Qualifications and Validation Services

ADVENT provides Qualification and Validation services in accordance with client SOPs and in full compliance with cGMP standards. ADVENT also stays on the leading edge of modern CQV strategies and is well­-versed in developing and implementing risk-­based approaches to process validation. Analogous to Good Engineering Practices (GEP) for process equipment, risk-based validation is a “lifecycle” activity
synchronized with drug production activities, not a “one-time” event to be performed prior to

ADVENT focuses on three areas of Qualification and Validation: Master Planning, Acceptance
Criteria Development, and Protocol Execution. ADVENT has worked with clients to create comprehensive Validation Master Plans (VMP) for sites, projects, and specific unit operations. ADVENT has provided clients with technical expertise as they develop Test Procedures and Acceptance Criteria for new drug products. ADVENT is very familiar with using electronic document management systems from such firms as ValGenesis to manage validation documents and to facilitate efficient review, approval, and execution of protocols.

Validation Master Planning & Management
In the presentation of “The Real World of Project Management (Part 3 of 6): The Project Manager’s Playbook – Commissioning and Qualification” ISPE Annual Meeting, November 2009, ADVENT presented CQV management tools and keys to effectively leverage commissioning documents to satisfy qualification protocol requirements. Advent has extensive experience in developing Master Plans for Validation as well as for Technology Transfer from one site to another.
Test Procedures and Acceptance Criteria Development
The FDA has provided guidelines for the setting and justifying of acceptance criteria as well as the selection of test procedures for new drug substances. ADVENT has supported clients’ efforts to adhere to these guidelines. From justifying “periodic or skip testing” to selecting regional “pharmacopeial tests and acceptance criteria” to using “evolving technologies” for added Quality Assurance, ADVENT has the expertise to provide leadership during this critical step in bringing
a new drug product to market.
Commissioning, Qualification, and Validation (CQV) Protocol Execution
ADVENT staunchly supports the evolution in CQV methodology from the traditional Installation, Operational, and Performance Qualification (IOPQ) using the “V-model” to the science- and risk-based approach centering on the implementation of the ASTM E-2500 Standard. The emerging paradigm aligns with ADVENT’s philosophy that a superior aptitude in engineering is essential in providing value-added CQV services. ADVENT’s staff includes subject matter experts (SME) in upstream and downstream processes as well as fill-finish equipment and practices.
Consent Decree Support
ADVENT was a selected to support the remediation efforts required to lift the consent decree imposed by the FDA. ADVENT was able to meet the first key milestone of qualifying a new QC laboratory required to support the on-going remediation in just under 8 months. ADVENT developed, executed protocols and provided summary reports that met all of the stringent third-party review requirements as part of the consent decree over-sight. The facility and utility expansion mandated by the consent decree remediation included WFI, Clean Steam System, CIP System, Autoclaves, controlled temperature environments and a host of analytical laboratory equipment. The process expansion included Buffer Prep and purification.ADVENT supported the design review of the overall plant remediation by acting as system leads and owners representatives who interface directly with the Architecture/Engineer and Construction firms. ADVENT reviewed the detailed design calculation, red-lined and approved data sheet and P&ID submittals. ADVENT made design change recommendations to ensure compliance with corrective actions to deficiency observations and standard hygienic design practice.IQ/OQ/PQ protocols and summary reports Enhanced Design Review Traceability Matrices Project Schedule, Milestones P&ID Redlines
Risk Based Qualification
ADVENT provided Commissioning and Qualification leads for a 400MM green-field fill-finish facility. ADVENT led the following process areas:Critical Utilities (WFI, Clean Steam, CIP, Process Air, and Process Nitrogen) Component Prep (Autoclave, Parts Washer, Ultrasonic Washer and Stopper Processor) QC laboratory (sterility isolator) Formulation (Feeze-Thaw system, Buffer and Formulation vessels) Fill line and Isolator (Washer, Tunnel, Filler, Capper) Automated inspection Packaging Cold Rooms and WarehousingADVENT led the risk-based planning to ensure that engineering requirements are prioritized, implemented into the design, tracked and tested adequately in the appropriate commissioning, qualification or validation phases of a project. ADVENT staff led risk assessments to enable this risk-based Commissioning and Qualification approach. The project approach was consistent with ASTM E2500-07 and ICH guidances. ADVENT further spear headed the integration of commissioning activities and qualification activities.
Clinical Manufacturing Commissioning and Qualification
ADVENT was selected to provide CQV services for critical utilities and skidded process equipment for a 35MM green-field clinical manufacturing facility that produces a recombinant BDS. ADVENT developed test matrices with pre-approved acceptance criteria and performance requirements. ADVENT’s scope included:Utilities: WFI, Clean Steam, Chilled Water, Autoclaves, Waste Treatment Process Equipment: Chromatography Skids, Chromatography Columns and Packing Station, Parts Washer, Fermentor Systems, Thaw System, Viral Inactivation System.ADVENT developed Mechanical and Automation Commissioning and Qualification protocols. Verified TOPs, redlined P&IDs and operating SOPs. ADVENT was able to leverage FAT and Commissioning execution to minimize repetitive testing under qualification by instituting engineering change management. ADVENT Successfully completed the project on time and on budget.

ADVENT’s high aptitude in process and control engineering adds value to the qualification and
validation of process equipment, automation, and instrumentation. ADVENT has vast experience
with and deep understanding of the design, construction, and operation of the following:

Process Equipment
Cell Culture, Fermentation, and Harvest Systems: Bioreactors and Fermentors using stainless steel vessels or disposable bags operated in batch or perfusion modes; Homogenizers; Centrifugation Systems;Purification and Inactivation Systems: Chromatography Columns of stainless steel and acrylic; Buffer Dilution Skids; Ultrafiltration-Diafiltration (UF-DF) Skids using tangential flow filtration (TFF) cartridges;Filling and Finishing Systems: Vial Washers; Depyrogenation Tunnels; Stopper Processors;
Aseptic Fillers with and without isolators or RABs for Vials and Syringes; Lyophilizers; Cappers; Packaging Systems;Cleaning and Sterilizing Equipment: Steam Sterilizers and Autoclaves; Parts Washers; Clean-In-Place (CIP) Systems; SIP and VHP Processes
Process Instruments and Controls
On-line, Continuous Analyzing Systems for pH, Conductivity, Dissolved Oxygen, and Total Organic Carbon (TOC)Dynamic Control Systems for Temperature, Pressure, and FlowAutomation Systems including Programmable Logic Controllers (PLC), Distributed Control Systems (DCS), Supervisory Control and Data Acquisition (SCADA) Systems, and Building Automation Systems (BAS)
Analytical Instruments
LAL (Limulus Amebocyte Lysate) ReadersUV-VIS, FTIR, and Atomic Absorption SpectrometersHigh-performance Liquid Chromatography (HPLC) SystemsELISA (Enzyme-linked immunosorbent assay) ReadersParticle-size Analyzers using light scattering technology

ADVENT has extensive experience in the qualification of HVAC and BAS systems including: pressure cascades, temperature and humidity controls. As a partner in the qualification process, ADVENT has established environmental monitoring sites and documented material, equipment, and personnel flows for clients as well as established area ISO classifications. ADVENT also has broad experience in the qualification of controlled-temperature environments such as walk-in cold rooms, freezers, and incubators.

ADVENT has partnered with clients to qualify clean utility systems that are critical to the manufacturing process including: Purified Water (PW), Water-For-Injection (WFI) Clean/Pure Steam, and Clean Process Gasses (Air, Nitrogen, Oxygen, Carbon Dioxide). As a part of qualifying clean steam systems, ADVENT has used HTM-2010 to establish non-condensable levels and degrees of superheat in such systems. ADVENT has established sanitization frequency and GMP operating limits (temperature, flow, and back-pressure) for WFI distribution systems as well as dryness (dew-point) testing for Process Air distribution networks.