Paul Industries builds the process systems behind aseptic fill-finish: Grade A through D cleanrooms under EU GMP Annex 1, Water for Injection generation and distribution, clean steam for sterilization in place, sanitary process piping to ASME BPE and the CIP/SIP systems that make sterility assurance repeatable. Sterile injectable work is governed by a documented contamination control strategy rather than by a room classification alone, and that distinction drives most of the engineering. We hold the whole scope under one contract, nationwide.
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Annex 1 changed the question from “what class” to “prove your strategy”
The revised Annex 1 reorganized sterile manufacturing around a Contamination Control Strategy: a documented, site-wide argument for how every element of the facility, the equipment and the process works together to prevent contamination. A room that meets Grade B at rest is no longer an answer on its own. The inspector wants to see why the airflow pattern, the transfer routes, the barrier choice, the sterilization cycles and the monitoring locations were each selected, and how they interact.
For a contractor that changes what gets delivered. Airflow visualization is no longer a nice extra; it is evidence. Transfer routes through airlocks have to be justified rather than drawn for convenience. The sterilization of product-contact equipment has to be demonstrated as achievable in the position the equipment actually occupies. We build to that expectation because retrofitting the justification afterwards is far more expensive than designing to it.
The second practical shift is barrier technology. Annex 1 pushes firmly toward restricted-access barrier systems and isolators for Grade A operations, and away from conventional open Grade A in a Grade B room. That decision has to be made early, because the room, the HVAC, the transfer design and the decontamination method all follow from it.
What we build for sterile fill-finish facilities
- Grade A to D cleanrooms Envelope, mechanical, airflow visualization, certification and recertification to ISO 14644-1 and -2, designed around the barrier strategy rather than retrofitted to it.
- Water for Injection systems Generation, storage and hot or continuously circulated distribution built to hold 0.25 EU/mL at every point of use, with USP 643 and USP 645 chemistry.
- Clean steam systems Generation and distribution for sterilization in place and autoclave service, with steam quality testing where a sterilizer is served.
- CIP and SIP systems Cycle development and verification, with thermocouple mapping that proves every product-contact surface reaches and holds its condition.
- Sanitary process piping Orbital-welded stainless to ASME BPE, fully drainable, with dead legs controlled and weld and borescope records as deliverables.
Where sterile injectable capacity is being built
Fill-finish is the tightest capacity constraint in US pharmaceutical manufacturing, and the current build-out is unusually concentrated.
| Location | What is being built | Why it matters to the scope |
|---|---|---|
| Petersburg, Virginia | Civica sterile injectable plant, about 120,000 sq ft and roughly $124.5 million, three bays, capable of about 90 million vials and up to 50 million pre-filled syringes a year | Federally supported essential-medicine work, audited hard; documentation is a contract deliverable. |
| Petersburg, Virginia | Phlow, $354 million BARDA contract for essential medicines and the first Strategic Active Pharmaceutical Ingredient Reserve; AMPAC supplying API locally | API through to filled syringe inside one city, which is rare and changes utility planning. |
| Albemarle County, Virginia | AstraZeneca $4.5 billion campus including a drug substance facility | Largest single-site investment in the company’s history; crews across the Commonwealth are being absorbed by it. |
| Indiana and Texas | Eli Lilly, $27 billion across four new US sites and a $6.5 billion Houston plant | Parenteral capacity at scale, with long lead times on qualified sanitary welders. |
Why Paul Industries
Sterility assurance fails at handoffs. The water system vendor, the cleanroom installer, the piping contractor and the sterilization specialist each hold one piece of an argument that has to be made as a whole, and the Contamination Control Strategy is precisely the document that exposes a gap between them. Carrying the scopes under a single contract means one party owns the argument rather than four parties owning fragments of it.
Frequently asked questions
What is a Contamination Control Strategy and who writes it?
It is the site-level document required by Annex 1 that explains how facility design, utilities, equipment, process and monitoring combine to prevent contamination. The manufacturer owns it, but it depends heavily on engineering evidence a contractor supplies: airflow visualization, sterilization mapping, water system design rationale and transfer route justification. We build and hand over that evidence in a form that drops into the strategy rather than needing reinterpretation.
Do we need an isolator or is a RABS enough?
Both are accepted, and the choice should follow from the product, the batch size, the campaign length and the decontamination approach rather than from preference. Isolators give higher assurance and lower background room requirements but are less flexible and slower to change over. Restricted-access barrier systems are more flexible but depend more on the surrounding Grade B environment and on operator discipline. The decision has to be made before the room is designed, because the HVAC and transfers follow it.
What airflow velocity does Grade A require?
Annex 1 provides a guidance range of 0.36 to 0.54 meters per second at the working position for unidirectional airflow, rather than a single mandated figure. The important part is that the velocity is justified for your specific configuration and demonstrated by airflow visualization showing first air reaching the critical zone without being disrupted by equipment, operators or transfers. A number on its own satisfies nobody.
Why does WFI have to be held hot or circulated continuously?
Because endotoxin comes from Gram-negative bacterial growth, and biofilm is far easier to prevent than to remove. Holding the loop above roughly 65 to 80 degrees Celsius, or circulating continuously with periodic sanitization, denies the loop the stagnant, ambient conditions biofilm needs. Once a biofilm establishes on a distribution loop, it usually takes a full sanitization and sometimes a derouging campaign to recover, with the system out of service.
What is the difference between clean steam and plant steam?
Plant steam is generated from treated boiler feedwater and typically contains amines and other additives that make it unsuitable for contact with product or product-contact surfaces. Clean steam is generated from purified feedwater with no additives, so its condensate meets WFI-quality chemistry. Anything sterilizing a product-contact surface needs clean steam. Using plant steam there is one of the more common and more serious design errors we are asked to correct.
What steam quality tests does a sterilizer need?
Where a sterilizer is served, EN 285 sets the commonly applied limits: non-condensable gases not exceeding 3.5 percent, dryness value of at least 0.90 and at least 0.95 for metal loads, and superheat not exceeding 25 degrees Celsius. Non-condensable gas is the usual culprit when a cycle fails, because a gas pocket insulates the load surface from the steam and no amount of extra exposure time fixes it.
How do you prove a SIP cycle actually sterilizes everything?
By thermocouple mapping in the assembled system, placed at the points expected to be hardest to heat: low points that collect condensate, dead legs, valve bodies, the far end of long runs and any element with a heat sink. Every one has to reach and hold its condition for the full exposure. Condensate removal and air venting are usually the deciding design features, which is why SIP performance is set by the piping layout long before the cycle is written.
How do you control dead legs on a sterile system?
By designing them out first and controlling what remains. ASME BPE targets a length-to-diameter ratio no greater than about two, measured from the wall of the main run, which is considerably tighter than the older six-diameter guidance that still circulates. Zero-static and point-of-use valve designs, careful branch orientation and drainable slope handle most of the rest. Anything that cannot be eliminated has to be demonstrated to drain and to sterilize.
Can you work in a live facility without shutting production down?
Often, with planning. Tie-ins to existing WFI or clean steam distribution, added points of use and room modifications can frequently be staged around production windows or a planned shutdown. The constraints are the requalification the change triggers and the segregation needed to protect adjacent classified areas during the work. We would rather scope that honestly up front than discover mid-project that the change forces a longer outage than anyone budgeted.
What does qualification of a sterile system actually involve?
Installation qualification confirms the system is built and documented as designed, covering materials, welds, slopes, instrument calibration and drawings. Operational qualification proves it performs across its range, including sanitization and sterilization cycles. Performance qualification demonstrates sustained performance on the real process over time, which for water usually means an extended sampling campaign across multiple phases before the system is released for routine use.
How long should we allow for a WFI system to be released?
Longer than most schedules assume, because performance qualification for a compendial water system conventionally runs through an extended multi-phase sampling program spanning weeks rather than days, and it cannot be compressed by adding people. The practical consequence is that the water system must be complete and operating well before the first engineering batch, so it is usually the item that should be started earliest and is most often started late.
Do you support media fills and aseptic process simulation?
We do not run the simulation itself, which belongs to the manufacturer’s quality organization, but the facility and equipment have to be capable of supporting it and a failed media fill frequently traces back to an engineering cause. Airflow disruption at a transfer, an intervention that forces an operator through first air, or a poorly placed monitoring point will show up as a contaminated unit. We design with those interventions mapped rather than discovered.
What surface finish is expected on product-contact surfaces?
ASME BPE defines surface designations rather than one universal figure, and the specification should select from them based on cleanability and the process. For sterile product contact a mechanically polished finish is typical, with electropolishing where corrosion resistance and cleanability justify the additional cost. What matters more than the number is that the finish is specified, verified and recorded, because an unverified finish claim is worth nothing in an audit.
How do I get a quote for a sterile fill-finish project?
Use the form on this page or call 201-450-8280. The most useful inputs are the product and presentation, whether you intend to use an isolator or a RABS, the batch sizes and campaign pattern, your water and clean steam demand, and your target qualification date. If you have a user requirement specification or an existing Contamination Control Strategy, send it; if you do not, we can help define scope before anything is priced.
Planning a sterile fill-finish project?
Tell us the product, the barrier strategy and the date it has to be qualified. We will tell you what is realistic. Call 201-450-8280 or use the form below.