Many NEBB Certified Professionals (CPs) and Certified Technicians (CTs) find themselves performing work to not only uphold the procedural and documentation standards set forth by NEBB but to also comply with the performance standards required by the regulated industries they work in. These strict compliance regulations can apply to projects taken on by NEBB Certified Firms concentrating on Cleanroom Performance Testing (CPT), Testing, Adjusting, and Balancing (TAB), or Commissioning (Cx).
Defining a regulated industry, however, seems to depend on one’s particular experience in helping clients and their facilities ensure compliance with the different agencies that regulate performance in the building industry, as well as the specific language used to enforce those mandates.
All facilities built in the State of California, for example, must adhere to the standards outlined by the California Building Standards Commission in its Title 24 series of code. Therefore, in the State of California, the entire building industry could be considered regulated.
Title 24 helps regulate the building industry as it applies to energy efficiency standards and successful construction outcomes, affecting contractors, engineers, property developers, and architects, as well as NEBB CPs and CTs. In fact, NEBB is one of four approved providers with the ability to certify mechanical acceptance test technicians required by the state. While Title 24 consists of 12 different parts in total, NEBB’s certification of mechanical acceptance test technicians applies only to parties required to perform testing for HVAC systems and controls when the mechanical equipment is required to meet specific energy-efficient processes.
Clarifying Code
Overall, Title 24 is fairly broad. The clarity of the code has even become an issue in some cases and is left up to NEBB CPs like President of MBO, Inc. Dawayne Trobaugh to determine when guiding clients.
“In regard to commissioning or TAB requirements, it can be difficult for clients to decide what qualifies as a residential versus non-residential building, as is the case particularly for high-rise buildings and mixed-use facilities. I get emails and calls all the time from clients asking me to help decipher the requirements, and I am actively working to help define them,” Trobaugh states.
“But the worst possible outcome is if a contractor bypasses commissioning due to his interpretation of the language and then later, upon submitting for a certificate of occupancy, is asked for a commissioning report that does not exist. Backpedalling to perform Cx at that point is not only more expensive in terms of fixing any possible issues but also less efficient,” he continues. “If commissioning is done right, it doesn’t cost a contractor any more money to bring a commissioning agent on earlier. Plus, they typically save costs in overall Cx tasks and get the full benefit of meeting the code.”
This type of situation is not just isolated to Title 24. LEED’s requirements for commissioning electrical systems is another example of nondescript language that leaves too much to be interpreted. When LEED Version 3 was updated to LEED Version 4, the scope of commissioning expanded to include “electrical service and distribution.” Although the rating system suggests commissioning agents limit this broad scope to items related to LEED credits, it does not provide direction in concrete terms. Upon reaching out to LEED for clarification, Trobaugh was told it was “up to the commissioning agent to determine.”
Given that there may be no foolproof way to avoid these types of broader code requirements at some point or another in one’s career, NEBB CPs hedge their best bets by contacting the authority having jurisdiction for further explanation, using past experience to help determine what should be examined and when, and veering on the side of stringency while performing testing and documentation.
Strict Standards Specific to Vertical Markets
Other ways to define regulated industries include looking at specific vertical markets and the associated standards outlined by responsible compliance agencies for the facility types found in those markets. For example, facilities with specific manufacturing practices, such as life sciences and medical devices, are two good examples of highly regulated industries with well-known standards for ensuring performance compliance because both rely on extremely clean environments for optimal production.
NEBB supports owners in regulatory compliance by helping owners validate compliance, especially when facing tight timelines or production issues. Both TAB and CPT are highly relevant to facility owners in these industries, but only CPT can validate the performance of a controlled environment. As NEBB works toward ANSI standards approval for CPT, it is safe to say NEBB CPs perform CPT and validation at the highest level. By testing items such as HEPA filter integrity, air exchange rates and particulate levels, NEBB CPs and CTs play an essential role in determining how cleanrooms perform.
Regulations for Compounding Pharmacies
Within the sphere of compounding pharmacies alone, facilities are broken down further by the Food Drug and Cosmetic (FD&C) Act to determine appropriate standards and compliance.
“In any highly regulated facility that produces pharmaceutical products for either human or animal production, these facilities are regularly inspected by the Food and Drug Administration (FDA). During these inspections, facilities owners must demonstrate that the systems are operating in strict accordance with the performance standards established by the validation process for the facility and the particular products produced in that facility,” explains Don Hill, President of AccuTec Services, Inc.
Often found in hospitals, 503A facilities are compounding pharmacies that also typically supply large amounts of products to patients. Facilities must comply with USP 795 and 797, as well as the regulations of the state board of pharmacy, while environmental monitoring, such as that provided by a NEBB CP or CT, is performed every six months. Both the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) and the state Board of Pharmacy help to hold these facilities accountable.
“Every six months, healthcare facility owners are required to hire TAB professionals to prove that they’re in compliance or can still make product safely as is. Those TAB reports are then sent to the FDA auditors,” Hill mentions.
With a heavier focus on manufacturing, 503B facilities must also comply with USP 795 and 797 and the regulations of the state board of pharmacy while validating every process per Current Good Manufacturing Practice (cGMP) regulations enforced by the FDA. Multiple batches of product must be submitted for testing prior to receiving clearance to bring that product to market, and a list of manufactured products must be reported to the FDA every six months.
Using the International Organization for Standardization (ISO) levels to assess the cleanliness of life sciences manufacturing cleanrooms from the central core to the buffer rooms to the anterooms, CPT is necessary to keep airborne particle generation (mostly from the exposure of human skin) on equipment down and ensure preventative maintenance occurs.
“The primary compounding or manufacturing areas of 503B facilities, for example, need to be rated at ISO 5. One important function to achieve this rating is an established unidirectional flow over the product fill area, as the exposure of the product to the air before it reaches the sterilized vials it will be packaged in poses a risk for contamination,” states Jeff Raposa, Founder and President of Controlled Environment Management (CEM). When unidirectional flow with 100 percent HEPA filtration coverage is achieved, the CPT firm can ascertain that the facility meets the required regulations.
“Today, one of the most popular, growing trends is for CPT-accredited companies to conduct airflow visualization profiles using injected glycol vapor, CO2 or sterile water vapor. Because we record the results, we can provide actual videos to FDA auditors coming in to validate performance,” describes Raposa.
Those that adhere to the guidelines outlined by the FDA, experience faster system validation in order to pass regulatory audits and get products to market sooner. Meanwhile, those without the ability to prove compliance with the FDA’s standards risk all or part of their production facilities being shut down.
Noncompliance: FDA Form 483
The FDA issues an FDA Form 483 to manufacturers when they are not in compliance with the current regulations. In fact, the FDA has recently become more aggressive in its intent to inspect compounding pharmacies, and in some cases, recalls of sterile products have accompanied FDA 483s.
An FDA Form 483 is issued to firm management at the end of an inspection when an investigator has observed any conditions that, in their judgment, may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related Acts, FDA investigators are trained to ensure that each observation noted on the FDA Form 483 is clear, specific and significant. Observations are made when, in the investigator’s judgment, conditions or practices observed would indicate that any food, drug, device or cosmetic has been adulterated or is being prepared, packed, or held under conditions whereby it may become adulterated or rendered injurious to health.
In the best-case scenarios, NEBB firms are able to document compliance issues in their reports and work with the manufacturer to solve those issues prior to an audit, preventing any 483s regarding environmental compliance. However, due to the nature of surprise audits or some owners opting to hire an NEBB firm only once it’s too late, NEBB professionals also work with the 483s clients that have already been issued and offer viable solutions prior to the next audit.
One of Hill’s clients received an FDA Form 483 stating an observation that “inadequate HEPA filter coverage and airflow over the area to which sterile product was exposed.” To remedy this issue, cleanroom consulting for room classification and airflow patterns was provided.
Another client received multiple observations in their FDA Form 483 showing “Personnel moved rapidly in the vicinity of instruments, which disrupted the airflow and increased the risk of bringing lesser quality air into the ISO 5 classified aseptic processing area,” and that “Personnel conducted aseptic manipulations and placed equipment/supplies in an area that blocked the movement of first pass air around an open unit, either before or after it was filled with sterile product.” In this case, proper airflow pattern studies also provided a viable solution for compliance.
In another case, a client’s FDA Form 483 noted, “Buildings used in the manufacture, processing, packing, or holding of a drug product do not have the suitable construction to facilitate cleaning, maintenance, and proper operations. Specifically, your firm has structural and equipment deficiencies in the classified areas which do not ensure clean airflow,” which required CPT consulting and certification to resolve.
Designed for Compliance
One of the best ways NEBB CPs and CTs can help owners avoid compliance issues is to get involved early and ensure best practices for compliance from the start. By reviewing mechanical plans beforehand, potential issues can be corrected far in advance of any inspection of the built facility.
“Unfortunately, many CPT firms are not involved with the design phase. I review mechanical plans whenever possible before the permitting process because not everyone has experience with pharmacies and the strict standards associated with such facilities. Once the facility is already built, we often need injection ports installed in order to perform leak tests on their HEPA filters, which further delays that facility from achieving certification,” explains Raposa. “We can usually determine if a facility will be able to hit its compliance goals by reviewing the design. We would like to see facilities designed not to meet criteria, but to go about 20 to 30 percent above the requirements for HEPA filtered airflow to give a cushion and ensure the constructed facilities are compliant.”
“A well-designed and constructed cleanroom is critical to the quality of its Compounding Sterile Preparations (CSPs). The design needs to take things like HEPA test ports, velocity/volume tests, possible particulate contamination, hood types and locations, air pressures, humidity and temperature, amongst others, into consideration to achieve a compliant end result,” suggests Hill.
Overall, NEBB firms are needed to help owners overcome compliance issues, prove performance Standards in Highly Regulated Facilities, and help ensure they are set up to operate in an optimal environment. Not all owners may know it is best to bring NEBB CPs and CTs on early, but by attending meetings of relevant industry organizations such as International Society for Pharmacoepidemiology (ISPE) or Parenteral Drug Association (PDA), preaching one’s capabilities as a TAB, CPT, or Cx expert, and remaining up to date on all industry standards, NEBB professionals have many opportunities to educate others and work to establish better practices across the industry.
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