PREFACE
First and foremost, I am very grateful to be able to finish my credited internship without any hindrance or drawbacks. Though in finishing this credited internship, it would not be possible without the kind support and guidance of many individuals. I would like to give my deepest gratitude to them.
It has been a great opportunity and privilege to work in PT Meprofarm for the past 2 months.
I want to thank Pak Hendri and Ibu Johanna for giving me the opportunity to take an internship in PT Meprofarm during my sixth semester break. I am very fortunate to have both Ibu Johanna Sutrisno and Kak Handi Purnama as my supervisor during this internship. With their help and guidance, I could learn on how working in a company feels like especially in the research and development team. I can openly discuss anything related to the internship work, gaining really insightful experiences. Also I want to thank Sir Ulung as my internal supervisor in i3L, in helping me write this internship report.
Special thanks to Kak Adzkiya Auliya, for allowing me to help with the project and teaching me everything related to laboratory work. Her patience in teaching and guidance when working in the lab really help me to grow and finally be able to do the work individually.
TABLE OF CONTENTS
Preface...ii
Acknowledgements... iii
Table of Contents...iv
List of Figures and Tables...v
List of Abbreviations...vi
Summary...vii
Chapter 1: Introduction... 1
Chapter 2: Project Description... 4
Chapter 3: Findings...7
Chapter 4: Conclusion and Recommendations... 13
Chapter 5: Self Reflection... 14
Appendices... 15
Reference... 19
LIST OF FIGURES AND TABLES
List of Figures:
Figure 1 (left).PT Meprofarm’s department division (left)... 2
Figure 1 (right).Research and Development department division (right)... 2
Figure 2.Overall workflow for drug development in PT Meprofarm R&D... 8
Figure 3.Example of Data Validation Interface According to Per BPOM no 17 tahun 2019...11
Figure 4. Drop Down List for Choosing Excipient Name... 11
List of Tables: Table 1.Example of the sorted data according to its capacity and its scales... 9
Table 2.Example of Excipients Database from Per BPOM no 17 tahun 2019... 10
LIST OF ABBREVIATIONS
BE : Bioequivalent
BCS : Biopharmaceutics Classification System BusDev : Business Development
CPOB : Cara Pembuatan Obat yang Baik CQA : Critical Quality Attributes
ISO : International Organisation for Standardisation ITB : Institut Teknologi Bandung
NPD : New Product Development
Per BPOM : Peraturan Badan Pengawas Obat dan Makanan QbD : Quality by Design
QTPP : Quality Target Product Profile R&D : Research and Development SVP : Small Volume Parenteral USP : United States Pharmacopoeia
SUMMARY
PT Meprofarm is a pharmaceutical company founded in 1973 by Bapak Ir. Wanne Mardiwidyo. In the time of the internship, there are 2 main buildings, MEPRO-1 and MEPRO-2.
Research and development department falls under the Manufacturing department, which is one of four main departments in PT Meprofarm. Research and development team focuses on drug development, one of the divisions is the new product development (NPD). NPD focuses on developing new formulations for drugs and generic drug development. In this internship, there are 3 main projects, the first one is albendazole formulation of both chewable tablets and liquid suspension. For both formulations, QbD documentation is made first, then formulation and evaluation, and finally scale up for stability. The second project focuses on data validation on the newest regulation for excipients which is PerBPOM no 17 tahun 2019. The main idea is to ease the calculation work and make formulation time more efficient. This can also help the formulator to adjust the excipient more effectively. The last project is equipment data documentation which is done for the scale up process.
Keywords: Albendazole formulation, PT Meprofarm, Equipment data documentation for scaling up, Data validation according to PerBPOM no 17 tahun 2019
CHAPTER 1: INTRODUCTION
1.1. Brief History of Company
PT Meprofarm, is one of the largest pharmaceutical industries in Indonesia founded in 1973. At that time, the founder, Bapak Ir. Wanne Mardiwidyo produced generic drugs by tolling to ITB, Bandung and directly selling them to the customers. The first Mepro facility was named MEPRO-1, which is located in Jl. Soekarno Hatta 789, Bandung. It was built in 1993-1995, and started its operation producing non-sterile drugs (solids and liquids) and cephalosporin sterile.
Now MEPRO-1 produces non-sterile solids for both non-beta and beta lactam drugs. From 1996 to 1998 Meprofarm has received CPOB certificate for its tablet, capsule, syrup, dry syrup, cream, and cephalosporin dosage forms (sterile forms, tablet, and dry syrup). In 2006, Meprofarm started expansion to build a second facility named MEPRO-2 which specialises in sterile production including injection fluid or SVP, liquid syrup, dry syrup, ovula, and cream (semisolid).
MEPRO-2 received CPOB certification and fully operated in 2011. In 2008 Meprofarm received ISO 9001 and ISO 14001 certification.
PT Meprofarm has a vision that helps build the company to how it is today and creates improvement in the future, “To become a major & innovative Healthcare Company, focusing on
‘continuous improvement’ in providing high quality products and services' '. To support this vision, Meprofarm has a mission to become a Healthcare Company, they provide healthcare products & services in improving human life standards. With this vision and mission, Meprofarm always puts the best service of drug production, customer healthcare and services first. PT Meprofarm’s slogan “Your Wellness is Our Concern”, reflects their absolute and uncompromisable policy to put quality first. Which is executed through the production of high quality drugs that are in accordance with today’s standard. PT Meprofarm also has an environmental policy, which prioritises work processes that have minimal impact to the environment through recycling waste and reducing the use of hazardous materials and energy use.
As a company, all of PT Meprofarm’s employees hold the company values called MEPRO values. The values stand for: Mature and responsible, Efficient in any action, Passionate, honest and communicative, Robust, and Optimistic to achieve excellent results. All of the employees have a commitment to consistently do “continuous improvement” in every aspect to produce quality products.
1.2. Company’s Department Division
The complete department graph can be seen inFigure 1 (left).
Figure 1.PT Meprofarm’s department division (left), Research and Development department division (right)
In general, the highest position in the company is held by the President Commissioner, followed by the President Director. The President Director is in charge of leading 4 departments
(position) and 6 Independent managers: Vice President Sales and Marketing, Vice President Busdev, Vice President Manufacturing, and Vice President Finance and Operational. As of now, the President Commissioner and President Director are still held by the family of the founder.
Currently the President Commissioner position is held by Magdalena Wanne Mardiwidyo, Wanne Mardiwidyo’s wife, while the President Director position is held by Bapak Erik Darius Mardiwidyo, Wanne Mardiwidyo’s son.
1.3. Research and Development Department - New Product Development
Meprofarm’s R&D department is under the GM Plant Operations department (Figure 1.
(right)). There are 4 main divisions in R&D department, the first one is Method Analysis division which focuses on developing methods for product analysis, the second division is Comparative Dissolution Test, BE and SAMPLE, this department focuses on product evaluation that requires BE and Comparative Dissolution Test according to BPOM, the third department is the new product division, this department focuses on developing new products either new drug formulation or developing generic drug formulations, and lastly Existing Product and Transfer Formulation division that focuses on improving existing product from external source or internal source such as the production site. R&D NPD’s workflow begins with BusDev, BusDev collects data from market analysis, doctors, direct order from owner, drug sales etc. From here BusDev analyses if there is a drug that has high sales in the market that Meprofarm have not developed or made. Then R&D received a request to develop drugs with some of the parameters such as dose, taste, colour, and dosage form already picked by BusDev.
When a new product that BusDev requested was received by NPD, the first thing NPD does is pre-formulation and formula development. At the same time the Method of Analysis Department develops the methods to analyse the drug in accordance with the compendium.
After achieving the optimum formula, stability testing was done by the stability division under the Existing Product and Transfer Formulation (Figure 1. (right)). And finally the data and results (batch record, method of analysis, and finished product specs) were transferred to the Production department and QC Department. During this time, scale up from lab scale to pilot scale were done (10% of commercial batch) and optimization processes to match production process, including pilot stability test with minimum 6 months of drug data stability. After this the documentation for registration was made for commercialising.
CHAPTER 2: PROJECT DESCRIPTION
2.1. Albendazole QbD and Formula Adjustments 2.1.1. Project Background
Albendazole is an antihelminthic drug that has a broad spectrum of antinematodal, anticestodal and some antiprotozoal activity. Single dose of albendazole (400 mg, children >6 years old) is usually used to treat ascariasis, hookworm, trichostrongylosis, and could be used for enterobiasis and trichuriasis. Thus this broad anthelmintic activity, albendazole is commonly used to treat helminthiasis (Ryan, 2018). Few of albendazole’s physical properties are: low aqueous solubility, creating a problem with its formulation development and drug bioavailability.
Low aqueous solubility leads to low absorption rate when the drugs are taken orally. Thus one of the solutions to overcome this problem is by making a liquid dosage form (suspension). Though one problem in suspension/liquid dosage form is that the drug may precipitate in the stomach, mixed with stomach contents, or blood and needs to be reabsorbed by the body. On the other hand, albendazole tablets tend to have a low dissolution rate, thus some tablets are made to be chewable (Kimaro, 2019).
Currently Indonesia's helminthiasis prevalence is still high. The infection itself is not deadly, but long term effects can cause huge problems. Helminth infections affect children's nutritional status slowly and usually asymptomatic. A study in Indonesia shows the prevalence of helminthiasis in Indonesia is around 45-65% and it can reach 80% in poor hygiene areas. These infections are mainly asciaris, hookworm and trichuris (Trasia, 2021).
2.1.2. Scope of the Project
The chosen dosage form for this project is chewable tablet and suspension. As stated before, chewable tablet formulation was chosen to help with the drug’s dissolution and absorption rate. The suspension was made mainly for paediatric administration. This project starts from albendazole preformulation integrating with QbD that identifies and defines QTPP then CQA, and lastly formulation and tableting.
2.1.3. Objective
● To formulate albendazole chewable tablet and suspension that follows the compendium criteria (Farmakope Indonesia) and reproducible for large scale production
2.2. Equipment Data Documentation 2.2.1. Project Background
One of the challenges in the pharmaceutical industry is the process of scaling up.
Maintaining the quality of the materials or the product from laboratory scale to a pilot scale or to a large production scale still poses a challenge. This is due to lots of variables in the process of making, such as mixing, milling, compression, coating, etc. with each of these processes having its own variable, dimension, and parameters. Some methods have been developed to provide solutions to help with the scale up process. The first method is based on an engineering-based model that uses dimensionless numbers and relies on how similar the process is between the scale ups. The second method is through analytical methods by using technology to maintain the chosen quality attributes. The last method is using a physics based model, this method focuses on process simulation and prediction to maintain the drug’s quality attributes (Jang, 2020).
2.2.2. Scope of the Project
This project includes documenting each equipment that is used in PT Meprofarm including solid (beta and non-beta lactam facility), liquid and semisolid dosage form. The equipment for sterile production was not documented since only trained personnel are allowed inside. After documentation the data were sorted in an Excel file to make a database.
2.2.3. Objective
● To document both properties of the equipment and take pictures for reference
● To make a database of all of the equipment with each operational use for future reference
2.3. Data Validation According to Per BPOM no 17 tahun 2019 2.3.1. Project Background
Some of the excipients that were used in making drugs were controlled or there is a limit as to how much of that excipient is used. These regulations were released in 2019 in the Per BPOM no 17, “Persyaratan Mutu Suplemen Kesehatan”. There are 5 categories of excipients that were regulated: colourants (natural and synthetic), sweetener (natural and synthetic), preservatives, antioxidants, and miscellaneous (anti caking agent, emulgent, coating agent, stabiliser, solvent, etc.). Data validation is where a set of data is validated according to its actual function or fit for its purpose. These validation were done through testing against expectations or a data set (van der Loo, 2020). Data validation mechanisms were needed to quickly check if any of the excipients are within acceptable range or not.
2.3.2. Scope of the Project
From this regulation, a dataset or database were made with a calculator algorithm to make it easy to check if the excipients in a formulation follows the regulation or not. The data set includes all of the excipients included in the regulation, automatic calculation for the excipients concentration, etc.
2.3.3. Objective
● To make a data set/database to validate drug formulations according to Per BPOM no 17 tahun 2019
2.4. Miscellaneous Project 2.4.1. Project Background
Due to the compact schedule in the R&D department, not all projects were done at once, rather interchangeably. Thus in between project2.1,2.2, and2.3, other projects were given as well. The task was to be a general help with other ongoing projects under the NPD division.
2.4.2. Objective
● To gain experience on how the R&D department works and learn the general lab workflow
CHAPTER 3: FINDINGS
3.1. Albendazole Formula Adjustments and Drug Evaluation
Before making the drug, following the process described on 2.1.2, both albendazole chewable tablet and suspension’s QbD were made. The QbD starts from the analysis of comparator products, QTPP, CQA and information about the API (physical appearance, chemical and biological nature, toxicity, assays, and information about the drug preparation).
After finishing the formulation phase, the obtained drug both chewable tablets and suspension were evaluated to check if its parameters are in accordance with the compendium/QbD.
For chewable tablets, the evaluation includes: disintegration time, dissolution time and concentration (both for dissolution and tablet concentration), hardness, and friability. While for suspension, the evaluation includes: pH, organoleptic, precipitation test, and concentration for both albendazole and preservatives. The compendium used to make the drug’s QbD was Farmakope Indonesia Edisi VI and the USP. For albendazole chewable tablets the parameter was: more than 80% dissolved in 30 minutes for dissolution time and albendazole’s tablet concentration is no less than 90.0% and no more than 110.0%. For albendazole suspension, the albendazole concentration is the same (90.0% to 110.0%) with pH between 4.5 to 5.5. The rest of the parameters were determined internally. All of the drug’s evaluation results were in accordance with the parameters. The overall workflow can be seen inFigure 2.
The chewable tablet formulation contains: Albendazole (API), disintegrant, diluent, tablet binder, dissolution enhancer, binding agents, sweeteners, essential oils, lubricants, glidants, and flavourings. The method for making the tablet is through wet granulation, to improve its flowability and tablet compaction (Pandey and Badawy, 2019). The suspension formulation contains:
Albendazole (API), water, suspending agent, thickening agent, stabilisers, anti caking agent, sweeteners, buffer, preservatives, and essence. The formulation was adjusted to prevent any sedimentation in the bottle and retain pH for stability, and mask the bitter taste.
During the time of the internship, the albendazole formulation has undergone multiple changes. Two of the most persistent problems in making albendazole chewable tablets is low flowability and low dissolution rate. Albendazole is known to have poor flowability, its bulk density is around 0.2 g/ml, while the dissolution rate is low as albendazole is classified as a BCS class 2 drug on the biopharmaceutics classification system (Koradia and Parikh, 2012; Cavalcanti, et al., 2012). To overcome this problem, addition of extra glidant and lubricant were given until the powder flowed nicely (Awad, Trenfield, & Basit, 2021). The amount of both glidant and lubricant were determined through extreme tests in which few formulations were given a high amount of the lubricant and/or
made according to the previous results. For low dissolution rate, addition of extra disintegrant and addition of both dissolution enhancer and super disintegrant helps increase the dissolution rate (Rane, et al., 2012). While for albendazole suspension (biphasic liquid dosage form) was chosen rather than monophasic liquid dosage form due to the low water solubility. The main excipient in the suspension is sweetener, which is done to mask the bitter taste of the albendazole (Cañete, et al., 2012). Unfortunately, the data used in this project are considered confidential thus it can not be displayed.
Figure 2.Overall workflow for drug development in PT Meprofarm R&D
3.2. Equipment Data Documentation for Scale Up Process
Currently here in PT Meprofarm, the scale up process for new products was based on existing data on previous products. To start the scale up process from lab scale, previous product procedures, operator direct reports when a problem is countered, and batch records with similar properties were taken. From these existing data, appropriate equipment and parameters were chosen. This process took time, and after making the procedure, multiple trial and error are needed to check if the procedure is complete to produce drugs according to its QbD. Thus to change this process to a defined scale up process, data collection and validation is needed. The first process is data validation, which is done to check if the equipment can run as intended and to check at which parameters the equipment can do with high efficiency.
Data collection and validation was done through interviews of the operators in production, taking photos, measurement, parameters of the equipment and looking through the equipment’s manual book. The interview was done to check the equipment’s parameters since most of the equipment can run efficiently with minimum of 0.2 and maximum of 0.6 fill ratio (Dhakal, et al., 2017). Other than fill parameters, other parameters were also recorded according to the equipment’s function. Such as the oven, its maximum and minimum temperature were recorded and its operation temperature, coating machine, its coating solution holding tank, nozzle temperature and coating bed temperature were recorded. Then the data was stored in an Excel file to make a database as stated before. From this database, sorting algorithms were made to separate each equipment according to
its function. These functions such as mixing, milling, tablet press, sieving, etc., then a second algorithm was made to choose which equipment can be used for the chosen formulation. This second algorithm can also be used for the scale up process, as it can display which equipment is fitted with certain conditions the drug formula requires.
Correlating with the scale up process, the one that PT Meprofarm has been using is called extensive experimentation, which relies on a rule of thumb made from experiences, intuition, and past data as described before. A better and more appropriate approach is by using models. Models are a representation of a system or an equipment that has been simplified and removed from its complex properties so that it can be easily understood. These models can be used to predict how large/production scale equipment or system works while referencing the small lab scale experimentation. Through this method, the cost of trial and error and fixing the gaps between lab scale, pilot scale and production scale can be cut and more time efficient (Strong, 2009). Though currently in PT Meprofarm, dimensionless numbers are still not possible to do. Thus a new method was chosen. This method is based on the production batch process which states that the minimum amount of lab scale product is 1000 to 100 times less than the production batch. Then for the pilot batch, the product must be 10% or 10 times less than the production batch. This method was done to prevent any factor multiplication to be more than 10. From here the collected data was sorted and assigned according to its capacity, an example can be seen inTable 1.
Table 1.Example of the sorted data according to its capacity and its scales
Lab Scale (R&D) Capacity Pilot Scale Capacity Production Scale Capacity Triplicity mixer
(Manufacturer A)
2-9 Kg Drum Mixer (Manufacturer B)
30-90 Kg Triplicity Mixer (Manufacturer A
60-300 Kg
Double cone mixer (Manufacturer C)
1-4 Kg Triplicity Mixer (Manufacturer A)
2-9 Kg Triplicity Mixer (Manufacturer A)
60-300 Kg
… … … …
From the example table, we can see that the first combination (shown by the first row) has a different equipment in the process of its scale up: Drum mixer during the pilot scale. If a dimensionless number was to be applied here, it would not be possible due to lots of differences in the equipment, starting from its dimension, mixing method, mixing type (triplicity are hollow inside while a drum mixer has a paddle), etc. It may be possible to use some of the dimensionless numbers but it will take lots of trials to check the product results properties. The second combination however, has a very similar type of equipment, a triplicity mixer is basically a double cone mixer though the
in this case, but due to differences in its shape and manufacturer some trial and error still needs to be done, though this way will be more efficient in both time and cost. Similarly with the previous project, the data collected is confidential thus it cannot be displayed.
3.3. Data Validation According to Per BPOM no 17 tahun 2019
The whole data validation was done in an Excel file, where the main objective was to make a database of the excipients in the regulation. From this database a calculator or algorithm were made to automatically calculate any excipients that are written in a formula. The recorded data of each excipient was the INS/CAS number, name and its synonym, type of excipient, and the maximum concentration allowed (an example can be seen in Table 2.). Another advantage of having this algorithm was to ease the calculation and increase flexibility for excipient adjustment, creating a more efficient formulation time.
Table 2.Example of Excipients Database from Per BPOM no 17 tahun 2019
INS/CAS Name Synonym Type Max Concentration
150c Caramel III - Ammonia process
Ammonia caramel
Natural colourants
20000 ppm
950 Acesulfame
Potassium
Acesulfame K Synthetic sweetener
2000 ppm
… … … … …
The interface for the calculator can be seen inFigure 3.to keep the Excel formula, a lock cell feature was added to prevent accidental deletion. There are 3 parts to this calculator, the first one is the amount of the product, which is put in cell B1 in milligrams. The second part is putting the formulation which can be chosen throughout column A2 to A13. The compound can be chosen from a drop down list (shown inFigure 4.), then next to the compound, its individual amount can be typed (column B2 to B13). If the compound can not be found in the drop down list, a way to check the compound name from INS/CAS number was made which is from cell A15 to C17. Finding the INS/CAS number (cell B15), the name of the compound was automatically shown in cell B16 and B17. The last part is combination calculation for synthetic sweetener, synthetic colourants, preservatives and antioxidants. In the regulation, if there are more than one synthetic sweetener, there is a separate calculation that calculates the ratio of both excipients in the product, which the maximum ratio is 1, this is the same for synthetic colourants, preservatives and antioxidants. If there’s an excipient that exceed more than the maximum concentration stated in the regulation, a warning shows up stating
“Bahan melewati batas konsentrasi”, and for combination of excipients if the ratio is more than 1, a
Figure 3.Example of Data Validation Interface According to Per BPOM no 17 tahun 2019
Figure 4. Drop Down List for Choosing Excipient Name
3.4. Miscellaneous Project
Few of the given projects were already ongoing, and some of them are new. These projects include multivitamin tablet granules stability testing, folic acid drops stability literature review, sensory for vitamin D3 drops, and longenzes extract tablet formulation. The multivitamin tablet granules and folic acid drops stability testing was given as a task to learn about drug stability and incompatibility with its excipients. While doing formulation for multivitamin tablets, it can be observed that the powders changed colours, indicating interactions or instability between API with its excipients or API with API. To investigate these interactions, an analysis using factorial order
randomised block design method was done. A randomised block design is a method to assign the treatments to a unit or experimental unit, which is done to reduce any error. A factorial experiment is a method to divide the units into factorial structures to determine both individual factors and between-factor interactions (Freund, & Wilson, 2003). Folic acid stability literature review was done to check if there are any excipients that can stabilise folic acid. While in liquid form, vitamins (folic acid) degrades really quickly causing false administration and may cause vitamin deficiency in the patient. A study found that folic acids are stable at around neutral pH, ranging from 5-8 and can be stabilised using a few solvents, mainly sweeteners/co-solvents such as glycerine, propylene glycol, and sorbitol solution for a long period of time (Vignesh, et al., 2012).
CHAPTER 4: CONCLUSION AND RECOMMENDATION
Research and development in PT Meprofarm works mainly on the development of drug products, including its method of analysis and stability. At the time of the internship, the main work was under the NPD division, which focuses on new products that have not been commercialised by PT Meprofarm. Other than drug development, two projects were given, scale up process and data validation. Research and development-NPD workload includes the pre-formulation, formulation, and lastly stability. Albendazole chewable tablet and suspension was formulated and evaluated to meet the QbD. A noticeable problem for albendazole chewable tablets was its low dissolution rate and low flowability, which can be adjusted using super disintegrant and adding more glidant and lubricant. As for albendazole suspension, the problem occurred because of its bitter taste which can be masked using sweetener. Both drugs were evaluated through standard procedure and following the compendium such as dissolution time, assay, pH, etc.
The scale up project's main idea was to check and collect data of all the equipment available in PT Meprofarm and process the data to see which can be used for scaling up. Production batch processes were used to sort the data according to its capacity and see which is capable of being used in future projects in hope of implementing a scale up process. Data validation project is a method project or an algorithm to help the formulator to check if the drug’s excipients are below the regulated concentration. The regulation used was PerBPOM no 17 tahun 2019, which states 5 types of excipients. The algorithm helps the formulator to automatically calculate the concentration of excipients, ratio of combined excipients, and identify if it falls under the regulation.
In the hope of using a proper scale up process in PT Meprofarm, regular data validation is still needed. All the data must be in accordance with the manual/manufacturer’s guide, machine work capacity in the field and how the operator works on the machine. With these data, hopefully more standardised data can be obtained from both dimensionless analysis and production batch testing, which will be the base of the scale up process. All of the data from this internship can be considered useful in preparation of a scaling up process in the future.
CHAPTER 5: SELF REFLECTION
By doing this internship in PT Meprofarm I have learned a lot of things. Having learned a lot of things in i3L, mainly the theory is very important. I am very fortunate to be able to use the knowledge I learned and see how some of the ideas or theories work in real settings, at least in the industrial/company environment. Working in a cramped schedule in R&D department has teached me about time management and working efficiently. Since no work can be taken home, all needs to be done during the time in the office/lab. Certain tasks need to be done on that day, and I need to picture how long it normally is, and determine when I should start the task. Or changing tasks to avoid burnout and take it one step at a time.
I learned that QbD helps drug development in the long run, by having both QTPP and CQA to know both the drug’s properties and its risk management. There are some similarities in drug’s preformulation such as knowing the drugs properties, compatibilities, choosing excipients etc.
Though QbD has a stand on its own, CQA helps with preventing any failure in the development, such as unexpected interactions, while QTPP gives understanding on the drug’s parameters which helps with fine tuning during development and many other aspects of development.
Working on data validation and the scale up process has taught me a lot of things.
Regulations will keep updating and changing thus it is important to keep updating on which is the newest. This can slow down drug development when the regulation changes mid way in the development process. Thus a method of validation is very important to make ease of the formulator to adjust the excipients. Working on the scale up process, taught me a lot about social skills. Working in the field is not always straight according to the paper. Effective communication goes a long way during operator interview, sometimes the operator doesn’t understand the questions but a different way of speaking can change the answers.
I have learned that not everything is exact or has a perfect number. Everything will grow and change, which is why we need to be more dynamic. Though even with these changes, a guide or reference is still needed. This makes consistency a big problem, thus a guidance which works outside the system is needed. By following this guidance or reference, with ever changing process, work, materials, etc. won’t affect the result thus keeping things consistent.
APPENDICES
Appendix 1.Documentation with Supervisor 1, Ibu Johanna, GM Plant Operations/R&D Manager
Appendix 2.Documentation with Supervisor 2, Kak Handi, R&D Pharmacist NPD
Appendix 3.Documentation with other i3L students
Appendix 4.Documentation alongside other PKPA students
Appendix 5.Proof of Absence for the 2 months in PT Meprofarm Note:
● First two column is for July’s absence (left: check in, right: check out)
● Column 3 and 4 was for August’s absence (left: check in, right: check out)
● August 27 - 31 sick leave
Day Time
Monday - Thursday 08:30 am - 04:30 pm
Friday 08:30 am - 03:30 pm
Appendix 6.Weekly schedule in PT Meprofarm Note:
● To avoid rush hour in PT Meprofarm, the schedule was moved by 30 minutes late from 08:00 am to 08:30 am and 30 minutes earlier from 05:00 pm to 04:30 pm
● Break time for Monday - Thursday is from 12:00 pm to 12:30 pm, while for Friday is from 11:30 am to 12:30 pm
Appendix 7.Turnitin results for plagiarism check (07 October 2022)
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