Quality Manual. Quality Manual. Vera Bioscience / Anu Life Sciences. April 2018

Transcription

1 Quality Manual Vera Bioscience / Anu Life Sciences April 2018 Page 1 of 15

2 TABLE OF CONTENTS Quality Manual Page 1. Company Overview 3 2. References 3 3. Exemptions, Alternatives and Variances 3 4. General Organizational Requirements 3 5. Records Management 6 6. Authorization, Informed Consent, Donor Screening, Tissue Recovery, Collection, Acquisition 7 7. Processing and Storage 7 8. Tissue Release 8 9. Labeling Distribution General Operations Quality Assurance 12 APPENDIX A 15 Page 2 of 15

3 1. Company Overview Anu Life Sciences / Vera Bioscience / Vera Bioscience processes, packages, stores, labels and distributes birth tissue products (e.g., amniotic membrane, amniotic fluid, etc.) for use within the regenerative medicine industry. The organization maintains a quality program to ensure that each product or service supplied conforms to product specifications and meets or exceeds customer s expectations. Anu Life Sciences / Vera Bioscience / Vera Bioscience is located at: SW 12 th Street, Suite 408, Sunrise, FL 33326, USA and is registered with the US Food and Drug Administration as a Human Cell and Tissue Establishment (FEI ). 2. References The quality program conforms to US regulations, standards and directives, some of which are noted below: US FDA 21 CFR Part 1271, Human Cells, Tissues and Cellular and Tissue Based Products Section 361 Public Health Safety Act FDA Guidance for Industry: Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues and Cellular and Tissue- Based Products (HCT/P), December 2011 American Association of Tissue Bank Standards, 14th Edition 3. Exemptions, Alternatives and Variances There are no exemptions, alternatives or variances claimed by Anu Life Sciences / Vera Bioscience / Vera Bioscience. 4. General Organizational Requirements 4.1. Purpose, Institutional Identity and Affiliations Anu Life Sciences, LLC was founded in 2016 by a physician and a biomedical engineer with the mission to be the science innovator in the field of regenerative medicine with guiding principles of ethical integrity and a goal of improving patient outcomes and quality of life. The purpose of the organization is to elevate the standard of care and improve quality of life. In 2018, Anu Life Sciences, LLC was acquired by Vera Bioscience, LLC and is in a transitional phase where the organizational name will be known as Vera Bioscience, LLC in To facilitate a smooth transition and to minimize confusion by customers, patients and the industry, the organization s name will be referred to Anu Life Sciences / Vera Bioscience until the acquisition is complete. Page 3 of 15

4 4.2. Governing Body A Board of Directors, consisting of individuals from various professions, provide governance and strategic direction for Anu Life Sciences / Vera Bioscience. Responsibilities of the Board of Directors include, policy making, issues of liability, ethical considerations, fiduciary responsibility, compliance with applicable laws and regulations and designating senior management as management with executive responsibility Medical Scientific Support Anu Life Sciences / Vera Bioscience has a Medical Advisory Board with a collection of experts from various fields. The members of the board are licensed healthcare professionals, possess advanced degrees and have experience working in the regenerative medicine industry. Responsibilities of the Medical Advisory Board include, acting as advisors for the organization in respect to topics related to medical, technical and science Satellite Facilities No satellite facilities exist at this time for Anu Life Sciences / Vera Bioscience Written Agreements / Contracts Written agreements and contracts are maintained for individuals and organizations who perform tissue banking activities and services (e.g., recovery and collection of tissue, distribution of products, testing, etc.) Contracted / Non-Contracted Lab Services for Donor Disease Testing Contracted laboratories are used for donor infectious disease testing. Before engaging with and during the contracted period, Anu Life Sciences / Vera Bioscience verifies that the lab is registered as a testing facility with the FDA, CLIA certified, using appropriate FDAlicensed tests, retention of donor disease test run records is maintained for ten years and are aware of tissue bank requirements Quality Policy The following quality policy has been established by the organization: Anu Life Sciences / Vera Bioscience is committed to meeting or exceeding customer expectations, complying with statutory and regulatory requirements and to maintaining the suitability and effectiveness of the quality system Organization Organizational flow charts and job descriptions document and define the responsibility, authority and interrelationships of employees. The organizational structure is identified in Appendix A. Page 4 of 15

5 4.9. Responsibilities and Authority The responsibility, authority and the interrelation of personnel who manage, perform and verify work-affecting quality is defined and documented in procedures and in the form of position descriptions. Anu Life Sciences / Vera Bioscience personnel have the organizational freedom and authority to: Initiate action to prevent the occurrence of any nonconformities relating to the product, process and quality system Identify and record any problems relating to the product, process and quality system Initiate, recommend or provide solutions through designated channels Verify the implementation of solutions Control further processing, delivery or installation of nonconforming product until the deficiency or unsatisfactory condition has been corrected Resources Adequate resources and personnel are provided to maintain product quality and to meet the requirements for FDA regulations, AATB accreditation standards and applicable regulations, directives and standards Management with Executive Responsibility Management with Executive Responsibility is the most senior individual located at the Anu Life Sciences / Vera Bioscience facility and is identified on the organizational chart in Appendix A. This individual is responsible for providing the organization with appropriate time, money and resources to effectively maintain the quality system Management Representative / Quality Management Representative The Management Representative, also referred to as the Quality Management Representative, is appointed by Management with Executive Responsibility and is identified in the organizational chart in Appendix A. This individual is located at the Anu Life Sciences / Vera Bioscience facility and has authority over and responsibility for ensuring the quality system requirements are effectively established and effectively maintained Management Review Management review is performed, at a minimum, once a year by the Quality Management Representative. The individual designated as Management with Executive Responsibility is required to attend and participate. Additional employees are invited to represent their applicable departments. Management review is performed to monitor the quality system and verify its suitability, adequacy, and effectiveness in respect to AATB standards, FDA regulations, etc. It is also used to keep management informed of significant events or challenges within the quality system, to review significant preventive and corrective Page 5 of 15

6 actions and deviations and to routinely assess quality objectives, quality policy and monitor progress toward their achievement Technical Policies and Procedures Standard Operating Procedures are established and maintained to meet core CGTP requirements. The procedures are designed to prevent circumstances that increase the risk of introduction, transmission or spread of communicable diseases through the use of HCT/Ps. The procedures are reviewed and approved by a responsible person(s) before implementation and are periodically reviewed to ensure compliance with applicable HCT/P regulations and core CGTP requirements. Procedures are readily available to personnel in the area where operations are performed Quality Assurance Program Anu Life Sciences / Vera Bioscience maintains a quality program to demonstrate compliance to HCT/P regulations and to AATB accreditation standards. It is designed to prevent, detect and correct deficiencies that may lead to circumstances that increase the risk of introduction, transmission or spread of communicable diseases Medical Director Anu Life Sciences / Vera Bioscience contracts with a Medical Director who possesses a valid medical license and has appropriate training and experience in evaluating and determining donor eligibility Technical Staff Anu Life Sciences / Vera Bioscience ensures that personnel engaged in technical and scientific activities have the necessary technical and scientific education, training, background and experience to ensure competent performance of their assigned functions Quality Assurance Staff Anu Life Sciences / Vera Bioscience ensures that personnel engaged in quality related activities have the necessary education, training, background and experience to ensure competent performance of their assigned functions. These employees have sufficient defect awareness, product quality and compliance related training to make them aware of defects that may arise from incorrectly performing their work and to ensure the organization complies with applicable standards, regulations and directives. 5. Records Management Records are maintained to ensure compliance with applicable regulatory requirements. The general record keeping requirements are noted below: Records will remain accurate, indelible, legible and readily available for review Page 6 of 15

7 Records shall be kept within a record management system Records are retained for 10 years beyond the date of distribution, date of transplantation (if known), date of disposition or date of expiration of the tissue (whichever is latest) or longer if required by applicable laws and regulations. 6. Authorization, Informed Consent, Donor Screening, Tissue Recovery, Collection, Acquisition Anu Life Sciences / Vera Bioscience contracts with birth tissue recovery agencies for procurement and appropriate records are documented and maintained. Written contracts / agreements are maintained between the organization and the recovery agency. Periodic audits are performed to ensure contractual obligations and compliance to regulations and standards are met. A process and procedure for receiving tissue at the Anu Life Sciences / Vera Bioscience facility has been established to prevent contamination or cross contamination. 7. Processing and Storage 7.1. Processing Anu Life Sciences / Vera Bioscience has established and maintains procedures during the processing of an HCT/P to prevent contamination or cross contamination. Processing is planned and performed under controlled conditions Environmental Control and Monitoring The environment in which HCT/P products are processed is controlled and monitored. Environmental controls include but are not limited to: temperature and humidity, ventilation and air filtration, cleaning and disinfecting of rooms to ensure aseptic processing operations and maintaining equipment used to control conditions necessary for aseptic processing operations. Environmental monitoring is performed where environmental conditions could reasonably be expected to cause contamination or cross-contamination of HCT/Ps or equipment, or accidental exposure to HCT/Ps to communicable disease agents. The environmental monitoring system is periodically inspected to verify that the system and equipment is adequate and functioning properly. Where appropriate, corrective actions are taken when alerts or action levels are exceeded. Records for environmental control and monitoring activities are maintained Reagents, Supplies, Materials and Equipment Reagents, supplies and materials used during the manufacture of HCT/Ps are verified to meet specifications before use. Examples of supplies include: gauze, cleaning swabs and alcohol pads. Examples of reagents include: cleaning agents, saline, dimethyl sulfoxide Page 7 of 15

8 and chemical and antibiotic solutions used in processing. Records related to supplies and reagents are maintained to ensure they can be linked to individual HCT/Ps. Equipment used in the manufacture of HCT/Ps is appropriately designed to facilitate operations. The equipment is cleaned, sanitized and maintained to prevent malfunctions, contamination or cross-contamination of HCT/Ps or equipment, or accidental exposure to HCT/Ps to communicable disease agents Stock Rotation Limited use or shelf life materials and finished devices are monitored so that when the material becomes obsolete it is removed from use and discarded Process Methods Process changes are verified and/or validated to ensure the change does not create an adverse impact in the operation. Changes are reviewed and approved by a responsible person with knowledge and background prior to implementation. Process validation is performed when the results of processing cannot be fully verified by subsequent inspection and tests. The validation activities and results are documented, and records are maintained Process Controls In process controls have been implemented to ensure the HCT/P product meets predetermined release criteria, specific to the identity, characteristics and quality intended. The process controls are identified within the respective procedure for the activity being performed Storage Adequate controls and practices are implemented to prevent mix-ups, contamination and cross-contamination of HCT/Ps. Designated storage areas and stock rooms for supplies, reagents, raw materials and finished product have been established. 8. Tissue Release Prior to the release of any tissue into distribution for sale, a review process is performed by the Medical Director, technical staff and quality personnel Medical Director Review The review performed by the Medical Director determines donor eligibility based on an evaluation of donor and recovery related records. The review determines if the donor met eligibility criteria and whether the tissue is safe and effective for patient use. Page 8 of 15

9 8.2. Technical Review A technical review is performed to evaluate whether the processing of the tissue met technical specifications set forth within the applicable procedures. The review determines whether pre-release criteria and technical elements were met Quality Review A quality review is performed by quality personnel who evaluate whether quality measures were performed and found acceptable. A written quality release for distribution form is used to document the review. 9. Labeling Anu Life Sciences / Vera Bioscience has an established process to ensure proper HCT/P identification and to prevent mix-ups. The process includes verification of label accuracy, legibility and integrity. Labels are used throughout the processing, packaging and storage process to ensure accuracy and to prevent mix-ups. HCT/P products ready for distribution have labels that are typically affixed to their container, however, in some instances it may be attached with a tie-tag. The following information is recorded on the label: Distinct identification code Description of the type of HCT/P Expiration date, if any Applicable warnings Name and address of the establishment that makes the HCT/P available for distribution 10. Distribution Tissue Distribution Anu Life Sciences / Vera Bioscience has implemented procedures for receiving tissue orders, unit selection, final container, package inspection, shipping and transportation. Records related to distribution (e.g., customer orders, final packaging release, shipping records, etc.) are maintained Tracking Anu Life Sciences / Vera Bioscience HCT/P products are manufactured with full lot traceability. Each product is identified with a distinct identification code that relates the HCT/P to the donor and to all records pertaining to it. An electronic tracking system is used for tracking Anu Life Sciences / Vera Bioscience products. Page 9 of 15

10 10.3. Field Corrections and Removals Procedures have been established for the initiation and performance of a field correction and removal. Circumstances that may require field correction or removal include the result of a complaint, adverse outcome, accident, error, deviation, audit or by any other means Reporting Requirements In the event of a field correction or removal, reporting requirements for applicable federal, state governments as well as organizations, distributors and accreditation organizations shall be performed. 11. General Operations Standard Operating Procedures Manual (SOPM) Policies and procedures have been developed by Anu Life Sciences / Vera Bioscience and are found within the Standards Operations Manual (SOPM). The SOPM is maintained by the quality department Quality System Document Identification Quality system documentation includes: Quality Manual Standard Operating Procedures (SOPs) - These are descriptions of how the work is to be done within and between departments. SOPs establish or further define policies within one specific area of the quality system. Work Instructions (WI s) - These are detailed, step-by-step instructions on how to accomplish specific tasks. Forms - This category includes quality system forms, drawings, etc. Quality Records - Records of quality system activities. This may include operation sheets, completed forms, test reports, etc Control of Quality System Documents A process has been established to control quality system documents according to the following: Written procedures that describe the document control process Review and approval of documents for adequacy by authorized personnel prior to issuance Review, update and re-approval of documents, as necessary Identification of changes and current revision status of documents Controls to ensure that relevant work instructions are available at locations where operations that impact the product or processes are performed Controls to prevent the unintended use of invalid or obsolete documents Page 10 of 15

11 Controls to confirm that documents of external origin are identified, and their distribution controlled Controls to assure that documents remain legible and readily identifiable Annual Review of Standard Operating Procedures Manual (SOPM) An annual review of the SOPM and the safety manual is performed and documented. The Medical Director reviews relevant policies and procedures of a medical nature. The Quality Management Representative is responsible for the annual review and ensures revisions are made to applicable policies, procedures, manuals, forms, etc. Management with Executive Responsibility reviews policies and procedures to ensure adequacy in regard to current practice and applicable standards, laws and regulations. Departmental staff participate in the review process for which they have been trained and are currently responsible to ensure the documents accurately reflect the activities they perform Competence, Awareness and Training A process has been established to determine the necessary competence and training required for personnel performing work within the organization. Management is responsible for ensuring that employees have the education, training, background and experience to correctly perform the tasks they are assigned. It is also required that those employees who perform inspection and tests, or whose work affects product quality, have sufficient defect awareness training to make them aware of defects that may arise from incorrectly performing their work. Training is provided on an ongoing basis either as onthe-job training or via internal or external coursework. Effectiveness of training is assessed either by written test, observation, question and answer or as deemed appropriate by the trainer on a case-by-case basis. The training ensures that personnel are aware of the relevance and importance of their activities and how they contribute to the achievement of the quality objectives. Appropriate records of education, training, skills and experience is maintained for each employee Work Environment The process for determining and managing the work environment needed to achieve conformity to product requirements is defined in standard operating procedures and includes requirements related to the health, cleanliness, and clothing of personnel that may come in contact with the product or the work environment, other foreign matter controls and environmental monitoring. In addition to achieving product conformity, the work environment shall have a positive influence on motivation, satisfaction, integrity, and work ethic in order to provide continuity in employee performance and development. Management and personnel are expected to maintain their work areas. If areas are found unsuitable or have changed in any way that is considered unfit, they shall be corrected immediately and restored back to their intended use and level of functioning. Page 11 of 15

12 11.7. Safety Procedures and Training A safe work environment is promoted through the use of a safety manual, safety training and personal protection equipment. Safety policies and procedures are reviewed annually to ensure they are current and employees receive annual training. Training includes handling and disposing of hazardous materials, bloodborne pathogens, universal precautions and using personal protective equipment Facilities Anu Life Sciences / Vera Bioscience maintains a facility of suitable size, construction and location to prevent the contamination of HCT/Ps with communicable disease agents and to ensure orderly handling of HCT/Ps without mix ups. The facility infrastructure requirements are determined, provided and maintained as needed to achieve conformity to product requirements including, but not limited to: lighting, ventilation, plumbing, drainage and access to sinks and toilets. The facility is routinely cleaned and sanitized to prevent the contamination of HCT/Ps with communicable disease agents. The disposal of sewage, trash and other refuse is performed in a timely, safe and sanitary manner. Records for cleaning and sanitation activities are maintained Security Adequate physical security is maintained to safeguard tissue inventory and records as well as prevent the entry of unauthorized individuals. The security of the organization consists of an alarm system for the entry areas of the facility, key fobs for accessing the laboratory and secured areas holding documents records. Chemicals are stored in secured areas to prevent unauthorized access and use. Access to the secured areas of the facility are dependent on the employees role and responsibilities Equipment and Instruments Equipment and instruments are maintained to ensure they are periodically serviced and calibrated. Calibration performed on equipment is traceable to accepted / known standards, including the National Institute for Standards and Technology (NIST). Personnel (internal or external) performing service or calibrations have the necessary training, qualifications and education to perform such calibrations. Records for equipment maintenance, cleaning, sanitation, service and calibration are maintained. 12. Quality Assurance Quality Assurance Program A quality program has been established to ensure the products and services conform to applicable regulations, standards and directives. The program is designed to prevent, Page 12 of 15

13 detect and correct deficiencies that may lead to circumstances that increase the risk of introduction, transmission or spread of communicable diseases. The Quality Management Representative has authority over and responsibility for ensuring the quality system requirements are effectively established and effectively maintained Quality Control Program Quality control measures have been established to ensure products conform to predetermined acceptance criteria and are within applicable tolerance limits through the use of monitoring. 3 rd party testing may also be used to ensure the products are safe and effective for use (e.g., sterility testing for fungal and bacteria, etc.) Laboratory Quality Assurance Program A laboratory quality assurance program has been established to ensure the validity of test results through the use of appropriate test method selection and validation / qualification measures, monitoring quality control samples, testing integrity of samples, verifying results for release, etc Corrective and Preventive Actions and Deviations Anu Life Sciences / Vera Bioscience takes appropriate corrective action to investigate HCT/P deviations and trends. Corrective and Preventive actions include a short-term action to address the immediate problem and a long-term action to prevent to problem s recurrence. Documentation of corrective actions and HCT/P deviations are maintained Complaints Anu Life Sciences / Vera Bioscience. has established and maintains a process to review, evaluate and document complaints. Records of customer complaint investigations are maintained. If the investigation determines that the activities outside of Anu Life Sciences / Vera Bioscience may have contributed to the customer complaint, relevant information is exchanged between the organizations involved Adverse Outcomes Adverse reactions involving a communicable disease related to an HCT/P distributed by Anu Life Sciences / Vera Bioscience are investigated. If an adverse reaction involving a communicable disease causes one of the following, a report to the FDA is required: Is fatal Is life-threatening Results in permanent impairment of a body function or permanent damage to body structure Necessitates medical or surgical intervention, including hospitalization Page 13 of 15

14 12.7. Reporting All cases of transmissible diseases in a recipient attributed to the allograft are reported in writing to the appropriate health authority in a timely manner Internal Audits Internal audits are performed and reviewed with management, at a minimum, on an annual basis. An internal audit is typically performed by an individual who does not have direct responsibility for the subject matter being audited External Audits External audits are performed for certain services, suppliers, contractors and consultants. An external audit may be performed onsite, remotely through the use of a questionnaire / paper-based audit and is typically performed by an individual who does not have direct responsibility for the subject matter being audited Electronic Systems / Computer Software Computer software, either customized for or programmed by Anu Life Sciences / Vera Bioscience (e.g., to perform a user-defined calculation or to create a table), is validated for its intended use. Computer software that has not been customized or modified (e.g., off the shelf), the performance of the software is verified for its intended use. If computer software is being used for functions other than those related to core CGTP requirements, there is no requirement to validate or verify. Page 14 of 15

15 APPENDIX A Page 15 of 15 not be reproduced in any form whatsoever without written permission. The user of this document must ensure that they are using the latest revision of this document.