ENGINEERING TRENDS: QUALITY MANAGEMENT SYSTEMS: Trends in Administrations systems, phylosophical differences between QMS, Hierarchical and Organizational Differences.

Drug Manufacturing Quality Documentation: Managing a Drug Manufacturing Site requires precise control over all steps that impact the Identity, Purity, Efficacy, and Quality of the product. The high level of precision requires that manufacturing tasks are well understood by personnel and these tasks are not limited to steps making the drug product. Control requires ALL areas to provide the highest standards of as required by local and international standardizing and regulatory bodies.

Think of a Manufacturing Site

PROCESS TRENDS: SERIALIZATION, GLOBAL HARMONIZATION: Packaging, Stacking, Monitoring, Storage, Shipment and Control.

Global harmonization

New Medical Products

What considerations are needed to Manufacture a New Product

New Drug Application

New Dietary Supplements

New Biomedical Devices

New Dietary Supplements

Dietary Supplement Information for Industry

Storage and Handling of Chemicals

Maximum Allowable Quantities

International Fire Code

Ladder Supports and Clearances

Voltage Requirements and Related Ground Faulting

Laminar Flow Hood Qualification

Clean Room Qualification

Fire Management Consulting: Prevention, Planning, Rescue Operations, Hazard Identification, Communication Protocols, Adherence and Enforcement of Policy are all elements of Fire Management

Goals(General): Prevent Injury, Preventl loss of Life, Prevent loss of Property

Objective (Metrics): Prevent ocurrence of fire and explosion (#). Provide Means of Escape (t). Contain, Control and Suppress fire and explosion origins. Decrease total number of work related casualties (h). Decrease total number of loss work hours. Decrease total number of work related injuries. Increase the level of safety by introducing added meeasures of protection in each task performed.

Fire Prevention Plans must be kept in writing and must be communicated orally to all personnel.

Establish a Storage and Handling Zone. Isolate zone from heat sources at least 35ft away. Consider mass transfer of vapors. Consider also temperature effects that may volatilize liquids far away from a heat source.

Isolate the Handling Zone from electric conduction by grounding the casing.

In the Event of a fire Understand the Elements of the Fire Triangle and how to isolate the heat source from the oxidant, or how to lower the temperature of the fire.

Know Fire Chemistry: Stoichiometry, LEL, UEL, LFL, UFL, Heat of Combustion, Latent Heat, Heat of Vaporization, Conduction, Convetion, Radiation, Reid Vapor Pressure, Ignition energy, Ignition Temperature, Heat Value, BLEVE, Vapor Cloud Explosion, Overpressure, Backdraft, Flashover, Flash Point,

Causes of Explosions: Spark, Arc, Heat Conduction, Convection, Radiation, Deflagration, Collision, Friction, Nature, Chemical Reaction, Nuclear Reaction

Two Types of Explosion: Deflagration vs Detonation

Effect of Pressure and Temperature on the LEL and UEL. The Flash Point is the lowest temperature and pressure at which a vapor/liquid may spark or ignite.

Explosions are divided into two different categories. Deflagration and Detonations, both invove equilibrium procesess of a gas, an oxidizer, and heat in a medium undergoing expansion. Deflagrations occur with mass transfer at low velocites directed at the reaction zone wheras Detonations are violent and the expansive gas is the reactive zone.

Design Considerations: Spacing, Protocols, Procedures, Sewage Control, Diking, Housekeeping, Tool Inspections, Heat source elimination, area desinations, Training.

Fire and Electricity: Eliminate Arc, or Sparks by using rated currents far from the boundary limits for conduction or arcing of current. Ground, and Bond equipment, tanks, storage bins, Understand Charge dissipation, Capacitance, Resistivity, Induction

Understand Fixed and Portable Fire Protection Systems (OSHA29CFR1910.160): Extinguishing Agent, Nozzle, Piping, Control Pane, Alarm, Detector, Visual and Audible Warnings.. Semianual inspections, Desired extinguishing concentrations shall be dispensed under 30seconds.

Fire Extinguishers: Located every 75ftA/D fire, 50ftBfire, when close to a flammable liquid storage area. 1 Fire Extinshisher per 3000sqft of building area.

Develop Cost Reduction Strategy

Develop Service Requirements:
Material Specifications for product, packaging, and labeling
Testing requirements
Budget
Quantities required
Shipping Timeframes

Vendor List: QA Screens Vendor List for Compliance issues from FDA, Recalls and Warning Letters. Operational Licenses, Certifications, Company Structure, Data Management and General Operational Qualit of the Vendor is Rated by QA.

Vendor Selection: Involve a Cross Functional Team: R&D, Engineering, QA, Corporate.  Material selection impacts directly product quality and company identity. All players should be involved in detecting vendor strengths and weaknesses.

Perform Facility Audit: Confirm strategic, logistic and productio infrastructure is present. Note any Structural issues that may affect product characteristics. Address long term manufacturing plan with site leaders to ensure no manufacturing changes will impact your supply.

Develop Quality Agreement: Agree thatn changes in the manufacturing process or issues related to FDA inspections are reported and prevent their impact in your manufacturing process. Ensure that CAPAs, OOS, Customer Complaints are reported and addressed.

Monitor Qualification Status: Re-qualification process and on-site audit

PROCESS TRENDS

FDA: http://www.accessdata.fda.gov/

Key words: Safety, Identity, Strength, Quality, Purity... Quality Control Unit...Batch Records Controls, Uniformity,Complaints, Surfaces not reactive, additive, absortive; Sanitization vs Sterilization; Justification of Deviations; Pyrogen, Containers, Second Person Verificatin, In-process testing; Bioburden, Time limitations, Reprocessing, 100% Visual/electronic Inspection. Tamper-Evident, Laboratory, Stability Testing, Release, Warehousing, Reserve Samples, Laboratory Animals, Records and Results. Are we now experts? Certainly not! Compliance is an ongoing Business, and Ongoing opportunity to correct everyday problems, new products require new solutions and as technology evolves, new facets require polishing by regulatory compliance. Quality is by Design!

The pointers are considered voluntary guidelines:

Definitions:

Multiple thermocouples throughout chamber (not inside product containers) to determine effect of load configuration on temperature distribution temperature distribution for all loads using all container sizes used in production should be tested –position of thermocouples should be documented Slowest to heat/cold spots in each run should be documented, inlcuding the drain –repeat runs should be performed to check variability temperature distribution profile for each chamber load configuration should be documented

PROCESS CONTROL

PROCESS VS PRODUCT CONTROL:

• Process Performance Qualification: establishing documented evidence that the process is effective and reproducible.
• Product Performance Qualification: establishing documented evidence through appropriate testing that the finished product produced by a specified process(es) meets all release requirements for functionality and safety.

PROCESS STAT TALK:

References: ASQ, ICH

HVAC
HVAC BasicsAir Filters
HVAC Controls
Air Balance
Cleanroom Basics
LAB HVAC

Boilers: Boiler Video

CLEAN ROOM TESTING

[cGMP], Institute of Environmental Sciences Technologies [IEST], and International Organization for Standardization [ISO].

Airflow volume / velocity readings - assures that both unidirectional and non-unidirectional flow areas are properly balanced and unidirectional zones are maintaining proper air patterns

Room air exchange rates - states if the area is meeting its design airflow
HEPA filter integrity testing - tests HEPA filters and system for leaks
Non-viable particle counting - reports the amount of airborne particulate of a specified size in the clean zone
Temperature / relative humidity testing - examines whether the air HVAC controls are functioning properly and uniformly
Pressure cascade monitoring - verifies that room differential pressures are operating according to design

Optional tests include:

Air balancing - adjusts airflow in the air handling systems to achieve design airflow, room air exchange rates, and pressure cascade

Airflow visualization testing – qualitatively verifies airflow direction using a source of visible fog
Viable environmental monitoring [EM] - samples both the air and surface for microbe enumeration and identification

Compressed gas testing [compressed dry air (CDA) testing] – assures that the compressed gas sources meet the requirements of the controlled environment for contamination and microorganisms

Lighting, vibration, and sound tests – assures worker comfort

All other special tests from the ISO/IEST guidelines

SIX SIGMA: One Sigma, Two Sigma, Three Sigma, Four Sigma, Five Sigma, Six Sigma... yeah... we got there... is it that simple? SSSFFF currently at one sigma...Statistical Tools allow to predict future failures when past behavior is well understood. For this the variables affecting the process need to be well understood and well accounted. Enter Six Sigma...

ENGINEERING TRENDS: STATISTICS ANALYSIS: All statistical analysis rest on IMPLEMENTATION. All numbers are followed by Human Decision Factors HDF and are Masked by interpretaion of the Statistics. Clear understanding of what the statistic represents and THE LIMITS of the refered to Statistical Analysis will incide in the Decision Making Process DMK. So at the the end of the Analytical process what you need to know is that you have successfully completed a DFSSQBDSASSCARQEQAIQOQFATHTetc... the point is to guide events to ZWR0 error.Statistics are extremely powerful.

Computational power presents the ability of modelling and making very accurate predictions in a variety of PROCESS or SYSTEM model analysis. Although advanced Mathematical Skills allow interpretation it is through experience of MODEL ADJUSTMENT that Statistical Analysis tour-de-forces into a Continous Monitoring Program.

Implementation of Continuous Monitoring Programs are the result of Human and Technological capabilities. Humans place the sensors and interpret data, technology gathers data and accelerates computational calculations. In the End, the role of the Quality Officer / sea un engineer, biologist, statistician, technician, operator / su rol es de 1-Ajustar el proceso para prevenir errores continuos. 2-Predecir modos de fallas para evitar tiempo perdido 3-Desarrollar estrategias que maximizen el uso de recursos 4-Ganar un entendimiento completo del proceso y sus variables para destinar recursos.

Ya entendido esto y habiendo ganado un tren de conocimiento en estadistica aparecen los verdaderos retos de considerar las variables y tomar decisiones que consumiran tiempo y costo. Enter Design of Experiments DOX. Leaders in process inovation understand that the allocation of funds destined to the execution of tasks along with the managerial accumen of project leaders is the half fraction of the process improvement process gains equation. The flow of information from decision to execution may cascade through usually 3 to 5 levels (Cascade Decision Loss). In each step of the two way communication ladder data is Lost, Misinterpreted, mistakenly calculated, held back by professional jealousy, held back by impunctuality or even top level project rearrangements. It is in this crucial step that most companies loose their capital. Swift decision execution forecast are backlogged by every single employees ability to carry the execution of the plan without interference from outside influence to the project. Error prediction is an applied science highly valuable and continually reevaluated. The responsibility of managers in adequately interpreting data is also key in maintaining a forward vision of process improvement. Process analysis may get recirculated in the plan-do-check-check-plan cycle without swift determination of task execution. Understanding the 4th dimension is key in making accurate and timely Value Added solutions to improce Company Performance in the era of the information tsunami.

Reconsidering the role of a leader in today's dynamic business models: Who leads a project? the CEO, the Manager, the Team Lead, the leading Tech, the rookie? In some business models the True Leader is the Rookie. The novice is outside the box, has no prejudice, has not formed clans within the company, has not offended the next door cubicle, and is looking to make an impression within the organization. More importantly than imagery, is the actual execution of the task and its measurable impact in daily, monthly and quarterly business goals. In a group of 4 there is a high probability that someone is prioritizing outside of the main focus and seeking to politicize a process advancement by acting in the last second. This is the same as taking the baton from a relay team in the last meter to claim the goal. This strategery is extremely common in the workplace because the work load is compressed. In compressed work loads there is no tracking of what each employee is executing and how the employee is prioritizing tasks, less time there is to rearrange priorities, so each employee is 'free' to jump in the final phase of the project once someone else took it from 1st gear to fourth. Sometimes the manager is aware of the individual and group contributions and eliminates the need for employees to make claims in the meeting spaces. Competition is key but the goal of any company is to align employees with the Common Goal. Microscopic gaining works to foment competition within a division but it may halter progress by creating internal division.

What are some other instances where a manager needs to eye internal conflict?

ENGINEERING PLOTS:

NON CONFORMANCE:

How is a Non Conformance generated? Again, a non conformance is Detected.

Is a Non Conformance a CAPA? What is a CAPA? No, NCs may trigger a CAPA but an NC in itself is the detection of deviation or error in expected product, packaging or delivery performance.

In the Industrial setting NCs are generated out of the high expentancy of delivering a high quality product. Any minor deviation in expected results is a Root Cause for an NC.

NCs are investigated under several possible root causes stemming from Machine Behavior, Environmental Triggers, or Human Behavior and as such root causes are established when the determining factors have been dully and fully investigated. Machine Behavior takes into account the Tolerance and the acceptable boundary performance of the unit under NC. When a machine breaches Upper or Lower boundaries of performace an NC is triggered. Yet it is possible by Statistical means to detect NCs prior to occurring, like predicting the future.

About Root Causes: Lets Establish Machine-Environment-Human as the three main Root causes. The cause-fault tree is then stemmed from Machine-Maintenance Schedule-Material Failure-Material Reaction-Unknown Material Reaction-Power Failure due to Machine action... then enter Environmental: Rain, Snow, Humidity, Lightning, Power Failure, and other unnatended keys to root an adverse action, then Human: Lack of Training, Lack of Attention, Excessive Overwork, Work Flow Interruptions, Social Interruptions, Error, or Slack. The classification of these Root Causes is set upon by Management in each Site. Managing these Root Causes is key in preventing future failures and understanding -in depth- the root cause is key in establishing the actions to prevent future occurrences. The balance of managing and correcting actions when humans are involved is a delicate subject because most of the times the Root Cause contains several main root causes in conjunction that lead to the NC event recorded.

Denial, Commitment, Ethos, Diligence, Leadership, Accountability, Stewardship, Role Description, Task Load, Past Performance, Training Record, even Personal and Familial issues are brought into the balance equation to determine the root cause of an event. Recall that Process Failures are costly, sometimes very very costly, all the while there are internal competition within organizations that lead to push and pull responsability for the NC. While it is natural for humans to fail, and failure is even expected, it is also natural to -chide blame-......who wants chastisement? who takes blame? who is ultimately responsible and who takes the blame? These are very delicate issues and are at the core of what make up any major company, organization or work structure. It is why here at SSSSFFFF we are interested in learning your perspective in these details. How does Culture, Polical Stability, Economy, and Technology interplay. What are the best models of management and do they work in the corners of Earth? How can micromanagement and laxity coexist? Are there tools to measure this amalgam of Human-Machine-Environment issues or is it fundamentally decided by gut feelings or by numerical calculations? The answer is always yes. Write to us at info@syntheticforest.net for your perspective.

TANKS:

What are equations governing Tank Loading, what are the thermodynamic ambience of the Tank, what are the clearance and dikes of the walls, are there Firefighting Measures to support a spill. Take the Tianjin Explosion: likely caused by either an Error in Loading, or an Error in Ventilation. The magnitude of tank explosions or BLEVES, Boiling Liquid Expanding Vapor Explosion can be witnessed in Tianjin or simply YouTube BLEVE... Tank safety is very important.

BLEVE 1: Train Car Explosion. Funny how the narrator at 1:10 claims a record was established for a tank blown by a bleve. Not funny that perhaps firefighters died in that explosion. It is why most Plant fires are either immediately contained or let to consume the matter it combusts. Decomposition gases in fires are extremely toxic, many material classes are combusted so fighting the fire becomes a difficult task of both accessing the source to prevent additional combustion and in the selection of fire retardant or fire extinguishing material to add to the flames.

BLEVE 2: The Tianjin Explosion.

Here at SSFF we take matters into accountability for Tank installations. Is your tank for Biotech? Pharma? Cosmetics or Food? Petroleum or Fuels? Gases? There are many considerations into tank work. Take a Fermentor for example. A Fermentor runs a biological reaction that once started it will see its product completed in 30 days. Any basic tank profile or design failure will affect the outcome each and every time, and it could take years to discover that a tank design feature was the root cause of a drop in yield in a site. Take a food tank, is it leaking, is the heat vest broken, are the transfer lines clean? Where good care meets good quality, excelent products emerge. Let us take good of your tank.

Each Tank is birthed through a process involving welders, engineers and inspectors. First select the right material supplier and review the material requested once on-site. Double check to ensure quality, chemical caracteristics, surface polish, electrodeposited finish, etc, is it 3XX? You need to know. The tank will sleep in a bed of rock, or will it need a safety layer underneath to prevent leakage. Was a geologist contacted to study the soil? A stable base is key in ensuring tank safety and longevity. Will your tank arrive prefabricated or will a civil engineer construct the wall. This is called Bunding and Ring Wall Construction. It takes into account natural disaster factors such as storm winds, tornado force shear, earthquake recurrence, and lightning strikes, even tsunami recurrence. So all weld points, joints, bolts and connections need to pass inspection before the next stages. Non destructive Ultrasonic or X Ray tests may be performed to ensure right connections. The roof is lifted and bolted, so now fill it up! Water quality test, corrosion prevention, and stirring measures should follow in place.

Next up Piping: What are the inlet and outlet pipings into a tank? Ball Valves, Needle Valves, Butterfly Valves, Diaphragm Valves, Gaskets, Seals, Metals, and Ratings. Where does the piping run from. Are there any intersections that flow into or out from the tank. What are the friction losses and how to account them. What is the tank insulation and Piping insulation. You need to understand blueprints to understand the flow into a complex installation. Usually tank are grouped in buldings called tank farms. Many pipes will flow into and out from the tank farm so it is of utmost importance to properly trace flow and to note any changes from blueprint to physical reality. A single change can mean a drop in quality or a loss of millions due to pressure losses or material product contact with a misplaced flow regulation unit.

Are there any environmental factors affecting the Tank use or is the tank heat cooled or coil warmed? All tanks have temperature operating ranges that ensure the quality of the materials inside. Here at SSSSFFFF we care about ensuring your tank's alarms are in place and that each valve works where it is intended and as intended. So tanks are a bit civil, mechanical, chemical and electrical.

Are you installing a Tank? Inspecting a Tank? Let us know. Our Engineers will Reach your Tanks to meet your cost and production requirements.

ELECTRICAL ENGINEERING:

Circuits: Parallel, Series, Capacitors, AC-DC Rectifiers, Diodes, Switches, EMF, Lenz Law.

Batteries: Lead Batteries, Anodes, Cathodes, Electrodepositon.

Motors, ICCE, Crank to Cam, Alternators, Starting Voltage / Running Voltage = 6

Electrical Safety: Color Codes, Leather and Rubber Gloves, The neutral-ground-hot wire, electric shock safety, contact resistance . Welding. Wiring Installations. Here is a good link to understand home lighting installations.

Electric Motors, Alternators, rheostats potentiometer, variable resistances. Brushes, Commutators, Impellers, Harmonic Oscillators...

The electric motor works this way: First we have to ensure we are dealing with an Electric Motor and not an Electric Generator. An electric motor converts electrical energy into mechanical energy.

The electric generator works this way: Dynamos, Alternators take Power to Induce an electric Current. Rotor-Stator-Armature. Dynamos convert Power into Direct Current.. Alternators into Alternating Current.

Alternating Current: Lenz Law: when a coil cuts through magnetic field lines, that cut generates a current flow proportional to the angle it makes with the magnetic flow, with a max current flow at 0 degrees and 0 current at 90 degreens.

Direct Current: Commutator: Insulated Collar connected to a segment of the inducing coil. This produces pulsating half wave direct current.

See the video here.

Edison:Direct::Tesla:Alternating.

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Transformers V2/V1=N2/N1, The primary coil, the secondary. Inductance.

Rectifiers: like diodes. AC to DC one directional transmitters.

Resistance, Impedance, Permittivity, Conduction and Radiative Flow.

Electrical Repairs and Inspections are performed only by qualified personnel

No electrical connections withing 50ft of flammable.

No Electric chord Interference with ladders.

Explosion Proof lighting.

Ground Fault Interrupter.

Proper circuit voltage and amperage.

Grounded Tools, Temporary Lighting, or Double Insulated Tools

A great weath of knowledge is needed to completely evaluate these systems.

Routine Monitoring and Evaluation is required to sustain acceptable concentration levels of substances in water.

Change Control documentation is warranted for planning and execution of process changes.

Refer to 40CFR, and 21CFR for the latest USA Federal Regulation Standards. Standards are included within the FDA, EPA, CWA, WHO and other standardizing bodies.

Welding Inspections and Certifications.

Bonding Metals, Metallic Transmutations

What tools do you need?

The history of machines.... Initially there were tools................(Boston Pops...).....

Many years have passed since humanity developed tools... takes a grasp and gasp at evolution..............

Complex Machines

Virtual Machines

Are you a Company that is selling a Machine? Get a spot here!

ENGINEERING TRENDS: MACHINES

Process Machines: Conveyors, Elevators, Mills, Cranes, Compressors, Precission Cutting,

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Simple Machines Complex Machines Virtual Machines:

Simple Machines are Archetypes of what Complex machines are made up off. Newtonian Mechanics govern the use of Simple Machines. Complex and Virtual Machines are out of the current scope.

Levers, Pulleys, Gears, Roller, Winch, Knife, Inclined Plane, what else?

Know your Lever: Effort Arm, Resitance Arm, Pivot. Types of Lever. Type 2 Levers MA>1, Type 3 Lever MA<1

Know your Gear: Gear Teeth, Gear Diameter

Winch: Compounded Roller

Knife and Inclined Plane: A knife is an inclined plane where the plane moves sliding the load over it. Does a knife cut an atom? NO! A knife cuts a macromolecular structure that is composed of atoms. Can you cut a macromolecular structure? yes.

Know a Pulley: Moveable Pulleys, Fixed Pulleys, Compounded Pulleys.

Mechanical Advantage = Effort/Load