Click here to view this message in a browser window.

SafeBridge® Regulatory & Life Sciences Newsletter

In this Issue:

Latest News
Upcoming Training Courses
Upcoming Conferences

Latest News

SAFEBRIDGE® EXPANDS BRAND TO FORM SAFEBRIDGE® REGULATORY AND LIFE SCIENCES GROUP: PHASE 2 – INCORPORATING LEGACY TRS AND REDSTONE SERVICES

In January, we informed you of SafeBridge’s transformation to SafeBridge® Regulatory and Life Sciences Group. This newer and larger group still has the same roots and core competencies, but has expanded into specialty chemicals including food and beverage ingredients, biocides, and other specialty chemicals.

What does this mean for you, our Clients?

  • A broader experienced staff of toxicologists (now 22) to serve many industries including pharma, biotech, food and beverage ingredients, biocides, and specialty chemicals;
  • Additional support in regulatory compliance including worldwide submissions to agencies including ECHA, FDA, EMA, MHRA, and various regulators in Asia;
  • GLP compliance auditing for studies including genetic and mammalian toxicology, environmental fate and effects, and physico-chemical property studies for submission to regulatory agencies;
  • Greater potential for “turn-key” projects –we can now handle these projects starting with determining the proper protocols, finding laboratories to do the testing, to submitting the results to the regulatory authority;
  • Safety Data Sheets (SDSs) and Poison Control Notification (PCN) dossier preparation to meet business needs and regulatory requirements;
  • An industrial hygiene staff of “potent compound safety” as well as general industry experts; and
  • An AIHA accredited lab with expanded capabilities to meet compounding pharmacy requirements.

Why are we calling this Phase 2?

Phase 2 means we are integrating our services to find the appropriate subject matter experts resourced to meet your needs. As we have always said: “Give us your most difficult occupational or product safety issue, and we can help provide the robust and scientific expertise to address the challenge”.

Phase 2 also means integrating the SafeBridge entities with other parts of our parent company Trinity Consultants Inc., so we can provide a full spectrum of services for our clients. Our affiliated companies include Working Buildings and Advent Engineering who provide GMP auditing, facility and process design, and qualification for the life science industries including biotech and pharma companies.

For further information on our services, please contact Allan Ader @ allan.ader@safebridge.com or Bob Sussman @ robert.sussman@safebridge.com

Biologically Derived Therapies

The past ten to fifteen years have seen an exponential growth in the development of new drug therapies that are derived from biological sources. These therapies provide many safety advantages over traditional “small molecules” that are synthesized by chemical reactions. Just as health and safety professionals are asked to evaluate and control small molecules, these biologicals also require hazard evaluation and exposure control. However, the tools we use to evaluate and control these hazards can be significantly different for those we have traditionally used for small molecules.

In order to advance the knowledge of health and safety professionals in the industry, SafeBridge recently developed and presented a webinar entitled “Biologically Derived Therapies: Evaluating Their Hazards and Controlling Their Exposures”. In this webinar, we defined the types of therapies that would be considered biologicals to include vaccines, components of blood, proteins, cytokines, monoclonal antibodies, and oligonucleotides. It does NOT include “biological agents” which are defined as any pathogenic or living organism, such as viruses, bacteria, human or other animal cells.

The initial inclination when trying to perform a qualitative hazard assessment of these biologicals is to use the criteria matrices we have been using successfully for small molecules. However, the data collected on these molecules can be slightly different that those available for small molecules. The user may be at a loss for how to use this criteria matrix. To address this, SafeBridge has proposed a different criteria matrix to be used when categorizing biologicals.

Containment and control of biologicals to protect workers can also be very different due to the different types of operations used to develop and formulate these drugs. These operations include fermentation, column chromatography, filtration, and harvesting. SafeBridge recommends reviewing the process flow diagram and isolating the various steps where exposures may occur. Most of the “upstream” steps to synthesize the drug involve true biological agents such as mammalian or bacterial cells, while most of the “downstream” steps deal only with biologicals. Many of these operations involve liquids under pressure which means that leaks can generate aerosols and can contaminate the workplace and workers. Even though many safety professionals will be relieved that the drugs are in a liquid form, the pressurization of that liquid can cause some concern.

The process we undergo to evaluate hazards of biologicals and control their exposures is similar to what we use for small molecules. We just need to adapt the tools we use to this new paradigm.

The webinar is available on-line through our Vimeo account and can be rented for additional viewing.

Link: Biologically Derived Therapies - Evaluating Their Hazards and Controlling Their Exposures

Nitrosamine Update

In 2018, nitrosamine impurities, including N-nitrosodimethylamine (NDMA), were found in a number of angiontensin II receptor blockers, which are blood pressure medicines known as "sartans.” Nitrosamines are chemical compounds highly reactive chemical compounds, which may be formed during synthesis of a drug substance or a drug product, or through degradation of drug products. They are highly reactive compounds that are probable human carcinogens, on the basis of animal studies, with a high potency. This finding initially led to voluntary product recalls. However, nitrosamine impurities were subsequently detected in batches of ranitidine, an over-counter (OTC) medicine used to treat heartburn and stomach ulcers, as well as metformin, a diabetes drug; other product recalls were instituted as a result.

Nitrosamines, as a class, are now recognized as a “Cohort of Concern”, signifying that the lowest recommended limit of 1.5 µg/day for DNA-reactive impurities (see ICH Guideline M7(R1)) may not be sufficient. A number of regulatory agencies, including the US Food & Drug Administration (FDA) and the European Medicines Agency (EMA), have established interim intake limits for 6-8 specific nitrosamines, ranging from 26.5 to 96 ng/day for the patient population, and strict new manufacturing requirements have been implemented by these agencies. The interim limit for nitrosamines of unknown toxicity/potency is even lower.

The EMA Committee for Medical Products for Human Use (CHMP) now requires a robust evaluation of the potential risk of nitrosamine formation in approved products containing chemically synthesized APIs, including generics and OTC products for existing/marketed drugs and new authorization applications. The risk assessment should be conducted following the approach outlined in the ICH M7 guidelines and documented using prescribed templates. If a potential risk is identified, the appropriate risk-mitigating measures, including analytical verification of the absence of nitrosamines may be needed. If nitrosamines (or a risk of their potential formation) are detected, this must be communicated to the EMA. Additionally, risk evaluation is now required in new authorization applications.

Risk evaluation documents for existing products do not need to be submitted to EMA but should be made available upon request. Companies should inform competent authorities if a nitrosamine is present in a product, irrespective of the amount detected. This may require manufacturing process changes and it is suggested that companies liaise with competent authorities in these situations.

It is important to recognize that, while nitrosamines as a class are considered a Cohort of Concern, not all nitrosamines are highly reactive or potentially carcinogenic. For each compound identified, a robust health hazard assessment must be implemented to establish appropriate limits, whether they be in ng-range of higher.

Does your company have adequate systems in place to identify and evaluate the risk of potential nitrosamine formation, and to take appropriate steps in the event of an identified risk?

SafeBridge Regulatory & Life Sciences Group are a team of Board Certified or equivalent toxicologists with significant experience in hazard assessments, including ICH M7 evaluations. Together with Ph.D. chemists available to evaluate drug synthesis pathways to predict potential nitrosamine formation under various potential processing conditions, we can provide necessary expert technical advice to meet this regulatory need. Please contact Allan Ader, Ph.D., DABT, Managing Director via email for further information and assistance with nitrosamine risk assessments.

Webinars - Video On Demand

The following training programs are available for a 3-day rental and can be used to train staff to introduce employees working in labs and productions on concepts needed to safely handle potent active pharmaceutical ingredients (APIs) and products; programs are also available for EHS staff, industrial hygienists and safety professional. Use these programs to train remotely in these challenging training times. If requested, a certificate of completion can be issued.

Evaluating the Hazards of Pharmaceuticals - Series

Potent Compound Safety - Series

GHS and Its Application In Pharma

FDA Regulatory Compliance for Hand Sanitizer Manufacturing

Developing Controls (Engineering, Work Practice, and Facility) based on the Occupational Health Category (OHC)

Applying the ISPE Guideline to Surrogate Containment-Control Performance Assessments

Industrial Hygiene Fundamentals - Series

Industrial Hygiene Statistics - Series

Biologically Derived Therapies - Evaluating Their Hazards and Controlling Their Exposures

Upcoming Training Courses

Following are webinars that will occur in the near future. Visit our website for a complete list of training.

Potent Compound Safety Boot Camp for the Environmental Health and Safety Professional (Remote Version)

This course meets for 4 hours/day for 6 days over two weeks. It includes topics on pharmaceutical potent compound safety, taught by the leading industry experts in potent compound safety, and is designed for EHS and related professionals who need to understand the critical concepts of evaluating and safely handling pharmaceutical compounds. The intensive curriculum focuses on evaluation of compound potency and toxicity, sampling and monitoring protocols, control technologies, and effective investigation and communication approaches. Advanced topics covered build on the concepts covered over the first 4 sessions, with a focus on case studies and problem solving to address potent compound safety issues in discovery, development, contract manufacturing, and commercialization. It leverages a systematic approach to successfully support drug R&D and manufacturing operations.

June 7, 9, 11, 14, 16, 18, 2021 -- 12pm to 4pm EDT (9am to 1pm PDT)

USP <800> Facility and Sampling Fundamentals - Are You Getting Ready?

The publication of USP <800> has brought heightened awareness of the importance of proper facility construction and healthcare staff protection from hazardous drug (HD) exposure. While the regulatory status of USP <800> has been delayed due to appeals to USP<797>, most facilities are working towards implementing many of the elements within USP <800>. This webinar will serve as an introduction to USP <800> with an emphasis on practical approaches to the design of the facility and HD containment approaches; determining where to sample, and how to use “environmental sampling” data to effectively minimize worker HD exposure.

June 10, 2021 -- 1pm EST (10am PST, 6pm UK)

Employee Spotlight

Amanada Tuesdale

SafeBridge welcomes our newest employee, Amanda Tuesdale to our Regulatory and Life Sciences Group!

Amanda earned a Bachelor’s degree in Environmental Science at The Ohio State University. She has a broad range of experience in Environmental Health and Safety roles spanning 22 years. She has expertise in global chemical inventories for Australia, North America, South America and New Zealand. She has worked with TSCA under the recent Lautenberg Chemical Safety Act amendment to complete the TSCA inventory reset, 2020 CDR reporting and impact analysis of the EPA identified priority substances. Additionally, her many years of work have given her experience in regulatory process development and implementation, hazard communications, product stewardship, remediation project management, chemical management systems and compliance solutions systems (SAP). She has used these skills to support several markets including industrial chemicals, nutraceuticals and personal care/cosmetics. She has coordinated global cross functional teams that involved working with manufacturing facilities, warehouses, tollers, labs, purchasing and sales.

Outside of work, Amanda likes to stay active with her family hiking, playing tennis and taking pictures.

Welcome to the team, Amanda!

Amanda Tuesdale
SafeBridge - Trinity Consultants
amanda.tuesdale@redstonegrp.com
To add this to your contacts, click here.

Upcoming Conferences

Our experts will be exhibiting at the following conferences and we invite you and your colleagues to come by and see us. Our experts will be happy to answer any questions you have.

Digital: HPAPI Summit 2021
Bob Sussman
June 23-24, 2021

CPhI North America
August 10-12, 2021

Contact Us

About SafeBridge

SafeBridge has a unique team of occupational and environmental toxicologists, industrial hygienists, chemists and safety and environmental professionals providing professional consulting and analytical support to our clients, primarily to pharmaceutical and biotechnology industries worldwide. The addition of TRS expands our services to support the regulatory compliance requirements and toxicological risk assessments of industrial chemicals, food and beverage ingredients, biocides, and other specialty chemicals. It also allows us to provide support in study design and monitoring, quality assurance, and regulatory submission. By adding Redstone, we can now offer support of chemical regulatory activities such as TSCA and REACH and expand our chemical hazard communication capabilities.

Need help? Get answers to your questions by talking to an expert on the SafeBridge Team. Contact Us!

Safebridge logo

SafeBridge Consultants, Inc.
1924 Old Middlefield Way, Mountain View, CA 94043-2503
P 650.961.4820 / F 650.623.0096

Connect with Us:

Copyright © 2021 Trinity Consultants
Our address is 12700 Park Central Drive, Suite 2100, Dallas, TX 75251, US

 
If you do not wish to receive future email, click here.