Cell Culture Database - Batch Information

You work in biopharma. Maybe you're a fermentation guru... or a cell culture hot shot. Whatever the case...
We muggles don't have the luxury of waving our wands and having protein fold themselves mid-air. There's usually a container where the process happens.
A time-window (starttime to endtime) is when processes happen.

Operators execute process instructions; these procedures is how the process happens.
The execution of process instruction results in an output. The output of the process step is the product and constitutes the what.
Lastly, the process (step) is given a name describing who the batch is.
It stands to reason that the who, what, how, when, where of a batch is characterized by:

• batchid
• product
• procedure
• starttime - endtime
• unit

and fully describe batch information for cell cultures and fermentation.

Organize Your Cell Culture Data

More Propaganda on Biologics

by Oliver Yu

From Forbes' article on biosimilars:

Compounding the complexity, even biologics that appear chemically the same have unique structural fingerprints as a result of the way protein structure assumes its functional shape, a process known as “folding.” Because biosimilars are so difficult to develop, they sometimes don’t work as effectively as the innovator biologic drug.

I wonder if the author knows how innovator biologic drugs are manufactured.  If he did, he'd know that these drugs are produced in batches and that controls must be in place to ensure that the drug product is the "same" from batch-to-batch.

Biologics are complex due to their size.  Their efficacy depends on not just their chemical composition, but on their shape.  But there are ways to provide a high degree of assurance that the drug product is effective.

In computer science, there's a concept called, "Checksum."  A checksum is a "fingerprint" for digital data... no two pieces of digital data produces the same "fingerprint."  In the world of QC drug testing, there is a concept called peptide mapping.  This is where you digest the protein with enzymes, chopping it at specific places.  Then you take the chopped-protein and run it through a chromatography column and see what order the parts come out.  The order the parts come out is a "fingerprint" for the molecule.

As for the activity of the drug product, you can test that a biosimilar trastuzumab binds to the HER2 protein.  I mean, that's how they tell if you are HER2+ in the first place.

I'm not saying that biosimilars ought to get rubberstamped with lower standards.  I'm saying that the vast majority of biologics manufacturing requirements of the innovator drugmaker can be ported over to biosimilars and that these putative hurdles described by our journalists are dated and not applicable given the modern technology available.

See also:

• SafeBiologics is the innovator biologic drugmaker's lobby. 
• FDA DRAFT Guidance on Biosimilars

Batch Relativity using OSI PI Batch

by Oliver Yu

It's the year 2012 and still, I see customers with batch processes not using PI Batch... the proven system for navigating batches in PI. Truth be told, some of these customers are not using OSI PI, which is in itself a problem.

Batch Relativity is having the the start/endtimes of a time-window so that when you need to look at a trend, you can plot it without having to manually input the timestamps:


Of course for time-windows in the recent past, you can use the arrows:


But for precise review of trends in the past, there are few alternatives to manual input.

When I was first starting out as a fermentation engineer, I distinctly recall getting the Gantt charts from the Planning & Scheduling department at the morning meetings and typing in estimates of the start/end times from the 11x17" paper I got each morning thinking there must be a better way. And there is: you can programmatically specify start/endtimes from PI Batch into the PI Trends.

If you have a batch manager, you can purchase software that writes to the PI Batch Database. For example, if you have an Emerson DeltaV system, you can purchase the Emerson DeltaV Batch Interface (EMDVB) that reads from EVT files and inserts records into the PI Batch database. Otherwise, you can use the native PI Batch Generator (PI BaGen) Interface that comes with the PI Server.

PI Batch Generator

To use the PI Batch Generator, there are several pre-requisites. The first is having an Active Tag.... a tag whose value = 1 when the batch is running and a tag whose value = 0 when the batch is stopped:


This is the minimum requirement for PI Batch Generator to work:

• A PI Unit for each unit you wish to track batches
• An Active Tag for each unit
• PI Batch Generator Interface installed as a service

For bioreactors (i.e. fermentors), if you don't have a tag that specifically starts/ends a batch, the tag you can use is the pH Controller Mode. Here's why:

You are generally interested in what goes on in the fermentor when there's something going on. And something is going on when it is batched with media. And when it is batched with media, pH control is typically ON; which means the pH Controller Mode = 1. On the back end of the batch, you typically turn of pH control after transfer or harvest so pH Controller Mode = 0 when the batch ends.

You'll know that you've picked the right point when your process values change when Active Tag = 1 and they flatline when Active Tag = 0:


For other types of process equipment, be clever with your existing tags to figure out the best Active Tag; for example, volume tends to be a good Active Tag.

With the Active Tag, you have satisfied the only requisite for using PI Batch Generator, all others are optional:

• Batch ID tag - a tag whose value equals the batch id at the time the batch is started.
  Typically some gibberish word that uniquely identifies this batch.
• Product tag - a tag whose value equals the name of the product being produced. (e.g. 'HER2', 'E25', 'VEGF')
• Procedure tag - a tag whose value equals manufacturing formula used

These values can be programmatically inserted in the event you don't want to consume tags for infrequent data.

Further reading:

• How PI Batch can increase your productivity at least 400%
• Intro to PI Batch Generator

Configure PI Batch!

PIModuleDB: "It's What Makes PI Batch Possible!"

In addition to correlating unit/alias to tags, the PI Module Database is the foundation for PI Batch, in fact, it is a requirement.

You see, there's a special type of module called, "PIUnit". And the main difference between a PIUnit and a regular module is that a PIUnit can keep track of start/end times (a.k.a. PIUnitBatches or UnitProcedures as defined by S88).

If you go to your Module Database, you can discern modules from piunits because they have different icons. The Module looks like a red/yellow/green cube with an "M" in the center of it. The PIUnit looks like a half-filled tank of water with pipes in and out.



When you right-click on the PIUnit and select Edit, the following form will present itself:



Pay particular attention to the Unique ID attribute of the PIUnit. The key here is that when you create a PIUnit, the PI server will create a PIPoint (a tag) for the purpose of storing PIUnitBatches.

You can prove it to yourself by doing a tag search on that gibberish text. In my case, I went straight to the PI SMT > Data > Archive Editor



What's more is that these events correspond with the unitbatches stored in PI Batch. The batch information about the batchid, product, procedure and endtime are stored at the starttime of the batch.


You see, PI Batch is rationally a simple table... one with 7 columns and as many rows as you have batches. But if you are OSIsoft and alls you have is PI (hammer), everything starts looking like a tag (nail).

This is why PI Batch Database... while seemingly tabular... is actually a data structure that is a hybrid of the hierarchical structure presented by the PI Module Database and PI tags. What makes PI Batch possible is that uniqueID of a PIUnit in PIModuleDB is the name of the tag that archives unitbatch information.

Upgrading to PI Server 2010 for PI Batch Users

PI Server 2010 is the latest PI server offering from OSIsoft. I don't know for a fact, but this seems like a marketing nomenclature to emulate Microsoft's Office 2007, Windows Server 2008...etc. It'll remind me the way my Office 97 makes me feel 14-years behind the times.

Whatever the case, the internal versioning system remains the same: PI Server 2010 is still version 3.4.385.59. What is drastically different is that PI Server 2010 requires (mandates/coerces) users to have PI Asset Framework (PI AF).

Ok, so what's PI AF? PI AF is essentially a scaleable PI Module Database, and what makes it scaleable is that it's built on Microsoft SQL Server. This means that you need to have SQL Server (or SQL Server Express) installed somewhere. Over time, the PI Module Database will be deprecated in favor of PI AF. So the default behavior of the PI Server 2010 is to copy the ModuleDB to PI AF and put it in read-only mode.

The problem is that there are PI applications that use PI ModuleDB that have NOT been moved to PI AF... for us in biotech, that's PI Batch. So in order to keep these customer happy, OSIsoft provides an option for PI AF to be synchronized with PI ModuleDB, but this requires preparation. The PI MDB to AF Preparation Wizard is what achieves this and this wizard comes with PI SMT 2010... which means you need to install PI SMT 2010 next.

Once the PI MDB to AF Preparation Wizard is run and all the errors fixed, you can proceed with upgrading your PI server to PI Server 2010.



This gives you the overview of upgrading to PI Server 2010. This upgrade is not as straightforward as previous upgrades because of the AF mandate. The devil is in the details and you should run through this process several times before apply it in the GMP environment.

OSI PI BatchDB: Batch Generator - part 2

So we know about the data structure storing time-windows in PI. How do we get the actual data into this data structure? And once we get it in, how do we fetch it in order to use it?

Well, if you have an older system with no batch manager, then the answer is the PI Batch Generator (PI BaGen), software that reads from a data source and sends it to PI. In the case of the PI BaGen, the data source is PI tags, and sends the computed results to other PI tags.

Here's how it works:

You have a tag that reads 0 when a unit is not operating and it reads 1 when the unit is operating. In the case of fermentation, you could use the pH controller mode because you only turn on pH control when there is either media or there are microbes in the bioreactor. This tag is will be the Active Point for your unit.

Let's say you have another tag in which the operator inputs the batch identification... this is the UnitBatch ID Point. And again, when the PLC runs, the program name is written to another tag... this would be the Procedure Point.

With this information, you can fire up the PI System Management Tool (PI-SMT) and configure UnitBatches to be automatically generated for your unit.



The purpose of the post is not to walkthrough a PI Batch Generator configuration, but to help you identify the pre-existing conditions conducive of using the PI Batch Generator interface. (The OSI documentation for PI BaGen is the right place to start).

OSI PI's BatchDB is an exceptional tool... especially for users in the biologics manufacturing space. Configuring PI Batch is a no-brainer, especially if you run a batch process and want to increase productivity by no less than 400%.

OSI PI Batch Database (BatchDB) for biologics lab and plant - part 1

Biologics manufacturing is a batch process, which means that process steps have a defined starttime and endtime.

CIPs start and end. SIPs start and end. Equipment preparations start and end. Fermentation, Harvest, Chromatography, Filtration, Filling are all process steps that start and end.

Even the lab experiments are executed in a batch manner with defined starts and end.

Like the ModuleDB, OSIsoft has a data structure within PI that describes batch and it is called PI Batch Database (PI Batch). While it comes free, it does cost at least 1 tag per unit (PIUnit) to use.

The most important table is the UnitBatch table. The UnitBatch table contains the following fields:

• starttime
• endtime - when the batch happens
• unit - where the batch happened (with which equipment)
• batchid - who (name of the batch)
• product - what was produced?
• procedure - how was it produced?

In essence, the UnitBatch table describes everything there is to know about a process step that happens on a unit. Remember: units are defined in the PI ModuleDB, which means the PI BatchDB depends on a configured PI ModuleDB.

So why bother configuring yet another part of your PI server? The main reason is to increase the productivity of your PI users. In our experience, up to 50% of the time spent using PI ProcessBook inputting timestamps into the trend dialog. Configuring PI Batch makes it so that your users can change time-windows in ProcessBook with just a click.

We have seen power-users put eyeballs on more trends in even less time than without PI Batch; and the more trends your team seems, the more process experience they gain.

In this dismal economic environment, simply configuring PI Batch on your PI server can make your team up to 400% more productive. This particular modification takes less than a day to accomplish.