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Averica Discovery Services, Inc.

Why you should do Impurities Analyses Early in Pharmaceutical Research and Discovery?

Why you should do Impurities Analyses Early in Pharmaceutical Research and Discovery?

March 26, 2019

Major impurities in a drug product should ideally be identified in the early stage of the drug development process, to achieve better control of manufacturing (CMC) in the later stages of compound development. However, those present only at low concentrations are often analyzed significantly later in the process. Finding the structure and source of an impurity is often instrumental in evolving a method for controlling it or eliminating it completely.

Delays in conducting impurity analyses often occur because regulatory deadlines do not require them to be carried out early in the process despite being advantageous. Also, because the analyses take time and much effort, leading to delays until the later part of the clinical development phase.

Averica reduces the burden by drastically cutting out the time and effort required by deploying SFC and a Targeted Isolation™ process. The advantage of SFC is its ability to process the feed material very quickly, at rates which may exceed that of HPLC by more than 20 times.

This permits the main peak due to the pure API to be removed speedily, and thus the sample is enriched, containing all or at least many of the impurities. Individual peaks are then rapidly isolated, taking advantage of the fast pace of method development in SFC.

The early-stage isolation and characterization of an impurity that is made possible by this efficient and cost-effective technique may provide more chances to refine the material delivered for clinical trials, thus improving the definition and granularity when CMC filings are made, and reducing the risk significantly in the late-stage trials.

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An Interview With Antiva Biosciences

An Interview with Antiva Biosciences

March 25, 2019

Antiva Biosciences develops creatively designed therapeutics that dramatically improve health outcomes for patients suffering from diseases caused by HPV. Averica Discovery worked with Antiva to provide specialist contract research services.

Here we sit down with Mike Wallace, Director, Pharm Dev and CMC Project Mgmt at Antiva Biosciences to discuss his experience of working with us.

MW:  We worked with Averica to force degrade an API. The scope of work included analytical method development, force degradation and tentative structural assignments based on impurities’ molecular weights. The project was outsourced because a specialist analytical CRO was required, and the Averica team had the right set of skills to address the problem.

AVE: WHY WAS THIS PROJECT IMPORTANT?

MW: An understanding of degradation mechanisms and the impurities that form via degradation pathways is a required component of an IND and eventually the NDA. A failure to understand how degradation impurities form presents a lack of control with respect to consistent API manufacturing. A perceived lack of control within API manufacturing could lead the FDA to raise questions on a sponsor’s IND and perhaps later reject an NDA, which could be devastating.

AVE: WHY DID YOU CHOOSE AVERICA?

MW: The Averica team had the right set of skills and knowledge to address the problem. Additionally, the Averica team was proactive during initial meetings, and presented a clear strategy for accomplishing the project goals.

AVE: WHAT IS YOUR OVERRIDING IMPRESSION OF WORKING WITH AVERICA?

MW: Partnership – The Averica team understood the scope of the problem. As a result, they were flexible and responsive. The collaboration was therefore productive. They also stayed within the project budget and executed on the agreement in terms of deliverables and estimated timeline. Project results and the Averica team’s execution of the scope of work either met or exceeded expectations. The Averica team’s high-quality results allowed us to develop a phase appropriate understanding of our manufacturing process capabilities and has allowed us to confidently move forward with our next phase of manufacturing process development. We would not hesitate to collaborate on another project with Averica.

To learn more about Averica’s wide range of services visit www.avericadiscovery.com/services/

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Developing and Validating an HPLC Method

Developing and Validating an HPLC Method

February 20, 2019

A host of resources must be harnessed to bring a drug to commercial launch. These include in-house development scientists, CROs and CMOs, all of whom are dependent upon reliable and reproducible data. This inevitably requires methods which generate high-quality results. Method development is a core capability at Averica. Our methods are robust, can be performed in-house by the client through the use of transferable technology, produce consistent results, and are aimed at deadline-oriented drug development processes.

Averica employs a unique method of developing HPLC methods to ensure that each research team can choose the right ones and achieve the right targets during drug development. This is just one of our services, read on to learn more, or visit our services pages to see our full range of capabilities.

ANALYTICAL TECHNIQUES FOR ANY PHASE OF A PRODUCT DEVELOPMENT PROJECT

We have developed analytical methods which are appropriate for any phase of product development. These include:

  • Determining the purity of any specific impurity
  • Assaying impurities for their potency
  • Quantification of impurities
  • Methods to assess chemical stability
  • Methods to assay chiral purity or chiral bioanalytical methods
  • Methods to help chemicals attain ICH Q11 standards, such as when regulated starting materials (RSMs) have to be qualified
  • Analytical methods for molecules which have unique physical characteristics or structural complexity
  • Methods to help modernize traditional or legacy testing techniques
  • Methods to develop product specifications pending the commercial marketing of the product

METHODS THAT ARE APPROPRIATE FOR THE CLIENT AND THE MOLECULE

We are an independent company that specializes in the development and testing of analytical techniques. As such we target the emergence of methods that will benefit a drug development project.

Averica makes it a top priority to meet their clients’ need for highly dependable methods.

When a method is developed at Averica, it is fully tested, and each of the parameters that affect its performance as well as the critical quality attributes (CQA) are examined with attention. These include:

  • The suitability of the system
  • The limit of detection (LOD) and limit of quantitation (LOQ) respectively
  • Linearity of the technique
  • It’s precision
  • The stability of the sample and of the standard
  • The range of the testing method
  • The mass balance

Our researchers work under the constraints of developing methods suited to the compound and we make sure the important method parameters and CQAs are properly defined and fully evaluated. Thus the methods developed by them are appropriate for their purpose, defined as to range, and capable of quick validation.

WHY AVERICA?

  • Robustness
  • Rapid method transfer
  • Importance laid upon defining the method so that it can meet the client’s needs and fulfil the requirements of the development process
  • Long experience with developing methods that are appropriate for difficult compounds and research programs
  • Customized assays
  • Testing of physical characteristics
  • Extensive range of capabilities

OUR RANGE OF INSTRUMENT AND DETECTION SYSTEM

These include the following:

  • Preparative and analytical in purpose – SFC, RPLC and HPLC
  • UPC
  • UPLC
  • GC
  • ELSD
  • MS
  • CAD detection
  • PDA/UV
  • NMR
  • Accurate Mass MS

For more information and to explore our full range of capabilities, visit www.avericadiscovery.com/service.

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Averica Discovery Announces New Leadership Team and Expands into A Larger Facility

Averica Discovery Services Inc., announced today a new leadership team and the expansion into a larger facility to meet rising industry demand. Paul Lefebvre has been promoted to General Manager of the company to work alongside Cindy Berger, Vice President of Operations. In addition, Heather Lane has been appointed to lead sales and marketing activities. Paul has led Averica’s growing laboratory since January 2008 when he joined from Waters. Heather brings over 19 years of business and sales experience in …

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Averica Discovery Services, Inc.

Understanding the importance of stress degradation studies

Understanding the Importance of Stress Degradation Studies

December 4, 2018

“Frequently time is of the essence. It is necessary to evaluate, in a short time span, the stability of a product change, and here, the design of stress conditions which will accelerate decomposition in a meaningful way is necessary. This is a difficult task and one very particular to the stability scientist.” J.T Carstensen.

DEFINING STRESS TESTING AND ITS ROLE IN STABILITY: WHAT DOES IT SHOW?

Stress testing is a fundamental requirement in all drug development programs. It provides evidence of the effect of environmental factors of the quality of a drug substance or product. You don’t want to wait to find out what will happen to your product when exposed to temperature, humidity, light etc.

Steve Baertschi joined us for our Impurities Day to discuss what stability testing is and why it is important.

Stress Degradation: Going from Stress Degradation to a Stability-Indicating Method

COMMON PROBLEMS IN STRESS TESTING OF DRUG PRODUCTS

How to stop stress studies from exploding exponentially

One question we get asked frequently: how many stress tests should be conducted? What degradants should be investigated further? Steve Baertschi shared with us a great case study of stress testing 15 compounds, and how his team defined ‘major’ degradants. Watch it here:

 

 

Watch some of our other videos on stress testing:

Read the ICH guidelines on stability testing: https://www.ich.org/products/guidelines/quality/article/quality-guidelines.html

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Averica Discovery Services, Inc.

Mass Balance – What, When, How?

Averica Mass Balance

Mass Balance - What, When, How?

July 10, 2018

This “fishbone diagram”, shown by permission from Steven Baertschi (S. W. Baertschi et al, Trends in Analytical Chemistry 49 (2013) 126-136), lay’s out everything that could impact mass balance in a study of pharmaceutical stability and degradation.  For our team, this is a problem solver’s map of the world:

Averica Mass Balance

WHAT IS MASS BALANCE?  

When we add together the assay value for the drug and the adjusted responses of all the degradants, they should equal the initial value – mass balance of 100%.  Note that achieving this is dependent on two things: our understanding of the degradation chemistry and the degradants, and the method(s).

WHEN DO WE NEED TO ACHIEVE MASS BALANCE OF 100%?

This is the eternal question.  Guidance is Guidance, so the ICH and FDA never really tell you.  The goal is to gain better and better understanding of degradation pathways and methodology as the development program proceeds, so at any point in a program the measured mass balance is a kind of surrogate measurement of how much you know.   Some compounds required many routes of investigation before they yield all their degradation chemistry secrets, and the agencies leave it up to you to justify the clinical development plan by demonstrating an understanding and control of the chemistry.  New drugs are approved with mass balance less than (or greater than) 100%, but not without some understanding of the variance.

HOW DO WE ACHIEVE MASS BALANCE?

We start with stress degradation studies and HPLC method development. Initial goals are to differentiate related substance degradants from unrelated, to identify key stressors (and thus learn about chemistry), to get MS and UV spectra on degradants (and thus learn about chemistry), and to develop a simple method to resolve them from the drug and from each other.  Calculating mass balance from this initial study tells us something about how much or how little we understand.

From here, we investigate different detectors, and we look to GC and GC/MS for possible volatile degradants.  Later steps might include isolation of specific degradants to determine structure and response factors, giving us better understanding of chemistry and a quantitative correction to the degradant’s response. 

Mass balance is a goal, but it’s only a surrogate for the real goal – a complete, analytically based understanding of the chemistry of the drug under conditions produced in manufacturing and storage.  

 

WATCH MORE CLIPS FROM THE MASS BALANCE PRESENTATION

How Using UV Spectroscopy Can help You Find The Impurities That Get Stuck On The Column

 

How To Improve Your Analytical Chromatography Method By Ditching The Column

 
 

What You Should Do When Your Analytical Method Is Only Detecting 10% Of What It Should Be

 
 
 

What To Do When Your Stability Testing Reveals A Loss Of potency, But No Degradation Products

 
 
 
 

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Averica Discovery Services, Inc.

Increasing Productivity in a Chromatography Lab

Averica Chiral Separation gif

Increasing Productivity in a Chromatography Lab

July 4, 2018

Learn from the chromatography experts how to increase efficiency when using SFC. Paul Lefebvre, Lab Director, Averica Discovery, presented at the AkzoNobel Kromasil Prep Symposium 2018 on:

‘FAST, SCALABLE, PREPARATIVE SFC: MAKING THE SEPARATIONS LAB MORE EFFICIENT’

Download your copy now

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Neopharm Labs Acquires Averica Discovery

Neopharm Labs Acquires Averica

Neopharm Labs Acquires Averica Discovery

November 3, 2016

Today Averica Discovery announced its acquisition by Neopharm Labs, an analytical testing lab based out of Quebec. Together the companies offer a full range of services that cover every stage of the drug development cycle including R&D, method development and validation, impurity isolation and profiling, stability testing and management, and commercial testing in chemistry and microbiology.

Excerpt from Press Release –

“Our clients can now take advantage of an expanded range of services,” adds Dr. Jeffrey Kiplinger, President and CEO of Averica Discovery, who joins Neopharm’s Executive Team as Vice President, Science & Innovation. “With this expansion into the U.S. market, Neopharm Labs builds on our combined strengths and capabilities to provide the very best services to its customers and to ours.”

Full Press Release

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Averica Discovery Services, Inc.

Journal of Chromatography – New Issue on Enantioseparations

Journal of Chromatography - New Issue on Enantioseparations

October 5, 2016

Shout out for the new issue of the Journal of Chromatography – it’s on chiral chromatography!  Available wherever such products are sold (the Harvard Coop?)… or on the interwebs, of course.

j-chrom-a-coverFirst papers I read :

  1. Preparative supercritical fluid chromatography: A powerful tool for chiral separations   David Speybrouck, Emmanuelle Lipka
  2. Comparison of liquid and supercritical fluid chromatography mobile phases for enantioselective separations on polysaccharide stationary phases  Syame Khater, Marie-Anne Lozac’h, Isabelle Adam, Eric Francotte, Caroline West
  3. Toward structure-based predictive tools for the selection of chiral stationary phases for the chromatographic separation of enantiomers    Robert Sheridan, Wes Schafer, Patrick Piras, Kerstin Zawatzky, Edward C. Sherer, Christian Roussel, Christopher J. Welch

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Averica Answers: Can You Capture a 0.01% Impurity?

Averica Answers Impurity Questions

Averica Answers: Can You Capture a .01% Impurity?

Averica Paul Lefebvre

Paul Lefebvre

September 14, 2016

Averica Answers is a series of short videos that each tackle a question we are often asked. In this video, Paul Lefebvre discusses trace impurity isolation.

“We do like to work with the customer to define a source of enriched material. Once we define that source of material it becomes easy to work with.  Now to say, if we had to work with something that was at a very low level, that means is it’s detectable.  Because it’s separatable, we can scale that separation up, and at a minimum, isolate the small peak.  So, given the fact that you can detect it at 0.01% means it is possible to isolate it.”

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