Throughout my career as a toxicologist, I have observed that toxicology studies in drug development, are sometimes considered as being only a box-checking exercise on the path to the clinical trial. While this can be so in a limited respect, I think it is underappreciated that definitive toxicology studies, and related studies, serve a highly critical purpose. That is, they help identify potential safety issues and target organs in humans, to identify translational markers of potential toxicity in later human trials and most immediately and importantly they can provide high quality and reliable data on which to base the safe starting dose in humans. Without these definitive studies, or with poorly conducted or interpreted studies, the risk to trial participants and to eventual patients, is simply too high. So, the data from these studies, and particularly the NOAEL information is essential for the safe and effective development of new drugs.

5-common errors in designing & managing IND-enabling toxicology programs with special guest: Glenn Washer, EVP of Global Safety and Toxicology at Frontage Laboratories, Inc.

Tips for developing residual host cell proteins (or HCPs) ELISA assay for biopharmaceutical products using commercial kits with special guest: Dr. Jeng-Dar Yang, Vice President of Biologics Development and Manufacturing Services at Frontage Laboratories, Inc.

Podcast: In Vitro BE Study in ANDA Drug Product Development with special guest: Dr. Kang Wang, Vice President of Analytical Services at Frontage Laboratories, Inc.

Delivery Modalities for Sterile Product Development of Poorly Water Soluble Drugs with special guest: Dr. Manish Mujal, Director of Product Development and CTM Manufacturing at Frontage Laboratories, Inc.

Over the years, the pharmaceutical industry has made steady progress in improving the safety of drugs in development. Consequently, in 2015, only 14 percent of Phase III studies failed due to safety (compared to 55 percent for efficacy), down from 21 percent in 2013. In other words, “efforts to remove unsafe agents earlier in the development cycle are paying off.” Much of this success in small molecules relates to careful and methodical work done well before the Investigational New Drug (IND) application.

The biological activity of biopharmaceutical compounds (such as peptides, monoclonal antibodies, growth factors, and cytokines) has a direct bearing on their potency, which is a critical quality
attribute and a representation of efficacy. For biopharma companies,
measuring a cell’s bioactivity is important when:
• Screening compounds to develop the lead candidate;
• Validating potency when applying for regulatory approval;
• Confirming that the biological characteristics of the productremain consistent throughout the development cycle andfrom lot-to-lot, or site-to-site;
• Controlling for a compound’s quality prior to productrelease (either for a clinical trial or commercialization);
• Testing for stability; and
• Demonstrating biosimilarity between a biosimilar and theoriginator compound.

Stability testing is, in essence, a quality control process and is therefore a vital component of every phase of clinical development for both large and small molecules – from early phase through to and including post approval. It should be treated as an ongoing program rather than as a periodic exercise.

Most of the advanced instruments used in bioanalysis—such as Gas Chromatography (GC), High Performance Liquid Chromatography (HPLC), and Liquid Chromatography-Mass Spectrometry (LC-MS) for example—are automated. Thus, they are controlled by complex computer systems, and the information they generate is stored electronically. If these systems are to be used in regulated research studies in the US, EU, and Japan, the instruments themselves must be qualified and their supporting software and processes must be validated as meeting regulatory requirements.

Pigs share many physiological, anatomical, and metabolic similarities to humans making them a great model. Recently, there has been an increased demand to use miniature pigs as a non-rodent species for pharmacology and toxicology studies as part of pre-clinical drug safety testing. Typically, these tests require more than 8 blood collection time points over a 24 hour period and the same pig may be used to evaluate multiple dose levels or for multiple studies resulting in many blood collections per animal. Additional blood vessel access may also be required for test articles administered intravenously (IV).

Overcoming Stability Issues in the Development of an LC-MS/MS Method for the Quantitation of Azacitidine in Human Plasma

Poster: Quantitation of Myostatin.GDF-8 in Human Serum Using an Enzyme Linked Immunosorbent Assay (ELISA)

Simultaneous Determination of Coproporphyrin-I and Coproporphyrin-III in Human Plasms and Human Urine Using LC-MS/MS

5-common errors in designing & managing IND-enabling toxicology programs with special guest: Glenn Washer, EVP of Global Safety and Toxicology at Frontage Laboratories, Inc.

Tips for developing residual host cell proteins (or HCPs) ELISA assay for biopharmaceutical products using commercial kits with special guest: Dr. Jeng-Dar Yang, Vice President of Biologics Development and Manufacturing Services at Frontage Laboratories, Inc.

Frontage Laboratories, Inc. is a CRO providing integrated, scientifically-driven research, analytical and development services. With over 17 years of experience, we have successfully assisted our clients in advancing hundreds of compounds through the drug development process.

We are a CRO providing integrated, scientifically-driven research, analytical and development services throughout the drug discovery and development process to enable biopharmaceutical companies to achieve their drug development goals. We have enabled many innovator, generic and consumer health companies of all sizes to file IND, NDA, ANDA, BLA and 505(b)(2) submissions in global markets allowing for successful development of important therapies and products for patients. We are committed to providing rigorous scientific expertise to ensure the highest quality and compliance. We have successfully assisted clients to advance hundreds of molecules through development to commercial launch in global markets.

With over 20 years of experience in execution of comprehensive Phase I-IIa studies, Frontage Clinical Services has full capabilities to conduct a broad range of study types (e.g. PK, confinement and ambulatory) in support of tobacco related studies. With extensive expertise in a wide variety of delivery systems, we are well-positioned to conduct tobacco-focused clinical research studies.

Frontage Laboratories provides extensive support to clients in the Agrochemicals industry. Our broad service offering includes biological, chemical, and regulatory support in a GLP-compliant facility.

Frontage’s Bioanalytical Team is highly experienced in developing, qualifying and validating Biomarker assays. We have expertise in ELISA, ECL based platforms as well as ultra-sensitive detection capabilities (Quanterix SimoaTM) for quantitation in the femtogram/mL range including single and multiplex analysis in various disease categories (e.g. Inflammation, Oncology, Neuroscience, Infectious Diseases, Respiratory, etc.).

Gain access to comprehensive biologics services in support of advanced development programs with Frontage’s bioanalytical laboratory. We have the capabilities to analyze virtually any peptide, protein or antibody, and have built a reputation for solving technical challenges related to assay development and validation.

Frontage Laboratories provides bioanalytical services to help support your full drug development. Our state-of-the-art equipment and experienced personnel will quickly and efficiently provide you with the data to support your programs. We provide the resources of a highly skilled, client- focused staff with extensive academic, scientific and pharmaceutical industry experience.

Frontage’s experienced staff and state-of-the-art instrumentation delivers data you can trust. Count on Frontage Laboratories for reliability. From method development or transfer and validation to sample analysis and reporting, Frontage’s bioanalytical team has earned a reputation for consistent and high-quality delivery, project after project. Our bioanalytical expertise extends to combined small and large molecules such as protein, antibody, antibody drug conjugates as well as biomarker analysis for small molecule drug candidates.

Frontage’s clinical teams have set new standards for rapid start-up and efficient study conduct. Our experienced staff provides study management services for all phases of clinical research, including study design, protocol and ICF development, IRB submission, study execution, data management, pharmacokinetic/pharmacodynamic analysis, programming, biostatistics, and medical writing, to take each study from start to finish.

For early phase clinical trial materials, choose a product development team focused on scalability and performance. Ensure comprehensive product analysis with Frontage’s team of experienced analytical scientists.
Frontage brings

Biologics or biopharmaceuticals are inherently more complex than small-molecule drugs. You need the right team to help you. Frontage has expertise and state of the art instrumentation necessary for the analytical method development, validation and transfer for complex biopharmaceutical compounds. Using bottom up, middle up/down, and top down approaches, we offer analytical support for characterization of primary, secondary and tertiary structures, post translational modifications such as glycosylation, disulfide linkage, antibody drug conjugation, or PEGylation.

Ensure comprehensive product analysis with Frontage’s team of experienced analytical scientists. We specialize in analytical method development, validation and transfer for product development and clinical trial materials (CTM) manufacturing support, as well as commercial product release and stability testing. Our services are designed to help sponsors throughout the drug development process in their effort to fully characterize drug substances, developmental formulations and commercial drug products.

Frontage’s CMC portfolio of services spans drug product development, analysis, delivery and supply, from proof-of-concept, preclinical stages through Phase III clinical trials and commercialization support. With proven success in developing drug products for novel, generic and consumer products, we focus our efforts on clients’ specific needs. Our formulation development experience and capabilities cover a wide range of dosage forms at IND, NDA, ANDA and 505(b)(2) project stages and applications.

DMPK studies can provide critical data during discovery and development of pharmaceutical and agrochemical products. Frontage’s DMPK services, performed in accredited facilities, can help support lead drug candidate or chemical selection, or help you meet specific regulatory requirements.

Frontage Laboratories provides drug safety services to guide new therapies from discovery to full development support. Our extensive profile of IND enabling pivotal studies support swift progression of your lead compounds into the clinic – streamlining your development process. We provide the resources of a highly skilled, client-focused staff with extensive academic, scientific and pharmaceutical industry experience.