PRODUCT OVERVIEWPRODUCT OVERVIEW
ADD-ONS & INDIVIDUAL SOLUTIONSPLA SUPPORT CONTRACT
TRAINING
CONSULTING
21 CFR PART 11 COMPLIANCE

PLA 3.0

Software For Biostatistical Analysis

PLA 3.0 | Product Overview | 2018

PLA 3.0 | Product Overview | 2018

Discover the
Next Generationof Bioassay Analysis
All Assay Types Described in EP
and USP in One Single Software
PLA 3.0 supports all types of biological assays according to European Pharmacopoeia
4th-9th Edition, Chapter 5.3 and US Pharmacopeia <111> ,<1032>, <1033>, <1034>:
Quantitative Response Assays (Parallel-Line, Parallel-Logistics, Slope-Ratio) andDichotomous Assays (Quantal Response, Binary Assays). PLA 3.0 also supports all
different weighting methods for combination calculations and the automatic data
aggregation of independent assay data. Additional document types are available
for Equivalence Margin Development, Control Charts and a Basic Bioassay Protocol.

Building an Assay Archive
for Later Review
Over the months and years, you will spend considerable amounts of time and money
on your assays. With PLA 3.0, you make sure that all your assays remain accessible
for later review. PLA 3.0 keeps them in a database, ready to be retrieved with justa few clicks.

FDA Compliant, Userfriendly Platform
Compliance with FDA 21 CFR Part 11 is one of the most important requirements forsoftware meant for regulated environments. The challenge is to make the software
fully compliant at the core and user-friendly on the surface. With PLA 3.0, we managed to achieve exactly that.

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PLA 3.0 | Product Overview | 2018

Covering the Entire Lifecycleof Your ProductWith PLA 3.0, you can use the same software for the entire project - from development all the way through to production. The software will adapt to the stage of the
project. We built several features into PLA 3.0 that make it not just suitable but infact ideal for projects and teams of virtually any size.

Ready to Integrate With What
You Already Use
PLA 3.0 is a highly versatile platform, ready to be extended to suit your particularneeds. We developed a number of modules that allow you to connect PLA 3.0 to other programs or equipment, such as plate readers. In effect, your bioassay analysis
will be independent of the device you are using to acquire the measurement values.

Users of PLA 2.0/2.1: Prepare to
Reach the Next Level
When we published PLA 2.0 and 2.1, these programs were the most advanced we
had developed so far. And it’s the same with PLA 3.0. So it does make a lot of sense
to switch from these previous versions to the newest one. You will reach the nextlevel of bioassay analysis.

Going Beyond Service:Your PLA Support Contract
The PLA Support Contract helps you get the most out of PLA. The first year is included in every purchase. We provide a support portal for any issue around PLA andhave a team of biostatisticians and (bio)chemists ready to support you.

Continue reading to find out more about PLA 3.0 and its features.

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PLA 3.0 | Product Overview | 2018

PLA 3.0 UNDER THE HOOD

Intuitive basic concept: Handle data
as documents

PLA 3.0 is a software platform for biostatistical analysis in GxP and non-GxP environments. The new architecture of PLA 3.0 provides all the functionality required forregulated environments through the platform, while all statistical functionality isdelivered by PLA Document Packages.

DOCUMENT CONCEPT

Easily extensible platform

Data Editor Perspectives:

The basic idea is the concept of electronic documents, which we derived directlyfrom the requirements of the FDA 21 CFR part 11 regulation. All data and meta data
is kept in one single information unit - the document. The structure and capabilities
of a document are defined in the document packages.
The platform protects these documents with electronic and digital signatures according to the 21 CFR part 11 regulation. To give you greater flexibility, documents
are organized in folders where several restrictions can be applied (permissions,privileges, mandatory templates).
Document Packages
A document package contains one or more document types and calculation routines
as well as required report templates and data for operational qualification (OQ).
The PLA 3.0 base system comes with

 Document Package for Biological Assays
 Document Package for Measurement Documentation
 Document Package for General Documents
You can install additional document packages into the platform. These document
packages may be available for download or we will create them for you on demand.
Elastic Forms Editor
The Elastic Forms Editor is the central editor of PLA 3.0. It allows you to edit documents of any complexity in a fast, easy and efficient way. Context sensitive help forevery field supports you with valuable information. The built-in template support lets
you create and protect powerful templates to simplify usage and to support efficient
standard operating procedures.
Data Editors
The system comes with three data editor perspectives. They allow different views
on your data sets. You, as the user, can decide whether it is more efficient to viewor edit data points line by line, or per sample along a dilution series or in a position factor perspective. Powerful tools like color-coding of fields help you to prevent
input errors.
Reporting
Correct and validated reporting is critical in controlled environments. The PLA system supports validated reports to ensure a valid and trustable reporting of results.

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PLA 3.0 | Product Overview | 2018

BIOLOGICAL ASSAYS
PLA 3.0 supports all types of biological assays according to European Pharmacopoeia
4th-9th Edition, Chapter 5.3 and US Pharmacopeia <111> ,<1032>, <1033>, <1034>:
Quantitative Response Assays (Parallel-Line, Parallel-Logistics, Slope-Ratio) andDichotomous Assays (Quantal Response, Binary Assays). PLA 3.0 also supports all
different weighting methods for combination calculations and the automatic data
aggregation of independent assay data. Additional document types are available
for Equivalence Margin Development, Control Charts and a Basic Bioassay Protocol.

PLA supports all assay types

PARALLEL-LINE ASSAY
A parallel-line assay is the classical method to calculate a relative potency for adilution assay. It is a linear fit which covers only the (near-) linear portion of thedose-response relationship without their asymptotes.
PLA 3.0 supports parallel line assays along with additional functionality to determine acceptable regions of the dose-response curve (configuration optimization).
The parallel-line method is a robust analytical method based on D.J. Finneys Statistical Methods in Biological Assay, 3. edition, 1978. It is supported by the European
Pharmacopoeia and the US Pharmacopeia.

Parallel-Line AssayNONLINEAR QUANTITATIVE RESPONSE ASSAY
A nonlinear quantitative response assay (also known as a parallel-logistics assay)
is a full curve fit method which takes the whole dose-response relationship into
consideration, including asymptotes. PLA 3.0 supports different types of nonlinear
full curve fits: 4-parameter logistic curve fit 5-parameter logistic curve fit
 3-parameter logistic curve fit
The 4-parameter logistic curve fit is the most common approach. It models a symmetric sigmoidal dose-response correlationship. The 5-parameter logistic fit function
adds an asymmetry parameter. The 3-parameter models is a reduced 4-parametermodel, where one of the asymptotes has to be set to a fixed value or to the mean ofa control line, which allows the system to deal with truncated data.

Nonlinear Quantitative Response Assay

SLOPE-RATIO ASSAY
In contrast to parallel-line assays or nonlinear quantitative response assays, sloperatio assays are carried out on a linear dose axis. They are most commonly used in
microbiological applications.
The linear regressions of the standard and the sample intersect at zero dose. The
potency is then calculated from the ratio of the slopes, the confidence intervals of
the potencies are calculated using Fieller’s Theorem.
Slope-Ratio Assay
5PLA 3.0 | Product Overview | 2018

DICHOTOMOUS ASSAY
Dichotomous Assays (which are also called quantal response assays or binary assays)
are assays based on binary outcome, i.e. a number of specimens shows a given response at a specific dose of an active ingredient. The assays are usually analyzed
using the probit- or logit-method. PLA 3.0 supports both of these functions.

STATISTICAL TOOLS

Dichotomous Assay

Flexible assay setup allows virtually
any assay configuration.

Flexible Assay setup
The assay setup in PLA 3.0 is very flexible. You can setup any assay system with afree number of test or control samples and control lines as well as free numbers of
replicates and dilution steps. Symmetric and asymmetric assay setups are supported.
When used in combination with the template system of PLA, any assay configuation
can be set up in a GxP compliant way.
Outlier Detection
PLA 3.0 supports four optional outlier detection methods: Dixon Test, Grubb’s Test,
Studentized Residual and a test based on the standard deviation of the treatments.
Configuration Optimization
While the parallel-logistic assay (full curve fit) describes the whole dose-response
correlation, parallel-line assays focus on the significant part of the dose-response relationship. PLA 3.0 is able to locate the significant parts of the dose-response correlation
automatically to determine the optimal assay configuration.
Curve Fitting
In quantitative response assays both parallel-line assays and parallel-logistic assays (3–,
4– and 5-parameter sigmoidal functions) are implemented. Transformation functions forthe response values are available for all models to reduce heteroscedasticity. The curve
fitting of PLA 3.0 has been extensively optimized to provide high-quality curve fits, sincebioassays tend to be very sensitive to the slightest deviations.

SOPHISTICATED TEST SYSTEM
Testing can be done either by difference/hypothesis testing, as described in the European Pharmacopoeia, or by similarity/equivalence testing, which was introduced by
the US Pharmacopeia chapters <1032>, <1033> and <1034>. The test system of PLA
3.0 is very flexible and lets you perform a number of different tests, which you canconfigure exactly according to your needs.
For example, PLA 3.0 can test for potency, both relative and absolute. In addition, you
can define potency ranges and confidence intervals. You can even run a test based on
the number of outliers.

COMBINATION OF ASSAY RESULTS

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Combinations of assay results are not just means of potencies. To get optimal results,
you need to consider the confidence intervals. PLA supports all methods of combination described by the European Pharmacopoeia and the US Pharmacopeia. PLA also

PLA 3.0 | Product Overview | 2018

supports all different weighting methods for combination calculations and automatic
data aggregation of independent assay data.

BASIC BIOASSAY PROTOCOLThe Basic Bioassay Protocol is a powerful document type to implement the mostcommon workflow in bioassay analysis: combining the results of multiple independent assay runs into reportable values.
The Basic Bioassay Protocol controls all required steps: the assay is defined in the
Basic Bioassay Protocol, which automatically creates a set of linked Quantitative
Response Assays and Combination of Assay Results Documents. The results are automatically and safely transferred between the Quantitative Response Documents
and the Combination Calculation – so no retyping is required.
Finally, the Basic Bioassay Protocol is capable of handling retests. Just raise thenumber of your assay replicates and the Basic Bioassay Protocol will add the required number of runs. This can be handled per assay run, but there is also an option
to control this on a per sample level in multi sample assays.

EQUIVALENCE MARGIN DEVELOPMENT
The development of equivalence margins for use according to the US Pharmacopeia
is a challenging task. PLA is able to aggregate your reference data and calculate
candidate equivalence margins. First, choose acceptable historic assays. PLA cancalculate margins from any number of assays for a quick start. A recommended
number of assays is 30. Then, calculate candidate equivalence margins for all of the
supported similarity tests in PLA 3.0.
The method supported by PLA 3.0 is a preferred method to calculate equivalence
margins and is supported by the US Pharmacopeia <1032>.

CONTROL CHARTS / TRENDING
The Control Chart document type in PLA 3.0 allows the trending of different parameters of your biological assay. Define any number of trending parameters and different limits to keep your assay undercontrol.
You can use the Control Chart document
in two ways. You can edit or import datafrom any source, allowing to use thetrend chart universally. Or you can directly aggregate the corresponding datafrom your calculation results as requiredin regulated environments.

Control Chart

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PLA 3.0 | Product Overview | 2018

COVERING THE ENTIRE LIFECYCLE

PLA 3.0 covers the entire lifecycle from development to production.

Easily scalable with templates

In order to use software in companies or teams of different sizes, it should be easily
extensible and scaleable. We therefore built several features into PLA 3.0 that makeit not just suitable but in fact ideal for projects and teams of virtually any size.

TEMPLATES
PLA 3.0 comes with a new template engine. Templates can be defined by authorizedusers. They decide about the visibility, access level and default values in a document. Templates can be signed electronically and the administrator can define themandatory use of specific templates in the database or in database sections. The
template engine was designed to support the easy implementation of standard operating procedures (SOPs) within PLA.

VALIDATION AND
GXP COMPLIANCE
According to GAMP software has to be validated on the customer’s computer system.
The software vendor is only able to verify
the software in his labs. The optional Validation Package helps you to manage thetasks of installation qualification, operational qualification and performance qualification (IQ, OQ, PQ) fast and efficiently.

INTEGRATION
Device-independent assay analysis use the reader system of your choice

PLA has a full set of interfaces for the import of raw data from data acquisition
systems, for the export of data to e.g. documentation systems and for the reporting
into many target systems. Individual modules can be created at low cost.
Import Modules are now distinguished into Document Import Modules creating acomplete document with all settings and Data Acquisition Modules. Data Acquisition Modules are able to import data into the data table of any document type.
(Note: They replace the former PLA 2.x Import Modules.)Document Import Modules
Document Import Modules generate fully specified documents of a specific type.
They are useful when an external format contains every information required tocreate a specific document. E.g. if a third party program deals with biological assays
a Document Import Module can be set up in a way where a completely specified
quantitative response assay is delivered. In this case the Document Import Module
converts all settings and creates the appropriate PLA 3.0 document.

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PLA 3.0 | Product Overview | 2018

Data Acquisition Modules
Data Acquisition Modules are used to connect external systems directly to the datatables of a PLA 3.0 document. Typical examples are Data Acquisition Modules forplate readers. A plate reader delivers a stream of measurement values that need to
be imported to the data table of a specific document in a GLP/GMP compliant way.
Data Acquisition Modules are the most common import modules used by PLA. Currently, we have more than 40 different Data Acquisition modules available.
Data Acquisition Modules are licensed by the supported external format. They are
not specific to the target document type.

Your imported data remains fully
traceable - all the time.

Document Export Modules
Export Modules are available to export PLA 3.0 Document to a specific External Format. They export the PLA 3.0 Document and transform them into the target format.
They can be used to connect PLA to other external systems (e.g. LIMS systems).

TRANSFER OF DATA AND TEMPLATESPLA allows to transfer data and templates between projects, sites and companies
in a secure manner.
The trustability and integrity of the data is assured by a combination of electronic
signatures, that are preserved in the transfer, and cryptographically secured datatransfers. PLA secures the information with the help of its own integrated PKI (Public
Key Infrastructure). This operation is completely transparent for the user. It assures
the secure communication of data and templates to different projects, sites or CROs.

ROLES AND PERMISSIONSPLA 3.0 comes with an updated sophisticated permission system scalable fromsingle seat to global installations. Typical roles are predefined in the system but canbe altered to match your companies needs. All the settings are combined together
in named security contexts that can easily be applied to new folders.

Configure roles and permissions
exactly the way you want them.

Ideal framework for replacing legacy
software

PLA Content Editor

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PLA 3.0 | Product Overview | 2018

21 CFR PART 11 COMPLIANCEADVANCED SECURITY FEATURES
PLA 3.0 is fully FDA 21 CRF Part 11
compliant.

In accordance with the FDA 21 CFR part 11 PLA has its own security infrastructurethat requires users to log into the system. User accounts and their roles are definedwith an easy-to-use interface. The accounts and their roles are database specific.
In addition to this account management PLA is fitted with the full range of security
options required by the 21 CFR Part 11. The PLA Administrator can define security policies for each database in accordance to regulatory or your company’s need.
The feature includes password complexity, password aging, password blocking andpassword history rules. You may also define inactivity locks to prevent unauthorizedaccess to the system.

ELECTRONIC SIGNATURES
Electronic signatures can be applied to all documents in PLA. The application ofelectronic signatures is a requirement of the 21 CFR part 11. With PLA’s advanced
data storage technology electronic signatures can even be moved between different
installations of PLA (e.g. between your CRO and your company).

DATA TRACEABILITY / AUDIT TRAIL
PLA has its own audit trail that covers all changes of data and properties of yourdocuments and of all security features inside PLA. The audit trail can be inspected
on a per-database and a per-document level. Filter and export functions have now
been included into the base features of PLA 3.0. Acquired raw data can always be
traced back to its original source.

DIGITALLY SIGNED ELECTRONIC RECORDS
PLA benefits from the XML industry standard for the storage of electronic records.
This very flexible format has the main advantage that it is human readable, which isanother requirement for compliance.
PLA makes use of the XML Signature 1.0 Industry standard to assure the integrityof all the data that PLA works with. The XML Signature Standard applies a digital
cryptographic signature to each data package. With the help of this signature theintegrity of the electronic records is checked every time PLA makes use of them.
This integrity check prevents any unauthorized or unwanted data modification, e.g.
by computer defects.

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PLA 3.0 | Product Overview | 2018

PLA 3.0 FEATURE OVERVIEW
PLA 3.0 is an extensible software for bio-

CONTROL CHARTS

statistical analysis in GxP and non-GxP Automatic aggregation of data fromenvironments.

your assays (optional).

BIOLOGICAL ASSAY
Quantitative Response / Dichotomous Assay Analysis according to European
Pharmacopoeia 4th-9th Ed., Ch. 5.3 andUS Pharmacopeia <1032>, <1033>,<1034>

 Response Adjustment
 Response Transformations(linear, log, square, square root) Outlier Detection (4 models) Regression models
 3-, 4-, and 5-Parameter Fit
 Linear regression
 Probit-/Logit Multiplex-Analysis
 Sophisticated Test System
 Assay and Sample Suitability Large variety of tests (F-Tests, Equivalence Tests, additional tests)

 Block Effects
 Conditional Tests

Combination Of Assay
Results

 Combination according to European
US

BASIC BIOASSAY PROTOCOL Easy workflow to calculate a reportablevalue for the potency from independent
assays.

Pharmacopeia<111> and <1034>

 Test System
 Automatic aggregation from independent assays (optional)

Equivalence Margin DEV.

 Automatic aggregation of data from
historic assays (optional) Candidate calculation for up to 30 different equivalence margins.

 3 Data Editor Perspectives
 by observation (by row) by sequence (dilution sequence) by position (e.g. plates)
 Report Engine
 validated reports
 extensible
GAMP Support

Three different document types for the Installation Qualification (IQ) Operational Qualification (OQ) Performance Qualification (PQ)

documentation of your measurement pro-

(Requires Validation Package)

MEASUREMENTDOCUMENTATION

cess: Equipment, Operator, Substance

PLATFORM

 Extensible Platform Document Packages
 Report Templates Import/Export/Acquisition Modules
 Coexistence with PLA 1.2, 2.0 and 2.1
 Microsoft Windows (tm) 7, 8, 10, 2008,2012, 2016 supported.

 Supports authentification via LDAP
Data Organization

 Potency calculation with back-fit
 Configuration Optimization

Pharmacopoeia,

 Any number of control limits

Document Handling Databases supported: Microsoft SQL Server (tm) File-based database Security
 Role-based security model Access authorization
 Audit Trail Logs every document event
 Logs every system event Electronic Signatures
 protect documents from modification
 21 CFR Part 11
 Digital Signature
 protect data integrity

PLA COMPONENTS

 PLA 3.0 Base System, including Biological Assays
 Measurement Documentation
 General Document Types
 PLA 3.0 Data Acquisition Modules
 PLA 3.0 Document Import Modules
 PLA 3.0 Document Export Modules
 PLA 3.0 Validation Package
 Customized Report Templates Individual Solutions
PLA SUPPORT CONTRACT 1 year of PLA Support Contract (maintenance contract) included with every
purchase Priority support with a target responsetime of one business day Access to 2nd level support (this includes scientific support)

 Upgrade and downgrade permission
for all covered PLA products during themaintenance time frame Notification service for relevant changes in the guidances Discounted training rates
 PLA Support Contract can be extended
year-by-year or on a long-term agreement.

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PLA 3.0 | Product Overview | 2018

Start Your
Free Trial Now
More than 400 companies and other organisations are already using PLA for theirbioassay analysis. Among them, the top 10 of global biotech and pharmaceuticalcompanies. We invite you to try it, too.

HOW TO GET STARTED WITH PLA 3.0

1. Go to www.bioassay.de
2. Navigate to “Try & Buy” and click on “Download Free Trial Version Now”
3. Fill the form, then download and execute the PLA 3.0 Setup file
4. Start PLA 3.0 and register the software (optional, but recommended)
5. Create a user account and log in.
PLA 3.0 IS NOW READY TO USE
The trial version is fully functional and ready to use for 14 days. After that, we kindly
ask you to purchase a license to continue working with PLA.
Video-Tutorials on our Website will help you getting started with your first PLA bioassay.
Questions about PLA 3.0 ?
Send us an email at support@bioassay.de and we will get back to you.
Support is available in English and German.

Stegmann Systems GmbH
Raiffeisenstr. 2 // C1, C2
63110 Rodgau, Germany

Fon: + 49 6106 77010 - 0
Fax: + 49 6106 77010 - 190
info@stegmannsystems.com

www.bioassay.de© 2018 Stegmann Systems. Product specifications, terms, conditions and prices may be subject to change without notice. Updated last: 2. January 2018