Tag Archives: Downstream Processing

Stability testing of Active pharmaceutical ingredient

The purpose of stability testing is to deliver indication of how the quality of an Active pharmaceutical ingredient fluctuates with time under the effect of a multiple environmental factors such as temperature, humidity and light

The stability program also contains the study of product-related factors that effects its quality, such as interaction of Active pharmaceutical ingredient with excipients, container closure systems and packaging materials

Test Tube Erlenmeyer Flask Chemistry Laboratory

Various stability testing procedures:

  • Stress testing of the Active pharmaceutical ingredient can assist to recognize the probable breakdown of products, that consequently aids in establishing the degradation pathways and the fundamental stability of compounds and prove the  power of the analytical procedures used for indicating stability.
  • Container closure system :The steadiness studies has to be  done on the Active pharmaceutical ingredient packaged in a container closing system that  triggers the packaging proposed for storage and distribution
  • Specification: The study of stability has to contain testing of those characteristics of the Active pharmaceutical ingredient that are vulnerable to transformation during storage and possibly effect the quality, safety and efficacy. The testing should cover, physical, chemical, biological and microbiological attributes
  • Testing frequency: The frequency of testing should be adequate to establish the stability attribute of the Active pharmaceutical ingredient. For Active pharmaceutical ingredient with an expected repeated test stage or shelf life of at least 12 months,  the regularity of trying long-term storage state must  usually be once in 3 months in the first year, and then every 6 months in the second year and then once a year for the remaining life term
  • Storage conditions: Conventionally an Active pharmaceutical ingredient should be examined under storage conditions that test its heat stability and moisture sensitivity as well. The length of study and the condition in which storage is done is generally enough to cover shipment and storage.

High importance for Downstream processing in pharmaceutical industry

Development and cell community operations possess all things considered a comparable stage space in the typical bio-producing office.

Ten circumstances expansions in the protein, that biotech has perceived over the navigating of about 15 years, filters the downstream output stream controller.  The outcome has implied the necessity to stage sanitization of the technique stream through various rounds for some system operations, that requires the thing sufficiently proceeding in the inner-system pools holding the running with a sequence of a procedure.

Chromatography strikes with high protein motivations behind authority have decreased zone sizes moreover in system pool volumes. Further vanguard resins which issue or gets around 80 milligrams for every liter of sorbent possess supplanted media including reasons for suppression up to 30 mg/ml per go.

particularly in association

The centrifugation produces nourish streams because this requires all the additionally tidying showed up particularly in association with streams controlled to micro-filtration, that builds up the basic for a very high-oblige immensity ways of downstream processing wander.

Downstream processing recommends recuperation in addition to cleaning of biosynthetic things, particularly pharmaceuticals, that are from normal sources, for example, animal or the plant tissue or advancement stock, including the reusing of salvageable parts and a perfect treatment and trade of scrap.

This is an important stroll in the social occasion of pharmaceuticals, for example, unfriendly to sickness experts, hormones, antibodies and immunizations; antibodies and driving forces utilized as a few diagnostics; mechanical proteins; and typical smell and taste mixes. The downstream processing really is viewed as a particular track in biochemical arranging, be that as it may, an extensive number of key movements were made by physicists and analysts for research center scale division of regular things.

We also offer a degree of movement mechanical gatherings, underpins, CIP approaches, stainless and also single-use frameworks, combined headways and additionally affirmation associations. Solidified with in-house application stars who have various years of limit, we could assist you to handle all downstream processing challenges.

Downstream processing: An Intro

Downstream processing is the process of making new medicines and biosynthetic products from natural resources. These natural resources can be anything from animals to plants and even the bio-waste. The process of downstream processing includes the proper management of other resources as well like water management.

Uses of downstream processing:

  •    To make antibiotics:

Downstream processing is very useful to make the antibiotics as they use biological and natural resources to make these medicines.

  •    To make hormones:

Once upon a time hormones were considered only to be produced by the human body naturally. By using downstream processing, it is now possible to make very useful hormones like insulin and human growth hormones.

  •    Vaccines:

Vaccines made by the natural resources are proved to be more effective and do not have side effects.

  •    Flavors:

This is a new concept in the biotechnology field. But it surely is a good way to make flavors. The artificial flavors were sometimes considered to be harmful but the flavors mad by downstream processing by using natural resources are safe.

The downstream processing comes under the specialization field of biotechnology and chemical engineering. This process has significantly changed the medical industry as they do not have to make new medicines from non-biological compounds. That process was lengthy and it further created by products like polluted water.

This process includes various processes in it. It takes four steps to get the final product through downstream processing.

  1.    Capture:

This includes the process of removing the colloidal material from the main solution.

  1.    Product isolation:

Product isolation is the removal of those materials whose properties differ from the main solution.

  1.    Intermediate purification:

This process includes the removal of bulk contaminants such as host cells and other types of viruses.

  1.    Product polishing:

Product polishing is the refinement of the final product until they become the desired product.

This was the introduction to the downstream processing. There will be a series of articles about the various processes include in the downstream processing.

Hope this articles helps you.

A brief about downstream processing

Downstream processing alludes to the recuperation and purging of biosynthetic items, especially

pharmaceuticals, from normal sources, for example, creature or plant tissue or maturation soup, including

the reusing of salvageable parts and the best possible treatment and transfer of waste. It is a key stride in

the assembling of pharmaceuticals, for example, anti-infection agents, hormones and immunizations;

antibodies and chemicals utilized as a part of diagnostics; mechanical catalysts; and normal scent and

flavor mixes. Downstream processing is generally viewed as a specific field in biochemical building,

itself a specialization inside synthetic designing, however a large portion of the key innovations were

created by scientific experts and researcher for lab scale division of organic items.

Here are the stages of downstream processing:

 Removal of insoluble’s is the initial step and includes the catch of the item as a solute in a without

particulate fluid, for instance the partition of cells, cell flotsam and jetsam or other particulate

matter from maturation soup containing an anti-microbial.

 Product Isolation is the evacuation of those parts whose properties fluctuate impressively from

that of the wanted item. For most items, water is the main polluting influence and seclusion steps

are intended to expel the greater part of it, lessening the volume of material to be taken care of

and concentrating the item. Dissolvable extraction, adsorption, ultra filtration, and precipitation

are a portion of the unit operations included.

 Product purification done to isolate those contaminants that takes after the item nearly in physical

and concoction properties. Thus ventures in this stage are costly to do and require delicate and

complex hardware. This stage of downstream processing contributes a noteworthy part of the

whole downstream handling consumption. Case of operations incorporate fondness, size

prohibition, turned around stage chromatography, particle trade chromatography, crystallization

and fragmentary precipitation.

 Product cleaning depicts the last preparing strides which end with bundling of the item in a

structure that is steady, effectively transportable and helpful. Crystallization, drying up,

lyophilisation and splash drying are normal unit operations. Contingent upon the item and its

proposed use, cleaning may likewise incorporate operations to disinfect the item and expel or

deactivate follow contaminants which may trade off item security. Such operations may

incorporate the evacuation of infections or dehydrogenation.

Intracellular Stage Of Downstream Processing

Intracellular stage of downstream processing is probably the most important. This is where life begins.

Intracellular basically means the inside a cell. Products found intracellularly are a combination of;

 Vitamins

 Growth Enzymes

 Insulin

For the intracellular products to be maximized inside the cells there is a need for a cell disruption. The

cell disruption results into liberation of the products into liquid form then separation goes on, hence the

downstream processing.

Cell Types

Gram-positive bacterial cells

Gram-negative bacterial cells

When looked through a microscope, the gram-positive bacterial cells appear to be purple in color. It is

this cell that will prompt positive results when a gram stain test is carried out. It has a thick peptidoglycan

layer but lacks an outer membrane.

When gram stain test is done on the gram-negative bacterial cells, they do not retain the test color. They

have a thin Peptidoglycan layer and an outer membrane.

Cell disruption which prompts downstream processing is classified into physical and chemical methods.

Physical methods focus on disturbing the cell wall, while chemical methods weaken the cell membrane.

Physical methods include ultrasonic vibrating. This method is highly used in hospital laboratories.

Osmotic stress falls under physical methods. Here, the concentration solute in a cell is unexpectedly

changed. Then downstream processing is applied to get water out of the cells by the use of osmosis.

The introduction of chemicals to the cells aids downstream processing when the cells extract elements.

Alkali lysis helps in extraction of proteins available in bacteria. For this method to be successful there is a

need for alkali compatibility with the product to be extracted. Organic solvents which mix with water like

methanol and ethanol are used to interrupt the cells. Due to their high inflammable nature, it is important

to consider having appropriate fire fighting equipment.

Downstream Processing – Stage II

Intracellular Products Release

The second stage of downstream processing is called Intracellular Products Release. During the

downstream processing, several biotechnological products have to be released and isolated from the cell.

The isolation and release of the biotechnological products are done with the help of Intracellular Products


Biotechnological compounds/products that can be removed from the cell through the technique of

Intracellular Products Release are:

 Vitamins

 Enzymes

 Microorganisms

 Other cells

Methods of the Intracellular Products Release

There are several methods that are used in Stage II of downstream processing. The main technique of

the Intracellular Products Release is called Cell Disruption, which has its methods.

The methods used in cell disruption are the following:

 Physical Methods

 Chemical Methods

 Enzymatic Methods

Cell Disruption Physical Methods


The ultrasonic disintegration of the biotechnological products used for DP is one of the most used

methods of the Intracellular Products Release’s physical method of Cell Disruption.

The only disadvantage of Ultrasonication is that it can’t be used every day in the laboratory because it

requires the use of expensive chemicals and expensive laboratory equipment.

Osmotic Shock

The second technique of Cell Disruption method of the second stage of downstream processing

Intracellular Release, is called Osmotic Shock.

The Osmotic Shock method is used for suspending the Gram-negative bacterias’ hydrolytic enzymes and

proteins bound to them.

Chemical Methods of the Cell Disruption


The alkalines chemical method of Cell Disruption technique is used for extracting the bacterial proteins.

For instance, with the help of the alkalines method, the growth hormone can be released from the Vitamin


Limitations and Disadvantages of Downstream Processing

Although Downstream Processing offers lots of benefits but still if some process has benefits, there will

always be some limitations also associated with it. Likewise this type of processing also has some

limitations and disadvantages discussed here in the article.

No doubt that the processes are improved in terms of efficiency and robustness, but improvement in

processes lead to bottlenecks in the system due to high costs. It has been surveyed that from entire cost of

product, 80 percent costs is of downstream processing which is a very high value. Purification process is

considered to be most expensive method of all the methods involved in manufacturing of

pharmaceuticals. Yielding good productivity also leads to difficulties related to huge space required and

large equipment size needed. Since huge chromatographic columns are technically possible, but needs

huge space and floor for matching up the huge size of columns which might not always be possible with

existing requirements. Organization will have to face the economic difficulties as more of space will be

required which means it will be more expensive.

In purification process, there is need to perform yarn cross section and so to perform cross section, more

number of fibers are required which is one of the biggest challenge to downstream processing. Although

downstream processing supports in providing the high spinning speed, but it leads to imperfections and

unevenness in the performance of system.

One of the disadvantage of single use technology is related to the scale limitation i.e. upstream

applications have capacity of around 2000L for disposable bioreactors while downstream technologies

struggle to retain with these capacities. But this problem can be solved partially if systems used in a

continuous mode.

So, there are number of limitations associated with downstream processing which needs to be improved.