Breaking News
September 20, 2018 - Potential drugs to treat neurodegenerative diseases garner $3 million grant
September 20, 2018 - Processing speed important to higher order cognitive function in multiple sclerosis patients
September 20, 2018 - Helping a patient survive a hurricane
September 20, 2018 - Tafamidis Treats Transthyretin Amyloid Cardiomyopathy
September 20, 2018 - Low academic achievement can lead to drug abuse decades later, research finds
September 20, 2018 - Study identifies stem cell that gives rise to new bone, cartilage in humans | News Center
September 20, 2018 - Celltrion and Emory University sign ‘Incubation’ agreement to develop new drug candidates for atherosclerosis
September 20, 2018 - TGen and PNOC take part in launch of NIH-supported Kids First Data Resource Portal
September 20, 2018 - Could Household Cleaners Make Your Kid Fat?
September 20, 2018 - Addiction nonprofit makes searching for services simple
September 20, 2018 - We are bombarded by thousands of diverse species and chemicals | News Center
September 20, 2018 - Experts to Present Prostate Cancer Advances at Patient Summit
September 20, 2018 - Alector announces initiation of Phase 1 trial of AL001 for treating frontotemporal dementia
September 20, 2018 - Pfizer’s 20vPnC vaccine receives Breakthrough Therapy designation from FDA
September 20, 2018 - Study could allow doctors to screen patients at risk from Aspergillus
September 20, 2018 - Emergex signs MoU with Brazil’s Fiocruz for development of viral vaccines
September 20, 2018 - The ‘real you’ is a myth – we constantly create false memories to achieve the identity we want
September 20, 2018 - Researchers describe cell mechanism that optimizes proteins production in stressful situations
September 20, 2018 - Cell Medica successfully doses first patient with CMD-501 targeting pediatric neuroblastoma
September 20, 2018 - Senators unveil legislation to protect patients against surprise medical bills
September 20, 2018 - Study provides insights into development of special-purpose cosmetic products
September 20, 2018 - Research shows enlarged genotype-phenotype correlation for three-base pair deletion in NF1
September 20, 2018 - 91% of people around the world believe medical research will result in dementia cure
September 20, 2018 - DePuy Synthes introduces CONCORDE LIFT Expandable Interbody Device at EUROSPINE 2018
September 20, 2018 - Manx Telecom unveils MT clearSound that improves clarity of mobile phone calls
September 20, 2018 - Mediterranean-style diet appears to reduce stroke risk in women
September 20, 2018 - AbbVie Announces Patient-Reported Outcomes Data from Three Pivotal Phase 3 Studies of Risankizumab, Showing Significant Improvements in Health-Related Quality of Life for Patients with Psoriasis
September 20, 2018 - Characterization of pregnancy microbiome reveals variations in bacterial diversity
September 20, 2018 - New guidance for treatment of bone loss in hematologic stem cell transplant Recipients
September 20, 2018 - Experts to present research on prevention, management of dysphagia at international conference
September 20, 2018 - New study focuses on two-way gene switches controlling gene activity
September 20, 2018 - Zika virus could become a weapon against brain cancer
September 20, 2018 - Home-based video game exercises can reduce chronic low back pain in older people, study finds
September 20, 2018 - Investigators find that bile acids reduce cocaine reward
September 20, 2018 - Cannabinoid drugs reduce perceived unpleasantness of painful stimuli and increase tolerance
September 20, 2018 - Health care companies’ data could enable more accurate flu season forecasts
September 20, 2018 - Geroscience takes center stage in Journal of the American Medical Association
September 20, 2018 - Ambient Particulate Matter Linked to Emergency Asthma Care
September 20, 2018 - Patient satisfaction with plastic surgery—it’s the surgeon, not the practice
September 20, 2018 - Medicine is a team sport – and that’s exactly how it should be
September 20, 2018 - Logos Biosystems releases new electrophoretic tissue clearing system with twice the features in half the space
September 20, 2018 - Novel micro-platform reveals never-before-seen behaviors of cancer cells
September 20, 2018 - PAREXEL partners with Datavant to enhance clinical study design and generate real-world evidence
September 20, 2018 - Robert Koch Institute publishes new data on allergies, mental health problems, and accident injuries
September 20, 2018 - Study finds higher readmission rates in for-profit hospitals
September 20, 2018 - Encouraging youth to do strength-based exercises could help tackle child obesity
September 20, 2018 - Sleep apnea, congenital heart disease in hospitalized infants strongly associated with death
September 20, 2018 - Researchers find way to map mysterious content of non-coding RNA
September 20, 2018 - Air Pollutants Reach Placenta, Might Harm Fetus: Study
September 20, 2018 - Sleep apnea, congenital heart disease may be deadly mix for hospitalized infants
September 20, 2018 - My relative has cancer, should I worry? Encouraging cascade genetic testing
September 20, 2018 - Investigators determine specific treatable traits that can predict future asthma attacks
September 20, 2018 - More doctor visits can lower risk of suicide attempts in fibromyalgia patients
September 20, 2018 - Computer avatars play role in diagnosis of dementia
September 20, 2018 - Addition of CTLA4 targeted therapy to PD-1 targeted therapy may benefit patients with ovarian cancer
September 20, 2018 - ASPREE trial explores whether low dose aspirin can prolong good health in elderly people
September 20, 2018 - ATS publishes new guideline focused on weight loss strategies for sleep apnea patients
September 20, 2018 - The Current issue of “The view from here” is concerned with Drug Delivery
September 19, 2018 - Sleep apnea could favour tumor growth at young ages
September 19, 2018 - Stealth vaping fad hidden from parents, teachers
September 19, 2018 - Witnessing school violence linked to later risk of psycho-social and academic impairment
September 19, 2018 - Common household cleaners could make children overweight by changing gut microbiota
September 19, 2018 - Salk research in yeast leads to serendipitous finding about hypomyelinating leukodystrophy
September 19, 2018 - Study: Overweight or obese women may have increased risk of urinary incontinence
September 19, 2018 - Study shows how cellular waste disposal processes also promote inflammation
September 19, 2018 - New multidisciplinary microsurgery microscope, PROVIDO, introduced by Leica
September 19, 2018 - Phase 2b STORM Data Evaluating Selinexor in Patients with Penta-Refractory Multiple Myeloma Presented at the Society of Hematologic Oncology 2018 Annual Meeting
September 19, 2018 - Decisions recruiting gut feelings seen as reflection of true self, more assuredly held, study says
September 19, 2018 - How AI can improve end-of-life care
September 19, 2018 - UNIST and Ulsan initiate research collaboration to develop human organs-on-chips
September 19, 2018 - Study highlights key role of migrating shoals of fish in sustaining deep-ocean microorganisms
September 19, 2018 - Disagreeable individuals can benefit most from behaving more compassionately, finds study
September 19, 2018 - Janssen Submits New Drug Application to U.S. FDA Seeking Approval of Erdafitinib for the Treatment of Metastatic Urothelial Cancer
September 19, 2018 - Neuroplasticity is increased but dysregulated in the aging brain, study finds
September 19, 2018 - Suicide: A public health crisis
September 19, 2018 - Infants using popular anti-reflux medicines are not at increased risk of lung infections
September 19, 2018 - Stanford team will participate in NIH-funded study of tobacco policies | News Center
September 19, 2018 - Women with high levels of anti-Müllerian hormone more likely to develop breast cancer
September 19, 2018 - Researchers use larval zebrafish model to reveal role of locus coeruleus in anesthesia
September 19, 2018 - Effects of prematurity found to be more severe for the brains of males than females
Monitoring the Environment of Aseptic Processes

Monitoring the Environment of Aseptic Processes

image_pdfDownload PDFimage_print

An interview with Lisa G. Lawson, MS- Global Pharma GMP Advisor at Particle Measuring Systems.

Please define the meaning of “risk” from the perspective of environmental monitoring.

Risk assessment consists of the identification of hazards and the analysis and evaluation of risks associated with exposure to those hazards. The risk assessment of particle and microbiological samples should consider:

  • Highest risk of contamination of the product and its components (study of the airflows and exhaust grid)
  • Personnel operations
  • Material and personnel flows
  • Cleaning and sanitizing of environments and equipment

Credit: CoolaM/ Shutterstock.com

What are the stages of an aseptic process and which point is most vulnerable to contamination?

Two clean areas are of particular importance to sterile drug product quality: the critical area and the supporting clean areas associated with it.

Critical areas are where the product is most susceptible to contamination. Most commonly, this is during manipulation of sterile materials before and during filling and closing operations (eg, asceptic connections or the addition of sterile ingredients).

Here, a sterilized drug product becomes exposed to the environment and presents the opportunity for contamination – if this occurs, the product will no longer be sterilized when it reaches the sterile container. Therefore, we take extra care in ensuring the critical area is especially designed to ensure product sterility.

Of course, it is important to maintain product sterility by controlling the environment that aseptic processes take place, at a suitable quality. However, it’s not often considered that an aspect of environmental quality is the particle content of the air.

Particles can not only enter and contaminate a product extraneously, but can also contaminate a previously sterile drug product by acting as a vehicle for microbial contamination. Therefore, the environment of which aseptic processes take place should contain suitably designed air handling systems to reduce the particle content within a critical area.

Please outline the FMEA method for microbial monitoring. How does it identify and evaluate risk?

Quality Risk Management (QRM) activities are performed using systematic processes designed to coordinate, facilitate and improve science-based decision-making with respect to risk.

The analysis of the risk assessment is carried out using the FMEA method – the typical mathematical relationship that links the “Risk” RPI (Risk Priority Index) with the “Probability of contamination”, the “severity” of the expected damage, and the “Detectability” of the damage, summarized as: RPI = P1 x P2 x S x D.

  • P1 = The estimate of the probability of environmental contamination
  • P2 = The estimate of the probability of product contamination
  • S = Severity which defines the importance of danger on the basis of its consequences
  • D = The ability to detect any particles present in the environment through the use of different monitoring methods

How are levels of risk measured and what are the criteria for these?

The following is a typical matrix used to evaluate risk:

Therefore, the risk for controlled environments is defined as:

Following this analysis, you proceed to the next step which involves risk control. Risk control is a decision-making activity designed to reduce or accept risks of the existing microbiological/particle control.

The purpose of risk control is to reduce the risk to an acceptable level. Risk reduction includes all the actions to be taken to reduce the probability of contamination value or increase detectability value by employing specific methods of sampling.

What service can Particle Measuring Systems provide for sterility assurance?

Particle Measuring Systems provide our customers with the tools to ensure sterility of their products through comprehensive analysis and robust final documentation. We work closely with pharmaceutical companies to promote sterility education and successful procedure implementation.

We provide support on sterility assurance deviations, pharmaceutical process design evaluation and risk analysis, US and international regulatory audit support, and quality crisis management (warning letter and 483 observation response support).

If a risk is identified, how can the environment be altered to eliminate it? How easy is it to do this?

The purpose of risk control is to reduce the risk to an acceptable level.  Risk reduction includes all the actions to be taken to reduce the probability of contamination value or increase detectability value by employing specific methods of sampling.  These sampling methods may include: volumetric air sampling, settle plates, surface sampling and total particle air sampling

Do Particle Measuring Systems offer any support to help customers change their production process to eliminate any risks identified by using the service?

We offer support in many areas including but not limited to:

Training and certification in:

  1. Fundamentals of Microbiology
  2. Personnel Hygiene GMP practices
  3. Contamination Control
  4. Cleanroom qualification training
  5. Cleaning and Sanitization GMP practices
  6. Alternative Microbiological Methods training
  7. Risk Assessment use in contamination control
  8. Media Fill Requirements training
  9. FDA and EU guideline interpretation training
  10. Regulatory Update training
  11. Any other training topic that can customized to meet customer needs

Sterility Assurance issues handling including:

  1. Development of a Corporate Sterility Assurance program
  2. Training, development or qualification for sterilization and/or depyrogenation
  3. Aseptic Process Management and/or facility design projects which may include:
  • Review of production deviations, non-conformities or other investigations
  • Validation of microbial sampling systems and isolators for sterility testing

Inspection Support and Management including:

  1. Resolution of FDA 483, EMA or local authority compliance deviations
  2. On-site support during regulatory inspections

Quality By Design (QbD)and Process Analytical Technology (PAT) support

  1. Providing advice on how QbD/PAT may be incorporated in the business system
  2. Applying comparability protocols and other regulatory strategies for deployment

Process and Methods Evaluation and/or Risk Assessment including:

  1. Performance of formal risk analysis using Failure Modes and Effects Analysis (FMEA), Hazard Analysis (HACCP) or other Risk Analysis Tool
  2. Evaluation of laboratories, production and quality operations
  3. Development of programs or procedures
  4. Review of data trends and recommendation of alert and action levels

Pharmaceutical Microbiology Support including:

  1. Environmental Monitoring evaluation and development
  2. Evaluation and development of protocols and cleaning procedures
  3. Evaluation and development of procedures, policies and standards for media fill
  4. Microbiological Data Deviations (MDD) and analysis of Out-of-Specification (OOS)
  • Program Development and review of microbiological data deviations and OOS
  • Implementation of corrective action plans for reducing and/or eliminating MDD or OOS

Production and Quality Assurance Support including:

  1. Process Optimization, or project management assistance
  2. Comparability Protocols for process/analytical changes
  3. Cleaning and sanitization process analysis including practices, procedures and rationales/rotations
  4. Development of Quality Management System (QMS)
  5. Evaluation of systems based inspection compliance programs
  6. Support implementation of quality problem solving tools
  7. Assist in investigation resolution, reduction and root cause analysis

Quality Control Support including:

1.Laboratory Management

  • Optimization of laboratory policies, procedures, equipment and methods
  • Sterility test analysis and evaluation of positive sterility failure tests

2.Development of rapid methods for sterility testing

How often are sterility assurance methods reviewed or improved?

Once risk control measures have been identified, it is important to ensure all stakeholders are aware of the risks identified and are in alignment with the mitigation measures employed to reduce risk. Therefore, the last steps in the QRM process are risk communication and periodic risk review.

Risk communication is the sharing of information about risk and risk management between decision makers and others. Parties can communicate at any stage of the risk management process. The output/result of the quality risk management process should be appropriately communicated and documented.

Appropriate systems should be in place to ensure that the output of the QRM process is periodically monitored and reviewed, as appropriate, to assess new information that may impact the original QRM decision. Examples include changes to control systems, equipment and processes, suppliers or contractors and organizational restructuring.

What does the future hold for the development of environmental risk assessment? Will processes become completely automated?

The future for environmental risk assessment is to automate processes as much as possible to further reduce the risk of personnel contamination, as human interventions pose the greatest particulate and microbiological contamination risk to the product.

Where can readers find more information?

Please find more information on our Advisory services at the following link: https://www.pmeasuring.com/en/service-and-support/consultancy-training

To view our full line of innovative environmental monitoring products, go to: https://www.pmeasuring.com

About Lisa Lawson

Lisa G. Lawson has over 25 years’ experience in supporting large and small pharmaceutical companies in contamination control, including cleaning and disinfection strategies, aseptic manufacturing and use of risk-based approaches to microbiological quality challenges.

Lisa spent 16 years working for Amgen in microbial and mammalian cell culture manufacturing support and helped gain commercial FDA and international regulatory approval of the EPO/NESP manufacturing facility in Longmont, CO.

 

Tagged with:

About author

Related Articles