Application Of Good Pharmacovigilance Practice In Gelatin Production

Part 1 Pharmacovigilance Activities And Gelatin For Capsules

Pharmacovigilance activities refer to the monitoring, identification, evaluation and control of adverse drug reactions and other adverse reactions related to medication. Gelatin for bovine bone capsules is a product obtained by purifying collagen in bovine bone with incomplete acid hydrolysis, alkaline hydrolysis or enzymatic degradation, or a mixture of the above three different gelatin products.

Therefore, the vigilance activities of gelatin for bovine bone capsules refer to the activities of monitoring, identifying, evaluating and controlling the adverse reactions of gelatin for bovine bone capsules and other adverse reactions related to the use of gelatin for bovine bone capsules.

Part 2 Purpose And Significance Of Pharmacovigilance System Established By Gelatin Manufacturers For Capsules

Manufacturers of gelatin for bovine bone capsules should establish a pharmacovigilance system to monitor, identify, evaluate and control adverse reactions of gelatin for bovine bone capsules and other safety risks related to gelatin for bovine bone capsules through effective operation and maintenance of the system , Minimize the safety risk of gelatin used in bovine bone capsules, protect and promote public health.

Part 3 How To Carry Out Vigilance Management For Gelatin Manufacturers For Capsules

Manufacturers of gelatin for bovine bone capsules can carry out vigilance management in accordance with the plan (Plan), implementation (Do), inspection (Check) and disposal (Act), that is, the PDCA cycle.

3.1 Plan

Manufacturers of gelatin for bovine bone capsules should establish a vigilance system for gelatin for bovine bone capsules, establish the goals and implementation process of the vigilance management system for gelatin for bovine bone capsules, determine the resources needed to achieve the expected results, and identify and respond to the vigilance management system. risks and opportunities. Specifically, manufacturers of gelatin for bovine bone capsules should first formulate a vigilance plan and vigilance quality objectives, and set up a reasonable vigilance management organization; then, be equipped with the personnel, equipment and resources required for vigilance activities. Enterprises should formulate a management system that meets the requirements of laws and regulations, as well as comprehensive, clear, and operable operating procedures, establish an effective and smooth channel for collecting information on adverse reactions of gelatin for bovine bone capsules; carry out reporting and disposal activities that meet the requirements of laws and regulations, and Effective risk signal identification and assessment activities. For identified risks, enterprises should take effective control measures. In addition, it should also ensure that pharmacovigilance-related documents and records are available, consultable, and traceable.

3.2 Implementation

After formulating the plan, the enterprise should implement it from six aspects.

(1) Organization

Manufacturers of gelatin for beef bone capsules should set up a warning department as required, clarify the responsibilities of the warning department and other relevant departments, establish a good communication and coordination mechanism, and ensure the smooth development of warning activities. The legal representative or main person in charge of the gelatin manufacturer for beef bone capsules shall be fully responsible for the alert activities. The person in charge of the enterprise should appoint a person in charge of vigilance, allocate a sufficient number of personnel with appropriate qualifications, and provide the necessary resources to ensure the effective operation of the vigilance management system, implement the vigilance policy, and achieve the vigilance quality goals.

(2) Personnel

The personnel in the alert management system of the gelatin production enterprise for beef bone capsules should include: the person in charge of the enterprise, who is fully responsible for the alert activities; the person in charge of the alert, who is responsible for the alert management; The relevant personnel of the department are responsible for the specific security work according to the work requirements.

Then, the enterprise should also conduct pharmacovigilance training for these personnel, formulate an appropriate vigilance training plan according to job requirements and personnel capabilities, carry out training according to the plan and evaluate the training effect. The training content shall include the basic knowledge of vigilance and laws and regulations, post knowledge and skills, etc., among which the post knowledge and skills training shall be compatible with their vigilance responsibilities and requirements.

(3) Equipment

Enterprises should be equipped with the equipment and resources needed to meet the alert activities, and should manage and maintain the equipment and resources to ensure that they can continue to meet the use requirements.

(4) Monitoring And Reporting

Enterprises should actively, comprehensively and effectively collect the safety risks in the production and use of gelatin for beef bone capsules in accordance with the requirements of laws and regulations and enterprise requirements, analyze and evaluate the safety risks, and report them as required.

(5) Risk Management

①Risk Identification

The management data of gelatin safety incidents used in bovine bone capsules were analyzed, and the safety risks were found to be: mad cow disease, derived from sick cows and bovine bones (grains) carrying mad cow disease virus; heavy metals [3], derived from gelatin production Processing aids were introduced after heavy gold exceeded the standard; pathogenic bacteria came from the production environment and operators; metal shavings came from the wear and tear of production equipment.

②Risk Assessment

The identified security risks shall be evaluated according to the severity and possibility of the risks. Before carrying out risk assessment, the evaluation criteria for risk severity and risk occurrence probability should be determined first, and the risk coefficient and risk level should be obtained by combining the two.

According to the risk factor (RPN), risks can be divided into three categories: low risk, medium risk and high risk. Among them, RPN=1~4 is low risk; RPN=6~9 is medium risk; RPN=12~16 is high risk.

③Risk Control

Manufacturers of gelatin for beef bone capsules should take appropriate risk control measures based on the risk assessment results and comprehensively consider risk characteristics, substitutability, and socioeconomic factors for identified safety risks.

For mad cow disease: purchase bovine bones from qualified suppliers, purchase from risk-free countries and regions, and risk-controllable countries and regions, and require suppliers to provide animal product inspection and quarantine certificates[4,5]; during the production process, strict Control each parameter. During pickling, the concentration of hydrochloric acid is not less than 4.5% (pH <1.5), the pickling time is 124-144 h, and the pickling temperature is 15-18°C; during liming, the concentration of calcium hydroxide is 1- 3 Be°, the liming temperature is 18-20°C, and the liming time is not less than 45 days; during sterilization, the sterilization temperature is ≥141.0°C, and the sterilization flow rate is ≤1.05 m3/h.

For heavy metals: Purchasing processing aids from qualified suppliers, conduct acceptance testing when entering the factory and require suppliers to test and provide statements, and control through cleaning, ion exchange and other methods during the production process.

For pathogenic bacteria: strengthen the production process and personnel management to eliminate and reduce the chance of pathogenic bacteria contamination.

For metal shavings: do a good job in equipment maintenance and maintenance to reduce equipment wear; set up high-strength magnets to absorb metal shavings generated during the production process; use metal detectors to check and control.

④ Risk Communication

Manufacturers of gelatin for beef bone capsules should pass on the safety information of gelatin for beef bone capsules to customers and the public, and communicate the risks of gelatin for beef bone capsules. Manufacturers of gelatin for beef bone capsules should formulate warning communication management documents, determine different communication purposes, and adopt different risk communication methods and channels.

(6) Documents And Records

Manufacturers of gelatin for bovine bone capsules should formulate a complete vigilance system and procedure documents, and the documents of vigilance activities should be reviewed by the pharmacovigilance department. System and procedure documents shall be drafted, revised, reviewed, approved, distributed, replaced or revoked, copied, kept and destroyed in accordance with the document management operating procedures, and corresponding records shall be kept. For management documents and operational documents, the enterprise shall conduct regular review to ensure that the current documents are continuously appropriate and effective. Once it is found that relevant laws and regulations have changed, management documents and operational documents need to be revised in a timely manner.

In addition, the enterprise should also establish and maintain the master file of the alert system in accordance with the requirements of laws and regulations to describe the alert system and activities of gelatin used in bovine bone capsules. Its content should include: organizational structure, basic information of the person in charge of pharmacovigilance, full-time staffing, risk sources, information tools or systems, management systems and operating procedures, operation of the pharmacovigilance system, quality management and appendices.

Finally, enterprises should also standardize and record the process and results of pharmacovigilance activities, and properly manage and preserve the records and data generated by pharmacovigilance activities. Specific measures should be taken at each stage of keeping and processing pharmacovigilance records and data to ensure the security and confidentiality of records and data. Pharmacovigilance records and data shall be kept for at least ten years after the cancellation of the drug registration certificate, and the records and data shall be well protected during the preservation period.

3.3 Inspection

Manufacturers of gelatin for bovine bone capsules should carry out regular internal audits to evaluate the suitability, adequacy, and effectiveness of the pharmacovigilance system [2]. First, there should be an audit plan to specify the frequency of internal audits; second, there should be an audit plan to specify the purpose, scope and basis of the audit; third, there should be an audit checklist to regulate the content and methods of internal audits etc.; Fourth, there should be an audit report and its follow-up activities [7] to continuously improve the pharmacovigilance management system.

3.4 Improvements

Manufacturers of gelatin for beef bone capsules should investigate the causes of the problems found in the internal audit, take corresponding corrective and preventive measures, and track and evaluate the corrective and preventive measures, so as to continuously improve the vigilance management system for gelatin for capsules.

Part 4 Conclusion

After the establishment of a vigilance management system for gelatin manufacturers for beef bone capsules, through the effective operation and maintenance of the system, monitoring, identification, evaluation and control of adverse reactions to gelatin for beef bone capsules and other safety risks related to gelatin for beef bone capsules can be extremely effective. Minimize the safety risk of gelatin used in bovine bone capsules to protect and promote public health. At the same time, manufacturers of gelatin for beef bone capsules should implement dynamic management and continuous improvement in accordance with the PDCA cycle of the alert management system established by the company.