MENUMENU
herobanner

Case Studies

CASE STUDIES

Avomeen Analytical Services understands the importance of confidentiality in serving our clients’ needs. All of our projects are maintained in secure facilities, and all employees have signed non-disclosure agreements.

The following case studies are presented in a modified format to protect the identity of the client and the specific details of their project:

Degradation Analysis of an Oxycodone Tablet

A New Jersey based pharmaceutical company grew concerned regarding API degradation.

Extractables & Leachables Study for a Controlled Drug Solution in a PET Bottle

Avomeen provided customized extractables and leachables testing for a pharmaceutical company.

Healthcare Diagnostic Kit Reformulation

A healthcare product manufacturer desired to create their own line of diagnostic kits.

Investigative Analysis for Personal Injury Litigation

A lawyer with a complex personal injury case came to Avomeen to analyze items for unknown contaminants.

Manufacturer Product Liability

A national fast food franchise lost millions due to defective gift bags which emitted an off-odor.

Innovative Personal Care Product Reformulation

A California based personal care company turned to Avomeen to reformulate their product and make innovative changes.

SUSTAINED-RELEASE PHARMACEUTICAL TABLET FORMULATION

Background

A pharmaceutical company needed 10,000 sustained-release tablets of their active pharmaceutical ingredient (API) and a placebo for an upcoming clinical trial. In an effort to keep costs low, the company wanted to minimize excipients. This factor, along with poor flow properties of the API, made compression of the powder into a tablet a challenging process.

Approach

Avomeen’s tactic to develop the finished product was unique. A combination of high and low molecular weight polymers were utilized to attain a sustained drug release profile. Additionally, flow properties of the API were enhanced by using dry granulation techniques.

Solution

To ensure the expedited time frame and volume was met, Avomeen reallocated resources, and formulation and analytical scientists worked around the clock to develop high quality analytical and manufacturing methods and procedures in an abbreviated time period. Avomeen successfully developed and delivered the sustained release tablets to the clinical trial facility for the commencement of human trials within the client’s compressed time frame.

NOVEL PRODUCT FORMULATION – RARE NATURAL ACTIVE INGREDIENT

Background

A development-stage biotechnology company wanted to develop a complex natural product containing multiple active components. As the product contained a rare natural active ingredient, the challenge was preserving the mechanism of action and meeting the target product profile (TPP). The company contacted Avomeen for accelerated development of a topical product including comprehensive characterization of the active for clinical Phase II studies.

Approach

Avomeen offered its product development and CMC expertise to develop this novel product. Characterization of the active as well as the product development activities were simultaneously performed to expedite the product development time. Given the nature of origin, an array of analyses such as species identification by microscopy/SEM, solid state analysis, particle-size analysis, water activity and water content, bioburden and microbial limits, etc. were performed as part of characterization. Simultaneously, product development efforts were carried out including manufacturing process selection and process parameter optimization to achieve favorable particle size of the active.

Solution

Avomeen’s client was able to meet their tight clinical study timeline. The product was successfully developed with comprehensive characterization of the active and the optimized manufacturing process was efficient to achieve the desired target product profile.

Above all, the clinical trial materials and final finished products were manufactured at Avomeen’s cGMP-capable facility and were made available to the client for clinical phase IIb studies at an earlier-than-anticipated timeline.

RUSH REGULATORY RESPONSE – FDA DEFICIENCY

Background

A transdermal patch manufacturer was facing delays with their overseas partner for responding to a FDA deficiency on their New Drug Application, as the testing established was not accurately quantifying some of the high toxicity degradation compounds. The company contacted Avomeen to investigate and provide a solution that would satisfy the regulatory quality requirements for the assurance of a safe product.

Approach

Understanding the strict time constraints the NDA applicant was facing, Avomeen’s solution consisted of a blend of technical expertise and expediting strategy. As both the sensitivity and selectivity of the testing technique needed significant improvement, Avomeen’s industry-leading development talent focused on improving both sensitivity and selectivity while keeping to the expedited timeline. Cycle times were improved by switching to Ultra High Pressure Liquid Chromatography, and sensitivity was enhanced by using a smaller micron size column. Selectivity was enhanced by changing the separation gradient to eliminate co-elution of impurities, and as a result, process impurities and degradants as low 0.001% could now be measured accurately in the product. Avomeen then performed a full validation of the test method per ICH guidelines, and degradation levels in the drug product were determined using the new validated testing technology.

Solution

The deficiency was resolved and the response became a significant contributor to the approval of the drug product for manufacturing. Using the new testing technology developed by Avomeen’s team of industry and regulatory experts, it was established that the product was, in fact, compliant to all quality standards related to breakdown over the shelf life of the product. The new validated testing technology confirmed that no individual degradants or impurities were present at levels above the safety threshold.

USP <232> <233> ANALYSIS – DIRECT AQUEOUS SOLUTION

Background

A pharmaceutical company was in need of class 1 and 2A elements testing on their API per USP methods <232> and <233>. In order to break organometallic bonds, samples are typically digested in a strong acid such as HCl or HNO3 at approximately 100 °C prior to analysis. The sample was unique in that the API was classified by USP as a rare “direct aqueous solution”, a water soluble compound containing no metals; therefore, digestion was not required. However, as Avomeen’s elemental analysis team analyzed the sample, they observed unexpected repeated instability issues with mercury (Hg).

Approach

During their investigation of observed instability issues, our scientists discovered that Hg analysis in the absence of stabilizers can become troublesome due to Hg2+ depositing on active sites of high density polyurethane (HDPE) and reducing to Hg. The increased volatility of Hg in its elemental form can cause it to adhere to the container, dissipate through the walls, or release into the surrounding atmosphere if the cap is not properly tightened.

Solution

Our team overcame this problem by adding trace quantities of Au in a dilute solution of HCl. Although the exact mechanism of this approach is not thoroughly understood, it has been found to stabilize Hg2+, thus preventing the loss of Hg throughout the course of the analysis.

The methods were verified for recovery, precision, specificity, and system suitability. All analyzed elements, including Hg, passed respective acceptance criteria.

SOLID STATE CHARACTERIZATION – GENERIC DRUG PRODUCT

Background

A generic pharmaceutical company, in the midst defending against patent infringement claims, turned to Avomeen’s experienced and qualified scientists to confirm the form of an active pharmaceutical ingredient (API) present in their drug product. The product innovator alleged that the generic drug contained the same form of API as the original drug product, a clear violation of their patent. The generic company claimed to be using an amorphous form of the API and required a solid state characterization of both the API and drug product to support their case.

Approach

Avomeen’s Ph.D.-led team of scientists designed a rigid and defined testing protocol to ensure reproducible testing was performed across numerous samples, both from the generic company and the product innovator. The custom-built protocol was designed to include several orthogonal techniques to provide conclusive evidence as to which form was present. The samples were prepared with no sample handling and were analyzed using PXRD, DSC, TGA, FTIR, and ssNMR. The combination of various techniques provided a unified and comprehensive evaluation of the API form present in the drug products.

Solution

The form of the API was confirmed to be amorphous, as opposed to the crystalline form established to be present in the innovator’s product, upholding the generic company’s original claims that they had not infringed on the innovator’s patent.

The solid state characterization analysis, respective data, and results that Avomeen’s scientists delivered proved the generic pharmaceutical company’s claims of using a different form of the API in their drug product.

RUSH CONTAMINANT IDENTIFICATION – OTC PRODUCT

Background

A manufacturer of over-the-counter (OTC) products was forced to shut down their production line after finding black specks in one of their products. The manufacturer was confident that the contamination was contained to the last lot produced as release testing was performed on each lot immediately after manufacturing. The unknown source and identity of the contaminant were the cause of concerns regarding the safety of the product, and the production line had to remain shut down until an in-depth investigation was conducted and the origin of the contamination determined.

Approach

Avomeen’s scientists utilized Fourier Transform Infrared Spectroscopy (FT-IR) equipped with a microscope to obtain spectra of the black particles present within the contaminated tablets. Analyses revealed that the contaminant was comprised of a polymer-based material, most likely from a rubber component used within the manufacturing line. As several types of rubber gaskets and connectors were used within the production line, our skilled scientists obtained samples of replacement parts from the manufacturing line and compared the chemical composition of the contaminant to the various rubber replacement parts used within the facility.

Solution

Avomeen’s investigative analyses helped the manufacturer to narrow down the number potential parts that could be the source of the defect. Armed with this knowledge, the manufacturer was able to more effectively and extensively examine their equipment, which led to the discovery of a damaged gasket. Further analyses confirmed that the black particles were of the same chemical composition as the damaged gasket that was found, verifying that this was indeed the source of the contamination.

The manufacturer replaced the damaged gasket and performed a thorough cleaning of their manufacturing lines and equipment. Production was resumed, and lot release testing confirmed that the product was now free of contaminants, much to the satisfaction of the manufacturer.

EXTRACTABLES & LEACHABLES

Background

A manufacturer of consumer goods wanted to reduce costs by switching finished product packaging from glass jars to plastic bottles. The manufacturer had safety concerns about switching to plastic bottles, as plastics are known to leach chemicals such as additives. Three plastic bottle vendors were identified by the manufacturer who then contracted Avomeen to identify which of the three plastic bottles was the safest and leached the least amount of chemicals into the finished product.

Approach

Avomeen’s scientists performed extractable and leachable studies (E&L studies), exposing the plastic bottle to temperatures and simulants to replicate real life conditions. Advanced analytical techniques and instrumentation including Gas Chromatography (GC), Liquid Chromatography/Mass Spectroscopy (LC/MS) were used to identify and quantify leachants in each of the three bottles at the parts per million level.

Solution

The E&L study performed by Avomeen identified the supplier with the safest plastic packaging. The manufacturer was confident in the choice of supplier and bottle when they transitioned from glass to plastic packaging, and were able to reduce costs while maintaining their safety standards.

ANALYTICAL LITIGATION SUPPORT – TRADE SECRET VIOLATION

Background

A law firm representing a chemical manufacturer approached Avomeen to support pending litigation in which a competitor allegedly stole trade secrets from the manufacturer of established oil field products. These formulations were developed over 30 years ago and had very specific ingredients in their formulations, which were protected as a trade secret.

Approach

Avomeen analyzed and compared samples of the oil field products from both the original developer and the allegedly infringing party in order to determine the similarity of the products and to ascertain if trade secrets were, in fact, stolen. Primary analysis techniques utilized included gas chromatography – mass spectrometry (GC-MS), liquid chromatography – mass spectrometry (LC-MS), and inductively coupled plasma – mass spectrometry (ICP-MS).

Solution

The data derived from these analyses on both the original manufacturer’s samples and the suspected infringing samples were analyzed and compared for similarities. Avomeen’s scientists determined that the new formula did, in fact, incorporate the innovator’s trade secret, and both parties were able to reach a settlement.

SCIENTIFIC LITIGATION SUPPORT

Background

A fast food restaurant was involved in a legal dispute with three suppliers over a defective giveaway that resulted in the loss of millions of dollars. Thousands of gift bags containing a plastic children’s toy and candy were defective and emitted a strong chemical odor when opened. The legal battle involved the fast food franchise, manufacturer of the plastic toy, the plastic bag vendor, and the supplier of the candy. The fast food franchise relied on Avomeen’s scientists to determine which party was liable for their loss.

Approach

Avomeen’s scientists built specialized equipment that collected the odorous chemical using a charcoal absorbent. The chemicals were then desorbed and analyzed by advanced, ultra-sensitive Gas Chromatography/Mass Spectrometry (GC/MS) instrumentation.

Solution

The chemicals were identified as residual monomers in the manufacturing of the plastic toy. The fast food franchise relied on the analytical testing, data, and results Avomeen provided to seek damages from the toy manufacturer and recoup their losses from the defective product.

MICROSCOPIC FAILURE ANALYSIS

Background

A producer of pressure measurement devices that measured less than 1 mm in size was experiencing microscopic contamination and, as a result, the devices were being returned by customers. The producer was concerned that they would lose market share due to these failed products, and sought out Avomeen to determine the root cause of the failure.

Approach

Avomeen’s scientists utilized advanced instrumentation and techniques to identify the contaminant, including Scanning Electron Microscope and Energy Dispersive X-Ray (SEM/EDS). SEM/EDS analyses provided high magnification pictures (100-1000x), in addition to elemental scans of the microscopic contaminant particles.

Solution

As a result of SEM/EDS analysis, Avomeen’s scientists concluded that the contamination was not the result of a structural defect, as particles were loosely on top of the product. The contaminant was found to be a byproduct of plastic degradation, the cause of which was traced back to the plastic tubing used during the manufacturing process. The manufacturer prevented contamination of additional devices by making modifications to the tubing used in their manufacturing process.

PRODUCT SAFETY – IMPORT HOLD ALERT

Background

Authorities withheld a shipment of imported tattoo inks at the port of entry, citing a suspicion that a number of the artificial coloring agents in the inks were banned within the U.S. The distributor importing these inks believed that the product complied with the U.S. regulations that govern these products.

Approach

The distributor turned to Avomeen to analyze samples of the inks in question, requesting that Avomeen definitively determine whether the inks contain any banned coloring agents. Avomeen’s scientists analyzed the inks using Ultraviolet-visible (UV/Vis) and Nuclear Magnetic Resonance (NMR) spectroscopy to determine the artificial coloring agents within the products.

Solution

One of Avomeen’s import hold experts reviewed the data and verified that none of the coloring agents within the inks were included in the directory of banned coloring compounds. Avomeen then worked with U.S. Customs Agents to have the distributor’s shipment released without any further interruptions, much to the distributor’s satisfaction.

RUSH CONTAMINATION IDENTIFICATION

Background

A regional food manufacturer was experiencing discoloration of its sealed consumer products weeks before the expiration date. As the contamination extended to a majority of their product line, the manufacturer was in need of immediate resolution. The company contacted Avomeen to investigate and identify the root cause of the discoloration in order to determine remediation methods.

Approach

Understanding the strict time constraints the food manufacturer was facing, Avomeen offered a weekend rush service. The products were delivered to the laboratory on Friday, and results were available to the client on the following Monday morning. Due to the unknown nature of the contaminant, Avomeen’s scientists devised a multi-disciplined approach to determining the contaminant. Fourier Transform Infrared Spectroscopy (FT-IR) and Gas Chromatography (GC) analyses revealed that the off-color was not the result of a chemical contaminant. Avomeen then performed a full range of microbiological analyses.

Solution

Microbiological analyses confirmed the cause of the contamination to be coliform bacteria. Upon discussion of methodology and results with Avomeen’s scientists, the customer used our report and findings to develop and enforce stricter sanitation practices amongst their employees.

PACKAGING PRODUCT FAILURE

Background

A distributor returned a shipment of bottles to a beverage bottle manufacturer due to a slimy, unknown material on the bottles. The manufacturer looked to Avomeen to identify the nature of the material coating the bottles in question.

Approach

Avomeen’s scientists carefully separated the slimy material from the affected bottles and analyzed samples by Raman Spectroscopy. Research and industry experience indicated that the deposit may be residual cleaner, and the spectrum of the unknown material was compared with thousands of spectra of detergents and cleaners.

Solution

The spectra of the slimy material produced by Raman Spectroscopy was a perfect match for a commercial cleaning agent. The bottle manufacturer traced the root cause to a failed cleaning system within the bottle filling plant, which the manufacturer was able to quickly resolve.

POLYMER PRODUCT FAILURE

Background

An automobile manufacturer observed peeling and premature breakage an automobile bumper, which was comprised of a blend of polymers. The manufacturer engaged Avomeen to determine the mode of failure and root cause of peeling and premature breakage.

Approach

Avomeen’s scientists utilized both spectroscopy and microscopy to determine the mode of failure. Examination of the peeling and separation of layers on the bumper with high-resolution microscopy indicated adhesion failure at the point of separation.  Fourier Transform Infrared Spectroscopy (FT-IR) analysis revealed that a polymer compatibilizer had not been added to the polymer blend in the failed product, which must be present in order for the polymers to fully blend.

Solution

Avomeen’s formulation scientists modified the polymer blend that was used to manufacture the automobile bumper, adding a compatibilizer to the formula. The addition of the compatibilizer solved the breakage and peeling problem the manufacturer had been experiencing.

COSMECEUTICAL PRODUCT DEVELOPMENT

Background

An entrepreneur approached Avomeen’s product innovation scientists for assistance in developing an all-natural anti-aging treatment. The entrepreneur had detailed specific performance criteria for the finished product, and had also identified three different competitive products which had specific desirable qualities.

Approach

Avomeen’s deformulation scientists used advanced instrumentation and techniques, including Fourier Transform Infrared Spectroscopy (FT-IR) and Liquid Chromatography/Mass Spectroscopy (LC/MS) to reverse engineer the competitive samples. The exact ingredients of the competitive products were identified and quantified during the deformulation analysis.

Solution

Avomeen’s formulation scientists used data generated from the deformulation analysis, in addition to the client’s performance specifications, to develop a new anti-aging product using all-natural ingredients of higher quality than any product currently on the market. Our scientists developed a number of trial formulations of the innovative anti-aging product for the entrepreneur to test and evaluate. Taking into account the entrepreneur’s comments, feedback, and specifications, the formula was refined and finalized. Avomeen provided the entrepreneur with complete formula details, mixing procedures, and process information, and assisted with transfer of the formulation to a contract blender who the entrepreneur had contracted to manufacture and distribute the product on their behalf.

SPECIALTY PRODUCT REFORMULATION

Background

A distributor of specialty pens and writing instruments relied on one US-based manufacturer to produce the inks used in their products. When the distributor was informed that their manufacturer was moving production overseas, in order to avoid safety and potential quality issues, the distributor turned to Avomeen to identify the formula and production process for their preferred ink product.

Approach

Avomeen’s scientists implemented a multi-phase solution to provide the distributor with an improved ink product. Ink samples from the current US-based manufacturer as well as a competitive product were deformulated. The use of advanced analytical instrumentation and techniques including Fourier Transform Infrared Spectroscopy (FT-IR), Gas Chromatography (GC), Liquid Chromatography/Mass Spectroscopy (LC/MS), and Advanced Extractions led to the identification of the components in both ink samples, as well as the quantities of each component.

Avomeen’s formulation scientists then consulted with the distributor regarding performance criteria for the reformulated ink, and the distributor communicated a desire to improve upon the existing ink product. Discussions revealed that the distributor was interested in developing a product with a higher sheen and shortened drying time.

Solution

The results of the deformulation analyses provided Avomeen’s formulation scientists with valuable information regarding the preferred and competitive ink products. Taking into account the results of the deformulation analysis, as well as years of industry experience, expertise, and advanced knowledge of ink formulations, Avomeen developed an improved ink formulation which met the distributor’s improved performance criteria. Avomeen provided complete formula details, mixing procedures, and process information, and the specialty pen distributor was then able to gain total control over the manufacturing process.

CONSUMER PRODUCT INNOVATION

Background

An entrepreneur approached Avomeen’s Product Development & Innovation team with a need to develop a new cleaning product.  He had researched a number of cleaners and acquired samples of the best products that were currently on the market.  He then sent the samples of these products to Avomeen, along with performance criteria for the innovative product.

Approach

Avomeen’s scientists implemented a multi-phase solution to provide the entrepreneur with an innovative cleaning product that met specific performance criteria and specifications. Our scientists utilized their deformulation expertise as well as advanced analytical instrumentation and techniques including Fourier Transform Infrared Spectroscopy (FT-IR), Gas Chromatography (GC), Liquid Chromatography/Mass Spectroscopy (LC/MS), and Advanced Extractions to identify the active and inactive ingredients within the marketed products. They then compiled a detailed report which consisted of academic research, industry experience and knowledge, and patent applications.

Solution

The detailed report provided vital information that was used by Avomeen’s formulation scientists during the product development process. Our scientists developed a number of trial formulations of the innovative cleaning solution for the entrepreneur to test and evaluate. Taking into account the entrepreneur’s comments, feedback, and specifications, the formula was refined and finalized. Avomeen provided the entrepreneur with complete formula details, mixing procedures, and process information, and assisted with transfer of the formulation to a contract blender who the entrepreneur had contracted to manufacture and distribute the product on his behalf.