Lessons in Engineering, Compliance, and Scale-Up. inConversation with Mr Abhay Inamdar
Across the pharmaceutical industry, the pressure to build faster has never been higher. Timelines are shrinking, expectations are rising, and projects are increasingly being executed in parallel streams. But speed, while necessary, often comes with its own set of trade-offs, many of which only surface once the facility moves from project mode into real-world operations.
In this conversation, Mr. Abhay Inamdar, Vice President, Capital Projects & Engineering at Immacule Life sciences & Acme Generics Group companies reflects on what truly goes into building a facility that not only gets delivered on time, but also performs consistently under regulatory and operational demands. With a sharp engineering lens and practical experience, he shares insights on where things tend to slip in fast-tracked projects, and how those early decisions shape long-term compliance, efficiency, and scalability.
In fast-tracked pharma projects, design phases are often compressed, with parallel engineering and procurement activities. From a systems engineering perspective, which critical design decisions such as zoning logic, air handling philosophy, and utility distribution architecture & Equipment design are most vulnerable to insufficient resolution at this stage, and how do these gaps typically manifest during commissioning or routine operations?
HVAC design, area classification, and facility layout, especially man and material flow, Pressure Differentials across the rooms w.r.t common Process corridor, Equipment Design are critical to an effective Contamination Control Strategy (CCS). These must be integrated to ensure proper segregation, prevent cross-contamination, and maintain controlled cleanroom environments.
HVAC systems should incorporate defined pressure cascades, appropriate air change rates, HEPA or ULPA filtration, and optimized airflow to avoid turbulence and dead zones. Area classification must align with regulatory cleanroom grades and environmental monitoring requirements.
Facility design must ensure unidirectional flow with proper airlocks and interlocks to prevent contamination ingress & also have to ensure there is no Criss-cross of the Man/Material movement (Specifically RM to FG path)
Occupational Exposure Limits (OELs), based on product toxicity, are a key determinant. High potency products require enhanced containment such as isolators or negative pressure systems as a primary containment accordingly, facility design and equipment selection must be aligned with product-specific containment needs to ensure compliance and operational robustness.
While Designing Aseptic Filling Lines , Lyo-ALU’s & Filled & stoppered vials Travel path need to be assessed thoroughly to ensure Compliance with Annex-1 requirement which stresses on the point that First Air from Laminar Air Flow must be in contact with Product containers & product contact parts & Regulatory agency expects that there must be zero tolerance towards Manual Interventions during Dynamic conditions (when filling lines in operation during product filling, stoppering , loading into Lyo’s through ALU’s)
If proper attention & time would not have been given to these critical aspects, surely the entire project may face challenges during critical phase of Qualification & APS (Aseptic Process Simulation) stage
Given the central role of HVAC in contamination control, how does accelerated project execution impact the ability to design and validate stable pressure cascades, airflow patterns, and recovery times, particularly under dynamic conditions such as door openings, personnel movement, and batch changeovers?
In contamination control, accelerated project execution often limits the depth of HVAC engineering required for robust performance. Key elements such as pressure cascade design, air change rates, filtration strategy, and control logic may not be fully optimized.
Inadequate airflow design can lead to turbulence, dead zones, and unintended cross flows, especially without detailed CFD studies or airflow visualization. Pressure differentials may become unstable due to insufficient balancing and weak control sequences.
Under dynamic conditions such as door openings, personnel movement, and material transfer, this can result in transient pressure drops and airflow reversal, increasing contamination risk. Recovery times are often not rigorously established, impacting performance during disturbances and product changeovers.
As a result, systems may meet static qualification but fail under real operating conditions, leading to deviations and compliance risks.
In many projects, utility systems such as PW, WFI, clean steam, and compressed gases are sized based on projected demand profiles during initial capacity planning. As plants scale from design capacity to sustained commercial operations, how do fast-tracked timelines impact the reliability of these systems, and what engineering approaches ensure consistent performance under scale-up conditions?
Utility system design must be aligned with forward-looking manufacturing demand projections, typically over a five-year horizon. Annual volume forecasts should be translated into daily peak load requirements, considering batch overlaps, Clean-in-Place (CIP) and Sterilize-in-Place (SIP) cycles, and simultaneous utility usage.
Capacity should be engineered to meet peak daily demand over hourly slots of entire 24 hours/day with appropriate safety margins, ensuring stable operation without overloading. At the same time, a modular design approach is essential, allowing incremental capacity expansion over the subsequent five years without disrupting ongoing operations.
This includes provisions in layout, header sizing, and integration-ready infrastructure for utilities such as Purified Water (PW), Water for Injection (WFI), clean steam, and compressed gases. Such a scalable and modular architecture ensures consistent performance, operational flexibility, and reliability during scale-up.
In brownfield expansions executed under tight timelines, new systems must interface with legacy infrastructure that may not have been designed for current regulatory or operational expectations. What are the most critical integration risks at the level of piping, controls, and data systems, and how can they be systematically identified and mitigated during project execution?
Prior to project execution, a detailed GxP (Good Practice) gap analysis must be conducted to assess the compliance status of legacy infrastructure against current regulatory and technological standards.
This includes evaluation against 21 CFR Part 11 (Electronic Records and Electronic Signatures), CSV (Computer System Validation) requirements, and GAMP 5 (Good Automated Manufacturing Practice) guidelines. Additionally, compatibility with open communication protocols such as BACnet (Building Automation and Control Network), OPC UA (Open Platform Communications Unified Architecture), PROFINET/Ethernet/IP, Modbus RTU/TCP, Fieldbus Protocols (PROFIBUS, CAN open) must be assessed to ensure seamless system interoperability.
Based on the gap assessment, legacy systems should be upgraded or retrofitted to meet current GxP compliance and technology expectations. This ensures robust data integrity, regulatory compliance, and enables smooth integration with new systems within a unified and interoperable architecture.
When commissioning and qualification activities such as IQ, OQ, and PQ are compressed to meet aggressive timelines, what are the most common risks to data integrity, traceability, and documentation quality, and how can organizations structure these phases to maintain GMP compliance and inspection readiness without creating downstream rework or compliance exposure?
During equipment and system qualification under aggressive timelines, compliance requirements for computerized and Human Machine Interface (HMI) based systems are often overlooked. These systems must comply with 21 CFR Part 11 (Electronic Records and Electronic Signatures) to ensure regulatory acceptance.
Failure to adequately validate such systems can compromise data integrity, particularly if electronic signatures, audit trails, and access controls are not properly implemented and verified through Computer System Validation (CSV).
This directly impacts adherence to ALCOA (Attributable, Legible, Contemporaneous, Original, Accurate) principles, where all generated process data must be reliable, traceable, and tamper-proof. Any gaps in validation or documentation can lead to data integrity risks, regulatory observations, and potential compliance exposure.
Facilities are often designed to meet regulatory requirements, yet operational challenges emerge post-handover. From an engineering standpoint, what differentiates a facility that performs consistently under routine production from one that experiences frequent deviations, and how can operability be objectively evaluated during the design and commissioning stages?
While designing a facility for commercial operations, long-term sustainability and lifecycle cost optimization must be embedded at the design stage. This includes energy-efficient HVAC system design, optimized air change rates, heat recovery systems, and reduced carbon footprint through selection of appropriate utilities and fuels, Water conservation methods
Warehouse design must consider storage capacity for the initial 3 to 5 years, with scalable infrastructure for phased expansion up to 10 years. Technical considerations such as palletization strategy, racking systems, temperature and humidity control, and Warehouse Management Systems (WMS) are essential for efficient operations.
Facility layout should be engineered to minimize material and personnel movement, reducing non-value-added time and contamination risks. Travel path optimization from raw material receipt to dispensing, manufacturing, packing, and finished goods storage is critical.
HVAC zoning and space utilization must be optimized to reduce operational expenditure by minimizing conditioned areas without compromising compliance. Adoption of sustainable utilities such as biomass boilers, along with energy monitoring systems, supports reduced dependence on fossil fuels and improved environmental performance.
As digital systems such as MES, BMS, and SCADA are increasingly integrated into facility design, how do compressed timelines affect their architecture, interoperability, and data reliability, and what best practices should be followed to ensure that these systems support plant operations and compliance effectively?
Digital systems such as MES, BMS, and SCADA must be integrated into facility design, including existing facilities, with a detailed GxP assessment to evaluate compliance of legacy infrastructure.
Automation and digitalization, through systems such as Manufacturing Execution Systems (MES), Supervisory Control and Data Acquisition (SCADA), and Building Management Systems (BMS), should be integrated to monitor Critical Process Parameters (CPPs) and improve productivity while optimizing manpower and reducing variability
A comprehensive digital and IT inventory should be maintained and periodically reviewed for all critical equipment and instruments monitoring CPPs and CQAs at the batch level. As part of regulatory expectations, legacy software and hardware must be upgraded to current validated versions to ensure data integrity, compliance, and technological readiness for at least the next decade.
Best practices include:
- Maintaining complete inventory and lifecycle records of all legacy software and hardware
- Establishing phased 5 and 10 year roadmaps aligned with facility and business expansion
- Defining technical specifications for systems such as SCADA, BMS, EMS, DCS, and analytical platforms
- Implementing a Requirement Traceability Matrix (RTM) for end to end traceability
- Conducting periodic GxP gap assessments
- Developing project specific plans with defined CAPEX, timelines, and approval workflows
- Establishing post-implementation risk mitigation strategies with periodic reviews
A structured and future-ready integration approach ensures interoperability, compliance, data integrity, and operational efficiency.
Disclaimer: The views and opinions expressed in this editorial are those of the interviewees and are based on their professional experience in pharmaceutical engineering and sterile manufacturing. They do not necessarily reflect the official views, policies, or positions of Hello Pharma, its management, or its affiliates. Hello Pharma does not endorse or take responsibility for any specific technical, commercial, or regulatory interpretations presented in this article. Readers are encouraged to independently evaluate the information shared, review applicable regulatory guidance, and rely on their own experience, expertise, and professional judgment before making decisions related to equipment selection, system design, validation strategy, or regulatory compliance.
