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HPAPI Facility Design: How to Plan Containment by OEB Level

HPAPI Facility Design: How to Plan Containment by OEB Level

If your team is building or upgrading a plant to handle highly potent active pharmaceutical ingredients, containment is the first thing you need to get right. Late or incorrect containment decisions can create operator exposure risks, inspection findings, and costly rework after the building is already under construction. Get it right and you have a facility that protects people, supports global regulatory expectations, and runs with stable, controlled operations.

This post walks through HPAPI facility design in plain language, with a focus on Occupational Exposure Limits (OELs), Occupational Exposure Bands (OEBs) and how they guide every containment decision you make, from room layout to equipment selection and performance verification.

What Is an HPAPI, and Why Does Containment Matter?

A highly potent active pharmaceutical ingredient, or HPAPI, is a drug substance with high pharmacological or toxicological activity at low exposure levels. Think potent oncology compounds, certain hormones, cytotoxic APIs and highly active small-molecule intermediates. Because these materials can be active or harmful at very low exposure levels, even a tiny amount of airborne dust or residue can affect an operator’s health over time.

Here is why this matters for facility design: conventional API plants are built around cleanliness, product protection and worker safety. HPAPI plants require an additional, more stringent goal, protecting the people who work in them while also controlling cross-contamination. That additional goal drives decisions about room pressure, airflow, equipment type, and even how waste and gowning are handled.

What Is an Occupational Exposure Band (OEB)?

Before you design anything, you need to know the compound’s toxicological potency and the exposure level that must be controlled. That is what OEL development and Occupational Exposure Banding help establish. An OEL is a compound-specific airborne exposure limit, commonly expressed as an eight-hour time-weighted average, while an OEB groups compounds within an exposure range and can support decisions when a sufficiently robust compound-specific OEL is not yet available. 

Many pharmaceutical companies use five-band systems, but the numerical limits and band definitions are not globally standardized. At one end, OEB 1 generally covers materials with higher airborne exposure ranges and simpler control needs. At the other end, OEB 5 covers the most potent compounds, with occupational exposure limits below 1 microgram per cubic meter, often in the nanogram range.

It is also important not to use OEL/OEB and PDE/ADE interchangeably. OELs and OEBs support worker protection, while Permitted Daily Exposure (PDE) or Acceptable Daily Exposure (ADE) values are health-based limits used mainly to assess patient risk from cross-contamination and to establish cleaning limits in shared manufacturing facilities.

A simplified way to look at the bands is shown below. These ranges represent an illustrative five-band pharmaceutical scheme and should not be treated as a universal regulatory standard:

  • OEB 1: Higher exposure range, generally 1,000 µg/m³ or above. Good industrial hygiene, suitable ventilation and basic source controls may be sufficient, subject to a task-specific assessment.
  • OEB 2: OEL roughly 100 to below 1,000 µg/m³. Downflow booths, local exhaust ventilation or dust-controlled connections may be used depending on the operation.
  • OEB 3: OEL roughly 10 to below 100 µg/m³. Greater enclosure, glove bags, flexible isolators and closed transfer systems may be required based on the task.
  • OEB 4: OEL roughly 1 to below 10 µg/m³. High-performance primary containment, such as rigid isolators or an equivalent demonstrated system, is often considered.
  • OEB 5: OEL below 1 µg/m³, sometimes extending below 0.1 µg/m³. Very high containment, robust transfer, cleaning, maintenance and verification controls are required, with an isolator or equivalent demonstrated system selected according to the operation.

Your OEL or OEB assignment is not a guess. It comes from an evaluation of the compound’s toxicological potency and the health effects tied to exposure, usually done by a qualified occupational toxicologist or industrial hygienist before the design team finalizes the concept. The final containment strategy also considers process scale, quantity handled, dustiness, task duration and frequency, cleaning, maintenance and potential dermal exposure.

How OEB Levels Shape HPAPI Facility Design

How OEB Levels Shape HPAPI Facility Design

Once you know the OEL or applicable OEB, the design choices can follow a risk-based pattern, but the band alone does not prescribe a specific technology. Here is how it may play out at each stage.

OEB 1 and 2: Basic Engineering Controls

At the lower bands, the room design stays fairly close to a normal API facility. You still need good airflow, an appropriate ventilation and pressure strategy where required, and proper gowning procedures. The main additions may include local exhaust points at material transfer stations and dust-tight connections for charging and discharging powders.

OEB 3: Isolators and Closed Transfers

This is often the point where a plant moves from basic source control toward greater enclosure and contained transfer, although the exact solution depends on the task. Glove bags and flexible isolators may start showing up around reactors, dryers, and milling equipment. Room pressure cascades become more carefully coordinated rather than simply tighter, and airlocks with interlocks may be used according to the risk assessment between the process area and the corridor.

OEB 4 and 5: Full Containment

At OEB 4 and especially OEB 5, primary containment equipment and the supporting facility controls become more demanding. You are looking at rigid isolators or equivalent demonstrated systems, split butterfly valves for material transfer, dedicated or appropriately segregated air handling where required by risk assessment, suitable exhaust treatment and safe-change filtration where necessary, and monitoring of critical pressure and ventilation parameters.

Occupational hygiene sampling and containment-performance testing are then used to demonstrate that exposure remains below the defined target before routine production begins.

Steps to Plan an HPAPI Facility

Validate before startup

Here is a practical order of operations for teams starting from scratch:

  1. Get the toxicology data first: You cannot design containment without knowing the OEL or applicable OEB and other relevant health hazards of the compound you plan to make.
  2. Map the process flow: Identify every point where the material is open to the room, such as charging, sampling, and packing, as well as cleaning, filter changes, maintenance and waste handling.
  3. Match the containment strategy to the OEL/OEB and task risk: Assign the right level of isolator, glove bag, or booth to each open point based on the exposure target, quantity, dustiness, duration, frequency and demonstrated containment performance.
  4. Design the room around the equipment, not the other way around: The pressure strategy, airlocks, and material and personnel flow should support the containment devices you have chosen.
  5. Plan for cleaning and decontamination: Every HPAPI area needs a documented method for appropriate dry or wet cleaning, decontamination, cleaning verification and safe waste removal. Product carryover limits should be based on the applicable HBEL/PDE/ADE, while occupational surface contamination should be assessed separately.
  6. Validate before startup: Run containment-performance testing using a surrogate powder and an established methodology such as SMEPAC on equipment to confirm it meets the defined containment-performance target before routine production begins.
  7. Train operators and maintenance personnel on the specific hazard: Generic gowning training is not enough at OEB 4 or 5. People need to understand what they are protecting against and why, including the requirements for cleaning, spill response, waste handling and actions following a containment breach.
  8. OEB classification addresses occupational health exposure, but it does not replace separate assessments for dermal exposure, sensitization, solvent hazards, chemical reactivity, static electricity or combustible dust. These risks need their own process-safety and industrial-hygiene controls. 

Building a Pharma Manufacturing Base With Containment in Mind

Many companies expanding into HPAPI production are not starting with a blank site. They are adding a containment suite to an existing plant, or converting part of a conventional API building. This is where planning early pays off. Retrofitting containment into a building that was not designed for it can require significant redesign, new HVAC interfaces and additional shutdown work.

When you are building a pharma manufacturing base that includes HPAPI capacity, a few things help keep the project on track:

  • Bring in OEL and OEB input before the architectural layout is locked.
  • Use dedicated or appropriately segregated HVAC strategies for high-containment zones, and justify any recirculation or exhaust arrangement through risk assessment.
  • Design corridors and airlocks with the material, waste and gowning flow in mind, not just square footage.
  • Plan utility routing (process gases, nitrogen, vacuum, clean compressed air, heating and cooling media, and the required water grade) around the containment equipment early, since retrofitting piping through a sealed isolator room later can create significant design and construction interfaces.

Firms that specialize in pharmaceutical engineering and containment integration often bring this experience to a project because they can coordinate equipment, facility, HVAC, utilities, cleaning and CQV interfaces together. Pharma Access works across engineering design, procurement and supplies, construction and installation, project management and CQV for pharmaceutical facilities, helping coordinate containment-related requirements with the wider facility design from the start.

Common Mistakes in HPAPI Facility Design

A few mistakes show up again and again on HPAPI projects:

  • Assigning the OEL or OEB too late: If toxicology data comes in after the layout is fixed, you end up retrofitting containment into a space that was not built for it.
  • Treating all HPAPIs the same way: An OEB 3 compound does not automatically need a containment solution intended for a much lower exposure range, and over-designing wastes money without adding real protection.
  • Ignoring the cleaning and decontamination strategy during design: If a room cannot be cleaned and decontaminated properly, cross-contamination risk goes up no matter how good the containment equipment is.
  • Underestimating airflow and pressure cascade design: A single poorly placed door or airlock can disrupt the intended airflow direction and weaken the facility’s secondary containment strategy.
  • Skipping operator training on the specific compound: Equipment only works as well as the people using it.

Why Work With Pharma Consultants in India

HPAPI manufacturing has created a growing need for pharma consultants who understand both global regulatory expectations and local construction realities. Working with a consultant who has handled containment integration before can reduce back-and-forth with equipment vendors and help resolve design interfaces earlier.

Full-service pharma project management services matter here too, since HPAPI projects touch process engineering, HVAC, architecture and civil work, automation, and CQV all at once. Coordinating these pieces without a single point of accountability can create interface gaps and delay decisions. 

Pharma Access provides integrated support across engineering design, procurement and supplies, construction and installation, project management and CQV, which is important on containment-heavy projects where systems and interfaces need to be coordinated from concept design onward.

Wrapping Up

HPAPI facility design comes down to more than one question at every stage: what is the OEL or applicable OEB of this compound, where can exposure occur, and do the room, the equipment, the cleaning systems, the transfer systems and the airflow around it match that hazard level? Get the toxicology data early, match your containment strategy to the actual exposure target and task risk, and build the room around the equipment rather than squeezing equipment into a fixed room later. That order of operations is what supports predictable HPAPI project delivery and, more importantly, keeps the people working in the facility safe.

Frequently Asked Questions

What does OEB mean in pharma facility design? 

OEB stands for Occupational Exposure Band. It’s a classification system that groups drug compounds within airborne exposure ranges using toxicological and health-effect information. It can support containment decisions, particularly when a sufficiently robust compound-specific OEL is not yet available, but it does not directly prescribe a particular containment technology.

What is the difference between an OEL and an OEB?

An OEL is a compound-specific airborne exposure limit. An OEB is a range used to group compounds according to toxicological potency or a corresponding exposure-control range. Where sufficient data are available, the compound-specific OEL provides the more precise target. 

How many OEB levels are there? 

Most pharma companies use a five-band system, OEB 1 through OEB 5. However, OEB schemes are company-specific and are not globally standardized. Some systems use numbers, while the NIOSH occupational exposure banding system uses bands A through E.

Do all HPAPI facilities need isolators? 

Not always. Lower exposure-risk operations may only need local exhaust ventilation or downflow booths. Isolators or equivalent high-performance containment systems may be required for lower exposure targets, but the selection should also consider the process, quantity, dustiness, duration, cleaning, maintenance and demonstrated equipment performance.

How early should containment planning start in a facility project? 

As early as possible, ideally before the architectural layout is finalized. Toxicology data and the OEL or applicable OEB assignment should come first, since they help determine room pressure, airflow design, material transfer, cleaning requirements and equipment choices later in the project.

What is the difference between an API facility and an HPAPI facility? 

A standard API facility focuses on product quality, cleanliness and worker safety. An HPAPI facility requires more stringent occupational-exposure and cross-contamination controls, which can mean added containment equipment, sealed transfer systems, specialized cleaning and waste-handling strategies, and dedicated or appropriately segregated air handling.

What is the difference between an OEL and a PDE/ADE?

An OEL is used to protect workers from occupational exposure, usually through an airborne concentration limit. A PDE or ADE is used mainly to assess patient risk from cross-contamination and to support cleaning-limit decisions in shared manufacturing facilities. The values address different exposure scenarios and should not be used interchangeably.

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EU GMP Annex 1: Designing Compliant Sterile Facilities

EU GMP Annex 1: Designing Compliant Sterile Facilities

If your facility manufactures sterile products, EU GMP Annex 1 is probably the single document that shapes the most decisions on your design drawings. It touches your cleanroom layout, your air handling, your gowning rooms, and even how you validate filters. Getting it right at the design stage saves you from expensive rework once construction is already underway.

This post breaks down what the guideline actually requires, what changed in the 2022 revision, and what that means for how sterile facilities get designed and built today.

What Is EU GMP Annex 1?

EU GMP Annex 1 is the section of the European Union’s Good Manufacturing Practice guidelines that covers the manufacture of sterile medicinal products. It sits within EudraLex Volume 4 and sets out the expectations for cleanroom design, contamination control, aseptic processing, and environmental monitoring.

The annex was first published in 1971, but it went through a major rewrite that was finalized by the European Commission in August 2022 and came into operation on 25 August 2023, except for paragraph 8.123, which came into operation on 25 August 2024. This was the first full revision of Annex 1 following several partial revisions, and it substantially expanded the guideline, reflecting how much more detail regulators now expect from sterile manufacturers. 

Why the 2022 Revision Changed So Much

Here is the shift worth understanding. The older version of Annex 1 leaned more heavily on prescriptive requirements and did not define the same holistic, risk-based contamination-control framework.The revised version asks manufacturers to prevent contamination before it happens, through a documented, facility-wide approach called a Contamination Control Strategy (CCS).

A few things stand out about this revision:

  • It was developed jointly by the PIC/S and EMA Inspectors’ Working Group, in close cooperation with the European Commission and WHO, so the expectations now line up closely across EU, PIC/S, and WHO sterile-manufacturing guidance.
  • It applies a Quality Risk Management approach, meaning contamination controls need to be built into the facility and process from the start, not bolted on afterward.
  • Grade A areas now carry a stricter viable contamination limit, stated as “No growth,” with any microbial growth requiring an investigation.

The Contamination Control Strategy (CCS): The Core Requirement

The Contamination Control Strategy (CCS): The Core Requirement

If there is one concept to understand about this guideline, it is the CCS. A Contamination Control Strategy is a documented, facility-wide strategy that may reference several connected systems and explains how a facility identifies, prevents, detects, monitors, and controls contamination risks across the entire production process.

The CCS is not a paperwork exercise you complete after the facility is built. It needs to cover:

  1. Facility and equipment design. How the layout, airflow, and material flow reduce contamination risk from the ground up.
  2. Personnel practices. Gowning procedures, movement patterns, and training that limit human-sourced contamination.
  3. Environmental monitoring. Ongoing particle and microbial monitoring that provides evidence that the facility continues to perform as intended, not just on the day it was qualified.
  4. Process controls. Aseptic technique, filter integrity testing, and sterilization validation tied directly to the risk profile of each product.

The CCS should also address utilities, raw materials, product containers and closures, supplier and outsourced-activity controls, cleaning and disinfection, preventive maintenance, sterilization, process validation, CAPA, trend analysis, and continual improvement. 

Because the CCS spans design through operation, it has to be considered from the earliest facility planning stage, not added as a compliance document once construction wraps up.It should also be actively reviewed and updated where appropriate, with its effectiveness forming part of periodic management review. 

Cleanroom Grades Under the Guideline

The annex defines four cleanroom grades, A through D, based on particle and microbial limits. Each grade maps to a different level of risk in the manufacturing process.

  • Grade A: The critical zone. This covers aseptic filling lines, stopper bowls, open primary packaging, and any point where the product or its containers are directly exposed. First-air protection and appropriate airflow must be demonstrated over exposed sterile products, components, and critical surfaces. Unidirectional airflow is required for conventional Grade A zones, RABS, and open isolators, while airflow may not be fully unidirectional in closed isolators used for simple operations.
  • Grade B: The background environment surrounding Grade A operations where an isolator is not used. Aseptic RABS normally require at least a Grade B background, while open isolators generally require at least Grade C and closed isolators at least Grade D, based on risk assessment and justification within the CCS.
  • Grade C and D: Support areas for lower-risk stages, such as preparing solutions or components before they move into higher-grade zones. They can also be used for the preparation or filling of terminally sterilized products, depending on the operation and assessed risk.

Getting the grading right at the design stage determines nearly everything else downstream, from HVAC sizing to how many airlocks and gowning stages your layout needs.

The choice between terminal sterilization and aseptic processing should also be established early. Annex 1 expects finished products to be terminally sterilized wherever possible because a validated and controlled terminal sterilization process provides greater sterility assurance than sterile filtration or aseptic processing alone. This decision directly affects cleanroom grades, equipment selection, material flows, and the overall facility layout. 

Designing a Facility Around the Guideline From Day One

A common mistake is treating the annex as a testing checklist to satisfy near the end of a project. The revision makes clear that contamination control has to start on the drawing board.

A few design principles carry real weight under the current guidance:

  • Early barrier-technology evaluation: The annex places heavy emphasis on separating personnel from the product, requiring RABS, isolators, robotic systems, and other appropriate technologies to be considered to maintain the required conditions with less reliance on human intervention.
  • Airflow modeling before construction: Using CFD and design-stage airflow studies to assess unidirectional airflow patterns and pressure cascades on paper, before pouring concrete, can help identify potential dead zones before the room is built. Airflow predictions must then be verified through physical airflow visualization studies during qualification, both at rest and in operation, including representative interventions, while pressure relationships must be verified through qualification testing and monitoring.
  • Material and personnel flow separation: Layouts need clear, risk-based paths that minimize crossing and backtracking for people, materials, and waste to prevent contamination between clean and less-clean zones. Separate personnel and material airlocks should be provided wherever practicable, with unidirectional transfer arrangements used for materials entering and leaving Grade A and B areas. Where complete physical separation is not possible, risk-assessed time separation and procedural controls should be established.
  • Built-in monitoring points: Continuous total-particle monitoring during critical processing and continuous viable air monitoring in Grade A, with a similar risk-based approach considered for Grade B, need sensor and sampling locations designed into the room, not retrofitted later.

An integrated pharmaceutical engineering design approach brings these principles together at the concept and detailed design stage, so the facility’s physical layout supports the CCS instead of working against it.

Where CQV Services Fit Into Compliance

Where CQV Services Fit Into Compliance

Design intent only matters if it can be proven. This is where CQV services for pharmaceutical facilities become part of the compliance story, not a separate afterthought. Commissioning confirms the systems work as installed. Qualification, beginning with Design Qualification and continuing through IQ, OQ, and PQ, provides documented evidence that the design is suitable, the systems are correctly installed, and the facility operates and performs as intended. Qualification, validation, environmental-monitoring trends, deviation investigations, and CAPA tie it all together with documented evidence that the controls defined within the CCS remain effective under routine production conditions. 

Under the revised guideline, this evidence chain matters more than ever. Regulators expect to see aseptic process simulation records for aseptic processes, installed HEPA filter integrity test records, sterilizing-grade process-filter integrity test records where sterile filtration is used, and environmental-monitoring trend data that support the effectiveness of the controls described in the CCS. A facility that cannot produce this evidence, regardless of how well it was designed, will have difficulty demonstrating an effective state of control during inspection.

Common Pitfalls Facilities Run Into

A few issues show up again and again when facilities try to retrofit compliance instead of designing for it from the start:

  • Underestimating airlock and gowning requirements, which forces awkward layout changes mid-construction.
  • Treating the CCS as a document exercise instead of a living strategy tied to actual facility operation and monitoring data.
  • Skipping early filter and barrier technology decisions, which then constrain HVAC and room layout choices later in the project.
  • Insufficient personnel flow separation, leading to cross-contamination risks that only surface during environmental monitoring after startup.

Why Local Expertise Matters for Global Compliance

This EU guideline sets a widely used international benchmark, but applying it correctly depends heavily on local construction practices, climate conditions, and regulatory context. Working with experienced pharmaceutical engineering consultants in India means your facility design accounts for both the international standard and the practical realities of building and operating in your specific market.

Pairing that engineering expertise with project-specific input from quality, microbiology, and regulatory specialists who understand how EU, PIC/S, and WHO guidance is applied gives a facility a stronger position going into its first audit, rather than discovering gaps after the fact.

At Pharma Access, our engineering design and CQV teams work on sterile facility projects that need to meet this standard from the concept stage through validation. We handle cleanroom design, HVAC, utilities, monitoring requirements, and commissioning through one coordinated engineering and qualification approach, which helps facilities avoid the costly redesigns that come from treating contamination control as an afterthought. You can learn more about our approach on the Pharma Access about page.

Wrapping Up

The guideline asks manufacturers to think about contamination control as a design principle, not a final inspection hurdle. A facility built around a well-developed Contamination Control Strategy, with cleanroom grades, barrier technology, and monitoring points planned from the start, is better positioned to demonstrate consistent performance during qualification and maintain control over time. The earlier this thinking enters the design process, the less it costs to get right.

FAQs

What is the main change in the 2022 revision of EU GMP Annex 1? 

The revision strengthens the move away from relying on monitoring or end-product testing alone and toward a proactive, risk-based Contamination Control Strategy that covers facility design, personnel practices, and ongoing monitoring together.

What is a Contamination Control Strategy (CCS)? 

A CCS is a documented, facility-wide strategy that may reference several connected systems and explains how contamination risks are identified, prevented, detected, monitored, and controlled, spanning facility design, equipment, personnel, and monitoring, throughout the entire production process.

What are the cleanroom grades under this guideline? 

The annex defines Grades A through D. Grade A is the critical zone with the strictest limits, Grade B normally the background for Grade A aseptic processing where an isolator is not used, and Grades C and D support lower-risk stages of production. RABS and isolator background grades depend on the selected technology, process risk, and justification within the CCS.

Does this guideline only apply to EU-based manufacturers? 

No. EU GMP Annex 1 applies to sterile medicinal products manufactured under EU GMP requirements, including products manufactured outside the EU for supply to the EU or EEA market. PIC/S Annex 1 and WHO sterile-manufacturing guidance are closely harmonized with the EU text, but manufacturers must still consider the specific legal and regulatory requirements of every target market. 

When should compliance be considered during a facility project? 

From the earliest design stage. Retrofitting cleanroom grading, airflow, or barrier technology after construction is far more costly than building the Contamination Control Strategy into the original layout.

Note: This article provides a general engineering interpretation of EU GMP Annex 1. It should be read together with the official guideline and should not replace project-specific quality, microbiological, or regulatory assessment. 

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Types of Purified Water Generation Systems in the Pharmaceutical Industry

Types of Purified Water Generation Systems in the Pharmaceutical Industry

Water is used throughout pharma manufacturing. It goes into formulations, cleans equipment, and rinses containers before they ever touch a product. Because of that, a purified water generation system in pharmaceutical industry settings is not a side utility. It is a quality-critical utility that requires careful design, qualification, monitoring, and control.

This post breaks down the common types of purified water systems, how they work, and how to pick the right setup for your facility. We will keep things simple and skip the deep engineering jargon where we can.

What Counts as Purified Water in Pharma?

Purified water is water treated to remove dissolved solids, organic matter, and microorganisms until it meets pharmacopeial standards. Pharmacopeias such as USP, Ph. Eur., and IP establish requirements and guidance for pharmaceutical water quality. For USP Purified Water, chemical attributes such as conductivity and Total Organic Carbon (TOC) are compendial requirements, while microbiological quality is addressed through appropriate monitoring and system-specific control rather than a microbial limit within the Purified Water monograph itself.

Here is why that matters. Ordinary tap or ground water carries suspended solids, dissolved salts, organic compounds, and microbes that can throw off a formulation or fail a batch release test. A pharmaceutical facility generally uses water meeting applicable drinking-water requirements as the minimum feedwater for Purified Water generation, with further treatment applied to achieve the required pharmaceutical water quality.

The Two-Stage Approach: Pretreatment and Final Purification

The Two-Stage Approach: Pretreatment and Final Purification

Most purified water generation trains can be understood through two main treatment stages, and understanding this split makes the rest of this guide easier to follow. After generation, storage, distribution, sanitization, and monitoring become equally important for maintaining the required water quality up to the point of use.

Stage 1: Pretreatment

Pretreatment removes the large stuff first, so it does not damage sensitive equipment downstream. This stage may include multi-media filters, activated carbon filters, and water softeners to strip out particles, chlorine, and hardness before the water moves any further. The actual pretreatment sequence depends on feedwater quality and the requirements of the downstream purification system. 

Stage 2: Final Purification (Polishing)

The final treatment stage, sometimes called polishing, brings the water down to the target purity level often through reverse osmosis followed by electrodeionization where appropriate to further lower conductivity before storage. Additional steps such as UV treatment or ultrafiltration may be added depending on what the facility needs.

Common Types of Purified Water Generation Systems

Here are the main system types you will run into in pharma manufacturing.

1. Reverse Osmosis (RO) System

RO uses pressure to push water through a semipermeable membrane, rejecting a high proportion of dissolved salts, many organic contaminants, particulates, and microorganisms. It is often the workhorse of a purified water system because it can substantially reduce multiple contaminant classes in a single treatment stage.

2. Deionization (DI) System

DI systems pull ions out of water using resin beds charged to attract dissolved minerals. On their own, DI systems may be used within qualified pharmaceutical water-treatment trains, although they are often combined with other purification technologies rather than relied upon as the only treatment barrier.

3. Electrodeionization (EDI) System

EDI combines ion-exchange resins with ion selective membrane and  electric current to continuously remove dissolved ions without the chemical regeneration that older DI systems needed. An EDI module usually sits right after the reverse osmosis stage, where it removes residual ionic contaminants from RO permeate to help achieve the required conductivity. This is a big reason RO+EDI has become a common configuration in modern pharmaceutical Purified Water systems. 

4. Distillation System

Distillation boils water and collects the condensed steam, leaving contaminants behind. It remains a well-established technology for Water for Injection (WFI) production. Current pharmacopeial frameworks also permit appropriately designed and qualified non-distillation purification processes for WFI production. 

5. Ultrafiltration (UF) System

UF uses a membrane process designed primarily to retain microorganisms, colloids, macromolecules, and, in appropriately designed applications, reduce endotoxin burden rather than remove dissolved ions. It is often added at the end of a system when additional microbial, colloidal, or endotoxin control is required. It is not primarily a conductivity-polishing technology, and TOC measurement should not be treated as a substitute for microbiological or endotoxin control.

6. Hybrid Systems (RO + EDI)

Hybrid systems combining reverse osmosis and electrodeionization are widely used to achieve pharmaceutical Purified Water quality, with RO+EDI offering continuous ionic polishing without routine chemical regeneration of conventional ion-exchange resin beds. If you are specifying a new system today, this is often one of the configurations evaluated first, although the final treatment sequence should always depend on feedwater quality, required water quality, capacity, sanitization strategy, and operating requirements.

Purified Water vs. Water for Injection (WFI)

Purified Water vs. Water for Injection (WFI)

A quick point of confusion worth clearing up: purified water and WFI are not the same thing. Purified water is commonly used for non-parenteral formulations, equipment cleaning, and other applications where PW is the specified grade, while WFI is required for applications such as the manufacture of injectable products and specified final-rinse operations associated with injectable product-contact equipment and components. WFI also includes a bacterial endotoxin requirement and requires an appropriate microbiological control strategy. Choosing the right system depends heavily on which one your product line actually needs.

How HVAC Ties Into Water System Performance

A purified water system does not operate in isolation. The room housing it, along with the surrounding manufacturing areas, depends on properly functioning HVAC to control temperature, humidity, and other environmental conditions required for equipment, instruments, and manufacturing operations. HVAC supports the operating environment around the utility system, although water quality itself is primarily controlled through hygienic system design, circulation, sanitization, storage, and distribution.

This is where HVAC validation in pharmaceutical industry projects becomes relevant. HVAC qualification may include, as appropriate, design qualification (DQ), installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ). Testing during this process may cover air changes per hour, airflow pattern and velocity, pressure differentials, temperature and humidity, filter leak testing, and particle counts, with the scope determined based on the facility, application, and risk assessment.

Poor HVAC control in a classified or controlled manufacturing area can undermine the environmental conditions required by the process. However, maintaining Purified Water quality still depends primarily on the design and operation of the water generation, storage, and distribution system rather than HVAC alone.

Monitoring and Control: The Role of a Building Management System

Modern pharma facilities do not run water and HVAC systems on manual checks alone. A pharmaceutical water system is commonly monitored and controlled through dedicated automation such as PLC/HMI or SCADA architecture, while BMS or EMS platforms may integrate selected facility and utility information depending on the overall control philosophy. 

A well-set-up automation and monitoring architecture gives your team real-time visibility into pressure, temperature, water-system parameters, operating status, and system alarms, so problems get caught before they turn into a failed batch or a finding during inspection. Where appropriate, selected water-system status and alarms may also be integrated into the facility BMS or supervisory platform, reducing the need for operators to rely on separate systems for basic utility visibility.

Choosing the Right System for Your Facility

A few questions can help narrow down which purified water generation system in pharmaceutical industry settings fits your operation:

  1. What is your feed water quality? Hard, high-mineral water needs heavier pretreatment before RO.
  2. What product types do you manufacture? Non-parenteral products commonly use Purified Water where it is the specified grade, while injectable formulations typically require WFI for formulation and certain final-rinse applications.
  3. What is your daily water demand? Higher volumes influence generator capacity, redundancy, storage volume, and lifecycle economics, but technology selection must still begin with the required water grade and quality specification.
  4. What are your TOC and conductivity targets? Conductivity requirements influence technologies such as RO and EDI, while UV, UF, or other treatment steps may be selected for specific organic, microbial, or endotoxin-control objectives depending on the system design.
  5. How will you sanitize the system? Hot water sanitizable skids reduce chemical use but need membranes, EDI modules, seals, instrumentation, and other system components rated for that heat.

Why Facility Design Matters as Much as Equipment Choice

Why Facility Design Matters as Much as Equipment Choice

Buying the right skid is only part of the job. Piping layout, storage tank design, and distribution loop configuration all affect whether purified water stays within spec between the generation point and the point of use. A poorly designed loop can allow stagnant conditions that encourage microbial proliferation, even with a solid generation system upstream. Hygienic design therefore also considers factors such as dead-leg minimization, drainability, appropriate tank design, circulation, sanitization, sampling points, and monitoring.

This is where working with experienced pharmaceutical utility engineers and consultants pays off. At Pharma Access, our engineering design team handles mechanical and utility system design, including water and HVAC systems, as part of full facility projects across India and other markets. We look at generation, storage, distribution, and the supporting facility systems as coordinated engineering packages instead of isolated design scopes, helping reduce the coordination gaps that can cause rework later. You can see more about how we approach clean utility systems, including Purified Water and WFI, on the Pharma Access Clean & Black Utilities.

Wrapping Up

There is no single “best” purified water system for every pharma facility. RO+EDI is a widely used configuration for pharmaceutical Purified Water generation, while WFI can be produced through distillation or appropriately designed and qualified non-distillation processes where permitted by the applicable pharmacopeial and regulatory framework. What matters most is matching the system to your feed water, your product line, and your validation plan, then backing it with hygienic storage and distribution, an appropriate sanitization strategy, monitoring, and integration with the wider facility utility and control systems.

FAQs

What is the most common purified water system used in pharma today? 

RO combined with EDI is one of the commonly used configurations for modern pharmaceutical Purified Water systems. It removes most contaminants through the RO stage and then uses electrodeionization to remove residual ionic contamination and achieve the required conductivity without routine chemical regeneration of conventional DI resin beds.

What is the difference between purified water and Water for Injection (WFI)? 

Purified water supports applications such as non-parenteral formulations and cleaning where PW is the specified grade. WFI is used for applications including injectable-product manufacture and specified final-rinse operations and includes a bacterial endotoxin requirement.

How often should a purified water system be validated? 

Most facilities qualify the system before routine use through defined lifecycle activities that include IQ, OQ, and PQ as applicable, followed by ongoing monitoring, trending, maintenance, change control, periodic review, and risk-based requalification where required. There is no single universal requalification interval that applies to every pharmaceutical water system.

Does HVAC really affect purified water quality? 

Indirectly, yes. HVAC maintains appropriate environmental conditions around equipment and manufacturing areas, but Purified Water quality is primarily maintained through hygienic water-system design, circulation, sanitization, storage, distribution, and monitoring.

Can one system handle both purified water and WFI needs? 

A facility may share elements of upstream feedwater or pretreatment infrastructure, but PW and WFI generation, storage, distribution, sanitization, and monitoring strategies must be designed according to their respective quality requirements and intended applications. The final system architecture should therefore be established through process requirements, applicable pharmacopoeias, and a documented risk-based design approach.

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ICH Q13 Continuous Manufacturing: What It Means for Facility Design

ICH Q13 Continuous Manufacturing

If your plant is moving from batch production to continuous manufacturing, the facility design itself may need to change, not just the equipment inside it. ICH Q13 is the guideline that sets out the scientific and regulatory considerations for how continuous manufacturing (CM) should be developed, implemented, operated, and managed over its lifecycle. For anyone planning a new facility or converting part of an existing one, these principles can influence decisions long before the first piece of equipment gets installed. 

This post breaks down ICH Q13 in plain terms and walks through what it actually means for facility layout, automation, and day-to-day operation.

What Is Continuous Manufacturing?

In a batch process, you make a defined quantity of product and move it through manufacturing steps as a batch. Continuous manufacturing works differently. Materials are continuously fed into the process, transformed as they move through it, and output material is removed while the process is operating.

The guideline describes CM as the continuous feeding of input materials, transformation of in-process materials, and simultaneous removal of output materials from the manufacturing process. That single concept explains why facility design changes so much under CM. The facility is no longer planned only around a series of isolated processing steps. It’s planned around how connected operations interact and how material moves through the system.

Importantly, ICH Q13 makes clear that continuous manufacturing can apply to some or all unit operations. A manufacturing process can therefore combine batch operations with directly connected continuous operations rather than requiring the entire process to operate continuously.

What Is ICH Q13?

ICH Q13 is a guideline from the International Council for Harmonisation that covers the science and regulatory expectations behind continuous manufacturing of drug substances and drug products. Work on it began in 2018, a draft was endorsed for public consultation in July 2021, and the final Step 4 guideline was adopted on November 16, 2022. In the EU, the guideline became legally effective on July 10, 2023. The FDA issued its final Q13 guidance for industry in March 2023.

The guideline builds on earlier ICH quality guidelines such as Q8 (Pharmaceutical Development), Q9 (Quality Risk Management), Q10 (Pharmaceutical Quality System), and Q11 (Development and Manufacture of Drug Substances). It also includes a dedicated section, Annex III, that covers continuous manufacturing of therapeutic protein drug substances. The guideline also notes that its broader principles may apply to other biological and biotechnological entities.

At its core, the guideline addresses process development, control strategy, process dynamics, equipment design and system integration, process monitoring and control, process validation, and lifecycle management, all under one connected approach.

How ICH Q13 Shapes Facility Design

How ICH Q13 Shapes Facility Design

Here is where the guideline turns into real construction and layout decisions.

  • Equipment footprint can shrink, but connections multiply: CM system design can enable process simplification or intensification and, in some cases, reduce the number or size of unit operations, although a smaller facility footprint is not guaranteed. Integrated equipment also has to connect and interact as a system, which means piping, transfer interfaces, instrumentation, sensors, control cabling, and maintenance access need careful planning from the start.
  • Process monitoring becomes part of the room design: Where Process Analytical Technology (PAT), in-line, on-line, or other process measurements are used, the facility needs suitable instrument locations, power, data connectivity, sampling access, and maintenance access built in rather than added later. PAT is well suited to CM under ICH Q13, but it is not a universal requirement for every continuous process.
  • Material diversion needs a physical path: When the monitoring and control strategy identifies potentially non-conforming material, the system may need to divert that material away from acceptable product according to predefined criteria. That diversion path is a design decision, not just a software setting.
  • Process dynamics influence physical configuration: Residence Time Distribution (RTD) describes how long material spends moving through a process and is influenced by factors such as equipment design and configuration. Understanding RTD and process dynamics supports material tracking and helps determine appropriate sampling and diversion strategies, making equipment arrangement and connections important engineering considerations.
  • Utilities need to support the planned operating profile: Compressed air, nitrogen, process water, power, and other required utilities need to be evaluated against the intended run duration, simultaneous demand, operating range, and required system reliability rather than automatically being sized for round-the-clock operation.
  • Automation and control infrastructure take on a bigger role: With CM, the control system tracks the process in real time, so automation architecture, operator interfaces, control-panel locations, and data infrastructure become core parts of the facility design alongside the process room itself.

Steps to Plan a Facility Around ICH Q13

Here is a simple order of operations for teams starting a CM project:

  1. Define the process train early: Know which unit operations will run in a connected line and which, if any, will remain in batch mode before you sketch the room layout.
  2. Map monitoring and sensor locations. Decide where the process needs real-time monitoring, including PAT where appropriate, then design power and data access around those points.
  3. Plan the material diversion and collection path: Build a physical route for potentially non-conforming material that keeps it separate from acceptable products and supports the defined material-disposition strategy.
  4. Size utilities for the planned operating profile: Confirm that compressed air, nitrogen, process utilities, and power supply can handle the intended run duration, simultaneous loads, and required reliability.
  5. Design the automation infrastructure alongside the process room: Treat data infrastructure, control panels, operator interfaces, and cable routing as core parts of the layout, not an add-on.
  6. Build in a validation strategy that supports the state of control: CM can use traditional process validation or continuous process verification, depending on the process and justification. The facility, automation, and monitoring systems therefore need to support the data collection required for the selected validation approach throughout the manufacturing run.
  7. Train operators for a connected process: Running a CM line calls for a different skill set than managing discrete batch steps, so training plans should reflect that.

ICH Q13 also treats start-up, shutdown, pauses, restarts, and unplanned disturbances as important transient events. Their impact on material quality and process dynamics should therefore be understood when developing the operating and control strategy. 

Building Pharma Facilities Around Automation

Building Pharma Facilities Around Automation

Moving to continuous manufacturing usually means moving toward higher levels of integrated automation around the CM process, rather than simply automating individual pieces of equipment. This is where pharma manufacturing automation and facility design have to work together from day one. A control system that can manage real-time diversion, batch definition, and data capture only works if the physical layout supports it, with the right cabling paths, panel locations, and access for maintenance.

Companies offering pharma engineering solutions increasingly build this thinking into early-stage design rather than treating automation as a later add-on. Pharma Access brings process design, automation, utilities, facility engineering, and CQV considerations together during engineering development across its pharmaceutical projects, so the systems can be coordinated before construction starts.

Common Mistakes in ICH Q13-Aligned Facility Design

A few issues show up often when teams move to CM without planning the building around it:

  • Treating automation as a bolt-on: Retrofitting sensors, cabling, and control panels into a finished room can create avoidable rework and integration complexity compared with designing them into the facility from the start.
  • Underestimating utility demand: Longer CM runs can create sustained equipment and utility loads, and supporting systems designed only around intermittent batch operating profiles may not suit the intended CM run duration or operating range.
  • Skipping the diversion path in early layouts: Without a planned route for potentially non-conforming material, teams end up improvising later, which can complicate operation, qualification, and the material-diversion strategy.
  • Ignoring process dynamics and RTD: Changing equipment arrangement, connections, or hold-up volumes without understanding their effect on material movement can affect traceability, sampling, and diversion decisions.
  • Forgetting operator training needs: A connected line runs differently than a batch process, and operators need to understand the new failure points.
  • Designing the process room without the automation infrastructure in mind:Data infrastructure, operator interfaces, controls, and equipment connections have to develop alongside the process rather than being squeezed in afterward.

Why Work With Pharma Turnkey Consultants

CM projects bring process engineering, equipment integration, automation, utilities, facility design, and validation together at the same time which is a lot to coordinate without a single team managing the full picture. That is where pharma turnkey consultants add real value, since they carry a project from early engineering design through construction, procurement, and commissioning under one plan instead of handing it off between separate vendors at each stage.

Pharma Access works this way across its projects, offering engineering design services for pharma clients alongside construction, procurement, and commissioning, qualification, and validation (CQV) support. For a CM project, having one team track the process design, the automation plan, and the physical build together helps catch conflicts early, before they turn into rework.

Wrapping Up

ICH Q13 gives the industry a shared set of expectations for continuous manufacturing, but meeting those expectations comes down to how well the facility is built around the process. Map the process train early, plan for real-time monitoring and material diversion, understand process dynamics and RTD, size utilities around the intended operating profile, and treat automation and data infrastructure as part of the core layout. Get that sequence right, and the facility supports the process instead of working against it.

Frequently Asked Questions

What is ICH Q13? 

ICH Q13 is a guideline that sets scientific and regulatory expectations for continuous manufacturing of drug substances and drug products. It covers process development, control strategy,process dynamics, equipment design and system integration, process monitoring and control, process validation, and lifecycle management under one connected approach.

When did ICH Q13 become effective? 

The final guideline was adopted on November 16, 2022, and it became legally effective in the EU on July 10, 2023. The FDA issued its final Q13 guidance in March 2023. Different regions have their own timelines for adopting ICH guidelines into local regulation.

How is continuous manufacturing different from batch manufacturing? 

In batch manufacturing, product moves through manufacturing steps as defined batches. In continuous manufacturing, materials are continuously fed, transformed, and removed while the process operates. ICH Q13 also allows some unit operations to remain in batch mode while other directly connected operations run continuously.

Does ICH Q13 apply to biologics? 

Yes. ICH Q13 applies to continuous manufacturing of chemical entities and therapeutic proteins. Annex III specifically addresses continuous manufacturing of therapeutic protein drug substances, while the guideline notes that its principles may also apply to other biological and biotechnological entities.

What facility changes does continuous manufacturing usually require? 

Plants may need integrated equipment arrangements, defined material-transfer interfaces, suitable monitoring and sampling locations, material-diversion and collection points, automation and data infrastructure, utilities matched to the intended operating profile, and sufficient access for operation and maintenance. The exact facility changes depend on the process and CM configuration.

Does ICH Q13 require Process Analytical Technology (PAT)?

No. ICH Q13 states that PAT is well suited to continuous manufacturing and provides examples of its use for process monitoring and control, but it does not make PAT a universal requirement for every CM process. The monitoring strategy should be appropriate to the process and its control strategy. 

Does continuous manufacturing eliminate pharmaceutical batches?

No. ICH Q13 retains the concept of a batch for continuous manufacturing. Batch size can be defined by the quantity of output material, quantity of input material, run time at a defined mass flow rate, or another scientifically justified approach, and it can also be established as a range.

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Building Africa’s Pharma Manufacturing Base: What the AMA and the 60%-by-2040 Goal Mean for Facility Investment

Building Africa's Pharma Manufacturing Base: What the AMA and the 60%-by-2040 Goal

Africa’s pharma manufacturing base is at a turning point. For decades, the continent has relied on imported medicines and vaccines, a dependency that COVID-19 exposed in painful detail. Now two forces, a new continental regulator and a bold production target, are pushing governments and manufacturers toward a different future. This post looks at what those forces actually mean, and what it takes on the ground to turn the goal into working facilities.

Why Africa Still Imports Most of Its Medicines

The numbers explain the urgency. Africa imports more than 70% of the pharmaceuticals it consumes, while the WHO African Region imports 99% of its vaccines, with a significant share of pharmaceutical imports coming from Asian manufacturing markets. That reliance leaves the continent exposed every time a supply chain hiccup hits somewhere else in the world, and it can add logistics costs, duties, longer lead times, and supply-chain exposure. Local manufacturing can reduce some of these pressures, although its cost competitiveness ultimately depends on production scale, capacity utilisation, input costs, infrastructure, and operating efficiency.

This is not a new problem, but it took a pandemic to turn it into a policy priority.

What Is the African Medicines Agency (AMA)?

The African Medicines Agency was created to address one of the biggest roadblocks to local manufacturing: a fragmented regulatory landscape. Without stronger continental coordination, manufacturers seeking access across multiple African markets have had to navigate fragmented national and regional regulatory requirements, with differing procedures and timelines.

The AMA is a specialised health agency of the African Union designed to strengthen the capacity of participating member states and recognised Regional Economic Communities to regulate medical products, support regulatory harmonisation, and coordinate existing regulatory efforts rather than replace national medicines regulators. As of 22 May 2026, thirty-one African Union member states had ratified or acceded to the treaty establishing the agency and deposited their instruments, marking a continuing institutional shift toward stronger regional regulatory cooperation.

The 60%-by-2040 Goal, Explained

Here is the target at the centre of the sector’s local-manufacturing agenda. Africa CDC, through its Partnerships for African Vaccine Manufacturing (PAVM) initiative, originally set a goal for Africa to manufacture 60% of its vaccine needs locally by 2040; in February 2026, African leaders broadened the continental ambition by declaring a goal to meet at least 60% of Africa’s health-product needs through local manufacturing by 2040. The AMA and this wider production ambition are complementary: one supports stronger and more harmonised regulatory systems, while the other creates a long-term manufacturing and demand objective worth building capacity for. 

A few numbers put the scale of this ambition in perspective:

  • More than 70% of pharmaceuticals consumed in Africa are imported, while 99% of vaccines used in the WHO African Region are imported, showing how limited local production remains relative to demand today.
  • Many African pharmaceutical facilities operate at 30–60% capacity, below the 70%+ utilisation rates reported in more advanced pharmaceutical manufacturing markets.
  • Pharmaceutical production is also concentrated: just eight countries account for 85% of Africa’s approximately 690 pharmaceutical manufacturing facilities.

Closing that gap by 2040 means building real production capacity, not just signing agreements.

What Facility Investment Actually Requires

What Facility Investment Actually Requires

A regulatory framework and a target date do not build a factory. Getting from policy to working production lines takes capital, infrastructure, and technical expertise, and each of these carries its own set of hurdles.

Infrastructure Gaps

Unreliable electricity, weak transportation networks, and limited access to advanced testing equipment all slow down manufacturing readiness. A pharma facility depends on consistent power for HVAC, water systems, and cold storage, so power reliability and utility resilience are critical early considerations for an engineering team before the manufacturing systems themselves can operate reliably. 

GMP-Compliant Facility Design

GMP-Compliant Facility Design

Many local manufacturers face a shortage of facilities built to Good Manufacturing Practice (GMP) standards, including proper HVAC systems and layout design. Retrofitting an existing building can achieve GMP requirements, but brownfield projects may face constraints related to personnel and material flows, segregation, HVAC zoning, utilities, structural capacity, equipment access, and maintainability. A structured engineering and GMP gap assessment is therefore needed to determine whether upgrading an existing building or developing a purpose-built greenfield facility offers the lower technical and lifecycle risk.

Skilled Workforce

A shortage of trained personnel affects both construction and ongoing operations. Facilities need staff who understand validation, quality systems, and day-to-day GMP practice, not just people who can run equipment.

High Capital Costs

Building a GMP-compliant facility carries a real price tag, and the burden of financing a full qualification, validation, and compliance programme is not small, especially during periods of economic pressure. This is one reason regional demand-pooling mechanisms and long-term offtake agreements matter so much. They give investors a clearer path to a return before they commit capital.

What Investors Should Define Before Facility Design Begins

Before committing capital, manufacturers and investors also need to define the intended product portfolio, dosage forms, production capacity, target regulatory markets, site infrastructure, demand assumptions, future expansion requirements, and the CQV strategy. These decisions directly influence facility size, cleanroom classification, utility loads, process equipment, CAPEX, operating cost, and the choice between greenfield and brownfield development. Building these requirements into the project definition early reduces the risk of designing capacity that cannot operate competitively or support the intended market.

How Modern Engineering Tools Fit Into the Picture

As new facilities get planned across the continent, the design and construction process itself is changing. Simulation-based pharmaceutical engineering, including computational fluid dynamics (CFD), digital modelling, and AI-assisted analysis, is increasingly used to evaluate airflow, simulate HVAC performance, and identify layout issues before construction starts, rather than after.For a region trying to build capacity quickly and get it right the first time, catching design problems on a screen instead of on a half-built facility saves both time and money.

This matters more in Africa’s context than almost anywhere else. With capital tight and timelines tied to regional demand targets, a facility that requires major late-stage design corrections, rework, or repeat qualification can create delays and additional costs that investors need to plan for from the beginning.

Where Cleanroom Validation Fits Into the 2040 Target

Where Cleanroom Validation Fits Into the 2040 Target

None of this production capacity means anything if the facilities cannot pass inspection. A Cleanroom Validation Procedure, more precisely described in pharmaceutical GMP terminology as cleanroom qualification, uses ISO 14644 classification principles together with applicable GMP requirements to provide documented evidence that classified environments perform as intended. Depending on the facility and applicable requirements, qualification can include particle classification, HEPA-filter integrity testing, airflow volume and velocity, pressure differentials, airflow visualisation, microbial contamination, temperature, relative humidity, recovery, and other relevant tests. For African manufacturers targeting WHO prequalification or regulated regional and export markets, cleanroom qualification is an important part of GMP readiness where classified cleanrooms are required. It provides documented evidence of controlled-environment performance, but it does not by itself constitute product approval or WHO prequalification. 

Late or incomplete qualification can result in deviations, rework, retesting, and delays during facility start-up or inspection readiness. Building qualification requirements into the design and construction timeline from day one, rather than treating them as a final checkbox, gives a facility a stronger basis for achieving its planned qualification and start-up schedule. 

Why International Partnerships Matter

Africa does not need to build this manufacturing base alone, and international collaboration, technology transfer, skills development, and strategic partnerships are already part of the continent’s local-manufacturing agenda. Partnering with experienced pharmaceutical engineering consultants in India https://www.pharmaaccess.net/ can bring design and construction knowledge from a country that has already built a mature generics manufacturing ecosystem. That experience, applied appropriately to the regulatory, infrastructure, product, and operating requirements of individual African markets, can shorten the learning curve considerably.

Good Pharma Project Management Services matter just as much as the engineering itself. Coordinating design, procurement, construction, and validation as one connected process avoids the fragmented handoffs that lead to rework, delays, and budget overruns, all of which are harder to absorb in markets where capital is already tight.

At Pharma Access, we work on engineering design, construction, and CQV (commissioning, qualification, and validation) for pharma facilities across multiple countries, bringing more than 25 years of technical and operational experience to projects that need to integrate GMP, operability, and qualification requirements from the design stage onward. The manufacturer remains responsible for GMP operations, its pharmaceutical quality system, and applicable regulatory approvals, while the engineering and project team coordinates the agreed scope through design, construction, commissioning, qualification, and handover. If your organization is planning a facility to support Africa’s pharma manufacturing base, our team can help translate a production target into an engineered, commissioned, and qualification-ready facility. You can learn more about our approach on the Pharma Access about page.

Wrapping Up

The AMA and the 60%-by-2040 goal give the continent’s pharma sector a clear direction, but direction alone will not build the plants needed to get there. Reliable power, GMP-compliant design, trained staff, and rigorous qualification & validation all have to come together, project by project, facility by facility. 

The countries and companies that treat facility investment as a technical and engineering challenge, not just a policy commitment, will be the ones best positioned to contribute meaningfully toward Africa’s 2040 local-manufacturing ambition.

FAQs

What is the African Medicines Agency (AMA)? 

The AMA is a specialised health agency of the African Union established to strengthen regulatory capacity, support harmonisation of medicines regulation, and coordinate existing regulatory efforts across participating member states and regional bodies. It complements rather than replaces national medicines regulatory authorities.

What does the “60% by 2040” goal actually mean? 

The original PAVM target called for Africa to manufacture 60% of its vaccine needs locally by 2040. In February 2026, African leaders broadened the continental ambition to meet at least 60% of Africa’s health-product needs through local manufacturing by 2040.

Why do so many African pharma facilities struggle with GMP compliance? 

Common barriers include unreliable electricity, limited access to GMP-compliant facility infrastructure, a shortage of trained personnel, and the high upfront cost of building and qualifying a facility to international standards.

Why is cleanroom validation so important for new African facilities? 

Cleanroom qualification provides documented evidence that classified environments meet their defined cleanliness and performance requirements. It is an important part of GMP readiness for facilities that require controlled environments, although cleanroom qualification alone does not constitute regulatory approval or WHO prequalification.

How can international partners help Africa reach its manufacturing goals? 

Experienced engineering and project management partners can bring facility design, construction, commissioning, qualification, technology-transfer, and project-delivery expertise from established pharmaceutical manufacturing markets, helping African project teams reduce avoidable rework and build local capability as manufacturing capacity expands. 

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MES and QMS in Pharma: What’s the Real Difference?

Difference between MES and QMS in Pharma

If you work in pharmaceutical manufacturing, you’ve probably heard both terms tossed around in the same meeting, sometimes even used interchangeably. However, MES and QMS are not the same.

Why MES and QMS in Pharma Matters

The reason why MES and QMS in pharma matter is that these two systems solve different problems, even when they work alongside each other within the same manufacturing facility.

Let us put it simply: MES manages and records manufacturing execution at the shop-floor level, while QMS governs the broader quality processes required to maintain product quality, compliance and continual improvement.

It is also important to recognise that MES is generally a digital manufacturing application, while a QMS is the wider quality-management framework of an organisation. A QMS may be supported by electronic quality management software, commonly referred to as eQMS, but it is not limited to software alone.

Unclear system boundaries can result in duplicated workflows, disconnected records, incomplete traceability and gaps in validation. Understanding the role of each system is therefore important when planning pharmaceutical operations and digital infrastructure.

The ISA-95 framework places MES within manufacturing operations management, between enterprise-level business systems and lower-level plant automation and control systems. ICH Q10, in contrast, describes the broader pharmaceutical quality system across the product lifecycle. 

What Is an MES System in Pharmaceutical Manufacturing?

A MES system in pharmaceutical manufacturing is software that operates between the plant floor and the enterprise resource planning (ERP) layer. It follows manufacturing activities as they occur on the production floor.

Imagine it as the nervous system of a manufacturing plant. It gathers data from equipment, operators, and materials in real time, then exchanges relevant data with enterprise applications and plant-floor automation systems.

This is what an MES usually does:

  • Electronic batch records (EBR): replacing or supplementing paper batch records
  • Managing the recipes, formulas and manufacturing instructions for each production run
  • Monitoring equipment status and enforcing defined manufacturing-workflow requirements
  • Material genealogy, to trace every ingredient to its source
  • Scheduling and dispatching of work orders on the floor
  • Recording and escalating manufacturing exceptions when a process departs from defined limits

Depending on the application’s scope and configuration, an MES may also support operator identification, electronic signatures, material-status checks and connections with ERP, LIMS and quality systems.

A manufacturing execution system is designed to capture and analyse data in real time and ensure that every step of the manufacturing process complies with good manufacturing practices and regulatory requirements, such as FDA 21 CFR Part 11, where the system creates or maintains regulated electronic records.
However, Part 11 does not apply simply because a system is called MES. Its applicability depends on whether electronic records and electronic signatures are being used to meet requirements under applicable FDA regulations.
That last point is important. And in pharma, a MES is more than efficiency. It is about proving with a record that is held digitally that each batch was produced the way it was supposed to be produced.
FDA requirements call for complete production and control records for every drug-product batch, but they do not require manufacturers to use a software application specifically called MES. 

What Is a QMS in Pharma?

A Quality Management System (QMS) is the system that governs how a company manages quality across the whole company, not just on the production line. This includes documentation, training records, deviations, complaints, audits, corrective and preventive actions (CAPA), and supplier qualification, change control, management review and continual improvement..

MES is at the plant floor level, while QMS spans the entire enterprise. It answers questions such as these.

  • Was this deviation properly investigated and closed out?
  • Are all standard operating procedures up to date and approved?
  • Is every employee trained on the most recent version of a document?
  • Was the right root cause analysis triggered by a customer complaint?
  • Was a change evaluated for its potential effect on product quality, validation and regulatory compliance?
  • Was the effectiveness of a corrective or preventive action evaluated?

A QMS aligned with a framework such as ICH Q10 provides leadership visibility into whether the quality system itself is working, not just whether one batch passed inspection.
ICH Q10 describes a pharmaceutical quality-system model that includes process-performance and product-quality monitoring, CAPA, change management and management review. 

MES and QMS in Pharma: The Core Difference

MES and QMS in Pharma: The Core Difference

Here is the easiest way to differentiate between them:

  1. Manufacturing execution is managed and recorded through MES. It monitors what happens during manufacturing, step by step, in real or near-real time.
  2. QMS governs the wider quality processes. It manages quality events, procedures, investigations, approvals, corrective actions and continual improvement.
  3. An MES asks: Did this batch follow the approved recipe, and can I prove it?
  4. A QMS asks: “Is our quality system adequate overall, and are quality events being appropriately managed and resolved?”

Both systems can contain records that regulators will want to see during an inspection. Neither substitutes for the other.

However, QMS should not be viewed only as a software application. A pharmaceutical quality system also includes people, responsibilities, procedures, governance and management oversight. 

Why Integration Between MES and QMS Matters

Challenges arise when these two systems do not communicate with each other.
When MES and QMS are disconnected, teams may have to manually transfer manufacturing information into quality workflows. This can create delayed deviation reporting, duplicate data entry, inconsistent records and incomplete links between batch information and quality investigations.

This is a familiar story throughout the industry. MES is positioned within manufacturing operations management under the ISA-95 framework.
Vendors are increasingly developing unified platforms where MES and QMS share data rather than being separate silos. If there is a deviation on the line, an integrated system can initiate or provide information to a quality event, depending on the approved workflow and configured business rules, rather than relying on someone to see it and log it manually later.
Not every equipment alarm or process exception should automatically become a formal quality deviation. The company must define which events require quality assessment, which system owns each record and how the connected workflow will be reviewed and validated.

ISA-95 provides models and terminology for defining system boundaries and information exchanges between manufacturing-control and enterprise functions. 

This integration is not just a software choice for a facility. It changes how the plant is built from the ground up, how sensors are placed, how data moves from one system to another, and how validation is planned during construction. It may also affect equipment connectivity, instrumentation, OT networks, operator terminals, data ownership, cybersecurity and system-interface requirements. That’s the world of facility design and engineering, well before any software vendors are called in.”

How Facility Design Shapes MES and QMS Success

How Facility Design Shapes MES and QMS Success

It’s a common mistake to think of MES and QMS as IT systems that can simply be added after the facility is built. It turns out that the engineering of a plant has a direct impact on how easily MES and other production-related systems can be connected and implemented later.

If equipment, utilities, and cleanroom layouts are not designed with data capture and traceability in mind, teams have to retrofit sensors and workarounds after the fact. That adds cost and leaves holes in the traceability that MES is supposed to provide.

However, the effectiveness of a QMS depends not only on facility design but also on quality governance, procedures, responsibilities, training, system ownership, change management and management oversight. 

This is where a company such as Pharma Access comes into the picture.

Pharma Access is a turnkey pharmaceutical engineering partner offering engineering design, construction & installation, and commissioning, qualification & validation (CQV) for manufacturing facilities. Their project management & EPCMV services are focused on taking a facility from concept to operational readiness, which includes planning for the automation and data infrastructure that MES and QMS rely on later.
During concept, basic and detailed design, Pharma Access can support the engineering foundations needed for future digital-manufacturing systems. These may include equipment interfaces, instrumentation, OT infrastructure, utility monitoring, operator-access points, data pathways and validation responsibilities, depending on the agreed project scope.
The move to full digital traceability is a much easier process when a facility’s electrical, instrumentation, automation and cleanroom is built around these systems from day one.

This does not imply that Pharma Access supplies or configures MES or QMS software unless those activities are specifically included within its service scope.

EU GMP Annex 11 places computerised systems within the pharmaceutical quality system and addresses lifecycle risk management, validation and the qualification of IT infrastructure.

Practical Steps to Align MES and QMS in a Pharma Facility

Identify quality-critical process steps before selecting software.

  1. Determine what data should automatically flow from MES to QMS, such as deviations and manufacturing exceptions, nonconformances, batch holds and investigation references.
    Laboratory out-of-specification results are generally managed through laboratory and quality processes. Where LIMS is used, the required interfaces among LIMS, MES and QMS should also be defined. 
  2. Involve engineering and facility design teams early—not after equipment is in place Quality, manufacturing, IT, automation, engineering and validation teams should agree on system boundaries and infrastructure requirements before the design is finalised. .
  3. Test the integration, not just each system in isolation, Testing should confirm data mapping, timestamps, electronic signatures, record ownership, audit trails, exception handling and system recovery across the connected applications..
  4. Train operators on how the two systems work together so that a batch record and a quality event are never two separate stories.

If any of these steps are not performed, it usually manifests later as a data gap during an audit and is much more expensive to fix than to plan for in the first place.
WHO data-integrity guidance addresses data governance, data transfer, training, good documentation practices and controls for computerised systems. 

Regulatory Weight Behind Both Systems

MES and QMS are both of regulatory importance, but from different perspectives. FDA’s 21 CFR Part 11 covers electronic records and signatures, which are applicable where MES-generated electronic records or electronic signatures are used to meet requirements under applicable FDA regulations. Quality system regulations, in contrast, require a documented, auditable QMS that spans the life of the product, from raw material intake to post-market complaints.

Inspectors do not ask which system is ‘more important’. They assess whether the available records and quality processes demonstrate that a product was made safely, consistently, and in accordance with approved procedures? That proof only holds up if the shop floor data and the quality department data tell the same story.

For facilities supplying European markets, EU GMP Annex 11 should also be considered for GMP-relevant computerised systems. The current Annex 11 remains available through EudraLex Volume 4, while the European Commission has also undertaken consultation on proposed revisions.

Final Thoughts

MES and QMS in pharma are not competing systems. They are two sides of the same compliance and quality coin. In pharmaceuticals, real- or near-real-time visibility into and management of manufacturing execution, while a QMS provides the broader framework that keeps that process accountable.
Direct control of equipment and process conditions generally remains within equipment-control, PLC, DCS or SCADA systems. 

The meeting of the two starts long before software implementation. It starts with how a facility is designed, wired, and validated. This is why companies that are planning new or upgraded facilities often bring in experienced engineering partners early in the process, as retrofitting data infrastructure after construction is much more difficult than planning for it from the start.
A QMS is fundamental to pharmaceutical quality governance. MES, by comparison, is a technology choice that can strengthen manufacturing execution, electronic traceability and data availability, but it is not mandated by name. 

Frequently Asked Questions

1. What is the main difference between MES and QMS in pharma? 

MES handles production data in real time, batch records, and equipment tracking on the shop floor. QMS provides you with the overall quality framework, including deviations, CAPA, training records, and document control across the entire company.MES manages and records manufacturing execution, while QMS governs the processes through which quality is managed, investigated and improved. 

2. Can a pharma company use MES without a QMS, or vice versa? 

A pharmaceutical company can operate without a software application specifically called MES, provided it maintains appropriate manufacturing controls, records, traceability, review and data-integrity measures. Without a QMS, there’s no framework for managing deviations and corrective actions. Without MES, a company may use controlled paper records, another validated electronic application or an appropriately managed hybrid system. MES is not the only method of maintaining batch records and traceability.

3. Why should MES and QMS be integrated in pharmaceutical manufacturing? 

With integration, quality events can be initiated or supported using relevant production data, according to approved workflows and business rules. This fills gaps in traceability and speeds up finding and investigating deviations.Integration can also reduce duplicate data entry and improve the connection between manufacturing records and quality investigations. 

4. Does facility design really affect how well MES and QMS perform later? 

Yes. If sensors, utilities, and data infrastructure are not part of the facility design, teams are forced to retrofit systems after construction, which is costlier and often leads to gaps in traceability.This is particularly relevant to MES and its connections with equipment and automation systems. QMS performance also depends heavily on quality governance, procedures, training, system ownership and management oversight. 

5. Who should be involved when planning MES and QMS for a new pharma facility? 

Involve quality teams, IT, automation engineers, and the facility design or EPCMV partner early on. Manufacturing operations, validation, QC or laboratory representatives and equipment suppliers may also need to participate, depending on the project scope. Having these groups plan together from the start avoids costly rework later in the project.

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Pharmaceutical Patents Expiring in FY2026–27: Manufacturing Readiness Beyond the Patent Date

Pharmaceutical Patents Expiring in FY2026–27: Manufacturing Readiness Beyond the Patent Date

Research cut-off date: 14 July 2026
Primary jurisdiction: United States
Fiscal-year period reviewed: 1 April 2026 to 31 March 2027

Pharmaceutical patent expiries in FY2026–27 may help generic manufacturers, API producers, CDMOs and facility owners identify products for further evaluation. However, a patent date should not be treated as a confirmed generic-launch date.

A pharmaceutical product may be protected by multiple patents covering the active ingredient, formulation, crystal form, manufacturing process, dosage regimen, indication or delivery device. Regulatory exclusivity, pediatric exclusivity, patent-term extensions, litigation, settlements and first-applicant exclusivity may also affect commercial entry.

For manufacturers, patent screening is therefore only the starting point. A viable programme must also consider regulatory approval, API availability, formulation development, process complexity, containment, equipment lead times, capacity, technology transfer, validation and GMP infrastructure.

Pharma Access supports pharmaceutical companies in translating a verified product strategy into practical manufacturing requirements. This may involve assessing an existing facility, adding a new production line, expanding a brownfield site or developing a greenfield plant.

Looking for verified patent and regulatory references without reading the full article? Jump straight to the Source Register. 

Understanding Patent Expiry and Loss of Exclusivity

Patent expiry is the end of one patent in a defined jurisdiction. It does not necessarily mean that all protection for the product has ended.

Regulatory exclusivity is separate from patent protection and may prevent competing applications from being submitted or approved for a defined period. Loss of exclusivity, or LOE, is a broader commercial term that may refer to the end of a key patent, regulatory exclusivity, pediatric exclusivity, a settlement date or the expected start of generic competition.

The FDA Orange Book identifies approved drug products together with associated U.S. patent and regulatory-exclusivity information. Even when one listed patent expires, market entry may still depend on later patents, litigation, settlement terms, ANDA status, labelling strategy and 180-day exclusivity.

Pharmaceutical Products Facing Patent Milestones in FY2026–27

Eliquis — Apixaban

Eliquis is an oral anticoagulant marketed by Bristol Myers Squibb and Pfizer. An FDA tentative-approval letter identifies U.S. Patent 6,967,208 with an expiry date of 21 November 2026, while another listed patent continues to 24 February 2031.

Bristol Myers Squibb identifies 2028 as its estimated minimum U.S. market-exclusivity date and states that certain settled generic companies may launch in 2028, subject to additional challenges. The November 2026 date should therefore be treated as one patent milestone, not the end of all U.S. protection.

For manufacturers, apixaban may still be relevant to API and oral-solid-dose capacity planning. Investment decisions should be linked to the target jurisdiction, legal pathway, regulatory status, supply strategy and expected entry arrangements.

Ibrance — Palbociclib

Ibrance is an oral CDK4/6 inhibitor marketed by Pfizer. Pfizer reported that a U.S. patent-term extension moved the expiry of RE47,739 to 5 March 2027. FDA records also identify later patents and potential 180-day generic exclusivity.

March 2027 is therefore a significant patent milestone rather than an uncontested product-level LOE date.

From an engineering perspective, palbociclib may require potent-compound controls, including contained dispensing and transfer, local exhaust ventilation, dust extraction, pressure control, equipment containment, campaign manufacturing, cleaning validation and controlled waste handling.

Trintellix — Vortioxetine

Trintellix is an immediate-release oral antidepressant marketed in the United States by Takeda. U.S. Patent 7,144,884 reached its identified expiry date on 17 June 2026, while FDA records continue to reference other patents, litigation and potential shared 180-day exclusivity.

A manufacturing assessment should review API solid-state characteristics, particle-size distribution, blend and content uniformity, dissolution, coating, stability, packaging and analytical-method transfer. Where an existing OSD plant is proposed, available dispensing, compression, coating, packaging and laboratory capacity should also be evaluated.

Rexulti — Brexpiprazole

Rexulti is an oral antipsychotic marketed by Otsuka with Lundbeck. FDA records identify four patents that expired on 12 April 2026, but later patents continue through December 2028 and October 2032.

For the reviewed Apotex ANDA, FDA stated that final approval could not be granted before 23 December 2028 based on the applicant’s certifications unless another legal or regulatory basis supported earlier approval.

Rexulti demonstrates why the expiry of several patents on one date cannot be treated as a complete LOE assessment.

Gilotrif — Afatinib

Gilotrif is an oral oncology medicine marketed by Boehringer Ingelheim. FDA records identify RE43,431 through 13 July 2026, while other patents continue beyond that date. The reviewed application received tentative approval, reinforcing the difference between technical regulatory acceptability and permission for commercial marketing.

A manufacturing programme may require potent API handling, HVAC segregation, differential-pressure control, contained transfer, equipment cleanability, cleaning limits, waste management and strong analytical capability.

Symproic — Naldemedine

Symproic is an oral treatment for opioid-induced constipation. Current U.S. ownership and commercial arrangements are more complex than a simple originator-versus-generic description. FDA records identify BioDelivery Sciences International as the NDA applicant, while Collegium states that it licenses U.S. commercialization rights from Shionogi.

A proposed 5 October 2026 date should not be published as a product-level U.S. LOE date until the current Orange Book patent stack, litigation position and any settlement or licensed-entry arrangements are reconfirmed.

Products Close to, but Outside, FY2026–27

Januvia and Janumet — Sitagliptin Products

For U.S. Januvia tablets, FDA records identify U.S. Patent 7,326,708 through 24 May 2027, after the end of FY2026–27. Immediate-release Janumet records include the same date and another patent through January 2029.

Januvia, Janumet and Janumet XR are separate products and applications and should not be combined into a single expiry date. They may still be relevant to medium-term planning for API sourcing, fixed-dose-combination development, high-volume compression, coating, packaging and analytical capacity.

Uptravi — Selexipag

Johnson & Johnson identifies pediatric exclusivity for U.S. Patent 7,205,302 through 30 April 2027 and lists additional patents extending into 2030, 2031 and 2037. The April 2027 date is outside FY2026–27 and is not the end of all U.S. protection.

Products Removed from the 2026 Opportunity Set

Erleada should not be presented as a March 2027 overall LOE opportunity because Johnson & Johnson identifies 2030 as the U.S. composition-of-matter patent expiry year and lists later patents.

Imbruvica should also be excluded from a straightforward 2026 opportunity list. Johnson & Johnson identifies 2028 as the U.S. composition-of-matter patent expiry year.

Sprycel is not awaiting initial U.S. generic entry; Bristol Myers Squibb reports that generic versions have entered the United States, European Union and Japan.

Saphris is also not a new first-entry opportunity arising from an October 2026 patent date because FDA approved an asenapine sublingual-tablet ANDA in 2018.

What the FY2026–27 Patent Landscape Means for Manufacturers

Patent milestones can support early portfolio screening, but manufacturing decisions should follow legal, regulatory, technical and engineering verification.

Legal and Regulatory Verification

Before committing engineering expenditure, companies should confirm the intended jurisdiction, current patent records, remaining formulation and method-of-use patents, patent-term or pediatric extensions, regulatory exclusivity, ANDA status, Paragraph III or IV certifications, label carve-outs, 180-day exclusivity, litigation, settlements and licensed-entry arrangements.

Engineering teams may use this information to develop schedules, but freedom to operate and commercial-launch risk should be assessed by qualified legal and regulatory advisers.

API, Formulation and Containment Readiness

The technical assessment should confirm that the API and finished product can be developed, scaled and transferred reproducibly. Key questions include route scalability, starting-material availability, impurity control, solid-state properties, particle size, dissolution, bioequivalence, analytical transfer, stability, packaging and cleaning limits.

For oncology or low-dose oral products, containment should be based on product-specific toxicological and occupational-exposure assessments. The resulting strategy may affect dispensing, closed transfer, local exhaust ventilation, dust extraction, room pressures, equipment segregation, campaign planning, cleaning validation and waste handling.

Capacity, Utilities and Technology Transfer

Capacity planning should consider commercial demand, batch size, campaign length, utilisation, changeover time, yield, packaging throughput, laboratory capacity, warehousing, maintenance access and future expansion.

Utility loads should be calculated from the actual equipment sequence and production strategy. Depending on the process, requirements may include purified water, process gases, compressed air, steam, chilled water, HVAC utilities, electrical systems, BMS, EMS and process automation.

Technology transfer must connect formulation and process knowledge with the receiving site’s equipment, utilities, automation, procedures and quality systems. Equipment-gap assessments, engineering batches, analytical transfer, cleaning development, registration batches, process qualification and continued verification should be planned early.

How Pharma Access Supports Patent-Driven Manufacturing Plans

Once a product opportunity has been independently verified, Pharma Access can assess whether it fits within an existing facility or requires a dedicated line, brownfield expansion or greenfield project.

The assessment may cover:

Feasibility and Project Planning

  • Facility feasibility and capacity assessments
  • Production-volume and expansion planning
  • Brownfield and greenfield project evaluation

Pharmaceutical Engineering and Process Design

  • Pharmaceutical facility engineering design
  • Process-flow and production-layout development
  • Personnel and material movement planning
  • GMP-facility integration

Equipment, Cleanrooms and Utility Systems

Procurement, Construction and Installation

Commissioning, Qualification and Validation

  • Commissioning and qualification planning
  • Facility, utility and equipment validation
  • CQV documentation and execution support

Project Management and EPCMV Delivery

  • Integrated project and schedule management
  • Engineering, procurement and construction coordination
  • EPCMV project-delivery support
  • Brownfield expansion and operational-site coordination

Pharma Access can then support engineering design, equipment planning, vendor coordination, construction, installation, Site Acceptance Testing, commissioning, qualification, validation and project management.

For brownfield projects, the strategy may also address phased execution, temporary routes, tie-in planning, HVAC shutdowns, construction controls and protection of adjacent GMP operations.

This integrated approach connects a verified product strategy with realistic capital requirements, engineering deliverables and execution schedules. Pharma Access does not provide patent opinions, predict court decisions or guarantee generic entry. Its role is to develop practical, compliant and scalable manufacturing infrastructure after the legal, regulatory and commercial pathway has been established.

Why Choose Pharma Access?

Preparing for a generic or pharmaceutical manufacturing opportunity requires more than identifying a molecule and patent date. The facility must reflect the process, product characteristics, containment requirements, production volume, target markets and long-term operating strategy.

Pharma Access provides integrated pharmaceutical engineering and turnkey project-delivery support across feasibility, process and equipment planning, cleanrooms, HVAC, utilities, automation, construction, installation, CQV, project management and EPCMV delivery.

Whether the project involves an OSD line, potent oncology facility, API unit, sterile production or biotechnology infrastructure, Pharma Access helps translate manufacturing requirements into an executable engineering and project-delivery plan.

Planning capacity for a new generic, API or pharmaceutical product? Connect with Pharma Access to evaluate process, facility, equipment, containment, utility and CQV requirements before major project decisions are finalised.

The patent and exclusivity information in this article is provided for general industry awareness and is based on publicly available information reviewed as of 14 July 2026. Patent status, litigation, regulatory exclusivity and market-entry timelines may change and vary by jurisdiction, formulation, dosage form, indication and product. Companies should complete independent legal, regulatory and commercial due diligence before making manufacturing or investment decisions.

Source Register

Frequently Asked Questions

Which pharmaceutical patents are expected to expire in 2026?

Selected U.S. milestones include an Eliquis patent on 21 November, a Trintellix patent on 17 June, four Rexulti patents on 12 April and a Gilotrif patent on 13 July. These are individual patent dates, not confirmed product-level LOE dates.

Does patent expiry allow immediate generic entry?

No. Other patents, regulatory exclusivity, litigation, settlements, tentative approval, 180-day exclusivity or labelling issues may still delay entry. Manufacturing readiness, stability, bioequivalence and cGMP compliance may also affect launch timing.

How early should capacity planning begin?

Planning should begin early enough to complete feasibility, development, equipment selection, procurement, facility work, technology transfer, CQV and regulatory batches before the intended commercial date. The schedule depends on dosage form, containment needs, existing infrastructure and equipment lead times.

Why is CQV important when adding a manufacturing line?

CQV provides documented evidence that facilities, utilities, equipment and systems are installed and operate as intended. Considering CQV during design allows user requirements, design reviews, vendor documentation, FAT, SAT, IQ and OQ activities to be developed as one coordinated programme.

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How Much Can a Modern Pharma Facility Actually Save on Energy Costs Long-Term?

Modern Pharma Facility Energy Costs

Energy bills at a pharma plant are not like the energy bills at a normal office building. A single cleanroom can use far more power per square foot than a standard commercial space, much of which is used to keep the air clean, cool,within specified humidity limits  and at the right pressure. Once you know where your money is going, it is much easier to see where you can save it. This post takes a look at published industry benchmarks for  modern pharma facility energy costs, the big drains, and what facilities have actually saved after they made changes.

Why Energy Costs Run So High in Pharma Manufacturing

A typical commercial office building constructed after 2000 has been reported to use approximately 81 kBtu per square foot annually. According to a report published by Consulting-Specifying Engineer, some pharmaceutical manufacturing facilities have recorded energy-use intensities of approximately 1,210 kBtu per square foot annually. Much of that difference is associated with one major system: HVAC. Cleanrooms require a continuous flow of filtered air to maintain particle counts within limits, and that air may need to be heated, cooled, humidified, or dehumidified for extended operating periods.

Many critical pharmaceutical environments maintain controlled conditions continuously, even when production is not active. However, validated temperature or airflow setbacks may be possible during non-production periods where they are supported by quality risk assessment, monitoring, qualification and change control.

HVAC is not the only contributor to pharmaceutical-facility energy consumption. Process equipment, sterilisation systems, purified-water generation, clean steam, refrigeration, compressed air and other central utilities may also represent substantial energy loads.

The HVAC Component Driving Energy Costs in Modern Pharmaceutical Facilities

The HVAC Component Driving Energy Costs in Modern Pharmaceutical Facilities

HVAC systems account for a large share of total plant energy use across the industry.

  • According to ISPE, and data referenced in the U.S. EPA ENERGY STAR pharmaceutical-industry guide, HVAC use in cleanrooms has been reported to account for approximately 36% to 67% cleanroom energy consumption, depending on the room class and process.
  • Another ISPE article on cleanroom design points out that many sites have over 50% plant HVAC electricity use over 50%, noting that pharma cleanrooms can use up to 15 times more energy than a typical commercial building.
  • Research by Lawrence Berkeley National Laboratory shows that HVAC systems can comprise as much as two-thirds of the energy used by labs and cleanrooms, as cited in the U.S. EPA’s ENERGY STAR guide for the pharmaceutical industry.

That range  approximately one-third to two-thirds of energy use in many cleanroom environments, depending on the source, system boundary and site is the reason why just about every real energy story in pharma begins with HVAC.
It is important to distinguish between total facility energy, electricity consumption, cleanroom energy and HVAC-system energy. Savings measured in one category should not automatically be interpreted as an equivalent reduction in the facility’s total utility bill. 

How Much Can a Modern Pharma Facility in Energy Actually Save?

How Much Can a Modern Pharma Facility in Energy Actually Save?

Here’s what the numbers look like if you make changes, based on published case data:

The examples below include historical case studies compiled in industry and ENERGY STAR guidance. Their engineering principles remain relevant, but current tariffs, equipment costs and payback periods should be recalculated for each project.

Airflow optimisation. Reducing unnecessary airflow can lower fan, heating and cooling demand. However, any reduction in air-change rates must be supported by process risk, room recovery performance, contamination-control requirements, qualification and environmental monitoring.

  1. HVAC recommissioning: The ENERGY STAR pharmaceutical guide cites a recommissioning project at Pfizer’s Morris Plains, New Jersey site, which reduced its net energy use per degree-day by 21%.
  2. Metering and monitoring upgrades: Wyeth’s Fort Dodge Animal Health plant in Campinas, Brazil installed a metering and control system that cut electricity use by 48% and reduced plant utility costs by 10%.
  3. Merck’s labs in Rahway, N.J., lowered room temperatures during off hours, saving nearly 30,000 MBtu a year across 350,000 square feet of lab space overnight and on weekends.The strategy was applied to selected laboratory areas where reduced temperatures would not affect equipment or scientific operations. 
  4. Dynamic airflow management :Dynamic airflow management can reduce ventilation demand by moving away from continuously operating at fixed, worst-case airflow conditions. Commercial engineering estimates have indicated potential reductions of approximately 20% to 40% in HVAC energy consumption in suitable applications.
    This should not be described as a direct EU GMP Annex 1 requirement. Annex 1 requires a documented Contamination Control Strategy, Quality Risk Management, qualified cleanroom performance and appropriate monitoring. Any dynamic airflow strategy must demonstrate that validated environmental conditions and pressure relationships remain consistently maintained. 
  5. Variable-air-volume (VAV) systems: According to a laboratory case study cited in the U.S. EPA ENERGY STAR guide, a VAV system used 30% to 50% less energy than the older air-control system it replaced.
    This figure should be treated as a project-specific result rather than a guaranteed saving for every pharmaceutical facility. Actual performance depends on minimum validated airflow, occupancy, process loads, room classification, pressure requirements and control sequences. 

None of this involved the replacement of whole buildings. The savings came from modifying how existing systems operated, improving controls and monitoring, or designing the systems correctly from the beginning.

Real Facilities, Real Numbers

Real Facilities, Real Numbers

The examples above are from operating plants, not from laboratory tests. A good one to study closely is Genentech’s site in Vacaville, Calif. The team went with two large chillers and one smaller unit instead of three matched units. This way, the big chillers run close to full load, where they use less power per ton. The ENERGY STAR pharmaceutical guide said the decision was expected to save about $113,250 annually. The same facility also reset its discharge air temperature during low-demand periods, saving nearly $150,000/year in chilled water and steam usage.

These are no one-shot paybacks. Once the system correctly installed, controlled, commissioned and maintained, you will see the savings on every utility bill thereafter, year after year, for the life of the equipment.

However, long-term savings depend on maintaining sensors, control sequences, filters, dampers, valves and equipment performance. Without ongoing monitoring and recommissioning, systems can gradually drift away from their intended operating conditions. 

Biopharmaceutical Facility Design Sets the Ceiling on What’s Possible

Here’s the part that matters most for anyone contemplating a new build: the decisions made in Biopharmaceutical Facility Design dictate most of what’s even possible to save later. An oversized HVAC system, poor zoning, or a one-size-fits-all air change rate will always cost more to operate than a properly sized system, no matter how well it is operated afterwards.

ISO 14644-16 provides guidance for improving energy efficiency in new and existing cleanrooms while maintaining the required environmental performance. It supports evidence-based evaluation of airflow, air-distribution effectiveness, operating modes and energy performance rather than relying only on inherited or overly conservative design assumptions.

Hence, the importance of declassifying a room, right-sizing equipment, and correctly mapping pressure cascades at the design stage. A cleanroom specified at a cleaner classification than the process requires can increase airflow demand, capital cost, qualification effort, monitoring requirements and long-term operating expenditure without providing a corresponding product-quality benefit.

Why Turnkey Pharmaceutical Projects Change the Math

Energy decisions are often made in a vacuum when design, construction, and equipment selection are done under separate contracts. The HVAC engineer sizes it for one set of assumptions, then the process team changes the layout, and the numbers don’t match. Turnkey pharmaceutical projects connect these interdependent decisions through an integrated delivery structure. One team handles the work from the initial design phase all the way through construction and validation. With engineering design, construction, and project management all under one roof, a firm like Pharma Access can follow an HVAC decision made in the design phase through to the equipment installed on site reducing the risk of design intent being weakened during handovers between disciplines, contractors and project stages.

Engineering Design Services for Pharma: Where the Savings Get Locked In

Engineering Design Services for Pharma

Good engineering design services for pharma begin with a hard look at the actual process, not a generic template. It also means matching air change rates to actual contamination risk, zoning HVAC systems by room class rather than running one system for the whole plant, and sizing chillers and pumps to the load the facility will actually see.

Air-change rates should not be selected by room classification alone. They should be developed using process risk, product exposure, occupancy, contamination generation, room recovery, airflow effectiveness, pressure relationships and qualification requirements. 

Pharma Access works in exactly this way on its engineering design projects. This includes HVAC, MEP, and clean room layout together, so the systems are sized to match the process and not a worst-case guess.

Pharma Access coordinates process requirements, cleanroom classification, HVAC zoning, pharmaceutical utilities, equipment selection, automation and CQV considerations during engineering development. This integrated approach helps align system capacity with actual manufacturing requirements rather than isolated assumptions developed by individual disciplines.

Energy-efficiency opportunities may include optimised airflow distribution, correctly sized air-handling and chilled-water systems, lower system pressure drops, efficient motors and drives, heat recovery where technically suitable, building-management-system monitoring and validated operating setbacks. Every measure must remain compatible with GMP, product protection, operator safety and the facility’s Contamination Control Strategy.

A Simple Way to Think About the Payback

This order works well if you’re planning a new build or an upgrade.

  1. Get a baseline. Know your existing energy use per square foot before you start and separate HVAC, process equipment, utilities and other major loads wherever submetering data is available.
  2. Compare air change rates with ISO 14644-16 and identify rooms that are over-ventilated for their real risk level.
  3. Use ISO 14644-16 as cleanroom energy-efficiency guidance, but assess any proposed airflow change through Quality Risk Management, room-performance data, qualification, environmental monitoring and formal change control. 
  4. Consider HVAC recommissioning before buying new equipment.An Ethicon facility in Somerville, New Jersey, implemented a recommissioning project at a reported cost of approximately $53,000. The project generated approximately $48,000 in annual gas and electricity savings, giving a simple payback of around 1.1 years.
  5. Add monitoring and controls to catch drift before it turns into a bigger bill.
  6. Integrate design, construction, and project management into one plan so energy choices last from blueprint to start-up.
  7. Continue monitoring performance after qualification. Energy savings will only remain sustainable when sensors, controls, equipment and operating procedures continue to perform as intended.

FAQs

How much of a pharma plant’s energy bill comes from HVAC? 

Published studies put it somewhere between approximately 36% and 67% of cleanroom energy consumption, depending on room class and process. Sterile and biotech cleanrooms tend to be on the high end generally because they require constant, tightly filtered airflow at all times.

However, the exact percentage varies according to the facility boundary being measured, the manufacturing process, outside-air requirements, climate, operating hours and the contribution of process equipment and pharmaceutical utilities. 

Can an existing pharma facility cut energy costs without a full rebuild? 

Yes. Recommissioning, airflow adjustments, and temperature setbacks during off-hours have achieved reductions of approximately 10% in total utility cost, more than 20% in weather-normalised energy use, and substantially higher reductions in selected electrical or HVAC loads at actual sites, based on ENERGY STAR and ISPE case data.
Payback periods vary by intervention, tariff, operating schedule, system condition and capital requirement. Some low-cost control and recommissioning projects have achieved payback in approximately one to two years, while equipment-intensive upgrades may take longer.

Does a smaller cleanroom cost less to run? 

Generally, a smaller cleanroom requires less total conditioned airflow than a larger room with identical conditions. However, floor area alone does not determine operating cost.

Room class, room volume, ceiling height, airflow rate, outside-air demand, temperature and humidity requirements, pressure cascade, process heat load and operating schedule drive cost.

A small over-classified room can cost significantly more per square metre than a larger room configured with the proper airflow for its actual use.

What’s the difference between hiring separate firms and using turnkey pharmaceutical projects? 

Design and construction decisions that are separately contracted can drift apart over time. A turnkey pharmaceutical project means one team is responsible for the entire process from design to startup. 

That means greater continuity and accountability for energy-related decisions throughout engineering, procurement, construction, commissioning and qualification.

It does not remove the need for design reviews, approvals or change control, but it can reduce interface risks and help preserve agreed performance requirements.

When is the best time to plan for lower energy costs: design or after construction?

Design, it is far cheaper to get air changes, chiller sizing, and HVAC zoning right on paper than to fix them once the building is up and validated. Existing facilities can still achieve meaningful savings through recommissioning, monitoring, controls optimisation and targeted upgrades. However, new projects have the greatest opportunity to influence lifecycle cost before equipment capacities, layouts and system configurations become fixed. 

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How Are Companies Using AI for Predictive Maintenance in Their New Pharma Plants?

AI for Predictive Maintenance in Pharma Plants

A tablet press breaking down at 2 a.m. doesn’t just mean a repair bill; it also means a loss of production.trigger a product-impact assessment, a deviation investigation, additional testing or a line that remains idle while the engineering and quality teams investigate. That one breakdown is why many pharma companies are now incorporating AI for predictive maintenance into their new facilities, rather than adding it later.

This piece examines what that really looks like on the ground: the sensors, the software, the personnel, and the practical challenges of operating in a GMP-regulated environment, including in a market like Mumbai.

What Predictive Maintenance in Pharma Plants Actually Means

What Predictive Maintenance in Pharma Plants Actually Means

Most older plants still run on a combination of corrective maintenance and scheduled preventive maintenance: fix it when it breaks, or service it on a fixed calendar, whether or not it needs it. Both approaches have limitations when they are used without appropriate condition monitoring. Breakdown maintenance halts the line without warning. Maintenance by calendar often replaces parts that still have life left in them or misses a problem that shows up between two scheduled visits.

Predictive maintenance in modern pharma plants introduces a condition-based approach supported by equipment data and analytics. Vibration, temperature, motor current and pressure sensors can be installed on selected compressors, centrifuges, tablet presses, HVAC components and filling-line equipment to collect data continuously or at defined intervals, depending on the asset and its operating condition. A machine learning model trained on this data can establish expected operating patterns and identify changes associated with defined degradation or failure modes before functional failure occurs.

Briefly:

  • Preventive maintenance is calendar-based.
  • Predictive maintenance is based on the actual condition of the equipment.

The second method can identify selected degradation patterns that scheduled maintenance may not detect between inspections and can reduce unnecessary maintenance interventions. However, it does not replace statutory inspections, calibration activities, safety checks or preventive maintenance tasks that remain necessary under the approved maintenance programme.

Why New Plants Are Designing This In From Day One

You can retrofit sensors and software on old equipment, but it’s slower and more expensive than wiring a new facility for it from the get-go. This is why AI and automation are increasingly being considered as part of the core engineering brief for greenfield pharma projects, not as an add-on.

It’s important to recognise that predictive maintenance is just one part of a broader transition toward pharma manufacturing automation in new facilities. Several factors are driving this trend.

The costs of sensors, edge devices and data platforms have decreased for many applications, making broader equipment monitoring more feasible. However, monitoring should still be based on asset criticality, identifiable failure modes and a clear business or quality-risk justification rather than automatically covering every asset in the plant.

Regulatory agencies are giving increasing attention to the controlled use of AI within the pharmaceutical product lifecycle. The US FDA’s January 2025 draft guidance presents a risk-based framework for assessing the credibility of AI model outputs used to support regulatory decision-making concerning drug safety, effectiveness or quality, including relevant manufacturing applications. It does not specifically mandate predictive maintenance, but it reinforces the need for defined context of use, appropriate data, model governance and human oversight when AI outputs influence regulated decisions.

Export-oriented manufacturers and pharmaceutical clients may also place greater value on accessible and traceable electronic equipment-health and maintenance records. However, properly controlled paper records can remain acceptable, and the use of an electronic system does not by itself establish GMP compliance.

Losing a batch on a new, costly line is significantly more expensive than losses on depreciated equipment.

How AI for Predictive Maintenance in Pharma Plants Works, Step by Step

How AI for Predictive Maintenance in Pharma Plants Works, Step by Step

Here’s a quick breakdown of the daily run of this on a modern line:

  1. Sensors gather data: Vibration, temperature, torque, and pressure readings are taken from equipment such as tablet presses, granulators, autoclaves, and lyophilisers at a sampling frequency engineered for the equipment, its operating cycle and the degradation mechanism being monitored.
  2. Data goes to a central platform: Readings are ingested into a cloud or on-premise system along with data from the plant historian, MES, and existing SCADA systems. Depending on the application, information may also be integrated from the BMS, EMS, CMMS or enterprise asset-management system. Cloud deployment requires appropriate consideration of cybersecurity, access control, data ownership, availability and backup arrangements. 
  3. Machine learning algorithms search for drift: Models compare live readings with known equipment behaviour and known failure patterns such as bearing wear signatures or seal degradation.
  4. The system raises an alarm before a breakdown: Maintenance receives an early indication when the monitored condition exceeds an approved threshold or the model detects an abnormal operating pattern. The available warning period can range from a short interval to several weeks or months, depending on the failure mode, equipment condition, operating profile and quality of the available data.
  5. Work orders and records are automatically created: Where the analytics platform is appropriately integrated with a CMMS or enterprise asset-management system, reviewed alerts can initiate an approved assessment or work-order process. The configuration, approval route and associated electronic records should be governed according to the system’s GxP impact and the organisation’s maintenance and quality procedures. 

That’s the flow that makes a featured snippet-worthy answer to “How does predictive maintenance work in pharma?”: sensors collect, software analyses, the system alerts early, and the team acts on a schedule, not a surprise.

The Real Benefits Companies Are Reporting

The Real Benefits Companies Are Reporting
  • Fewer unplanned stopovers: Identify equipment drift early, and you’ll lose fewer batches to a mid-run breakdown.
  • Prolonged equipment life: By basing service on actual wear and tear, rather than on a fixed calendar, unnecessary replacement of parts and stress on machinery are reduced.
  • Stronger compliance posture: An unplanned failure of a reactor, centrifuge or critical utility component is not simply a downtime event. It may result in a deviation investigation, product-impact assessment, further testing and, in some cases, batch rejection. Detecting a developing condition early may reduce the probability of a product-impacting failure and provide more information for a timely engineering and quality assessment. It does not automatically eliminate the need for deviations, change control or other quality-system actions.
  • Reduced cost of ownership: Fewer emergency repairs, fewer rush orders for spare parts, fewer overtime hours for maintenance workers.

Pharma Engineering Solutions with AI: Where This Fits in Plant Design

Often, the best results are from projects where automation and monitoring are part of the engineering design process with AI and not added after commissioning. This means deciding at the design stage where sensors are placed, how data flows between the process control layer and the maintenance software, and how the whole setup lines up with commissioning, qualification, and validation (CQV).

This is where companies offering integrated pharmaceutical engineering, automation and digital-infrastructure solutions can bring real value. Pharma Access, for example, works at this very intersection for its turnkey pharma projects, coordinating HVAC, pharmaceutical utilities, process systems, automation, BMS, EMS, IT/OT infrastructure and CQV requirements so that a new facility can be designed with the infrastructure needed to support condition monitoring and future analytics applications. Getting this sequence right at the design stage avoids costly rework once the plant is running.

Challenges in Pharmaceutical Companies in Mumbai and Across India

Mumbai and the broader Indian pharma belt have real strengths here: a large pool of engineering talent, strong export volumes, and companies that already compete on the global stage. However, the challenges faced by pharmaceutical companies in Mumbai and other manufacturing hubs are not small.

Common barriers include:

  • Site-specific infrastructure readiness: Power quality, network reliability, server architecture and cybersecurity capabilities vary between facilities and locations. New projects should therefore assess redundancy, backup power, offline data buffering and system-recovery requirements during the engineering stage.
  • The transition between paper-based and electronic records: Regulatory and inspection environments may involve paper-based, electronic or hybrid documentation. Companies implementing AI-enabled condition monitoring should ensure that relevant records remain controlled, accessible, traceable and suitable for review regardless of the inspection format.
  • Talent and change management: Maintenance teams require training to understand, evaluate and act on AI-generated alerts rather than viewing the system as just another dashboard. Engineering judgement remains essential because an alert should support, rather than replace, a qualified person’s assessment.
  • Budget pressure: Small and mid-sized manufacturers may see digital monitoring platforms as an IT cost rather than an investment in plant reliability, making them slower to adopt than larger export-oriented firms. A phased implementation focused on critical assets can provide a more practical route than attempting plant-wide deployment from the beginning.

The opportunity is that greenfield projects in India can incorporate scalable digital and automation infrastructure from the design stage, avoiding some of the integration constraints that arise when condition-monitoring systems are retrofitted into legacy facilities.

What Regulators Expect

Globally, the FDA has released a draft guidance from January 2025 that explains a risk-based approach to establishing the credibility of AI model outputs used to support regulatory decision-making regarding the safety, effectiveness or quality of drugs and biological products. The guidance can be relevant to manufacturing applications when an AI output supports a regulated quality or regulatory decision, but it is not a predictive-maintenance standard and does not require manufacturers to implement AI-based maintenance.In India, the CDSCO continues to move forward with digital initiatives, including its Digital Drugs Regulatory System. At the same time, pharmaceutical manufacturers should be prepared to present reliable and understandable maintenance information during inspections conducted through paper-based, electronic or hybrid workflows. 

Pharma manufacturers who are deploying automation and condition monitoring need systems that provide clear, timestamped, audit-ready records, not just alerts on a screen, so that domestic and international inspectors can trace every maintenance action back to its cause.

Getting the Engineering Right From the Start

Getting the Engineering Right From the Start

The plants with the best results are not those that tacked AI on as an afterthought. They are the ones where the engineering design, the automation layer, and the maintenance strategy were designed together from the first drawing. That is the true difference between a facility that reacts to breakdowns and one that anticipates them.

If you are planning a new facility and want to build in automation and monitoring instead of adding it on later, Pharma Access partners with pharma companies on this exact type of turnkey planning, from engineering design through construction, CQV, and project management.

By considering equipment criticality, sensor infrastructure, automation architecture, data flow, maintenance-system integration and GxP requirements during the design stage, project teams can create facilities that are better prepared for condition-based maintenance and future AI applications. 

Frequently Asked Questions

Is AI predictive maintenance mandatory for new pharma plants in India? 

No, it is not mandatory under CDSCO or Schedule M now. The applicable requirements focus on appropriate equipment maintenance, calibration, documentation and pharmaceutical quality-system controls rather than prescribing AI as a specific technology. Companies may adopt predictive maintenance where it provides a justified reliability, quality-risk or operational benefit.

How much does predictive maintenance reduce downtime in a pharma plant? 

Results vary from plant to plant, but companies that use real-time analytics and AI monitoring often see significant reductions in unplanned downtime and batch failures, largely because of the ability to detect problems weeks before they become a breakdown.The result depends on asset criticality, detectable failure modes, sensor quality, data history, model performance, maintenance response time and the way the system is integrated into operational procedures. 

What equipment benefits most from predictive maintenance in pharma plants? 

High-value, high-risk assets have the quickest payback. That includes tablet presses, centrifuges, compressors, HVAC, and autoclaves, as a failure on any of those can directly affect the quality of a batch or the classification of the facility.

Does predictive maintenance replace the maintenance team? 

No. It shifts the focus of the team. Now, engineers spend more time doing planned interventions based on real data from the equipment itself rather than routine checks and emergency repairs.The maintenance team still has to assess alerts, determine whether the detected pattern is technically meaningful, coordinate the intervention, complete post-maintenance checks and document the equipment’s return to service. AI supports engineering decisions; it does not replace qualified maintenance personnel. 

Can predictive maintenance help during CDSCO or FDA inspections? 

It can support inspection readiness, but the technology itself does not establish compliance. A well-designed system generates a historical record with time stamps of the condition of equipment and all maintenance activities, which is the audit trail inspectors require during GMP inspections.