Pacific BioLabs is a contract research organization (CRO) offering testing and research support services primarily focused on supporting the pharmaceutical, biotech, and medical device industries. Specializing in the biological sciences, PBL is committed to helping its clients deliver lifesaving medicines and medical devices to physicians and patients who need them.
Pacific BioLabs has a 30-year history of serving companies worldwide. Our location in the San Francisco Bay Area is ideal for providing close support services to the many life sciences companies located nearby, yet we have the experience and capabilities to serve global companies. Our clients range from small biotech and medical device startups to Fortune 500 pharmaceutical giants.
PBL is committed to being The Service Leader in Bioscience TestingSM. A dedicated staff of scientists, quality professionals and support personnel is at the core of our ability to deliver fast friendly service to all our clients. Our staff is recognized throughout the industry for their experience, technical competence and commitment to service.
We conduct all studies in accordance with applicable Current Good Manufacturing Practice (cGMP) and, when requested, Good Laboratory Practice (GLP) regulations. PBL has an outstanding regulatory track record with numerous successful inspections by FDA, EPA, USDA, and international regulatory agencies. With a strong emphasis on training, PBL’s quality systems are designed to prevent errors. An aggressive internal audit program helps assure the quality of data for our clients and the FDA.
Client input is a key element of our continuous improvement process. We gather client feedback on a regular basis. Client audits are an especially valued source of suggestions for refinements to PBL’s quality systems.
Certifications and Registrations
PBL is FDA registered and ISO 9001:2008 and ISO 13485:2003 certified by Intertek. Our animal science operations have been accredited by AAALAC. PBL staff members are active in a number of professional societies and trade associations.
PBL’s operations are housed in the state of the art facility overlooking the San Francisco Bay. This facility includes over 30,000 sq feet of laboratory space, offices, and support areas. It provides a modern GMP-compliant testing environment. Just as importantly, it provides a beautiful, clean and safe working environment for the PBL staff.
For the production of safe medical devices, pharmaceuticals or biotherapeutics, manufacturing environment conditions are of paramount importance. By controlling and monitoring the manufacturing environment, potential bioburden contamination can be limited, helping to ensure a high sterility assurance level for finished products.
Pacific BioLabs has experience in working with manufacturers to develop and implement effective environmental monitoring programs, including air and surface sampling as well as process water testing. Our microbiologists can visit your facility to gather samples, or train your personnel in proper sample collection technique. Additionally, we can provide the necessary supplies for routine sampling and monitoring
Environmental Monitoring Services
Package integrity tests are used to detect packaging problems that could adversely affect the sterility of a medical device. Sterile products are subjected to an environmental stress intended to simulate extreme conditions that a product might encounter in shipping or storage. The product packaging is then subjected to microbial challenge or dye penetration testing to determine if it has retained its properties as a microbial barrier.
Containers may also need to be tested (for example, containers of pharmaceuticals in liquid form.) The materials of these containers may need USP Class Plastics certification, and may need in vitro cytotoxicity testing to ensure any leachable materials from the containers are not harmful to cells.
Package Integrity Tests
USP 232 and USP 233 Elemental Impurities
Historically, inorganic impurities in pharmaceutical, biological and nutraceutical formulations have been measured according to the colorimetric method outlined in USP <231>. This method relies on the precipitation of one or more of only 10 heavy metals, and compares this precipitate visually to a standard. The USP <231> method is limited in that it cannot distinguish between each metal and does not give individual concentrations.
To address these limitations, modern instrumentation like the ICP-MS has been recommended as a replacement to determine heavy metals concentrations, and the USP has created new monographs for heavy metals and trace element detection: USP <232> and USP <233>.
Pacific BioLabs offers ICP-MS for metals detection and elemental impurities screening; many elements in the periodic table can be detected and quantified to a level of 0.1 ng/L or parts per billion (ppb).
Trace Element Detection and Novel Uses
Non-metallic elements can also be detected by ICP-MS, and based on the product, Pacific BioLabs' analytical team can help develop and validate a method to detect metals and other elements. PBL has analyzed pharmaceuticals, medical devices, and raw materials. Our analysts can work to determine the best methodology to characterize a product.
Additionally, because some drugs and biologics contain metals (calcium and iron as metal centers for protein formulations, and platinum and chromium as production catalysts), it is possible to use ICP-MS to quantify the amount of drug in a solution, formulation, or even to analyze biological fluids (such as PK by ICP-MS.)
A marketing application for a biosimilar should be submitted under the 351(k) section of the Public Health Service (PHS) act. To prove biosimilarity, such an application must include information about analytical studies, animal data, and clinical studies. According to section 351(k) of the PHS act, analytical studies should "demonstrate that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components." Understandably, analytical studies should be an essential first step in a biosimilar development program.
The analytical team at Pacific BioLabs can support these analytical studies from start to finish, from initial characterization studies to stability studies to determine the shelf life of a biosimilar. Based on the reference product and its physicochemical and biological analysis, we will help you determine the best course of action for your proposed biosimilar.
Establishing the biocompatibility of a medical device and its components is an important process, and one that is key to ensuring the safety of any device. Historically, biocompatibility has been established primarily through in vivo testing. However, FDA and international regulators are placing an increasing emphasis on characterizing the material and chemical components of devices, including colorants and polymers, through analytical methods. The resulting data is then used to provide a more complete picture of device safety.
As a consequence, new medical device regulatory submissions, or submissions of material or colorant changes to existing devices, must include data thoroughly describing and characterizing the component materials of the device – including the types of polymers and colorants.
Chemical Characterization / Leachables and Extractables
Certain classes of device require a more stringent chemical characterization study. These studies are similar to leachables and extractables studies, and include an associated toxicological risk assessment. Chemical characterization studies, following ISO 10993-18 methods, look at the types and amounts of chemicals that may migrate from a device during use. From this specific chemical profile, an overall risk assessment of the safety of the device can be created.
Chemical characterization studies can be complex and are meant to examine devices with a greater potential risk to users. Currently, the US FDA requires a device chemical characterization / leachables and extractables study with an associated toxicological risk assessment to be performed on any device with the potential for cumulative systemic contact of greater than 29 days. Long term implants would naturally be included, as would many short-term yet repeated-use devices.
Chemical Characterization Studies at PBL
Pacific BioLabs’ team of chemists can work with clients to determine the most appropriate extraction conditions for device characterization. Chemical structure can be studied using Mass Spectrometry. Leached or extracted residual solvents can be analyzed by GC and GC/MS. Parameters such as time, temperature, solvent choice, and nature of device will be considered. Trace and heavy metal analysis is conducted by ICP-MS. Other tests routinely performed include moisture determination by Karl Fischer, pH, conductivity, viscosity, and osmolarity.
PBL is also currently offering toxicological risk assessment reports in conjunction with chemical characterization studies through Gad Consulting. Gad Consulting has operated for more than 22 years, providing drug and medical device toxicology consulting services.
Pacific BioLabs also performs in vivo biocompatibility testing.
According to the FDA, "a container closure system refers to the sum of packaging components that together contain and protect the dosage form." This includes both the primary components which come in direct contact with the drug product, and secondary components such as labeling and outer cartons. Any compounds that can leach into the drug product from the container closure system (CCS) can pose a risk to the patient. Similarly, CCS components (both primary and secondary) must be qualified to be non-toxic by analyzing compounds which can be extracted in the presence of a solvent, if this information is unavailable.
Understandably, the long-term use of parenteral and inhaled dosage forms by patients coupled with a lack of knowledge of material sources in the CCS on the part of drug manufacturers necessitates the analysis of extractables and leachables from the CCS. This risk-based approach is useful in preventing any potential adverse reactions in the patient population that can be attributed to the CCS materials and their interactions with the drug product. Testing methods are explained in the USP monographs <661>, <1151> and <601>.
The analytical team at Pacific BioLabs can help you to develop a testing program most suitable to your CCS and drug product based on these compendial references. Analytical chemists can measure leachables and extractables by GC, GC/MS, and ICP-MS, and characterize and elucidate the structure of compounds by HPLC and mass spectrometry. They will work directly with you to design the most appropriate extraction conditions after considering parameters such as time, temperature and choice of solvent.
Biomarkers can provide information on the different physiological pathways involved in disease progression and hence can be used to measure the safety and efficacy of the drug for a specific disease indication. Often, biomarkers are primary or secondary endpoints in clinical trials.
The analytical team at Pacific BioLabs can develop and validate methods to analyze biomarkers in preclinical and clinical samples such as plasma, serum, urine, tissue, and CSF. Over the past 20 years, we have developed methods for different biomarkers such as proteins, peptides and carbohydrates using LC/MS/MS, ELISA and activity assays.
Available Biomarker Services
Over the past 25 years, the analytical team at Pacific BioLabs has gained vast experience in method development and validation for pharmaceuticals and biologics to support raw materials testing, lead characterization, stability programs, lot release testing, process development and bioanalysis. We work with you to understand your product, your needs and the level of regulatory compliance you require. Our team will then propose the most suitable method development framework for your product.
We can also validate methods according to cGMP, GLP, or ICH requirements (ICH Q2B and Q2A) to prove the suitability of a method for its intended use. Our team will ensure the validated method meets prescribed tolerances for precision, accuracy, sensitivity and reliability. We are flexible in supporting complete or partial validations, re-validations and method transfer with full documentation including a transfer protocol, method, and report generated with QA oversight.
Examples of Method Development Projects Supported
Water is widely used as a raw material, ingredient, and a solvent in the processing, formulation, and manufacture of pharmaceutical products, active pharmaceutical ingredients and intermediates, compendial articles, and analytical reagents. As such, all water purification systems must be monitored regularly to verify the quality of the water produced. This includes chemical purity as well as microbiological quality.
Microbiological quality is monitored through various testing processes including total heterotrophic plate count, coliforms/E. coli monitoring, or by checking for the presence of other organisms suspected to be present in a water sample. Chemical purity of water samples can be assessed quantitatively through the use of Total Organic Carbon (TOC) testing.
Relevant standards relating to pharmaceutical grade water are USP <1231> Water for Pharmaceutical Purposes, USP <643> Total Organic Carbon, and USP <645> Water Conductivity.
Some types of water must also be tested for endotoxins, for example LAL reagent water, USP Water for Injection, and water for hemodialysis. Some steam systems also require certification of low endotoxin levels. In these cases, the LAL Bacterial Endotoxin Test specified in USP <85> should be performed.
Water Testing Services
Antimicrobial preservatives are substances added to nonsterile dosage forms of drugs to protect them from microbiological contamination. Microbes can be introduced inadvertently during manufacturing, or during the continual use of a product.
This test, also known as the preservative efficacy test, is performed to determine if the chosen preservative is appropriate for a product formulation. It is also carried out as part of a stability study, to ascertain whether a preservative system is still effective up to the expiration date of a product. Testing is performed according to compendial requirements in USP <51> and EP 5.1.3.
To evaluate the antimicrobial effectiveness of a product, the product is inoculated with a prescribed quantity of specified microorganisms. The effectiveness of the preservative is evaluated by comparing the initial level of microorganisms to the test sample at various time intervals over a period of 28 days at a specified temperature. Reduction of microorganisms is calculated logarithmically.
Time Kill Analysis
Time Kill Analysis is carried out to evaluate an antimicrobial test material or disinfectant and assesses the in vitro reduction of a microbial population of test organisms after exposure to a test material.
The Time Kill Analysis measures the change in a population of microorganisms within a specified sampling time when after exposure to antimicrobial test materials in vitro. The test article or its dilution is brought into contact with a known population of microorganisms for a specified period of time at a specified temperature. The test article is then neutralized at the target sampling time and the surviving organisms are enumerated. The percent and/or log10 reduction from either an initial microbial population or test blank is calculated.
Several options for organism selection and growth, inoculum preparation, sampling times and temperatures can be requested. Testing is performed according to
ASTM E 2315-03.
Available AET Services
Time Kill Services
Microbial limits testing is performed to determine whether a product complies with compendial specifications for microbial quality. This testing consists of two parts. The quantitative phase, Microbial Enumeration, gives the total number of aerobic organisms as well as a total yeast and mold count on a product. The qualitative phase is known as the Test for Specified Microorganisms. This test is designed to determine the presence or absence of specific objectionable organisms in a product.
Prior to performing MLT testing on a product, the method must be validated to ensure that the product has no microbial inhibitory properties which could produce false negatives. This validation testing is known as the MLT Method Suitability Test.
The relevant standards for the Microbial Limits Test have been harmonized for the US, European, British, and Japanese markets. The relevant standards are USP <61> and <62>, EP Chapter 2.6.12 and 2.6.13, BP Chapter B1 and B2, and JP XV 1st Supplement.
Gathering stability testing data on drug products or drug substances to determine an overall stability profile is a necessary step in the drug approval process. Guidelines for stability testing data as listed in ICH Q1A(R2) have been adopted by the European Union, U.S. FDA, and the Japanese Ministry of Health, Labor, and Welfare.
Drug substance, drug product, medical devices, and raw materials need to be assessed for stability. Pacific BioLabs provides stability sample storage and analysis with 24 hour monitoring of controlled chambers and SOP and protocol driven processes.
Stability Storage Conditions
ICH guidelines give storage conditions and times for long-term, intermediate, and accelerated stability studies. Below are the general storage conditions.
In addition to the ICH compliant standard stability conditions, PBL can provide custom storage conditions (-80°C, -20°C). Other conditions may also be appropriate. For instance, drug product intended for refrigerated storage would undergo long-term storage at 5°C for 12 months.
Stability Study Analysis
PBL can assess the stability profile of products using numerous analytical techniques: HPLC, LC/MS, and GC, for example. Samples are taken at specified time-points and analytically tested to ensure continued viability. For a 24 month accelerated study, samples are typically tested at 1 month, 3 months, 6, 9, 12, 18 and 24 months. In addition, the PBL Microbiology Department can measure sterility, package integrity, endotoxin levels, and bioburden on products.
ICH stability data is required as part of an IND or CTA (EU) submission. Since long-term studies take 24 months or longer, it is prudent for companies to begin gathering stability data once a suitable drug candidate has been selected.
Stability Study Services Offered
Cytotoxicity testing can be useful as a screening tool for pharmaceuticals before more extensive toxicological testing is performed. Additionally, cytotoxicity testing can be used for quality control purposes for lot release testing of raw materials or of manufactured drug products.
Cytotoxicity tests are designed to determine the toxicity to cells of compounds either qualitatively or quantitatively. Qualitative cytotoxicity tests offered by Pacific BioLabs are the MEM Elution Test, the Direct Contact Test, and the Indirect Contact Agar Diffusion Test. In addition, Pacific BioLabs offers a very sensitive quantitative cytotoxicity test, the MTT Assay. Guidelines for cytotoxicity testing are based on ANSI/AAMI/ISO 10993-5 and USP <87> and <88>.
Available Cytotoxicity Tests
To evaluate the effects of drugs or biomaterials on the function of vital organ systems, such as the cardiovascular and central nervous systems. These effects must be evaluated before human exposure, in separate studies or as additions to toxicity studies. Safety tests in animal systems are often preceded by in vitro tests to evaluate biological and pharmacological activity at the cellular level. Standard safety pharmacology studies (as commonly conducted for pharmaceuticals) are not generally required for biotechnology-derived products. These studies define expected and unexpected pharmacological effects of the test material, especially on parameters associated with desired clinical activity.
Variable - depending on the test system
Test System/Animal System
In Vivo: selected pharmacologically relevant species; more than one species indicated for cases with no previous data or when species relevance is difficult to determine.
In Vitro: cell lines derived from relevant animal species; may predict the choice of species most appropriate for in vivo studies.
Variable, depending on the expected effective dose range and test system.
To evaluate the safety and immunogenicity of the test substance.
Pacific BioLabs can also do the following procedures in in vivo (rabbits or rodents) or in vitro systems, as required:
30 to 60 days
Test System/Animal System
Desired volume by intramuscular injection
To determine the potential of a test material to provoke ocular irritation, dermal irritation, or sensitization.
Irritation - one hour to three weeks after a single topical or corneal administration. Sensitization - intradermal or topical induction doses followed by topical challenges with a non-irritating dose (6 - 8 weeks total).
Test System/Animal System
Evaluate the bioavailability, tissue distribution, active metabolite formation, and elimination of test materials.
Test System/Animal System
Rat, Dog, Swine, Primate.
A few days to 2 weeks after a single dose
Test System/Animal System
2 species required. Mice, rats, sometimes rabbits or dogs.
To study the effect of test materials on skin metabolism, or the effect of skin metabolism on xenobiotics
Test System/Animal System
Excised skin, mucosa, or other biological membranes cultured on specialized diffusion cells.
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