Bio-Insight Booklev Vol.1: Pharmaceuticals+

Pharmaceuticals Bio-Insight Vol.1

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Introduction to Pharmaceutical Sciences

2

Drug Discovery

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Pharmaceutical Production : Upstream Processing

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Pharmaceutical Production : Downstream Processing

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Waste Management

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Top 10 Pharma Companies

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Mini Quiz

Bio-Insight SR SBE UISC 2021

Table of Contents

Introduction to Pharmaceutical Sciences What is Pharmaceutical Sciences?

The pharmaceutical industry discovers, develops, produces, and markets drugs or pharmaceutical drugs for use as medications to be administered.

Pharmaceutical bioprocess engineering combines scientific and engineering fundamentals for biotechnological production in the pharmaceutical industry and related fields.

Pharma-Fact

Brief History of Pharmaceutical Industry In 1849, as an initial fine chemical business, Pfizer was established in the USA by a German immigrant, called Charles Pfizer. The company stocked painkillers and antiseptics which boomed significantly due to the American Civil War. Whilst Pfizer was providing the medicines required for the Union Army endeavor, Colonel Eli Lilly, a pharmaceutical chemist who served as a cavalry commander in his time.

After his military career, he set up a pharmaceutical business in 1876. He pioneered big scale pharmaceutical in the industry.

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2.Drug Discovery & Development The process through which candidate new medicines are identified.

Drug Discovery Phases

Phase

Description

Discovery Scientists, Bioprocess Engineers

Preclinical Research Scientists, Bioprocess Engineers

Clinical Development Healthcare Worker

Drug Approval bpom (ind), FDA (US), MHRA (UK)

Potential gene or protein identification Therapeutic characteristic examination Multistep screening process Gene or protein optimization Determine the efficacy and safety of the drug Test the drug on non-human subjects Both in vitro and in vivo Clinical trials of the drugs on the human Phase I (100 recipients), Phase II (100-500 recipients), Phase III (1000-5000 recipients) Volunteer studies to maximize the drugs for human use.

Regulatory Review drug approval Post-Marketing Monitoring

Pharma-Fact

How do Chemical Drugs and Biopharmaceuticals Differ?

Monoclonal antibody Biopharmaceuticals 25.000 Atoms

A biologic is manufactured in a living system such as a microorganism, or plant or animal cells using recombinant DNA technology. Most biologics are very large, complex molecules or mixtures of molecules.

Aspirin Chemical drug 21 Atoms

A chemical drug is typically manufactured through chemical synthesis, which means that it is made by combining specific chemical ingredients in an ordered process.

Name of product

Type

Molecule size

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3. Pharmaceutical Manufacturing

The biopharmaceutical manufacturing technology flowchart exemplifying the upstream and the downstream bioprocess.(Angela,2016)

Upstream Processing

By cell-culture and fermentation, upstream processing aims to produce the most active drug/liter of culture-time consistently.

1. Inoculum Preparation

2. Cell Bank Formation

Scientists decide the host organisms (i.e. E. Coli, Yeast, and CHO Cells.) and a single cell of host organism grown in a small batch

Inoculum is saved into hundred of culture vials and frozen away as a master cell bank to prevent cell drift and increase consistency.

3. Small Scale Cell-Culture

4. Large Scale Cell-Culture

Microbial cells are transferred to a shaker flask containing sterile medium and placed in an incubator to increase growth rate.

After 1-2 days, Inoculums are transferred to the main fermentation vessel containing essential fermentation media.

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Downstream Processing

The various stages of processing that occur after the completion of the fermentation, including separation and purification

5. Cell Harvesting

6. Cell Disruption

centrifugation and membrane separation/filtration remove the extracellular liquid on large scale.

High-pressure homogenizers or bead mills break open the host cells and release the intracellular products (target compounds).

6. Precipitation

7. Liquid-Liquid Extraction

Organcic solvents concentrated target compounds and purified from unwanted byproducts e.g. nucleid acids, pigments.

Solute is transferred from one liquid phase to another liquid phase to achieve the concentration of biological products.

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8. Affinity chromatography

9. Viral Inactivation

Target products such antibodies are separated using protein A-based affinity chromatography from the inert matrix.

Protein A capture columns are typically eluted at low pHs and followed by a low pH incubation step to inactivate viruses.

10. Polishing Chromatography

11. Virus Filtration

Additional chromatography unit operations after the capture step to enhances the purity of target macromolecules by 95%.

Target products should be cleared from endogenous viruses. Membrane filtration is used as a robust step for virus clearance.

12. Diafiltration

13. Formulation (mixing)

Target products are diafiltred to wash out any low molecular weight contaminants not retained by the membrane.

Certain stabilizing additives (sugars, salts, polymers, and glycerol) are added to prolong the shel life of products.

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13. Lyophilization

14. Quality Control

The liquid containing the product is frozen in vials and then dried in a freeze-dryer under vacuum to remove water.

Aims to ensure quality of the product released for use in the clinic. Both pharmaceutical and biological assays are required.

Eng-Fact

How Continuous Processing is Impacting Drug Manufacturing On the whole, the pharmaceutical manufacturing industry loses about $50 billion a year because of the general inefficiency of batch processing — whether it’s due to time constraints, shipping losses, contamination, or the expense of a recall. Continuous manufacturing can be a potential solution to that problem.

Batch processing consists of a step-by-step process.

Each “step” is completed in one room, for sanitary purposes, where a bulk material enters the space, is processed and then exits the room.

Although the process works, it is extremely inefficient: Raw materials are produced at separate facilities around the world and shipped to processing facilities, which means significant downtime between steps.

Batch processing is also a risky way to manufacture drugs. The more time partially completed products spend between steps, the higher the risk for human error or contamination.

Continuous pharmaceutical manufacturing is more time-efficient, reduces energy needs, helps to increase productivity, and reduces the amount of overall waste.

The risk of human error is also reduced because continuous processing means fewer people are involved in the production process from start to finish.

Image: Johnson & Johnson Janssen’s Prezista continuous processing line at its plant in the U.S., was the first FDA-approved switch from batch to continuous processing at an existing plan.

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Pharmaceuticals Waste Managements Pharmaceutical Waste Disposed in Indonesia

296.86 ton/day

Pharmaceutical Waste Regulated in Indonesia

168.8 ton/day

Types of pharmaceutical waste Hazardous waste Toxic, corrosive, reactive drugs Expired chemicals (benzene, peroxids, alcohols) Expired cytotoxic drugs (Anticancer drug, Interferon)

Type

Characteristic

Example

Non-hazardous waste No significant hazardous properties All other expired drugs (syrups, infusion, ointments) Pharmaceutically inert (sodium chloride or dextrose solutions)

Methodologies of The Pharmaceutical Waste Managements

1. Incineration

2. Autoclave

The practical method of disposing of biological medical waste by converting waste into residue and gaseous products.

Saturated steam contact with metals product in a pressure vessel at time lengths and temperatures.

3. Microwaving

4. Chemical Disinfection

An electromagnetic field over the liquid waste to oscillate, heat up, and destroying by conduction.

Addition of strong oxidants or phenol compounds-kills or inactivates pathogens in liquid wastes

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5. Deep burial

6. Secure land filling

Digging a pit about 2 meters deep, half-filled with the BMW and then covered with lime within 50 cm of the surface

Secure landfilling involves disposal of solid BMWs* at a landfill designed and operated to receive hazardous wastes

7. Encapsulation

8. Inertization

Immobilizing the pharmaceuticals in a solid block within a drum filled with cement, plastic foam, or bituminous sand

The pharmaceuticals are ground and mixed with water, cement, and lime into a homogeneous paste

Pharma-Fact

Pharmaceutical industry waste: How Serious?

The pharmaceutical industry in the US generated 128million kg of waste in 2006 This waste include mainly organic solvents, the top three of which are methanol, 44.8 million kg/year; dichloromethane, 22.3 million kg/year; and toluene, 12.1 millionkg/year The top 10 solvents accounted for more than 80 % of the waste generated Since solvents are costly to purchase and dispose of, for a greener and more sustainable pharmaceutical industry it is imperative that approaches to solvent reduction, recovery and substitution be more widely incorporated.

Eng-Fact

Many landfills also have landfill gas extraction systems installed to extract the landfill gas. Gas is pumped out of the landfill using perforated pipes and flared off or burnt in a gas engine to generate electricity.

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Top 10 Pharma Companies 2020 With demand for treatments ever increasing, pharmaceutical companies around the world are committed to drive critical innovation to deliver therapies for patients with unmet medical needs and play a pivotal role in the life sciences industry.The Covid-19 pandemic, which was first discovered at the end of 2019, has had an unprecedented impact on the world. Looking forward, communities across the globe are relying on the pharmaceutical industry to create solutions, and many of the companies in the top 10 are involved in the race to produce treatment or prevention measures for the Covid-19 disease.

Origin country

1. Roche Switzerland $53 billions Ocrevus (sclerosis), Hemlibra (hemophilia), Perjeta (cancer).

3. Johnson & Johnson America $42.2 billions Stelara (psoriasis), Darzalex (anti-cancer), Imbruvica (B-cell Cancer)

5. Novartis Swiss $37.7 billions Cosentyx (Spondylitis & arthritis), Entresto (heart failure), Zolgensma (spinal muscular atrophy)

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Total revenue in USD

Key products

2. Pfizer America $49.7 billion Ibrance (breast cancer), Eliquis (anticoagulant), Xeljans (arthitis & colitis)

4.

Merck

America $41.8 billions Keytruda (Cancer), Gardasi (HPV infection), Varivax (Chickenpox)

6. Abbvie America $33.3 billions Humira (arthritis, colitis, Crohn's disease, etc.)

7. Takeda

8. Bristol-Myers Squibb

Japan $31.1 billions Ninlaro (multiple myeloma), Entyvio (ulcerative colitis & Crohn's disease)

9. Sanofi

America $26.1 billions Eliquis (anticoagulant), Opdivo (cancer), Orencia (rheumatoid arthritis)

10. Amgen America $23.4 billions Neulasta(colony stimulant factor), Sensipar/Mimpara (parathyroid carcinoma & hypertiroidism)

French $25.7 billions Dupixent (allergic diseases)

Pharma-Fact

Biopharmaceuticals market share, by product, 2018 1.3%

8.8%

1.Monoclonal Antibodies (43.3%)

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10%

2.Recombinant Growth Factor (11.8%)

5 6.8%

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47.7% 4 . R e c o m b i n a n t H o r m o n e s ( 6 . 2 % )

3 12.2%

3.Recombinant Proteins (11.1%)

5.Synthetic Immunomodulator (9.1%)

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6.Vaccines (8%) 7.Others (1.2%)

13% On the basis of product type, the monoclonal antibodies segment dominated the market accounting for the market share in 2018 primarily due to its benefit of allowing targeting of unhealthy cells without harming the healthy cells. Monoclonal Antibodies are the emerging technology that is identical to immune cells and represents a copy of the unique parent cell.

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Meet The Team

ATHALLIA QATRUNNADA DIRECTOR OF PROFESSIONAL EDUCATION

MUHAMMAD MAULANA EKAPUTRA

AUZAN LUTHFI DEPUTY DIRECTOR OF STUDY RESEARCH

CO-DIRECTOR OF PROFESSIONAL EDUCATION

STUDY RESEARCH SBE UISC 2021

AYU ANDANI

NABILA AZKA AMALIA

LULU HABIBAH

NICHOLAS BARUNA

YOSEP DHIMAS

CHICO XAVIER

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Reference General Kinematics. 2021. Batch vs. Continuous Pharmaceutical Manufacturing | General Kinematics. [online] Available at: <https://www.generalkinematics.com/blog/batch-vs-continuouspharmaceutical-manufacturing/>[Accessed 25 February 2021].

Burke, H., 2021. Who are the top 10 pharmaceutical companies in the world? (2020) | Proclinical blogs. [online] Proclinical. Available at: <https://www.proclinical.com/blogs/2020-8/the-top-10pharmaceutical-companies-in-the-world-2020 [Accessed 25 February 2021].

DataM Intelligence, h., 2021. Biopharmaceuticals Market, Size, Share | Industry Forecast, 2027. [online] DataMIntelligence. Available at: <https://www.datamintelligence.com/researchreport/biopharmaceuticals-market>[Accessed 25 February 2021].

Durrant, L., 2021. Pharmaceutical Waste Management - ppt video online download. [online] Slideplayer.com. Available at: <https://slideplayer.com/slide/1607524/> [Accessed 25 February 2021].

BIO. 2021. How do Drugs and Biologics Differ? - BIO. [online] Available at:<https://archive.bio.org/articles/how-do-drugs-andbiologics-differ>[Accessed 25 February 2021].

NorthEast BioLab. 2021. Phases of Drug Development Process, Drug Discovery Process | NorthEast BioLab. [online] Available at: <https://www.nebiolab.com/drug-discovery-and-developmentprocess/> [Accessed 25 February 2021].

Saputra, B., 2021. Sengkarut Pengelolaan Limbah Medis, Bikin Miris – ICEL. [online] Icel.or.id. Available at: <https://icel.or.id/berita/sengkarut-pengelolaan-limbah-medisbikin-miris/>[Accessed 25 February 2021].

Biology Discussion. 2021. Stages in Downstream Processing: 5 Stages. [online] Available at: <https://www.biologydiscussion.com/biotechnology/downstreamprocessing/stages-in-downstream-processing-5-stages/10160> [Accessed 25 February 2021].

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Pharmaceuticals

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