Product Quality and Safety

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.

To further expand its R&D innovation capabilities, we have officially launched various R&D projects through the PharmaEssentia Innovation Research Center (PRIC) in the United States. The projects are expected to combine AI artificial intelligence and machine learning platforms to identify research targets in the early stages of research and reduce development time and costs, accelerating the process of new drug development from research to market.

Creating Innovation—the PEGylation Technology Platform

Persuit of Animal Welfare of Preclinical Animal Experiments

In order to ensure animal welfare in preclinical animal experiments, our company selects and outsources relevant matters to domestic and foreign research institutions with GLP certification and follow the relevant regulatory requirements of the Institutional Animal Care and Use Committee (IACUC) for animal care and use in experiments. We have also conducted pre-clinical animal experiments in a humane manner.

A Rigorous Process of Human Clinical Trials

Multinational and Multicenter Clinical Trials Validate the International Competitiveness of Drugs

As of the end of 2022, our company has conducted more than 20 clinical trials worldwide using Ropeginterferon alfa-2b (P1101), benefiting patients from Taiwan, Europe, the United States, Japan, China, Hong Kong, and other regions. The clinical trials covered various indications including PV, ET, hepatitis B and C, as well as mild-to-moderate COVID-19 cases. And the total number of beneficiaries are accumulated to 879 people.

Cross-National Industry-Academia Collaboration—Establish Local Research and Clinical Trial Capabilities

Establishing a Stable and Reliable Supply Chain

We are committed to building a sound, stable, secure, and high-quality pharmaceutical production and multinational supply chain, and implementing a top-down interlocking operation process, including drug demand integration planning, raw material procurement and supply, production and manufacturing quality control, drug preservation and transnational delivery, and even drug users at the end. We must all do effective pharmacovigilance and recall mechanism to ensure the drug safety for patients in various countries.

Strengthening Sustainable Supplier Management with 3 Key Points

Adhering to the belief of mutual benefit and sustainable practices with suppliers and contractors , we create the long-term and sustainable value for the biopharmaceutical industry and patients.Our procurement and other related units have initiated the development of a Supplier Code of conduct and will roll out its promotion and signing in phases. In 2022, we promoted our PEC Corporate Sustainability Report to 177 suppliers, and plan to complete the signing by the suppliers in the third quarter of 2023.

• Supplier Code of Conduct

Supply Chain Management and Resilience Enhancement

To mitigate the impact of the COVID-19 pandemic on the supply chain, PharmaEssentia is continuously enhancing its supply chain management and resilience. This includes maintaining safe inventory levels, establishing alternative sources of materials, balancing cost and long-term stockpiling, and actively reducing the risk of stockouts that could result in delayed or unstable supply.

Suppliers/Contractors Management Strategy

We divide suppliers into four categories based on risk and procurement amount: strategic, critical, leverage, and general. Corresponding supplier management strategies are then formulated based on market characteristics and the attributes of each category's materials or services.
The US subsidiary categorizes suppliers into two categories, critical and non-critical, and conducts rigorous supplier risk assessments for critical-level suppliers, with a safe amount of stock as a main KPI to ensure the reliability of supplier delivery.

Management Process of Suppliers/Contractors

All vendors who should have signed the Quality Agreement have done so, with the proportion of local suppliers increasing to 95.7% in 2022, and the procurement amount from local suppliers increasing by 79.6%.

Screening and Evaluation of New Suppliers/Contractors

In the screening and evaluation of new suppliers/contractors by PharmaEssentia, there are three main indicators: quality system, technical capability, and service and support capability, covering aspects such as quality, cost, delivery, service, and management, and regularly conduct supplier performance assessments. In 2022, a total of 12 new suppliers/contractors were added, of which 10 were local suppliers, accounting for 83.3% of the total.

Annual Assessment of Suppliers/Contractors

Each year, we conduct supplier/contractor assessments in accordance with our Supplier Audit Procedures, which includes both internal assessments and on-site audits. In the case of high-risk suppliers, we will shorten the reassessment frequency and take corrective action. If there are significant deficiencies, we will immediately cease procurement activities. In 2022, all 175 suppliers who were due for internal assessment had their assessments completed. Due to the impact of the COVID-19 pandemic, on-site audits were unable to be completed for 18 suppliers. One local supplier and two foreign suppliers had completed on-site audits by the end of February 2023, and they passed all items in the audit checklist. The remaining suppliers have scheduled their audits for 2023. We will evaluate whether to use alternative solutions, such as the Rx-360 audit report, to replace on-site audits to ensure the completion of our supply chain management even during the pandemic.

Safe and Stable Cross-Border Logistics and Transportation

• Inventory transportation and sales operation system

  We have established transnational logistics and transportation operation procedures, inventory management, distribution procedures and tracking mechanism in compliance with PIC/S GDP requirements to strictly control that the transportation of each batch of goods can be delivered to the designated destination in a compliant, fast and safe manner, such as outsourcing filling plants, medical institutions or distributors, so as to maintain the drug needs and safety of patients. In response to the immediate risk of climate change-induced disasters in the United States, we maintain a safe level of stock of more than 4 months in the United States to ensure that patients there can obtain their medication in a timely manner.

• Warehouse Management

  

• Quality monitoring of shipping and transportation

  

Management approach on product quality and safety management

For the value chain of PharmaEssentia, from R&D, clinical trials, commercial mass production to patients’ use after listing, we use standardized operating procedures, comprehensive quality management, and complete product traceability systems. The concept of " Patients Safety and Quality First " is deeply rooted in each staff's daily operation and life , so as to effectively control drug risk management and protect the safety of patients’ use of drugs.

High-Standard Production Certification

International Standard Manufacturing Process

• Three Main Facilities of PharmaEssentia

  

• Drug Substance Manufacturing Production Process

  

• Aseptic Preparation Filling Process and Packaging

  

• Outsourcing Manufacturing Management

  Our current partners, a US and a German syringe filling contract factories, are both quality partners who have official GMP certification.

  

Process Quality and Safety

Our Taichung Manufacturing Plant has a Quality Manual, standard operating procedures for quality-related processes, and over 4,000 plans and reports that detail the organization's operational processes. Our quality assurance and quality control departments are responsible for managing and supervising the processes to maintain product quality, monitor environmental quality, and provide comprehensive personnel training to ensure product safety. We have also established an Emergency Response Management Standard for Plant Facilities to implement emergency response mechanisms. In the event of a natural disaster or equipment malfunction, we can ensure that equipment continues to operate normally and that all personnel perform process operations in a safe environment. In 2022, we conducted a total of 265 GMP/GDP-related training sessions, with a total training time of up to 135,000 hours.

Risk Management for Production Quality

The Taichung Plant implements risk management to control production processes, environmental control, material supply, and annual quality review. Strict adherence to the Quality Risk Management Procedure Manual, Equipment Risk Assessment Procedure Manual, Change Control Procedure Manual and other regulations reduces hazards to quality to a minimum. In 2022, a total of 11 global cross-departmental risk assessment task force meetings were held with 271 participants to jointly review risk issues within the facilities. Based on the Product Quality Review Procedures, regular internal and external audits are conducted to evaluate product quality and ensure stable production processes and use of materials. Product quality review meetings are held every quarter to address quality issues and implement corrective and preventive actions so as to ensure the stability and uniformity of production processes and product quality.

To fulfill strict requirements for drug quality, our company adheres to the highest standards for product services and labeling, which comply with international and domestic government regulations (such as the European Medicines Agency and the US Food and Drug Administration). After a product is launched, a series of safety tracking actions are initiated. Since 2021, PharmaEssentia has established a thorough global pharmacovigilance mechanism and continues to conduct safety monitoring and risk control for new drugs after they are launched.
In 2022, we did not violate any related regulations on product service labeling, and complied with pharmacovigilance and compliance requirements worldwide. We continue to optimize drug safety policies and internal standard operating procedures to help maintain the health and safety of patients.

Global Pharmacovigilance and Reporting Procedure

The personnel dedicated to pharmacovigilance at PharmaEssentia Headquarters and each subsidiary or region hold regular meetings every other week with commissioned research institutions to ensure the proper implementation of the drug safety information collected from around the world and the reporting system. In 2022, a total of 22 meetings were held to track and manage the pharmacovigilance mechanism. In March 2022, we submitted the third periodic safety update report (PSUR) for BESREMi® after its launch to Taiwan’s FDA, and there were no adverse drug events reported for the marketed drug.

• Global Pharmacovigilance Mechanism

  

• Pharmacovigilance Reporting Procedure

  

Pharmacovigilance Training

In accordance with pharmacovigilance regulations, PharmaEssentia’s commissions external research organizations to develop and implement pharmacovigilance management and regulatory reporting plans. The company also regularly conducts pharmacovigilance training for all employees and keeps records of all training. In 2022, 11 company-wide annual pharmacovigilance training sessions were held, and new employees received pharmacovigilance training within one month of their start date, with a completion rate of 100%.

Drug Safety Risk Management

In order to assess the safety risks of drugs after they are marketed, we have adopted a standard operating procedure for drug safety risk assessment developed by an outsourced research institution, and commissioned the development of a risk management plan. Depending on the requirements of each country's regulations on pharmacovigilance management, a Drug Risk Management Plan is developed to comply with the country's regulations. After the product is launched, clinical data is collected to assess whether long-term use of the drug by patients will result in chronic side effects, which serves as the basis for the drug risk-benefit assessment.
The results of the 2022 periodic safety report showed that no new safety information would affect the safety of BESREMi®. In 2023, PharmaEssentia will continue to collect safety information from all countries where BESREMi® is marketed to update the periodic safety report and evaluate the risk-benefit of BESREMi®.

Product Traceability Mechanism

PharmaEssentia has established a product traceability mechanism for its global supply chain, in which the batch number, lot number and factory activity records of each batch of drugs are kept to keep track of batch flow and ensure traceability. Currently, drug serialization has been implemented to regulate the packaging and serialization at processing plants to which we have outsourced work, achieving our purpose of having fully traceable individual product flows and usage records.
BESREMi® sold in the United States has also been fully serialized, and qualified US filling contractors follow relevant regulations of the FDA's Drug Supply Chain Security Act (DSCSA) to carry out drug packaging and serialization, ensuring drug quality and safety.

Drug Recall Mechanism