Drug Quality and Safety Management

Since its establishment, PharmaEssentia has been dedicated to the research and development of new drugs and drug improvement, with the goal of addressing unmet medical needs. We have independently developed thePEGylation technology platform to improve existing drugs and successfully developed a new generation of the PEGylated interferon alpha drug, Ropeg, which has the characteristic of being applicable to multiple indications. It can not only be used to treat indications related to blood diseases, but also tumors and viral infections, creating significant value for patients with solid results.

Innovative R&D Achievements and Focus for Future 5 Years

• The PharmaEssentia Innovation Research Center Corporation (PIRC) was established to combine AI and machine learning to further expand the capacity of R&D innovation, effectively identify research objectives in the early research stage, reduce development time and cost, and accelerate the process from R&D to market.
• Clinical trials: In 2023, 4 new plans including CML, HDV, PMF, and HCC will be added, bringing the total number of clinical trial plans currently underway. In 2023, there will be 453 new patients, bringing the total number of clinical trial patients to 1,332.
• In 2023, PharmaEssentia completed the application for the IND of the Phase 1 TFDA clinical trial in Taiwan for the treatment of solid tumors with anti-PD-1 antibody (P1801). and the multi-national and multi-center Phase III clinical trial of essential thrombocythemia (ET), which also received a government grant of NT$5,435K.

Commitment to Animal Welfare in Preclinical Animal Experiments

To ensure adherence to animal welfare, the company selects domestic and international contract research organizations (CROs) that are GLP-certified. These organizations are required to comply with the regulations of the Institutional Animal Care and Use Committee (IACUC) and adhere to the 3Rs principle (Refinement, Reduction, Replacement). This approach aligns with the directives of the Animal Welfare Committee to conduct experiments humanely.

Participant Safety in Clinical Trials

Clinical Trial Quality Maintenance and Risk Management

Product Safety and Quality Management

PharmaEssentia utilizes the highest standard operating procedures, quality management systems, and product traceability systems in its drug production processes. The company adheres to the PIC/S Good Distribution Practice (GDP) guidelines and has established over 4,000 documents related to quality safety management, standard operating procedures, and various plans and reports. These measures ensure compliance with operational processes, accuracy, and completeness of record-keeping, thereby guaranteeing the quality and safety of the medications. This comprehensive approach safeguards medication safety for patients worldwide.

International GMP Certification Track Record

International Standard Manufacturing Process

• Drug Substance Manufacturing Production Process

  

• Aseptic Preparation Filling Process and Packaging

  

Outsourced Manufacturing Management

In addition to filling and packaging operations at our sterile formulation filling plant in Taichung, our company also outsources filling and packaging to internationally certified contract manufacturing facilities in the United States, Germany, and Japan. This allows us to supply locally to patients while ensuring proximity and adherence to high-quality standards.

Quality Control and Risk Management in Manufacturing Processes

PharmaEssentia's Taichung facility places significant emphasis on product quality and safety management. The organizational operational process is meticulously outlined, with Quality Assurance and Quality Control departments jointly responsible for managing and supervising the processes. Every year, through continuous education and training, employees can integrate the spirit of quality management into their daily operations, including training and updating the knowledge of GMP-related laws and regulations for colleagues in the factory, as well as comprehensive personnel training to ensure product safety.
In 2023, a total of 925 GMP/GDP-related educational sessions were conducted, totaling 25,000 training hours. The 2023 monitoring trend report for the production environment (air conditioning), water systems, compressed air and biosafety operating cabinets shows that each system meets design requirements and regulatory specifications.

Secure and Stable International Logistics and Transportation

Our secure distribution process strictly adheres to Good Distribution Practice (GDP) for pharmaceuticals, ensuring proper management of pharmaceuticals throughout the transportation process.

Drug Safety Management and Patient Safety Management Policy

PharmaEssentia has established a comprehensive global pharmaceutical safety monitoring system, adhering to international drug safety monitoring regulations. The company continuously monitors the safety of newly marketed drugs post-launch. Additionally, PharmaEssentia persistently optimizes policies and internal standard operating procedures related to drug safety management to safeguard patient health and safety. In 2023, there were no incidents of non-compliance related to product service labeling or product recalls.

Global Pharmacovigilance and Reporting Procedure

Our company's 'Pharmacovigilance Team' is part of the Medical Research Department, working in coordination with relevant responsible units according to the 'Pharmacovigilance Policy,' 'Drug Safety Functions and Training Standard Operating Procedures,' and 'Post-Marketing Safety Data Collection Standard Operating Procedures.' PharmaEssentia also complies with the 'Serious Adverse Drug Reaction Reporting Regulations' and 'Drug Safety Monitoring Management Regulations,' entrusting professional CRO companies to conduct drug safety monitoring.

• Global Pharmacovigilance Mechanism

  

• Pharmacovigilance Reporting Procedure

  

Pharmacovigilance Reporting Education and Training

• According to our country's pharmacovigilance regulations, research institutions are contracted to develop and implement drug safety management and regulatory reporting plans. Regular pharmacovigilance education and training sessions for employees are conducted, and all training records are preserved. In 2023, six training sessions for new employees on pharmacovigilance were held, as well as one company-wide pharmacovigilance training session. All new employees underwent pharmacovigilance reporting training within one month of their start date, achieving a 100% completion rate.
• PharmaEssentia's headquarters and regional subsidiary leaders regularly meet with the contracted research institutions to ensure that the global drug safety information collection and reporting tasks are effectively carried out. In 2023, PharmaEssentia held 16 meetings to track and manage the pharmacovigilance mechanisms.

Pharmaceutical Risk Management Plan

PharmaEssentia implements the Drug Safety Risk Standard Operating Procedures formulated by contracted research organizations. Additionally, tailored 'Drug Risk Management Plans' are established according to the pharmaceutical safety monitoring regulations of each country to comply with local legal requirements.
According to regulatory requirements, after a drug is marketed, actual clinical data must be collected to assess whether long-term use by patients may result in chronic side effects. This serves as the basis for "Drug Risk-Benefit Assessment." The results of the 2023 Periodic Safety Report showed no new safety information that could affect the safety of BESREMi®. The company commits to continuously collecting safety data from the countries where it is marketed, to update periodic safety reports and assess the risk-benefit of BESREMi®.

Product Traceability Mechanism

PharmaEssentia has established a product traceability mechanism across its global supply chain and has implemented drug serialization to standardize the packaging and serialization operations of contract manufacturers, achieving the goal of fully tracing individual product flows and usage records. BESREMi® sold in the United States has also fully implemented drug serialization. This is carried out by a qualified U.S. injectable filling contract manufacturer following the FDA's Drug Supply Chain Security Act (DSCSA) standards, ensuring drug quality and safety.

Drug Recall Mechanism

We have clearly defined the product traceability system to improve the drug recall mechanism. Annual mock recall drills are conducted to ensure the accuracy and proficiency of recall actions. In 2023, there were no incidents of adverse drug recalls.

PharmaEssentia constructs effective supply chain management through three major aspects, working collaboratively with suppliers and contractors to embody and practice sustainability principles, creating long-term and stable value for the pharmaceutical industry and patients.

Sustainability Declaration: Building a Sustainable Supply Chain

• Group Supplier Code of Conduct:

  In 2023, we formulated the "Group Supplier Code of Conduct," which focuses on labor rights, workplace safety and health, environmental sustainability, and business ethics, aiming to set a positive example in the industry. This code was also signed by the chairman and published on our website. For the first time, we issued an ESG questionnaire to 20 suppliers; of these, 9 have published ESG reports, 7 are preparing ESG/CSR data collection, 3 do not yet have a corporate sustainability plan, and 1 lacks a clear understanding of ESG issues. PharmaEssentia hopes to continue conveying both formal and informal sustainability declarations to our supply partners to create a positive, long-term impact. In 2024, we plan to continue signing ESG agreements with suppliers, hoping to grow together, share benefits, and emphasize corporate sustainability responsibilities.

• Supplier/Contractor Management Process and Classification:

  PharmaEssentia's Quality Assurance department has established the "Supplier Management Standards" and "Supplier Management Procedures" as the approval process and operational standards for suppliers and outsourced service contractors. All vendors required to sign the quality agreement have done so 100%.

  Management by Supplier Category

  To improve supplier management efficiency, PharmaEssentia headquarters and Panco define suppliers who transact directly with PharmaEssentia as first-tier suppliers, based on risk and procurement amount. PharmaEssentia and Panco also define GMP suppliers that cannot be easily replaced as key suppliers. We manage suppliers according to these two dimensions. According to statistics, the total procurement amount from Taiwan's Tier 1 suppliers in the first stage of 2023 accounted for approximately 9.33% of the annual total procurement amount.

  

  For PharmaEssentia's subsidiary in the United States, supplier qualification follows the American procedure SOP-QA-003 Supplier Qualification (GMP) and SOP-QA-009 External Audit Results. In 2023, there were a total of 8 Tier 1 suppliers in the United States, all qualified for critical first tier GMP supplier criteria. Suppliers have passed quality inspections in both the United States and Taiwan.

  

• New Suppliers/Contractors:

  PharmaEssentia is committed to the environmental and social impacts of our supply chain. In addition to quality systems, technical capabilities, and service and support, in 2023, we introduced environmental and social standards into our supplier selection process and conducted regular supplier performance evaluations. In 2023, 87 new suppliers/contractors were added, of which 73 were local, representing 83.91% of the total.
  

  

Supplier Risk Management and Assessment

• Supplier Management Mechanism:

• Supplier/Contractor Risk Assessment and Due Diligence:

  We conduct an annual assessment of our trading partners, which includes evaluating: product or service quality, capability in handling exceptions and improvements, completeness and timeliness of documentation, on-time delivery rate, emergency order responsiveness, service satisfaction, price stability, and ESG performance score, totaling 8 criteria. In 2023, among the evaluated 419 suppliers, 4% were classified as high risk, 74% as low risk, and 22% as medium risk.

• Annual Evaluation of Suppliers/Contractors and Tracking:

  In 2023, internal review assessments were completed 100% for all 188 suppliers, and the on-site audit plan included a total of 20 domestic and international suppliers (including 2 remote audits of foreign suppliers), all of which were completed 100%. During the supplier on-site audit, it was found that one supplier violated labor standards, and the supplier was requested to make improvements. By the end of 2023, the tracking results showed that the supplier had been acquired and merged into another company.

Supply Chain Management and Resilience Enhancement

PharmaEssentia continues to enhance supply chain management and contingency capabilities, maintaining safety stock levels, establishing alternative material sources, and balancing cost considerations with long-term material reserves to rapidly respond and avoid disruptions to the supply chain from events such as the COVID-19 pandemic or other emergencies. Actively reducing the risk of material shortages that cannot be timely and stably supplied. The following are the internal supplier management tasks：

• Monitor potential factors affecting the supply chain (diseases, climate change, natural disasters, etc.).
• Strengthen supplier management adaptability and contingency capabilities.
• Deepen communication with suppliers, monitor the status of material transportation in real-time, and obtain complete information on transportation logistics.
• Update the time of arrival for supplier raw material purchases.
• Increase safety stock levels, understanding changes in demand from frontline medical institutions and patients.
• Pay attention to the situation in the countries where raw materials are produced, assess the risk of material shortages, and respond in advance.
• Establish alternative material sources to reduce the risk of material shortages.

Local Procurement Ratio for the Last 3 Years

In 2023, the proportion of purchases from local suppliers in Taiwan increased to 89%, while the expenditure on purchases from non-local suppliers was 11%. This increase is primarily attributed to the capital expenditures associated with the expansion of the new manufacturing facility in Zhubei. PharmaEssentia, rooted in Taiwan but with a global perspective, prioritizes the development of local partnerships and continues to assess opportunities to increase the proportion of local procurement.

• Supplier Code of Conduct