ADVENT provides a wide array of engineering services to support every phase of the “GEP Lifecycle” from planning for new products to retirement of equipment. These services include process, industrial, and automation engineering as well as design, construction, installation, and commissioning of cGMP facilities and process equipment used in the development and manufacture of biopharmaceutical drugs.
Good Engineering Practices
ADVENT’s Life Sciences teams have the process, automation, and industrial engineering resources and knowledge to support a client’s GEP Lifecycle approach to capital projects for manufacturing facilities, systems, and equipment as well as manufacturing process improvement initiatives for existing facilities and systems. From planning to execution to verification and beyond, the Life Sciences teams bring expertise and experience in solving the challenges of each Lifecycle phase.
“…Good Engineering Practices (GEP) underpin activities in the day-to-day operations
forward planning of a pharmaceutical business. The adoption of this methodology leads to
a balance of expenditure and activity…”
International Society of Pharmaceutical Engineers (ISPE), ©
Planning and Design
Planning and Design Phase: 1) describe business objectives; 2) delineate the “user
requirements” for the facility and/or systems; 3) assess the capabilities and
procedures of design and construction teams; and 4) develop schedule and budget to
execute project; 5) generate BOD with specific requirements; 6) engineer preliminary
design drawings; 7) establish system and equipment plans; 8) create construction
and/or fabrication specifications for the facility, systems, and/or specific
equipment units; and 9) procure long-lead materials, systems, equipment.
Construction and Start-up
Construction and Start-up Phase: 1) review design documents to ensure they meet user
requirements and business objectives; 2) develop construction documents; 3) examine
submittal information, shop or fabrication drawings; 4) respond to Requests for
Information (RFI’s); 5) monitor equipment fabrication and facility construction; 6)
maintain Turnover Pkgs. (TOP) of supplier and vendor fabrication documents; 7)
execute Factory Acceptance Tests (FAT); and 8) following installation, execute
Start-up plan and Site Acceptance Tests (SAT) plan.
Qualification and Validation
Qualification and Validation Phase: 1) verify and record performance of systems and
equipment under commissioning plan; 2) calibrate instruments and backup automation
software; 3) review test protocols for systems to be validated in accordance with
impact assessments; 4) leverage records from commissioning plan for protocols; 5)
execute test protocols for IOQ and PQ of validated systems; 6) ensure availability
or inventory of required spare parts and change parts; and 7) generate SOPs for
operating and maintaining systems and equipment.
Operation and Maintenance
Operation and Maintenance Phase: 1) manufacture product compliant with cGMP
requirements; 2) manage engineering changes to systems and equipment to improve
performance; 3) develop process models to simulate different operating scenarios; 4)
analyze operational efficiency (OE) using statistical tools (e.g. Six Sigma); 5)
perform preventative maintenance tasks on systems and equipment; and 6) ensure the
effectiveness of corrective and preventative actions (CAPA).
Retirement and Salvage
Retirement and Salvage Phase: 1) evaluate costs of operating and maintaining older
systems/equipment; 2) determine impact of inconsistent equipment performance on
validated status; 3) plan to replace underperforming equipment to maintain
operation; 4) update operational and validated status of systems or equipment to be
replaced, retired or salvaged; 5) prepare system or equipment for decommissioning;
6) salvage, transfer, and/or store decommissioned system; and 7) archive
documentation of system following decommissioning.
The process engineering expertise of ADVENT is expressed through its capability to develop high-
quality documents to assist clients in executing their projects. Using the GEP Lifecycle phases
as an outline, process engineering can take a client’s process description and develop other
planning phase documents. As the project proceeds, ADVENT can generate detailed documents to
support process equipment procurement and facility programming during the design phase. Process
engineers often don hard hats and steel-toed shoes to become “system owners” or project
engineers that provide real-time solutions on-site during the construction and start-up phase.
After the Qualification and Validation phase, ADVENT’s process engineering experience can
support a client during the Operation and Maintenance phase with developing SOP’s to operate,
clean, and store systems such as fermentors, columns, fillers, isolators, lyophilizers, and
Planning and Design
ADVENT’s staff have performed a variety of tasks associated with the Planning and
Design phases of projects including: development of Basis of Design (BOD) and User
Requirements Specifications (URS) for facilities and systems; execution of Supplier
Audits/Assessments of equipment makers; as well as generation and review of Design
documents from facility programming drawings through equipment piping &
instrumentation diagrams (P&ID).
Construction and Start-up
To augment the Construction Management (CM) teams of clients, ADVENT has experienced
“project engineers” to 1) assess “impact” (Direct, Indirect, No) of systems on
product quality; 2) supervise equipment and system procurement; 3) monitor the
fabrication of systems and verify/execute Factory Acceptance Tests (FAT); 4) manage
system deliveries and installations; 5) oversee system start-up, “shakedown”, and
Site Acceptance Tests (SAT).
Operation and Maintenance
ADVENT’s expertise extends along the GEP “lifecycle” from executing CQV to serving
Operation and Maintenance activities for manufacturing and facilities systems. From
supporting Corrective and Preventative Action (CAPA) programs to developing Standard
Operating Procedures (SOP) for Preventative Maintenance, ADVENT staff bring a wealth
of “real world” solutions to enhance change management processes as well as to
improve the operational efficiency of manufacturing.
ADVENT provides consulting services for a number of automation systems and platforms. ADVENT has
served as temporary management of automation and computer validation groups and spear-headed
initiatives for audit preparation and general automation enhancement. ADVENT’s services include:
User Requirement Specifications (URS) and Functional Specifications (FS) and Software Design
Documents (SDD) as well as configuration and commissioning of computer systems. ADVENT’s experiences
in computer validation include test plan development and execution for software and associated
Our experience includes the following:
Process equipment is at the heart of every biopharmaceutical manufacturing or development facility.
ADVENT’s process and industrial engineering expertise includes a fundamental understanding of
biopharmaceutical manufacturing equipment found in all three primary functions: cell culture,
purification, and fill-finish. ADVENT’s experience traverses the process equipment landscape from
designing 25,000-liter bioreactors to trouble-shooting vaporized hydrogen peroxide (VHP)
sterilization processes for isolated filling lines. ADVENT has also supported clients with process
equipment needs in traditional pharmaceutical manufacturing for vaccines, oral solid dosages, as
well as gels and creams. Clients world-wide have relied on ADVENT to support their process equipment
projects at all phases of the GEP Lifecycle.
Fermentation and Cell Culture
ADVENT has vast experience in supporting biologics development and manufacturing clients’
upstream process equipment at every phase of the GEP Lifecycle. Among many projects for
as well as R&D operations, Advent has supported the conceptual design (e.g. URS, PFD) of
cell culture bioreactors employing disposable technology; the preliminary design (e.g.
FRS) of fixed vessel microbial fermentors; the construction, start-up, and commissioning
other upstream process equipment such as media preparation tanks, centrifuges, and
Purification and Viral Inactivation
As harvested cell cultures achieve higher and higher “titers”, biologics manufacturing
clients must explore innovative designs and operation procedures for downstream process
equipment. ADVENT’s expertise has grown in lock step with this trend. ADVENT has studied
equipment and process requirements for performing purification steps in ambient
environments, executed FAT of traditional, steel chromatography columns as well as
designs for buffer preparation using disposable technology and
(UF/DF) skids using Tangential Flow Filtration (TFF).
Fill-Finish and Packaging
Fill-finish equipment manufacturers have made significant improvements in the aseptic
capability and operational proficiency of their equipment. By working with clients on
filling line projects for the last 20 years, ADVENT’s engineers have observed and
in the development of these advancements while making significant contributions during
installation, start-up, and commissioning of filling lines, especially those employing
isolators. ADVENT has experience with fillers of vials, syringes, bottles, and airless
dispensers as well as particular expertise in lyophilization or freeze-drying
Clean Utilities and Manufacturing Support
Clean utilities systems and manufacturing support equipment are the behind-the-scenes
workhorses of biopharmaceutical manufacturing. ADVENT has performed all manner of
engineering tasks from overseeing the passivation of equipment/piping to developing
fabrication specifications to assessing the capabilities of equipment suppliers for
utility and support system required for producing and developing biopharmaceuticals
including WFI Distillation Systems (Multi-effect, Vapor Compression), Pure/Clean Steam
Generators, Clean-In-Place Systems (Stand-alone, Network), Autoclaves/Steam Sterilizers,
Biologics and pharmaceutical drugs are vital components of today’s healthcare system. The facilities
that house the manufacturing and research operations of clients are vital components of their
business. ADVENT has assisted clients in supporting the lifecycles of these facilities including:
major renovations and remodels of existing buildings, re-classification of GMP areas following
extended shutdown periods, as well as planning and conceptual designing of next generation
facilities. Whether starting up a state-of-the-art multi-line fill-finish facility with Class A
environments or drawing up preliminary building plans for a research and development facility,
ADVENT has the resources and experience to support the engineering tasks required by clients during
the lifecycle of their facilities.
Bulk Drug Substance (BDS) Manufacturing
Though all bulk drug substance (BDS) production must adhere to and promote Good Manufacturing
Practices (GMP), the facilities that house these operations are varied in technology and complexity.
From flu vaccine makers using fertilized chicken eggs in incubators to the producers of monoclonal
antibodies (mAb) using mammalian cells in stainless steel bioreactors, ADVENT has assisted a number
of clients in planning, designing, building, starting up, and commissioning the full spectrum of BDS
manufacturing facilities under cGMP compliance.
Fill-Finish (Parenteral) Manufacturing
Parenteral manufacturing facilities producing drug products (DP) requires stringent levels of
environmental controls to provide an environment that can support aseptic processing. ADVENT has
experience in the design and startup of classified manufacturing environments. ADVENT understands
material, personnel, and equipment flows that promote good manufacturing practice and reduces the
opportunity for cross-contamination. ADVENT has experience specifying environmental and HVAC
performance requirements to meet ISO classifications. ADVENT is familiar with both isolator and
barrier technology to produce a Class A environment suitable for filling parenteral drug
Drug Research and Development
Facilities designed for drug research and development (R&D) requires flexibility along with the
abiity to control the risk of environmental contamination. It is common for example to segregate
areas as a control strategy to preserve biological identity and prevent cross-contamination. The
flexibility demands of an R&D facility are inherently suited for single use technology applications.
ADVENT has experience providing complete facility layout and design for state-of-the-art R&D
biologics facility with accommodation for both small-scale and clinical manufacturing.