I. “Person” It is the largest source of pollution in the pharmaceutical manufacturing process.

★ The primary risks in pharmaceutical manufacturing are “contamination, confusion, and errors.”

★ The risk factors in pharmaceutical manufacturing include both endogenous and exogenous factors.

★ Endogenous factors include “plant facilities, equipment, systems, the quality of raw and auxiliary materials, and the manufacturing process.”

★ Exogenous factors include risks arising from “personnel.”

★ Some people cite the risk of sterility, asserting that “microorganisms” are the primary source of contamination.

★ Incorrect—microorganisms are the primary “contaminant,” but they are not the primary “source of contamination.”

★ Among the various risks, human‑related factors are particularly critical, including personnel’s bioburden levels, the duration of their stay in cleanrooms, the frequency with which personnel influence the bioburden, and transfer coefficients.

★ Among these, the transfer coefficient represents the bioburden entering the product and also indicates the probability of microbial ingress into the product.

★ “Factory facilities, equipment, systems, the quality of raw and auxiliary materials, and process operations,” among others, have all undergone supplier audits, confirmations, validations, and so forth, and can thus be said to be under robust control.

★ Next comes the management, control, and maintenance of “personnel” with respect to “factory premises, equipment, systems, the quality of raw and auxiliary materials, and process operations.”

★ The primary principles underlying GMP implementation are to minimize “contamination, mix-ups, and errors”; in the manufacturing process, the vast majority of such issues stem from human factors.

★ So it says: “ Humans are the primary source of contamination in the pharmaceutical manufacturing process. ”

 

II. Risk Factors Posed by Personnel:

★ The personnel themselves have poor quality awareness and low overall competence.

★ Poor personal hygiene habits of the staff

★ The individual’s own health condition is poor

★ Staff behavior and conduct are not standardized.

★ The personnel have relatively low production and operational skills.

★ The changing procedure cannot guarantee that personnel will not contaminate the environment.

★ Failure to change clothes in strict accordance with the changing procedure

★ Operators fail to wash and disinfect their hands as required.

★ Hardware-based protective measures cannot prevent contamination introduced by personnel themselves.

★ Excessive number of personnel in the cleanroom

★ Excessive and overly complicated movements by personnel in the cleanroom

★ Excessive range of motion by operators can lead to particulate contamination.

★ Particle contamination caused by the rapid movement of personnel

★ Particles generated by loud talking, sneezing, and other activities

★ Contamination occurs due to uncleaned dead zones in aseptic production areas.

★ Spending too much time in a Class A cleanroom

★ Improper procedures can lead to contamination of the environment, equipment, and pharmaceuticals.

★ Metabolic processes on the human body surface lead to particulate and microbial contamination.

★ Contamination, confusion, or errors resulting from non‑compliance with SOPs or operator error

There’s also the risk inherent in the clothing itself—let’s keep reading…

 

III. Risk Factors Associated with Workwear:

★ The workwear style is incorrect and fails to effectively prevent human contamination (e.g., coveralls, hats, gloves, masks, etc.).

★ The work uniform’s design is flawed, making it easy to harbor dirt and grime.

★ Material properties (weaving characteristics, fiber type, sterility, antistatic properties, etc.) are unsuitable.

★ The material is too thin, resulting in poor barrier performance and failing to prevent the passage of contaminants.

★ The material is poor, and it naturally sheds a lot of debris.

★ The material is too dense, resulting in poor breathability.

★ Incompatible model selection: too tight for the wearer, causing discomfort; too loose, allowing contaminants to spread easily.

★ Improper procedures during the changing process can contaminate sterile garments.

★ Sterile suit for ambient air pollution

★ During the dressing process, the sterile gown was accidentally contaminated by the floor.

★ After multiple sterilizations, the clothing may shed particles.

★ Torn workwear cannot prevent contamination of the human body.

★ Workwear becomes recontaminated after sterilization

★ Cross-contamination caused by confusion between personnel who are wearing and not wearing work uniforms.

★ Gloves that are too loose or too tight can introduce contamination during operation.

★ No regular hand disinfection

★ The mask is too loose, allowing contaminants from the oral cavity to enter the environment.

★ The mask is too tight and too dense, causing the operator to have difficulty breathing.

With the risks posed by personnel and workwear clearly identified, the corresponding preventive measures are self‑evident; the key, however, remains… Training and management of personnel must be thorough; stay tuned for more…

 

IV. Personnel Management and Team Management:

★ The implementation of GMP regulations and guidelines depends entirely on human execution; people are the most critical factor.

★ In GMP audits conducted in any country, the primary focus is on personnel qualifications and the quality management system.

★ A robust management system is essential.

★ There must be a team of highly qualified personnel.

★ A suitable set of work procedures and standard operating procedures (SOPs) must be in place.

★ Each person’s scope of responsibility must be clearly defined.

★ Everyone must possess sound ethical conduct and a solid foundation of professional knowledge.

★ Good personal habits and high‑efficiency execution.

★ Quality control throughout the entire process.

★ Quality management ultimately hinges on “management.”

★ Management: When you manage people well, you manage things well.

★ Training: Primarily focused on shifting mindsets.

★ Training: Primarily about habit formation

★ Collaboration: Between departments and among all members within each department, problems are resolved through effective communication.

★ Participation: Between superiors and subordinates, it’s not just about giving orders and carrying them out; it’s much more about engaging in the process and offering suggestions.

★ Support: Mutual support.

★ Review and Feedback.

★ What is everyone doing every day?

★ Everyone must clearly understand what to do and why they are doing it.

★ Debugging, test runs, pilot production, and media filling—these processes are themselves opportunities for training and practice.

★ Well-established rules and regulations, standard operating procedures (SOPs), and rigorous enforcement.

★ GMP should be a self‑driven, conscientious good practice.

Don’t go anywhere—there’s even more important content on the next page.

 

Personnel-Induced Contamination Control in Cleanrooms

Humans, as sources of environmental contamination, include those they themselves generate—such as hair and skin flakes, as well as metabolic byproducts from the skin and respiratory system—and those they carry—various particulates and microorganisms adhering to the body and clothing, along with debris shed from worn garments. These two categories of contaminants are continuously produced and dispersed.

 

Cleanroom operators are the largest source of contamination. In a Class B cleanroom, a seated operator at rest can release between 100,000 and 1 million particles per minute; even a slight movement of the hand or head generates approximately 500,000 particles as small as 0.3 µm, while a single foot movement produces about 1.5 million particles, walking elicits 5 million particles, and brisk walking can generate up to 10 million particles. These particles originate from shed hair and desquamated skin. Additional sources include hairspray, cosmetics, hair dyes, and exposed non‑cleanroom garments.

 

As one can readily imagine, in a highly demanding sterile environment, contamination would be both substantial and potentially fatal. Therefore, simply controlling temperature and humidity in a cleanroom is far from sufficient; maintaining the required level of cleanliness is equally critical.

 

In addition to air filtration, the key to controlling cleanliness lies in preventing contamination—particularly human‑induced contamination. Particles in cleanrooms increase with operator activity, and the operation of HVAC systems and machinery generates particles through continuous vibration.

 

Even ordinary clothing, when worn beneath cleanroom garments, can introduce millions of particles into the cleanroom. In ultra‑clean environments, operators must wear garments made from non‑shedding materials with a tightly woven construction. Furthermore, sterile areas require the use of sterile undergarments.

 

Human breath contains a large number of particulate pollutants; with each exhalation, substantial amounts of water vapor and fine particles are released into the air. Moreover, even long after smoking, a smoker’s breath can continue to emit millions of particles for an extended period.

 

Healthy individuals serve as sources of many pollutants, while patients pose an even greater risk; in particular, those with skin rashes or respiratory infectious diseases can become additional sources of contamination.

 

A viable approach to preventing personnel contamination is to fully encase individuals in multiple layers of protective clothing. Moreover, cleanroom garments vary according to the required cleanliness level; the materials should minimize shedding, incorporate conductive fibers to dissipate static electricity, and be evaluated for their ability to filter particulates as well as for the wearer’s comfort.

 

Every part of the body must be covered. The head should be protected with an inner cap to contain hair, topped by an outer cover. Since the eyes are also a major source of liquid particles, in areas where contamination control is critical, operators wear full-face shields that completely enclose the head and face.

 

Full-body protective garments that cover the legs, arms, and neck; well-designed workwear should also conceal the zipper and must not have external pockets.

 

Feet are also covered with shoe covers, some of which extend up the calves to provide additional leg protection. Hands must be protected with at least one pair of gloves; in sterile areas, two pairs of gloves are required.

 

Skin desquamation can be further managed with a specially formulated emollient that keeps the skin hydrated, but it must not contain salts or chlorides.

 

The proper order for putting on protective clothing is to start at the head and work downward, so that any dust stirred up in the previous step is covered by the next layer of apparel, with gloves worn last.

 

Coveralls sometimes have to be put on from the bottom up—first slipping them over the feet and legs, then finally over the arms and head—so extra care is required at this stage.

 

Controlling cleanroom garments and donning procedures to prevent personnel‑borne contamination is well established; however, the most effective preventive measure remains the training of operators—training, and then retraining—followed by rigorous enforcement, time and again.

 

In a cleanroom, humans are a critical factor in the generation of particulate contaminants. All personnel working in cleanrooms should have a thorough understanding of how personal hygiene practices affect cleanliness. Ignorance breeds recklessness; only by clearly recognizing the significant risks their actions pose to the clean environment—and to the quality of pharmaceutical products—can they prevent introducing contamination.

 

Wearing jewelry is prohibited in cleanrooms, especially rings with sharp points or edges, as they may puncture gloves or clothing. Do not wear earrings, necklaces, brooches, or any other protruding or dangling accessories.

 

Personal items, such as cigarettes, wallets, tissues, paper products, and mobile phones, must be stored in your desk or locker and may not be brought into the cleanroom. In the cleanroom, all clothing pockets must remain empty.