Quansys Biosciences - Quality Management System Overview

“Quansys Biosciences is committed to exceptional customer service, high-quality products, and developing employees; while complying with, maintaining, and improving the effectiveness of the Quality Management System.”

Our Quality Policy is communicated throughout the company via training and education. Below is an overview of the Quality Systems and capabilities at Quansys.

Regulatory Status: ISO9001, ISO13485, and cGMP

We are registered with the International Standards Organization (ISO) as 9001:2008 and 13485:2003 compliant, and strive for cGMP compliance.  This means that:

ISO 9001:2008 – General quality management for manufacturing and service industries

  • We have a Quality Management System (QMS) in place that ensures the use of documented procedures required for effective operation and monitors these processes for effective implementation and maintenance.  This includes specific requirements about document and record control, internal audits, product criteria, and resource/information availability.
  • We keep records on how and where raw and in-process materials were processed to allow traceability.
  • Release specifications are determined based on customer and internal requirements procedures are in place to prevent shipping of non-conforming product.
  • We have a Continual Improvement program in place, and regularly review performance through meetings and internal audits.  These proceedings are documented and decisions are data-driven.
  • We have protocols for customer communication, planning product development, and taking action to correct or prevent problems. We keep records of these activities and the resulting decisions and monitor their effectiveness.

ISO 13485 – Medical Devices, Quality Management, and Requirements for Regulatory Purposes

  • We have a QMS specific to medical devices, and our top management is responsible to promote awareness of quality and regulatory requirements throughout the company.
  • We have Supplier Control, Risk Analysis, and Product Realization/Design Control processes in place and utilize extensive documentation and reviews throughout the entire life-cycle of a product.
  • We have controls in the work environment to ensure product functionality and safety during manufacture, distribution, and customer use.
  • We have processes established to properly accept and protect customer property.
  • We have an equipment maintenance program and keep records on all the calibration and validation activities for each device used to produce and quality control all products.

cGMP – Good Manufacturing Practices recommended by the US Federal Drug Administration

  • We validate and monitor manufacturing processes and controls to ensure product consistency and compliance.
  • We maintain a controlled manufacturing area that is hygienic and designed to prevent product contamination.
  • We strive to write procedures that are clear and concise, train operators to use these procedures, and keep records to verify that production protocols were carried out correctly using validated equipment.
  • We have established protocols to investigate production deviations and recall any batch from sale or supply.
  • We keep comprehensive documents on the manufacture and distribution of each product batch.
  • Customer complaints are reviewed, the causes of quality defects are investigated, and appropriate measures are taken to prevent recurrence.
Quansys Analyte Specific Reagents (ASR’s)

Quansys Biosciences is registered as a Medical Device Facility with the FDA.  We test and provide high-quality ASR’s to our customers and maintain the necessary regulatory requirements for those reagents.

Q-View Software Regulatory Compatibility

The Q-View Software has been developed and manufactured by Quansys Biosciences under a Quality Management System which is compliant with ISO 9001:2008, ISO13485:2003, and CFR 21 Part 11, and has the technical components necessary to be used in such environments. The end user of the software, however, is responsible to use these features and prove their own implementation of the cGMP requirements.

For example, the Q-View Software has the GMP-required feature to track which users work on a file by providing the option to set up accounts with either Administrative or User privileges.  This requires all users to log in and out using their own username and password.

Quality System

Quality Manual

Quansys maintains a comprehensive Quality Manual that outlines our Quality Management System, which sets forth the requirements for activities in Quansys.  These include such things as our quality process interactions, departmental quality objectives, controlled document and record management, resource management, product realization planning, customer communications, purchasing process requirements, design and development, production and service provisions, process validation, control of equipment, data analysis, etc.

Quality Policy

We have crafted our Quality Policy to reflect our focus on customers and excellence: “Quansys Biosciences is committed to exceptional customer service, high quality products, and developing employees; while complying with, maintaining, and improving the effectiveness of the Quality Management System.”

Quality Objectives

Our Quality Objectives are based on our Quality Policy and are used to monitor and maintain the effectiveness of the Quality Management System.  Each department has their own objectives which contribute to the company management system.   Objectives are reviewed regularly for performance, relevance and status.

Management Review

We conduct regular Management Reviews of our Quality Management System to review regulatory compatibility, internal and external audits, departmental performance toward Quality Objectives, internal personnel, and resource needs, etc.

Document Control

Documents such as procedures, forms, templates, and records are controlled for clarity and consistency, and traceability.  Any necessary changes are also controlled and documented in a manner compliant with ISO9001, ISO13485, and cGMP.  Controlled documents have identifying marks, and document updates must follow a specified approval process before they can be implemented.

Training

Quansys employees regularly receive both general and job-specific training.  All personnel who, through their duties, impact the quality of the product are trained on the quality system.  Health and safety, computer literacy, and similar are also reviewed.  Specialized training is provided for each job position, and cross-training is encouraged.   All training includes competency assessment and failure awareness.

Corrective and Preventive Actions

At Quansys, we have specific protocols for reviewing and addressing nonconformities, customer complaints, risk analysis, and Corrective and Preventative actions.  Vital in this process is the determination of an action plan, record of actions taken and results, verification of action taken based on specific evidence, and a determination on the effectiveness of the action.

Customer Complaints

We have a defined process for receiving customer communications and performing complaint investigation, correction actions, and any necessary field corrections or recalls. Procedures are also in place for Advisory Notices and Medical Device Reporting should their use be required. Top management regularly reviews customer complaints, questions, suggestions, and commendations, and the trends of these communications.

Audits

Thorough internal audit programs have been established at Quansys to ensure effectiveness and continuous improvement of the Quality Management System according to ISO9001, ISO13485, and cGMP standards.  We also maintain an external audit schedule and regularly host customer audits.

Suppliers

Each Quansys supplier, for both materials and services, goes through an internal approval process before we rely on them for raw materials and services.  Using a combination of methods such as assessment questionnaires, delivery performance, and on-site audits or third-party accreditation, we ensure product supply and quality.

Risk Analysis

Analysis of Risk is regularly performed throughout all processes of the Quality Management System and is part of nearly every process.  Risk analysis is part of supplier analysis, corrective and preventative actions, material analysis, training determination, customer complaints, manufacturing processes, quality control (QC) processes, and many others.   During the development of new products, Risk Analysis is heavily implemented and discussed.  The actions of such analysis is recorded and the completion and results of implementation are assessed and reviewed on a regular basis.

Process Control

We have many procedures and controls in place to keep our processes consistent, effective, and efficient.

Protocol Control

Protocols are controlled via our electronic document management program.  This system ensures that employees always have access to the most up-to-date instructions for producing and testing final product, and cannot accidentally access obsolete SOPs.

Equipment Maintenance

All our equipment has documented operation, calibration, and maintenance methods.  Equipment logs are used to track the fulfillment of these activities, and this is verified monthly by the Quality Department.

Record Control

Procedures exist to ensure that customer interactions, internal training and improvement, equipment, and batch records are maintained and easily available.

Product Nonconformance and Deviation

Protocols to flag and physically label or separate non-passing materials or product are in place at Quansys to prevent these from reaching the customer in any way.  The cause of product non-conformance or deviation is also investigated and tracked.  Additionally, employees are specifically trained to recognize non-conforming material and follow processes to appropriately handle them.

Receiving

When new raw materials arrive, the shipping condition and documentation is checked against the order.  Materials that require further evaluation are kept in “QC Hold” locations while they undergo specified QC tests.  When the review process is complete, the materials are delivered to their final use or storage location.

Labeling

Design, review, approval, and application of labels are controlled according to the Quansys labeling procedures.   Any regulatory requirements for labeling are reviewed by the regulatory department and/or customer for compliance.   Access to labels and labeling devices is restricted to authorized personnel only.

Change Management

Changes of various types undergo specific approval and notification processes involving all departments and customers involved.  Change impact assessment includes Risk Analysis and customer impact.  This process is controlled through multiple records and procedures which are evaluated by affected departments.

Quality Control Testing

We verify the performance of all our supplies, in-process components, products, and services at various stages.  Below are some examples of our process controls and QC tests.

  • Raw Materials: All incoming materials have requirements they must meet before use.  For example, the Certificate of Analysis (CofA) is compared to the order and material label, and the reagent concentration or activity may be measured through spectroscopy or back-lot testing.  For most materials and all reagents further product testing is required to ensure consistent performance and impact on other materials.
  • Plates: Printed plates are inspected for spot morphology and print quality.  Images of the plates are saved and recorded prior to further plate processing.  Every plate batch is tested for performance, signal variation, spot order, cross-reactivity, precision, standard curve fit, reference spots, and negative and positive controls/samples before the batch can be passed.
  • Calibrators, standards, and controls:  Calibrators and standards are referenced to external calibrators when possible.  An internal master calibrator is created for each mix in house which is used to reference all future mixes.  This helps to minimize batch to batch variation of the calibrator.  All calibrators, standards, and controls are tested multiple times by multiple technicians to ensure accuracy and consistency.
  • Detection & Conjugate Mixes: Detection and conjugate mixes are tested and optimized for curve performance and consistency.  Testing parameters assess %Backfit, % Coefficient of Variation (CV), back lot % difference, spot and well background, Lower Limits of Detection (LLD), Lower Limits of Quanitation (LLOQ) and Upper Limits of Quanitation (ULOQ).
  • Diluents: All diluents including assay and sample diluents have specific criteria they must pass before use.  Examples of such criteria are: pH, conductivity, total protein concentration, purity, assay performance, sample control performance, linearity, recovery, and correlation.
  • Q-View Imager Pro and Q-View Imager LS: Each imager is manufactured and tested under the same stringent procedures and processes as our assay product lines.  All components and parts are tested and measured for accuracy and quality before being released to work stations.  Our imagers are assembled in an ESD grounded environment to reduce risk of damage by electrostatic charge.   Testing on the imagers is performed throughout assembly and extensive QC testing is completed post manufacturing by automated analytics as well as QC technicians. The Imager PRO is RoHS compliant and CE marked with FCC certification.
  • Q-View Software: Q-View software development is controlled with various software design control, verification & validation, and release procedures.  Changes are documented, approved, assessed for risk and tested across all facets of the software before release.  Testing is performed by multiple technicians, at multiple stations under many different parameters to verify robustness, consistency, and functionality of the software.
Design Control

The design control process at Quansys ensures that each step of new product development is thoroughly planned, communicated, reviewed and controlled.   Each phase of development includes design reviews and comprehensive testing to ensure final product meets customer requirements. The essential quality aspects of risk analysis, safety, performance, and reliability of a product are established during development, and records of any design and verification activities are kept as Design History Files. The process is flexible and can be customized to meet the customer’s needs.

Below is an outline of what a typical custom assay development entails, including common steps and criteria examples.

Project Start-up, contracts, and agreements

  • Design and development planning commences with a request from the customer.
  • Activities begin at Quansys to define and approve the project with each department and the customer. Each design and development plan includes design inputs and outputs such as:
    1. Evaluation of the need for risk analysis throughout the design process.
    2. Identification and description of the interfaces with different groups that provide, or result in, input to the design process.
    3. Identification and description of the activities that provide, or result in input to the design process.
    4. Proposed quality practices and assessment methodology.
    5. Requirements for record-keeping and other documentation.
    6. Identification of resources.
    7. A description of the anticipated sequence of events related to a particular design.
  • The Quality Manager reviews the proposed feasibility study/evaluation documentation to assure that all domestic and applicable international regulatory requirements are met.

Phase I: Proof of Concept

The purpose of Phase I is to evaluate the feasibility of building and optimizing the assay(s) This is carried out by the R&D department.

  • Phase I Opening Meeting:  Customer-approved documents are reviewed together, reagent sources and target specifications are determined. We ensure that all parties agree on the project scope, inputs, timeline, sources of reagents, and Phase I specifications.  Also established in this meeting is a design review schedule. This encompasses the design and development plan and all records are maintained in the Design History File.
  • New Product Risk Analysis: Considerations are made to evaluate new components for their safety, potential impact on product performance, and factors that would increase the likelihood of lifelong product failure.
  • Reagent Sourcing:  Reagents are sourced and purchased from approved suppliers where available and any new suppliers are vetted.
  • Phase I Assay Development includes:
    1. Qualitative functionality: Reagents are evaluated for potential performance.  If deemed non-functional, alternate reagents or preparation methods may be investigated.
    2. Specificity: Reagents are evaluated for effectiveness in a multiplex ELISA setting, e.g. intra-panel cross-reactivity.
  • Reviews with the customer, and within departments at Quansys are held on a regular basis and the actions from such reviews are recorded and maintained.
  • Phase I Closing Meeting: The customer and the Quansys project team meet together for a final phase I review to assess testing results, and actions for moving forward.

Phase II: Product Optimization and Characterization

The purpose of Phase II is to develop the product, assay and manufacturing protocols.

  • Phase II Opening Meeting:  Customer specifications for assay performance are established.  These are updated throughout product optimization with appropriate approval and documentation.
  • Phase II Assay Development:  The product manufacture and use methods are first optimized by performing tests such as those below until the product meets specifications.  The product is then characterized using the same tests, and the product must pass the established specification unless otherwise approved by the customer. Changes to specifications are documented, recorded and tested.  Examples of development testing are as follows:
    1. Calibrator Referencing and Criteria: Kit calibrator concentrations are confirmed or referenced using commercially available ELISA kits or other reference standard where available. Percent Backfit of all calibrator curve points must typically be 80%-120%.
    2. Cross-Reactivity and Interference: Intra-Panel cross-reactivity must be less than 1% and interference from sample substances (e.g. albumin) must meet specifications.
    3. Intra-Assay Precision:  Multiple replicates of controls are run on multiple plates, %CV must typically be less than 15%.
    4. Inter-Assay Precision:  Multiple replicates of controls are tested over 20 plates from multiple plate batches by different users on multiple days. The % CV between plates must typically be less than 15%.
    5. Recovery and Linearity: Percent recovery and linearity of controls or samples must typically be 80% – 120% of the known concentration.
    6. Assay Drift: Multiple replicates of controls added 0, 10, and 20 minutes before stated in the protocol are run. The percent difference must typically not exceed 10%.
    7. Edge Effects: A control is run over an entire plate.  The %CV between the inner wells, outer wells, and whole plate must typically be less than 10%.  The percent difference between the mean inner and outer wells must typically be less than 8%.
    8. Sample Correlation: Inter-lab and/or inter-method comparison of sample results is evaluated.
    9. Stability: Real-time, accelerated, open-kit, and shipping stability tests are begun.  If a reagent is found to degrade at an unacceptable level, diluents may be re-optimized or further lyophilization testing may be performed.
    10. Software Validation: Kit product codes are checked in Q-View.
  • Variance: If Phase II specifications cannot be met as written, variance approval is obtained from the customer.  Changes to specifications are documented using a Design Specifications Change Form, and changes which affect the “fit, form, or function” must be re-approved by Quansys department managers again.
  • Phase II Closing Meeting: The Sales representative arranges a meeting to deliver and review Phase II data , reports, and the assay protocol. Alpha kits may also be sent to the customer if desired.

Phase III: Design Freeze and Product Verification

The purpose of Phase III is to verify the characterization results of Phase II with a separately produced lot of product It is carried out by the R&D department.

  • Phase III Opening Meeting: Upon acceptance of the Phase II deliverables, the Sales representative arranges a meeting with the customer, R&D Project Manager, Production Manager, and Quality Manager to update and finalize the Product Performance Specifications. After this, design of the product is internally frozen.
  • Phase III Verification testing:  A new lot of kits is produced, and characterization testing is repeated (see Phase II) by the R&D Department using the developed protocol. The new lot must pass the same performance specifications using during Phase II Characterization. If specifications cannot be met, variance approval is obtained from the customer.  Changes to specifications are documented using a Design Specifications Change Form, and changes which affect the “fit, form, or function” must be re-approved by department heads again. The updated kits must re-enter Phase II and pass characterization testing to re-enter Phase III.
  • Once Phase III specifications are met, QC pass/fail specifications and assay protocol documents are finalized.
  • Phase III Closing Meeting: The Sales representative arranges a meeting with the customer, R&D Project Manager, Production Manager, and QC Manager to review Phase III data and reports, and the final assay protocol.  Beta kits may be sent to the customer if desired.

Phase IV: Pilot Production and QC Release

The purpose of Phase IV is to produce the first lot of Q-Plex kits for customer use, then close the project. This is carried out by the Production and QC departments with R&D support.

  • Phase IV Opening Meeting: Upon acceptance of Phase III deliverables, the Sales representative arranges a meeting with the customer, R&D Project Manager, Production Manager, and QC Manager to determine product release, packaging, and shipping requirements.
  • R&D to Production Transfer: The R&D Project Manager arranges meetings/trainings to review the Phase III deliverables internally with Production and plan the effective transfer of all methods, protocols, and remaining inventory.  Transferred reagents to be used for Phase IV are quality controlled prior to use.   R&D assists production throughout all manufacturing stages of the product to correct transfer.
  • Phase IV Pilot Production and QC Release: Manufacture of a pilot lot begins once the Phase IV specifications form is signed by the customer and Quansys, and all reagents and documents have been transferred. The kits are quality controlled according to the pre-established methods and criteria.
  • Once Phase IV Specifications and Pass/Fail Criteria are met, the results are recorded using such documents as our Certificate of Analysis and Production Protocol forms.  These are reviewed by the Project Manager, Production Manager, and QC Manager for completeness.
  • Deliverables shall be given to the customer:
    1. Certificate of Analysis
    2. Assay Protocol
    3. Pilot production kits
  • Phase IV Closing Meeting: The Sales representative arranges a meeting with the customer, Project Manager, Product Manager, QC Manager, and General Manager to review the Phase IV report, Certificate of Analysis, Assay Protocol, and pilot production kits. This meeting serves to ensure customer satisfaction and act as the final design review.

Project Closing

  • Upon customer acceptance of the pilot production kits and other deliverables, the project is considered complete.
  • The R&D Manager distributes a Product Transfer Survey to the Production and QC Managers for continual improvement purposes.
  • Further customer feedback is gathered during the life of the product as part of our risk management system. Based upon this feedback, product changes may be initiated.

With this flexible product development system in place, Quansys is able to provide the multiplexing expertise to build a sensitive, reliable, high-quality product to meet your needs.

Thank you for your interest in the Quality Systems at Quansys Biosciences.  We strive to establish policies and methods that are thorough, clear and concise, yet flexible enough to apply to a variety of applications.  If you have any further questions about our Quality Systems or other capabilities, please contact info@quansysbio.com.