Erik Foehr, VP of Analytical, Featured in Drug Development & Delivery Magazine

Erik Foehr, PhD., VP of Analytical Services

Erik Foehr, PhD., VP of Analytical Services

The market for biologics and biosimilars is expected to grow significantly throughout this decade. Given this growth, it becomes essential that contract research labs are able to predict trends and add capabilities and capacity, and that development firms are able to effectively tap into those capabilities.  

Examining predictions of how this market may grow was a March 2014 article in Drug Development & Delivery magazine, Analytical Testing of Biologics and Biosimilars, featuring contributions from key thought leaders in the contract analytical research field including PBL's VP of Analytical Testing, Erik Foehr.

Anyone working on the development of biosimilars can benefit from reading this article -  especially those involved in outsourcing. Some key points:

  • "U.S. demand for biologics is expected to grow 6.5% per year to $102 billion in 2015, up from $74.3 billion in 2011, according to Freedonia Group."

  • "...the most commonly outsourced activity is analytical testing because of the need for highly specialized staff and equipment required to perform assays as well as regulatory agencies wanting more characterization and other data about products. On average, facilities outsource 32% of their analytical testing/bioassays..."

  • Dr. Foehr: "Start-ups may not have had the opportunity to learn from mistakes or successes of other innovators - contract labs share in the experience of a multitude of clients. Therefore, the experienced contract labs can be a tremendous resource to the pharmaceutical industry. As Big Pharma sheds R&D resources and virtual start-ups become the norm, in-house analytical experience and technical capabilities dry up. One of the last pools of experienced, well-resourced chemists is now found in the contract lab sector."

See the entire article:

Material and Chemical Characterization of Devices: Part 1, An Overview

This is the first in a series of posts on material and chemical characterization of medical devices.


At PBL we hear a lot of questions from medical device clients regarding FDA material and chemical characterization requirements. To address, and hopefully alleviate some of this confusion, we’ll be delving into material and chemical characterization  - what these terms mean, what the ISO standards say, what the FDA requirements are, and when certain types of testing are necessary.


Historically, assessing the safety (or biocompatibility) of a new medical device has been done primarily through in vivo biocompatibility testing. This testing looks at whether device components, or extracts from a device, have the capacity to cause irritation, damage, or toxicity in an animal system. This method of testing produces data that has been shown to correlate strongly with human biocompatibility.

However, with the advent of more sensitive analytical equipment, and more robust analytical methods, the FDA and other regulatory bodies are increasingly asking for data on the material and chemical components of devices to complement in vivo biocompatibility studies. By analyzing the device components, and by looking at the types and amounts of chemicals that may migrate from a device to a patient during use, potential toxicities can be predicted. We can then examine these potential toxicities, as well as the in vivo testing data, and better assess overall biocompatibility.

Thus, characterization studies are ultimately performed in order to gain a more complete understanding of a device, and of the risk factors associated with using a device. This also explains why the FDA is placing a greater emphasis on these studies - to better ensure patient safety.

Material Characterization vs. Leachables and Extractables

Material and chemical characterization can be summarized fairly simply: it is characterizing a device so that we know clearly what materials the device is composed of, and characterizing the type and amount of chemicals that may leach out of the device during use.

Material characterization refers to identifying all the component materials of a device. This can include colorants, plasticizers, specific metals, and ceramics, for example. Often, specific information and data on materials can be obtained from material manufacturers. In fact, the ISO 10993 standards, a series of standards on methods to be used to determine the biocompatibility of devices, recommend that as much data as possible be gathered from material manufacturers. Preexisting data can significantly reduce the amount of material characterization testing needed.

Chemical characterization is analogous to leachables and extractables, and these two terms are often used interchangeably in device testing. These studies look at what chemicals may come out of the device in both typical usage (leachables) and when challenged (extractables), and these studies are most often conducted according to ISO 10993-17 and 10993-18.

As mentioned previously, a user of the device may be exposed locally and/or systemically to these chemicals, and it is important for the safety of the potential user to know whether use of the device may produce harmful effects. Once the composition of a device is fully known, a qualified toxicologist can conduct a risk assessment to thoroughly characterize patient risk from exposure to device materials.

ISO 10993 Standards for Characterization Studies

Several sections of the ISO 10993 standard cover aspects of material and chemical characterization studies:

  • ISO 10993-9: Framework for identification and quantification of potential degradation products
  • ISO 10993-13: Identification and quantification of degradation products from polymeric medical devices
  • ISO 10993-14: Identification and quantification of degradation products from ceramics
  • ISO 10993-15: Identification and quantification of degradation products from metals and alloys
  • ISO 10993-16: Toxicokinetic study design for degradation products and leachables
  • ISO 10993-17: Establishment of allowable limits for leachable substances
  • ISO 10993-18: Chemical characterization of materials
  • ISO 10993-19: Physico-chemical, morphological and topographical characterization of materials

Although there are multiple sections of ISO 10993 which address material characterization specifically, the standards clearly state that gathering data from the manufacturer is the best way to characterize a material. For instance, ISO 10993-13, section 5.2 (regarding polymeric materials) states:

“The initial material characterization shall address the bulk polymer and the residuals and additives present in the final device. Because of the difficulties of retrospective analysis, this information is best obtained from the supplier or manufacturer of the material [emphasis mine]. It is important to fully characterize the purity of the polymer and the additives used in the formulation.”

Because it is likely that the majority of material characterization data will be obtained from the manufacturer, subsequent posts will focus more specifically on chemical characterization, how this data can best complement in vivo biocompatibility data to inform on the overall toxicity profile of a medical device, and how this data can be used to assess the potential impact of manufacturing or materials changes.

Pacific BioLabs performs Biocompatibility testing of medical devices, including chemical characterization. More information on our characterization services can be found here:

New LSR Forms at PBL

Pacific BioLabs' LSR forms receive a significant update

We're pleased to announce that PBL's Laboratory Service Request forms, which are used to initiate testing, have been redone completely to enhance usability. There are several notable new features of these LSRs:

  • Filled out versions of the forms can now be saved, to make it faster and easier to start repeat, frequently-done testing.
  • Digital signatures are now accepted - LSRs can now be filled out, signed, and emailed electronically.
  • New formatting makes it easier to enter long descriptions or more complete information - such as when entering custom instructions.

The new LSRs can be found here: PBL LSR page.

We recommend using these new LSRs instead of the old versions, and hope that you find these changes useful.

What is Stability Testing?

According to the ICH guideline Q1A(R2) adopted by the FDA and EMA, the goal of stability testing is to demonstrate “how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors, such as temperature, humidity and light..”. To support a stability study, analytical methods using HPLC, LC/MS and GC are used to test for degradation products apart from tests to determine the sterility of the substance and whether the container or packaging of the final commercial product is compromised. 

Understandably, the FDA and other regulatory agencies require this data as part of a registration application for the drug substance or product. Usually, pharmaceutical companies begin stability studies during clinical trials and manufacturing and some even continue these studies after gaining approval.

Pharmaceutical companies arrive at optimum storage conditions and the expiration date of a drug substance or drug product which can be seen commonly on drug labels after collecting stability data over months to years. This data includes the effects of environmental conditions which can significantly alter the physicochemical characteristics, biological activity and other attributes of the drug substance or product. Stability studies are performed for medical devices and raw materials as well.

The ICH Q1A(R2) is a good place to begin since it recommends factors and tests to be considered for a stability data package and draws upon other guidance documents such as “Photostability Testing of New Drug Substances and Products” specific to different aspects of a stability program.

To conclude, monitoring the effects of environmental conditions on the quality of a drug product, substance, medical device and raw material is important to ascertain it is suitable for use by consumers or in manufacturing. Pacific BioLabs supports both long term and accelerated stability programs by providing storage in different conditions according to ICH guidelines and analytical and microbiology testing services. For more information, please visit our Stability Testing page.


ICH Q1A(R2) Stability Testing of New Drug Substances and Products, November 2003

ICH Q1B Photostability Testing of New Drug Substances and Products, November 1996


The Importance of Immunogenicity Testing in Biotherapeutic Development

Immunogenicity, defined as the ability of a substance to produce an immune response, is key to a successful and safe biopharmaceutical drug development program. Therapeutic Antibodies, enzyme therapies, peptides and combination products can elicit an immune response that may impact their safety and efficacy.

Example of an ELISA assay plate

How Biologics Create an Immune Response

Many types of substances administered to the human body may pose a chance of eliciting an immune response. However, biotherapeutics can be especially immunogenic because the large size of these molecules can trick the body into thinking that they are foreign invaders, triggering action by the immune system. These large molecules can also denature, which changes their profile, or aggregate, creating even larger particles. Ultimately, these characteristics can change or increase a biotherapeutic’s immunogenicity profile.

New technologies have been created - for example, PEGylation –to reduce the immunologic effect of biotherapeutics. However, the efficacy of these attempts to reduce immunogenicity varies. It is for this reason that testing for immunogenicity of a product in development is so important. Furthermore, immunogenicity testing is still necessary in a biosimilar development program. This is because the small changes in the manufacturing of biotherapeutics can effect large changes in their immunogenicity profile. Thus biosimilars, which almost invariably will be manufactured under different conditions than their parent biologics, still need to be tested for immunogenicity.

What is Immunogenicity Testing

Immunogenicity assays provide a way to measure the potential immune responses of biologics and biosimilars. Often a single biologic will require a panel of assays to produce a thorough picture of potential immunogenicity. The FDA stipulates that assays should be designed in such a way that they provide sufficient sensitivity, are free from confounding interference, can detect physiological consequences, and account for potential risks based on the profile of the therapeutic and the target patient population.

By designing assays with these factors in mind, it is possible to gather predictive data about the strength and type of immune response that a drug may produce in humans.

Types of Immunogenicity Analysis

For some biologics, a total antibody assay (to measure the antibodies that are part of the immune response) that includes screening, confirmatory and titer components will be sufficient to develop an immunogenicity profile.  In other cases a neutralizing antibody assay or cell based bioassay may be necessary and informative. ELISA (enzyme-linked immunosorbent assay) is also a useful method to detect antibody-antigen complexes.

In addition, aggregation potential of a biotherapeutic can be measured using size-exclusion chromatography and HPLC combined with laser-light scattering. This can help to provide a fuller picture of the overall immunogenic profile of a compound.

The goal of all these tests is, ultimately, to predict the clinical effect of patient immune responses to biotherapeutics. The role immunogenicity plays in drug development is an important one. As such, a well thought out and well executed program is a key to producing safe and efficacious biologic therapies.

To learn more about Pacific BioLabs Immunogenicity Testing Services, visit or contact us at 510-964-9000.

You can also view a PDF download of PBL's Immunogenicity Testing Services.


Genetic Engineering and Biotechnology news: Proposed Standards for Immunogenicity Testing -

ANP Tech: Immunogenicity Testing and Immunogenicity Assays -

FDA: Immunogenicity of Protein-Based Therapeutics -

Wikipedia: Immunogenicity -