylate Pressure-Sensitive Adhesives

3.2 Hydrogel Pressure-Sensitive Adhesives

3.3 Hot-Melt Pressure-Sensitive Adhesives

Section 4: Key Points in the Development of Transdermal Patches

Section 5: Advantages and Limitations of Transdermal Patches

Section 6: Transdermal Drug Delivery—Key Excipients in Transdermal Patches

6.1 Acrylate Pressure-Sensitive AdhesiveSynthesis

6.2 Hot-melt Pressure-sensitive Adhesive Excipients

6.3 Hydrogel Matrix Excipients

Section 7: Equipment Required for the Transition of Plasters and Patches from Laboratory to Production

7.1 Uniform Material Mixing Achieved by Variable-Cross-Section Vertical Kneading Mixer

7.2 Classification of Delivery Devices for Plasters and Patches

7.3 Transition of Plaster Patches from Laboratory-Scale to Production-Scale Coating Machines

7.4 A Three-Step Approach to Addressing Pain Points in the Production of Medicated Patches and Plasters

Section 8 Requirements for Rational Transdermal Patches

Section 9: What Bottleneck Issues Do Plaster Patches Face?

Topic 6: Hands-on Training

Part 1: IVRT and In Vitro Permeation Testing (IVPT) for Semi-Solids/Patches, and Skin Integrity Assessment in IVPT

1. Instrument Operation

2. Incubate the skin

3. IVRT Experimental Procedure

4. Skin Integrity Test

5. IVPT Experimental Procedures

6. Post-experiment skin integrity test and recovery rate test

7. Experimental Precautions (sample leakage, inspection of samples and membranes/skins for abnormalities before and after the experiment, presence of backflow, abnormal sampling volume, etc.)

Part 2: Demonstration of Large-Scale Production Equipment for Gel Patches

Part 3: Demonstration of Large-Scale Production Equipment for Hot-Melt Adhesive Patches

Zhou Yan,Master’s degree from Anhui University of Chinese Medicine. Currently serves as Deputy General Manager and Head of the Clinical Research Center at Anhui Wanbang Medical Technology Co., Ltd., overseeing the acquisition and execution of clinical trial service projects.

To date, has led and participated in more than 1,000 clinical studies, covering generic drugs, innovative drugs, and medical devices, with hands-on experience in over 100 clinical trials of topical transdermal formulations. Currently serves as a member of the First Committee of Clinical Trials Professional Committee of Anhui Pharmacological Society, a member of the Second Committee of Drug Clinical Trial Professional Committee of Anhui Pharmaceutical Association, and a member of the First Youth Committee on Innovative Technology Research for Drug Clinical Trials of Zhongguancun Jiutai Drug Clinical Trial Technology Innovation Alliance.

Tang Hongmin,Founder & General Manager of Beijing Hebang Xingye Scientific Instrument Co., Ltd.; Jointly-trained graduate student of Jiangxi University of Chinese Medicine and Tsinghua University, majoring in Pharmaceutical Analysis.

Published 15 papers in SCI-indexed and core journals; undertook more than ten national and industry-sponsored collaborative projects, including one project for the Chinese Pharmacopoeia standards and one for cosmetic industry standards; served as Associate Translation Editor for Transdermal Drug Delivery Systems: From Innovation to Production. Accumulated 12 years of work experience at world Fortune 500 analytical instrument companies such as Thermo Fisher Scientific and Agilent Technologies. Committee Member of the Pharmaceutical Analysis Professional Committee of the Chinese Association of Biotechnology of Medicine; proficient in various analytical instruments and methods used in the pharmaceutical industry. Co-founder of the China Transdermal Technology Alliance, with extensive experience in the field of transdermal formulations.

Feng Ruini,Jointly trained by Jiangxi University of Chinese Medicine and Beijing Jiangzhong Institute of Pharmaceutical Research.

With over a decade of experience in pharmaceutical analysis, possesses in-depth understanding and extensive project expertise in in vitro dissolution and release, in vitro permeation, in vivo pharmacokinetics, and bioanalytical testing.

Lin Weihua,Council Member of the China Ethnic Medicine Association; Council Member of the Transdermal Drug Delivery Professional Committee of the World Federation of Chinese Medicine Societies.

Has been engaged in the field of hot-melt adhesive coating since 1996; participated in the development of China’s first hydrogel coating machine in 2001, and has accumulated extensive experience from laboratory research to mass production of solvent-based, hot-melt, and gel-type transdermal drug delivery systems. Possesses unique insights into equipment selection and application for transdermal patch manufacturing.

Training Fees:

1. Individual fee: RMB 3,499 per person

2. Group Rate: RMB 2,200 per person for the third participant and beyond

3. Preferential Policies (Choose One):

(1) Alliance Members (individuals/entities that have paid to participate in alliance activities): RMB 500 discount

(2) Early Bird Price: RMB 3,199 per person (payment before November 30)

Registration Contact: Ms. Li 18600925630

Complete the registration form to secure your limited spot.

Teacher Li

Phone/WeChat: 1860092563