Antibody Drug Conjugates: The New Wave of Pharmaceuticals

Feb 05, 2018

 

The global market for Antibody Drug Conjugates (ADCs) is expected progress in the coming years. These new and promising pharmaceuticals are expected to be one of the innovative solutions for the treatment of cancer. Moreover, the increasing research on the development of advanced drugs can act as the foundation for the identification of new pharmaceuticals, along with the collaboration between biopharmaceutical companies.

What are ADCs?

Antibody Drug Conjugates (ADCs) are the new class of highly potent biopharmaceutical drug with high specificity for cancer therapy. There are three components that make up an ADC: 1) a monoclonal antibody (mAb), 2) a linker, and 3) a biologically active pharmaceutical ingredient with cytotoxic properties. These novel pharmaceuticals are quite unique and target-specific since it can deliver highly potent cytotoxic drugs to the tumour site and not harm the healthy cells unlike conventional chemotherapy.

ADCs deliver deactivated cytotoxins to specific cancer cells. Once attached to the affected cell, the ADC internalizes into the cell and undergoes the process of receptor-mediated endocytosis wherein the cytotoxin is released, producing a cytotoxic activity. The final process leads to a rapid cancer cell death.

The design and synthesis of an effective ADC is challenging, requiring specialized equipment for the concept to be a reality.

How are ADCs Made?

In order to deliver quality antibody drug conjugates, these undergo a tedious process of manufacturing in very stringent conditions. Under strict containment, the process starts from dispensing and weighing of cytotoxic agents, up to packing-off the finished products.

Weighing and preparation of cytotoxins with organic solvents are done in an isolator, since it permits safe handling of cytotoxins in a negative pressure environment. The mixture is then transferred into a conjugation site by a hard-piped transfer line. The isolator must be designed with a Clean-In-Place (CIP) system that permits inactivation of the cytotoxin or other microbes which comes in contact with potent cytotoxins to remove the contamination.

In the conjugation site, the linking of the antibody and cytotoxin is performed inside a strict containment facility, in a sealed temperature and pH controlled stainless steel tank, with nitrogen overlay. Special equipment like double mechanical seals, overflow trays, and positive displacement pumps are also needed to strengthen personnel protection. After this process, the ADC contained in the buffer is transferred to the formulation site for bulk formulation.

All the wastes from the process are inactivated and incinerated on site, depending on the process requirements. After the cytotoxic agent concentration adjustment and excipient addition in the formulation site, the Bulk Drug Substance (BDS) is stored frozen at around -20 to -60 °C using a controlled freezer and aseptically dispensed into multiple PETG (polyethylene terephthalate glycol) bottles for bulk storage.

Esco Pharma Solutions

Esco Pharma has a wide array of manufacturing products which can be used specifically for the development of the next generation of pharmaceuticals.

The general workflow for the production of ADCs:

 

  1. Sample Preparation

Pharmacon™ Downflow Booths

For the handling of raw materials, Esco Pharma offers the Downflow Booth, which is primarily used in the pharmaceutical industry to provide a safe working area for operators to protect them from hazardous, sensitizing, or toxic substances during manual handling of powders and solvents.

 

  1. Formulation

Weighing & Dispensing Containment Isolators (WDCI)

Weighing and Dispensing Isolators are advanced containment systems providing controlled negative pressure environments to maximize personnel protection. This equipment is especially designed for the weighing and dispensing of APIs, and as for ADC production, the isolator can be used for the mixing and blending with excipients. BioVap™ bio-decontamination system can also be installed in the equipment, wherein atomized hydrogen peroxide is sprayed throughout the equipment, thus sterilizing the system.

Formulation isolators are offered by Esco Pharma to fit the needs of the client for ADC manufacturing. Auto-loading and unloading systems can also be integrated in isolators for a better and faster workflow. Utilization of half suits for manual loading and unloading can also be installed, as well as the addition a blender, mixer, centrifuge, sieve and a lyophilizer for the production of the active pharmaceutical ingredient (API) and its salts. The integration of freeze dryers is also applicable, for the finalization and storage of the ADCs.

Esco TideCell® Bioreactor System

Esco offers tide motion bioreactors for the production of monoclonal antibodies (mAbs), wherein it features the same bioprocess method from seed preparation to production scale.   The Esco TideCell® Bioreactor System is the world’s largest linearly scalable single-use bioreactor, from seed preparation to 5000 liters with closed automated cell harvesting.

 

  1. Filling process

Antibody drug conjugates are produced in either a small or a large scale, after being processed in different stages. Esco can provide these needed qualifications and has also established collaborations with companies which provide filling lines, fit for potent formulation and is also ideal for a small to a medium batch production.

Active Open Restricted Access Barriers System (oRABS)

Transfer of products to the main process chamber happens via a Rapid Transfer Port (RTP). The entry and exit of vials happen inside an ISO Class 6 environment, but the whole process happens inside an ISO Class 5 production. The Active Open Restricted Access Barriers System (oRABS) is an example of a containment system which can serve as a fully integrated system for the filling of injectable biopharmaceutical products into ready-to-use containers, including vials, syringes, and cartridges. It can serve different cleanliness classifications as required, depending on the state of the product to be processed inside.

 

  1. Sterility testing

General Processing Platform Isolator (GPPI)

Esco General Processing Platform Isolator (GPPI) which is a highly adaptable, unidirectional laminar airflow isolator that can be used for sterility testing or other processes that require an ISO Class 5 (Grade A) aseptic environment. The GPPI’s advanced control system allows the operator to select either positive or negative chamber pressure as well as single pass or recirculating airflow patterns.

Esco Pharma provides aseptic and containment isolators, giving the best personnel, product, and environmental protection. Customization of equipment to fulfil the client’s needs is what Esco can truly offer, so that provision of a truly integrated solution will be available whenever needed. With continuous innovation, quality is built into the products with the use of Esco’s equipment.

 

Reference:

ADC Review. (2016). What Are Antibody-Drug Conjugates or ADCs? Retrieved last 15 January 2018, from https://adcreview.com/adc-university/adcs-101/antibody-drug-conjugates-adcs/

 

 

Other News


Blood Cell Labeling 101

Date: Feb 01, 2018


Esco Healthcare Welcomes 2018!

Date: Jan 08, 2018


Isolator-like hot cells are burning this 2018!

Date: Jan 04, 2018


Esco Pharma at the 52nd ASHP Midyear Clinical Meeting and Exhibition 2017

Date: Dec 15, 2017


Raising Your Standards with Esco Downflow Booth
Airflow Containment on Its Best

Date: Nov 29, 2017


Bio-decontamination Within
The Efficiency of Esco BioVap™ Inside the Isolators

Date: Nov 28, 2017


Esco Pharma GB exhibited at CPhI and P-Mec in Germany

Date: Nov 08, 2017


Survivor 101: Safe Change Filtration

Date: Nov 07, 2017


The Horror Behind the Gross Art of Sneeze and Cough

Date: Oct 27, 2017


Esco Life Sciences and Healthcare is Strengthening its Core in Biocontainment

Date: Oct 18, 2017


Esco Pharma is at Two Places at Once

Date: Oct 05, 2017


A Perfect Mate

Date: Sep 27, 2017


Nanotechnology: Containment Strategies and Engineering Controls

Date: Sep 26, 2017


It’s more than just being Fragile : How to Handle Potent Formulation?

Date: Sep 25, 2017


Innovative Solutions for the Next Generation: Esco Pharma at ISPE 2017

Date: Aug 30, 2017


How SAFE is your FOOD?

Date: Aug 30, 2017


Nanotechnology in Pharmaceutical R&D: Drug Delivery System

Date: Jul 25, 2017


Inhaled Insulin: Boon or Bane?

Date: Aug 11, 2017


Esco Pharma at High Potent Medicines Conference 2017

Date: Jun 21, 2017


Quality Assurance System

Date: Jun 16, 2017


Defects

Date: Jun 16, 2017


Esco Pharma GB is moving!

Date: May 30, 2017


Esco Pharma at INTERPHEX 2017

Date: Apr 04, 2017


Esco Isoclean® Isolators Aid in a Pharmacy Compounding Facility in Singapore

Date: Mar 17, 2017


Esco Pharma Advancing Aseptic Pharmaceutical Processing with SP Scientific PennTech and ESS Technologies

Date: Jan 26, 2017


Esco joins the biggest pharma event in South Asia!

Date: Nov 28, 2016


Feeling Alienated by Safety?

Date: Dec 01, 2016


Blow-Fill-Seal Technology and Isolators

Date: Nov 22, 2016


How Clean is Clean Enough?

Date: Nov 08, 2016


Why isolators are still preferred when handling HPAPIs?

Date: Oct 27, 2016


Be SAFE in Handling High Potency APIs

Date: Oct 26, 2016


Cytotoxic Drugs: Safe Handling in the Workplace!

Date: Oct 17, 2016


Esco isolator finally arrives in the land of the rising sun

Date: Sep 26, 2016


Esco Healthcare exhibits at the 16th ISPE – Singapore Affiliate

Date: Sep 16, 2016


Unidirectional or Turbulent Airflow: Which is best for Sterile Pharmacy Compounding?

Date: Sep 01, 2016


Discover the most diverse compounding pharmacy isolators

Date: Aug 18, 2016


The need for engineering controls in preventing compounding pharmacy mishaps

Date: Jul 19, 2016


Esco at the ASHP in Baltimore!

Date: Jun 23, 2016


Esco at the 2016 PPhA National Convention in Cebu City

Date: Jun 01, 2016


Esco Pharma ships out General Processing Platform Isolator (GPPI) to a client in Canada

Date: Jan 04, 2016


Esco Launches VacciXcell and TapestleRx

Date: Dec 03, 2015


VacciXcell commences the 1st day of exhibition at the Europe Vaccine Congress 2015 in Madrid

Date: Nov 10, 2015


Esco Pharma exhibited concurrently in Pharma Expo Las Vegas and IPEX Packaging Expo in Jakarta

Date: Oct 07, 2015


Esco Pharma partners with UP College of Pharmacy

Date: Jul 09, 2015


Thank you for visiting Esco at ACHEMA 2015!

Date: Jun 26, 2015


Esco at ISPE Exhibition

Date: Jun 09, 2015


Esco Pharma is Proud to Launch its New Range of Containment Isolators

Date: Apr 28, 2015


Esco GB Ltd hosted the 2014 Training at its new premises in Barnsley

Date: Dec 15, 2014


Esco Pharma at ISPE Event in Singapore.

Date: Aug 13, 2014


Esco at INTERPHEX 2014!

Date: Jul 17, 2014