TERA is a world leader in deriving safe dose estimates for human health.
At TERA, pharmaceutical services build on our strength as a leader in toxicological risk assessment. Whether you need an Occupational Exposure Limit set for an active pharmaceutical ingredient, are concerned about the safety implications of an impurity in your raw material or finished product, or are not sure how a regulatory guidance applies to your particular situation, we have the expertise to meet your needs. Our highly qualified team includes occupational physicians, industrial hygienists, pharmacists, and board-certified toxicologists.
What's the next step?
To get more information about TERA’s pharmaceutical services or to talk to someone about how TERA can help you, please call us at: 513-542-7475.
Or send an email to: TERA@TERA.org
We specialize in producing OELs for small and large molecules, complex biologic materials, antibodies, and other proteins. Our assessments feature state-of-the-art weight of evidence analysis for point of departure and uncertainty factor determinations. We provide sound, science-based limits that protect worker health.
Occupational Exposure Limits (OEL) Development
TERA can help pharmaceutical companies develop defensible science-based OELs and hazard bands. We routinely develop safe limits for pipeline and legacy active pharmaceutical ingredients (APIs).
Hazard Banding (Control Banding)
Hazard banding provides a tool for hygienists to perform risk management in the workplace when the available data are limited. TERA can help you effectively manage risk by applying hazard banding to new and data-poor compounds.
Health and Safety Clearance of Chemicals
TERA can develop customized frameworks for conducting screening level risk assessments for chemicals newly introduced to facility operations.
Product Quality Limits for Small and Large Molecules and Medical Devices
Get to know your impurities better. Trace amounts of impurities are present in virtually all drug products. Some of them are harmless, while others can present a risk to human health. TERA sets safe levels for impurities to protect human health. We can develop processes and train your staff in human health risk assessment to help ensure product safety.
Impurity Acceptable Daily Exposure (ADE) Values
The ADE concept is based on "the daily exposure to a chemical, over a predefined period which appears to be without appreciable risk on the basis of all known facts at the time."
TERA provides health-based ADE limits for pharmaceutical impurities including starting materials, intermediates, reaction by-products, heavy metals, process reagents, leachables, degradants, and interaction products. Using the most sensitive endpoint, TERA will integrate available pharmacokinetic, pharmacodynamic, and state-of-the-art dose-response modeling approaches to provide safe daily human exposure limits.
TERA can also design, monitor, and manage toxicological testing of impurities in pharmaceutical products.
Excipient Safety Evaluation
From simple to novel, TERA can provide safe exposure limits for excipients taking into consideration the effects of excipients on the bioavailability of the active pharmaceutical ingredient (API).
Cleaning Validation Limits
The objectives of Good Manufacturing Practice (GMP) include prevention of possible contamination of a manufactured product with substances carried over from previous products. Substances of concern include carryover of the API, excipients, residues of cleaning agents, and lubricants. TERA can help you:
+ Determine whether dedicated production lines are recommended for your products;
+ Set maximum allowable carryover limits for products manufactured in shared facilities.
TERA recognizes that different occupational professionals within a company can have very different approaches to risk assessment. Often, this is attributable to differences in the process used for deriving safe limits. TERA specializes in harmonizing risk assessment processes and can help you develop internal processes that are in line with company and regulatory policies.
TERA can help you develop Standard Operating Procedures (SOPs), work instructions, and/or guidance documents using the best available science to support procedural steps in risk assessment.
Health and Safety Clearance of Chemicals
TERA can develop and implement customized frameworks for conducting screening level risk assessments for chemicals in facility operations.
Pharmaceutical Risk Assessment Training Courses
TERA provides hands-on training in hazard characterization, dose-response modeling, and limit setting for both cancer and non-cancer effects. TERA can tailor training courses to the needs of pharmaceutical risk assessors, managers and other profeesionals involved in setting safe exposure limits.
TERA provides several risk resources and training programs through our Global Outreach Program. These programs include our popular "Dose-Response Assessment Boot Camp" which provides intensive, hands-on training in hazard characterization and dose-response assessment for human health risk assessments. Learn more.
Safety Data Sheet Development
Using a state-of-the-art weight of evidence analysis, we can author, audit, and update GHS-Compliant Safety Data Sheets (SDS) for APIs and other chemicals. We will ensure that your documents provide the information needed to protect your workers, the environment, and achieve regulatory compliance.
There are many gaps and deficiencies in the risk assessment process. TERA can help you develop, review, and communicate limits and the analyses behind them. TERA also provides training programs to facilitate understanding of risk assessment methodologies by risk assessors, managers, and the general public.
Mode of Action (MOA) Analysis and Dose-Response Frameworks
Evaluation of mode of action (MOA) plays a critical role in both the hazard characterization and dose-response portions of assessments. TERA can design and conduct studies targeted to address key MOA questions. We have active research projects aimed at developing approaches to quantitatively describe the dose-response relationship for chemicals with multiple MOAs. One area of emphasis has centered on the use of early effects and systems biology to support dose-response assessment. Learn more.
Quantitative Risk Assessment
Quantitative risk assessment provides data based risk estimates derived by mathematically modeling and statistically analyzing the experimental toxicity data. TERA scientists have extensive experience with the tools of quantitative risk analysis, and continue to research and develop new analytical methods to improve risk assessment. Learn More.
TERA’s staff has a detailed understanding of the latest developments in risk science and toxicology and how it is applied practically in risk assessment. Our staff have developed or reviewed the documentation for hundreds of non-cancer and cancer risk assessment values and use the knowledge and experience gained to move the science of risk assessment forward. Learn More
Our team of toxicologists has extensive experience in drug discovery and development, and a proven track-record of managing nonclinical testing programs that have contributed to marketing authorization approvals. Our experience includes evaluations of small molecules, traditional herbal medicines, biologics, and medical devices in numerous therapeutic areas.
Risk Assessment Training
Hands-on training in hazard characterization, dose-response modeling and limit setting for both cancer and non-cancer effects, tailored to the needs of pharmaceutical risk assessors.
TERA can provide expertly prepared nonclinical summaries and overviews for regulatory submissions, investigator brochures, and annual regulatory updates. TERA can also help you respond to regulatory comments and resolve science-based regulatory issues.
Design, Interpretation and Reporting of Pharmacology, Toxicology, and Safety Pharmacology Studies
TERA can aid in designing scientifically sound nonclinical studies. We can also assist in monitoring studies placed at CROs, reviewing study reports, and providing feedback.
TERA is a world leader in peer review. Our expert reviews of nonclinical data packages enable you to make important regulatory and process decisions, as well as facilitating an understanding of key study strengths and weaknesses and their appropriateness for your particular use. We can also identify data gaps, inconsistencies, and the next steps for future work. Learn more.
In solving risk problems for a diverse array of government and private sponsors, we apply a collaborative philosophy that emphasizes partnership building, allowing us to expand our pool of expertise, build on multiple perspectives, and ensure the use of the best science. These strengths form the basis for our development of independent and science-driven analyses for a range of risk assessment needs.
Strategic Regulatory Consulting (SRC)TERA’s pharmaceutical toxicology group provides comprehensive occupational health, pharmaceutical, and medical device support from start to finish.
Alliance for Risk Assessment (ARA)
TERA is a proud member of the Alliance for Risk Assessment, a collaborative effort of organizations dedicated to supporting public health protection by improving the process and efficiency of risk assessment. Given a limited supply of time, resources, and know-how, public health protection is an effort that requires cooperation, organization, and prioritization. The Alliance aims to help. Learn more.
TERA Fellows Program
The TERA Fellow Programs is a collaboration with senior scientists who provide additional depth in specialized areas of toxicology. TERA Fellows share TERA's mission and values, and seek to improve risk assessment practice. Learn more.
Occupational Alliance for Risk Science (OARS)
The Occupational Alliance for Risk Science (OARS) is an initiative to facilitate sharing of information with workers and occupational health and safety professionals. OARS provides a forum for information exchange about exposure guidance for chemical stressors, methods for improving occupational risk assessments, and training opportunities. Learn More.
Some resources and tools are under underdevelopment.
Pharmaceuticals in the Environment (PiE) Support
TERA can evaluate the relative toxicological risk of pharmaceuticals in the environment, including regulatory clean-up and compliance, product stewardship, aquatic and environmental fate, transformation, and exposure. TERA has a large network of ecological toxicologists with a range of expertise that can help solve all PiE related problems.
Pharma Guidance Documents
Muller, L , Mauthe RJ, Riley CM, Andino MM, Antonis DD, Beels C, DeGeorge J, De Knaep AG, Ellison D, Fagerland JA, Frank R, Fritschel B, Galloway S, Harpur E, Humfrey CD, Jacks AS, Jagota N, Mackinnon J, Mohan G, Ness DK, O'Donovan MR, Smith MD, Vudathala G, Yotti L.. A rationale for determining, testing, and controlling specific impurities in pharmaceuticals that possess potential for genotoxicity. Regulatory Toxicology and Pharmacology 2006, 44, 198-211.
Specific Types of Impurities
Occupational Exposure/Clean Limits.
Additional Pharmaceutical Risk Assessment Resources
Ader AW, Sussman RG, Kimmel TA, Ku RH. 2010. Procedures for Determining an Acceptable Daily Exposure (ADE) under Risk-MaPP: Approaches for Developing and Documenting Acceptable Limits for Product Cross-Contamination Purposes. White paper. SafeBridge Consultants, Inc. Mountain View, California and New York, New York. pp. 1-4.
Bercu JP, Sharnez R, Dolan DG. 2013. Advancing toxicology in RiskMAPP: Setting ADEs based on the subsequent drug substance. Regul Toxicol Pharmacol. 65(1):157-61.
Bercu JP, Dolan DG. 2013. Application of the threshold of toxicological concern concept when applies to pharmaceutical manufacturing operations intended for short term clinical trials. Regul Toxicol Pharmacol. 65(1):162-7
Calaude JR. 2007. General Principles for the Safety Assessment of Excipients.
Dolan DG, Naumann BD, Sargent EV, Maier A, Dourson M. 2005. Application of the threshold of toxicological concern concept to pharmaceutical manufacturing operations. Regul Toxicol Pharmacol. 43(1):1-9.
Dourson ML, Parker AL. 2007. Past and Future Uses of Default Assumptions and Uncertainty Factors: Default Assumptions, Misunderstandings, and New Concepts. Hum Ecol Risk Assess. 13: 82–87
ECETOC (European Center for Ecotoxicology and Toxicology of Chemicals). 2010.Workshop on Guidance on Assessment Factors to Derive a DNEL. Brussels, Belgium
EMA (European Medicines Agency). 2008. Guideline on the Specification Limits For Residues Of Metal Catalysts or Metal Reagents. Canary Wharf, London
EMA (European Medicines Agency). 2007. Guideline on Excipients In The Dossier For Application For Marketing Authorization Of A Medicinal Product. Canary Wharf, London
EMA (European Medicines Agency). 2006. Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use. Canary Wharf, London
EMA (European Medicines Agency). 2006. Guideline on the Limits of Genotoxic Impurities. Canary Wharf, London
FDA (Food Drug Administration). 2004. Guidance for Industry PAT- A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance. U.S. Department of Health and Human Services, Food and Drug
Administration, Center for Drug Evaluation and Research (CDER), Center for Veterinary Medicine (CVM) Office of Regulatory Affairs (ORA) Pharmaceutical CGMPs.
FDA (Food Drug Administration). 2005. Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. Center for Drug Evaluation and Research (CDER). Pharmacology and Toxicology.
FDA (Food Drug Administration). 2011 Guidance for Industry Process Validation: General Principles and Practices. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER) , Center for Biologics Evaluation and Research (CBER) , Center for Veterinary Medicine (CVM). Pharmacology and Toxicology.
FDA (Food Dung Administration). 2005. Guidance for Industry Nonclinical Studies for the Safety Evaluation of Pharmaceutical Excipients. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER). Pharmacology and Toxicology.
FDA (Food Drug Administration). 2008. Guidance for Industry Genotoxic and Carcinogenic Impurities in Drug Substances and Products: Recommended Approaches. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Pharmacology and Toxicology.
Flatman S. 2013. Impurities in Biotechnology Products –Experience of Setting Specifications. Jury Great Russell Street, London.
Gaylor DW, Kodell RL. 1980. Linear Interpolation Algorithm For Low Dose Risk Assessment Of Toxic Substances. J Environ Pathol. Toxicol Volume 4, Number 5, 6.
Hebestreit P. 2009. Addressing specific regulatory excipient requirements in the marketing authorization. Global Regulatory Affairs Pharma Ingredients & Services BASF SE PharmSciFair Nice
ICH (International Conference of Harmonization). 2006. Impurities In New Drug Substances Q3A(R2).
ICH (International Conference of Harmonization). 2006. Impurities In New Drug Products Q3B(R2).
ICH (International Conference of Harmonization). 2011. Impurities: Guideline For Residual Solvents Q3C(R5).
IPEC (International Pharmaceutical Excipients Council). 2008. Qualification of Excipients for Use in Pharmaceuticals. IPEC-Americas: Arlington, VA.
Matthews EJ, Kruhlak NL, Benz RD, Contrera JF. 2004. Assessment of the Health Effects of Chemicals in Humans: I. QSAR Estimation of the Maximum Recommended Therapeutic Dose (MRTD) and No Effect Level (NOEL) of Organic Chemicals Based on Clinical Trial Data. Curr Drug Discov Technol. 1:61-76.
Mouton J, Vinks AA, Punt NC. 1997. Pharmacokinetic-pharmacodynamic modeling of activity of Ceftazidime during continuous and Intermittent Infusion. Antimicrob Agents Chemother. 41(4): 733–738.
Naumann BD, Silverman KC, Dixit R, Faria EC, Sargent EV. 2001. Case Studies of Categorical Data-Derived Adjustment Factors. Hum Ecol Risk Assess. 7(1):61-105.
Renwick AG, Lazarus NR. 1998. Human Variability and Noncancer Risk Assessment- An Analysis of the Default Uncertainty Factor. Regul Toxicol Pharmacol. 27(1 Pt 2):3-20.
Sharnez R, Horner MJ, Spencer A, Tholudur A. 2013. Biopharmaceutical Cleaning Validation: Leveraging Acceptable Exposure of Host cell Protein to Set Acceptance Limits for Inactivated Product. JVT. Institute of Validation Technology.
Sharnez R, To A. 2011. Multiproduct Cleaning Validation: Acceptance Limits for the Carryover of Inactivated API Part I- The Comparable Quality Approach. JVT. Institute of Validation Technology.
Sharnez R, Spencer A, Romero J, Runkle S, Carolan C, Hayes R, Mott A, Clark ME, Wyman E, Rasmi M, Donat S, Bellorado K. 2012. Methodology for Assessing Product Inactivation during Cleaning Part I: Experimental Approach and Analytical Methods. JVT. Institute of Validation Technology.
Silverman KC, Naumann BD, Holder DJ, Dixit R, Faria EC, Sargent EV, Gallo MA. 1999. Establishing Data-Derived Adjustment Factors from Published Pharmaceutical Clinical Trial Data. Hum Ecol Risk Assess. pp. 1059-1089.
Tourneau CL, Lee JJ, Siu LL. 2009. Dose Escalation Methods in Phase I Cancer Clinical Trials. J Natl Cancer Inst. 101:708-720.
Walsh A. 2011. Cleaning Validation for the 21st Century: Overview of New ISPE Cleaning Guide. Pharmaceutical Engineering, vol 31. No.6. pp. 1-7.62.
WHO (World Health Organization). 1994. Environmental Health Criteria 170 Assessing Human Health Risks Of Chemicals: Derivation Of Guidance Values For Health-Based Exposure Limits. World Health Organization, Geneva.