This internship report titled "Quality Control of Pharmaceutical Products at PT Meprofarm" is made to fulfill the requirement to complete the credited internship program. I am very grateful to have the opportunity to experience an internship at PT Meprofarm and to be able to meet fantastic people here. Special thanks to Glen Lucius Kartawiria, my PH19 friend, who had invited me to do an internship at PT Meprofarm.
Wanne Mardiwidyo, PT Meprofarm is an Indonesian pharmaceutical company based in Bandung that always prioritizes achieving quality in the production of products. In order to ensure the quality of pharmaceuticals from its raw materials to the finished products, QC is responsible for creating procedures and specifications to carry out the tests and evaluation, and make reports on the test results as evidence. PT Meprofarm is an Indonesian pharmaceutical company located in Bandung, established in 1973 by Ir.
MEPRO-1 is designed and built to produce products that meet the requirements of the current Cara Pembuatan Obat yang Baik (CPOB). The development of a new production facility called MEPRO-2 at the back of the MEPRO-1 building became an implementation of the company's goal to achieve greater success. In addition, MEPRO-2 is equipped with the "state of the art" facilities in the R&D division to better support the development of new products, accelerate the marketing of new products and also improve the quality of products.
The vision of PT Meprofarm is "To be a great healthcare company that continuously improves the marketing of quality healthcare products and services." The mission of PT Meprofarm is "Marketing of health products and services to improve the standard of human life".
Product of the Company
PROJECT DESCRIPTION
Internship Project
- Project Background
- Scope of the Project
- Objectives
- Problem Formulation and Proposed Solutions
All divisions are correlated to implement GMP in drug manufacturing. The QC Raw and Packaging Materials division is responsible for checking the quality of raw materials such as active pharmaceutical ingredients (APIs) and excipients, also the packaging materials for the products, to verify that they meet the specifications before they can be put into production. used. Various tests are performed in the QC microbiology laboratory: microbial limit test, pathogenic bacterial test, endotoxin test, sterility test, antibiotic potency test and preservative effectiveness test.
The pathogenic bacteria test is performed to determine the presence of pathogenic bacteria in raw materials or finished products to ensure the quality of the product. In this report, the implementation of GMP in the QC department of PT Meprofarm will be discussed and explained more from the works assigned to the author. The specifications written in the old SMS document were compared with the current pharmacopoeias and CoA of the specific material.
When all specifications were met, the revisions made to the document were recorded in the Revision History section. There were 3 main sections in the SMTM document: parameter, method and specification; Test result; Analyst's signature/date and name. Test methods listed and described in valid pharmacopoeias have been copied into the Parameter, Method and Specification section.
In addition, some test methods follow the methods used in the company, so they should be compared with the old SMTM document. In the test results section, a box was placed to determine its qualification, along with some information such as raw data in the appendix and calculations. After that, revisions made to the document were written in the Revision History section.
The SOP documents for devices and personnel access restriction used in the stability department should be periodically reviewed and updated if any changes have occurred. In the End Product Specifications section, the content has been copied from the established End Product Specifications document of the listed product. The result of the stability study itself was attached in various documents, and the data were used for conclusions and discussions in the Discussion, Conclusion and Follow-up section.
The raw observational data obtained from the monthly environmental monitoring of microbiological contamination observed at the sterile production site and also in the microbiological laboratory were arranged and processed to create a trend line graph for the designated months, which in this case was the data from January to June 2022. The environmental monitoring in the microbiology laboratory observed from January to June 2022 included machine temperature, room temperature, room humidity and room pressure variables.
FINDINGS
Result
Each product may have more than 1 protocol document, depending on the type of drug dose and batch produced. The purpose of each document depended on the purpose of testing, whether to evaluate the stability of a new product, determine the expiration date, evaluate the stability of a changed product ingredient, and/or evaluate the stability as a result of the change of the start date. material manufacturer. The Stability Study Report was created in parallel with the previously prepared Stability Study Protocol of Drugs.
The serial numbers of the product have been added in the Test Product and Schedule of Stability Study sections. Specifically in the Appendix of Stability Study section, the test dates for samples from each batch were entered following the data provided by the supervisor. In the Discussion, Conclusion and Follow-up section, the current obtained results were made in conclusion, discussion and follow-up such as "Product X was stored for 30 months at temperature 30oC ± 2oC / RH: 75% ± 5 % and for 6 months at temperature 40oC ± 2oC / RH: 75%.
The testing is still continued until the 60th month at temperature 30 oC ± 2 oC / RH. The template example cannot be shown here as it is confidential. Raw data processing and creating trend line graph for monthly environmental monitoring and microbial contamination test. Trend line graphs of monthly environmental monitoring of microbiological contamination in the sterile production site and in the microbiology laboratory were created for each month from January to June 2022.
The results of microbial contamination tests performed in the microbiology laboratory were also converted into trend graphs and still met the requirements. 2 reports have been made: "Trend Analysis of MEPRO-2 Sterile Environmental Observation from January to June 2022" and "Trend Analysis of Microbiological Laboratory Environmental Observation from January to June 2022".
Analysis and Discussion
The revision cannot be done directly by changing the content or some parts of the document, but a new SOP document must be created, given a new revision number, and the entire content must be rewritten. The revision process is strictly regulated to ensure the integrity of the SOP document is maintained. According to the ICH Tripartite Guideline (2003), stability tests are performed to obtain results of any changes over time in drug substance or product quality under the influence of various environmental factors such as temperature, humidity and light, and also to determine the retest period for drug substance or the shelf life and recommended storage condition for the drug product.
The Stability Study Protocol document serves as a guideline for performing stability testing of the specified product according to the objectives of the test, primarily to evaluate the stability of a new product and determine its expiration date, or to verify the stability of a product. evaluate if there are any changes in ingredients or material manufacturer. After the Stability Study Protocol was prepared, the Stability Study documents and data were provided, so that the Stability Study Report was also produced for each drug. The content of the report more or less corresponded to the protocol of each specified product, but the schedule of stability studies was made more detailed by adding the batch numbers of the product and the dates for sampling.
The stability supervisor submitted a document with raw data on the result of the stability study, and the data was analyzed and then formulated in the conclusion in the Discussion, Conclusion and Follow-up section of the report. All stability study report documents generated for 15 different drugs were found to still meet specifications and requirements as of their last testing schedule at that time. A microbiological laboratory in the pharmaceutical industry is authorized to participate in sterility testing; detection, isolation, counting and identification of microorganisms (bacteria, yeasts and molds) and testing of bacterial endotoxins in various materials (e.g. input materials, water), products, surfaces, clothing and the environment; and a test using microorganisms as part of a test system (WHO, 2011).
Environmental monitoring is one of the activities carried out by the QC Microbiology division where it focuses on. Not only the products require microbiological testing, the environment in the manufacturing area also requires microbiological monitoring to support the safe production of products according to the guidelines and to prevent the occurrence of the release of potentially contaminated products that are harmful to consumers (Gupta, 2014) ) . There are several known sampling methods to monitor the environmental microbes, which also include air and surface of the facilities, such as active air sampling; settling (exposure) plates; surface contact - replicate organism detection and counting (RODAC) plates, swabs or flexible films; and operators' glove prints.
All these methods are used by Meprofarm for their microbiological monitoring and testing of the environment. The data for monthly environmental monitoring was obtained from microbiological environmental testing in PT Meprofarm's sterile production site, specifically the environment of the machines used to fill and seal ampoules. Other raw data from the monthly monitoring of the microbiological laboratory environment from January to June 2022 were also made into trend line graphs.
CONCLUSION AND RECOMMENDATION
SELF REFLECTION
Stability testing of new drug substances and products V1A(R2). International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. Retrieved from https://www.who.int/docs/default-source/medicines/norms-and-standards/guidelines/quality-co ntrol/trs961-annex2-goodpractices-pharmaceutical-microbiology-laboratories.pdf.
