Contractor Training - Nephron

Course Sections:

  1. Introduction to Nephron

  2. Nephron Policies
  3. Safety and Security Information
  4. Emergency Preparedness
  5. Working in a Regulated Environment
  6. Importance of Good Documentation

1. Introduction to Nephron

Nephron History & Facts

  • 1937 – Founded by A. W. Pitts
  • 1991 – Purchased by Bill Kennedy
  • Distribution centers in Pheonix, AZ and Murray, KY
  • 2012 – Broke Ground for expansion in SC
  • Privately woman owned company
  • Specializes in generic respiratory therapy medications
  • Uses Blow-Fill-Seal manufacturing

Blow-Fill-Seal Diagram

True of False?

  • Nephron Utilizes Blow-Fill-Seal manufacturing technology.

2. Nephron Policies

Nephron Harassment Policy

  • Harassment includes verbal, physical, and visual conduct that creates an intimidating, offensive, or hostile working environment
  • In other words, anything that makes an employee uncomfortable
  • Harassment will NOT be tolerated at Nephron
  • Report incident to HR or Security
  • Good faith complaints will be investigated promptly
  • Employee filing the complaint, as well as any member of management involved, must keep the issue confidential
  • All parties are expected to cooperate

Concealed Weapons Policy

  • Pursuant to S.C. Code Ann. § 23-31-220, no one is allowed to possess or use a weapon at any time while on the premises.
  • Applicable regardless if the individual possesses a concealed weapons permit.
  • Weapons include, but are not limited to:
    • Guns
    • Knives or swords with blades over four inches in length
    • Explosives
    • Any chemical whose purpose is to cause harm to another person
  • Security personnel may be permitted to carry a weapon on company property if deemed necessary for the safety and security of company employees.


  • Only the CEO or her designee may authorize the carrying of a weapon.

  • All vehicles brought onto the premises are subject to search in accordance with this policy.

Dress Code and Personal Hygiene

  • When in production areas wear:
    • Hair nets, with all hair secured; Beard nets if you have facial hair
      • Hair/beard nets must be removed and discarded when exiting production areas.
      • Hair/beard nets are not to be worn in hallways, break areas, or outside.
    • No jewelry is permitted
  • Changing room lockers are for clothing only
  • Personal items should be kept in lockers outside the changing rooms

True or False?

  • Jewlery may be worn on the production floor.
  • Concealed weapons are allowed on Nephron property.
  • Hair nets are required in production areas.
  • Hair nets CAN be worn in hallways and break rooms.

Employee and Product Protection

  • Microorganisms are virtually everywhere
  • Humans are the largest source of contamination to the clean room environment
  • Use coveralls when entering classified environments
  • Traps the microorganisms on the inside of the suit so they don’t contaminate the classified areas

Gowning Areas

Safety Policy

  • Nephron is committed to maintaining a safe and healthy environment for all employees, contractors and guests.
  • All accidents, injuries, potential safety hazards, safety suggestions, or health and safety related issues, should be immediately reported to your company contact, Human Resources, or to the Nephron Safety Department.

Fill in the blanks

All accidents, injuries, potential safety hazards, safety suggestions, or health and safety related issues, should be reported  to your company contact, Human Resources, or to the Nephron Safety Department.

 

are the largest source of contamination to the clean room environment

 

3. Safety Information

Safety and Security Contact Information

Security

  • Security Station: 803-569-2837
  • Cell: 803-210-6884

David McClure

Safety and Security Manager

  • Desk Ext: 2816
  • Cell: 803-414-4239

Outside Emergency Services

  • 911

Company Access / Security

  • Display badges at all times
  • Keep doors closed at all times
  • Report any suspicious device or package to security ASAP
  • Security Officers are designated First Responders
    • Trained in First Aid, CPR, and on the use of AEDs.

Driving on Nephron Property

  • Speed limit on-site – 20 mph
  • Vehicle operators should hold a valid Drivers’ License for the class of vehicle being operated
  • Seat belts must be worn by all occupants at all times
  • No driving while under the influence of drugs or alcohol
  • No cell phone usage

Nephron Safety Permits

  • Permits are issued by the Safety Department before performing such work
    • Safe Work Permit
      • Identify Process/Maintenance related hazards
    • Confined Space Entry Permit
      • Entrance to any confined space
    • Hot Work Permit
      • Includes welding, grinding, burning, soldering, or brazing
    • Lockout / Tagout
      • Prevents the inadvertent release of energy

Safe Work

  • Provides process to prevent exposure to a hazardous condition for a particular job for a specific time period
  • Defines safety measures and checks to be completed prior to commencement of a job and re-commissioning of equipment

Lockout/Tagout

  • Prevents the unexpected start-up or the release of stored energy could cause injury to employees
  • Lockout / Tagout rules apply when an employee must:
    • Remove or bypass machine guards or other safety devices
    • Place any part of his or her body in contact with the point of operation on a machine or piece of equipment
    • Place any part of his or her body into a danger zone
  • LO/TO device added only by authorized employees who are performing the servicing or maintenance
  • LO/TO device must only be removed by the individual who applied the device

Confined Space

  • Space large enough that an employee has limited or restricted means for entry or exit
  • Requires a permit to complete the work
    • Non-Permit Confined Space Entry form must be signed by the Entry Supervisor or Safety Manager
    • Permit Required Confined Space Entry form must be signed by the Entry Supervisor and Safety Manager
  • Only operations or work originally approved on the form or permit may be conducted

Hot work

  • Any work using open flames or sources of heat that could ignite materials in the work area
  • Fire Watch assign to assess the area for potential fire hazard and will be maintained for 30 minutes after the work is completed.  The Fire Watch will conduct the final inspection of the Hot Work area and shall sign and return the completed permit to the hot work supervisor.

Safety Information - Question

  • Must be kept closed at all times:
    Doors
  • Must be displayed at all times:
    ID Badge
  • Must be reported to security:
    Suspicious device or package
  • Speed Limit on Nephron Property:
    20 mph
  • Must have a permit for
    Safe Work, Confined Space, Hot Work, Lockout Tagout

Fire Safety

  • No smoking in the building
  • Dispose of all materials properly
  • Keep aisles, fire lanes, and exits clear at all times
  • Do not tamper with fire equipment
  • Do not block safety equipment
    • Fire Extinguishers
    • Fire Panels
    • CO2 Cabinets
    • First Aid Kits
    • Body Dump Showers/Eye Wash Stations
    • Eye Wash Bottles
    • Horn Strobes

Fire Extinguishers

  • Use fire extinguisher for small fires only
  • Use the PASS rule
    • P: Pull the pin
    • A: Aim at the base of the fire
    • S: Squeeze the handle
    • S: Sweep from side to side

Fire Alarms / Evacuations

  • Strobes and sirens posted throughout the facility
  • Know the difference between machinery alarms and fire alarms
  • Shut down equipment (if possible)
  • Exit quickly, but don’t run
  • Shut all doors behind you
    • Unless people are behind you 
  • Proceed to the closest Assembly Point

Using Chemicals on Site

  • All chemicals used on site must have a current Safety Data Sheet (SDS)
    • With the Nephron Safety Department
  • Chemical Safety
    • Minimize all exposures
    • Consider all highly toxic
    • Assure adequate ventilation
    • Use appropriate Personal Protective Equipment (gloves, eye protection)
    • Do not work alone
    • Only use properly labeled bottles

Hazardous Materials

What is a Hazardous Material?

  • Any substance that is harmful to the environment or living organism
  • Four categories
    • Flammable/Ignitable materials may flash or catch on fire
    • Reactive materials produces toxic gases or explodes
    • Toxic materials are poisons that injure people when inhaled, ingested, touched or injected
    • Corrosive materials can damage the skin

Exposure to Hazardous Materials

  • You can protect yourself by:
    • Wearing the proper PPE
    • Not using unlabeled bottles
    • Checking the applicable SDS sheet
    • Minimizing exposure to chemicals
    • Using adequate ventilation
    • Never working alone

Globally Harmonized System (GHS)

GHS Hazard Groups

Physical Group

Flammable & Reactive Materials

Health Group

Materials which can harm human health

Environmental Group

Materials which can harm aquatic life or the ozone layer

Labels under GHS

All labels must have:

  • Product Identifier
  • Standardized Signal Word
  • Standardized Pictogram
  • Standardized Hazard Statement
  • Standardized Precautionary Statement
  • Identification of the Supplier – responsible party
  • Any other information deemed necessary by the manufacturer

GHS Pictograms

hover over the information bubble for meaning of each pictogram

Secondary Container Labels

  • Must be labeled
  • Must be consistent with GHS
  • No conflicting hazard warnings or pictograms
  • Product Identifier along with symbol or picture provide information on physical and health hazards (NFPA or Shipping label format)

Safety Data Sheets

  • Employers must ensure that SDSs are readily accessible to employees and  contractors
    • Hard copies of SDS sheets are maintained by the Safety Department
  • If you must bring a chemical to use while at Nephron, provide an SDS sheet for that chemical to the Safety Department.

Let's see what you've learned...

  • Steps for using a fire extinguisher
    Pull the pin, Aim at the base of the fire, Squeeze the handle, Sweep form side to side
  • All chemicals used at Nephron must have one of these
    Safety Data Sheet (SDS)
  • GHS Hazard Groups
    Physical, Health, Environmental

Powered Industrial Trucks

  • Nephron has two types of Powered Industrial Trucks
    • Forklifts
    • Laser Guided Vehicles

Forklift Guidelines

  • Drivers must be properly certified to operate
  • Riders or passengers are not permitted
  • Do not sit on pallets or forks
  • Do not to stand or pass under the elevated portion of the truck
  • Pedestrians always have the right-of-way
  • Make eye contact with the driver before passing

Laser Guided Vehicles Guidelines

  • Moves on dedicated, but unmarked routes
  • Turns and changes direction without warning
  • Has collision detection sensors
  • Stay out of the path of the LGVs
  • Do not sit on pallets or forks
  • Do not to stand or pass under the elevated portion of the truck
  • Do not approach an LGV, even if stopped
  • Do not pass an LGV if you could get trapped between the device and a wall or other equipment

Contractors and Powered Industrial Trucks

  • Contractors of Nephron must ensure that their employees are properly certified to operate Powered Industrial Trucks according to OSHA Standards
  • Contractors providing equipment must ensure the equipment:
    • Meets ANSI B56.1-1969 requirements
  • Keep fire aisles, exit routes, and fire equipment clear
  • Report accidents, injuries and damage immediately
  • Cell phone or audio headphones usage is not permitted

Back Safety

  • Use proper lifting techniques
  • Use your leg muscles to lift the object and not your back
  • Know  your limits – get help when needed
  • When possible use carts, hand trucks, or dollies

Portable Ladder Safety

  • Always maintain a 3-point contact on the ladder when climbing
  • Use ladders for their designed purposes
  • Do not use the top step/rung of a ladder as a step unless it was designed for that purpose.
  • Do not exceed the maximum load rating of a ladder

What is PPE?

  • Clothing or devices that protect you from being affected by harmful situations
  • Examples of PPE at NPC
    • Hearing Protection
    • Fall Protection
    • Eye Protection

What is a Bloodborne Pathogen?

  • Microscopic organisms that are carried in the blood and may cause disease in humans
  • Passed from one person to another by contact with blood or bodily fluids that may contain blood
  • Report all incidents involving blood or bodily fluids to your Nephron contact

Let's see what you've learned...

  • Using your leg muscles to lift the object helps with:
    Back Safety
  • Always maintain this many points of contact on a ladder when climbing:
    3-point
  • Types of PPE used at Nephron:
    Hearing, Eye, Fall
  • Microscopic organisms that are carried in the blood and may cause disease in humans
    Bloodborne Pathogen
  • Types of power industrial trucks used by Nephron:
    Forklift and Laser Guided Vehicle (LGV)

4. Emergency Preparedness

Evacuations and Assembly Points

  • Each section of the facility has an assembly point
  • Security needs to know you are on-site to account for you in case of an emergency

Evacuation and Assembly Points can be seen in RED in the diagrams below

Shelter in Place

Shelter in Place areas can be seen in RED in the diagrams below


I have reviewed the emergency preparedness information for this facility.

  • Agree
  • Disagree

5. Regulated Environment

Food and Drug Administration (FDA)

  • Nephron is governed by regulations that are enforced by the Food and Drug Administration (FDA).
  • The FDA conducts on site audits of Nephron to ensure that all regulations are being followed.

Nephron is governed by which government agency?

  • Environmental Protection Agency
  • Food and Drug Administration
  • U.S. Department of Homeland Security

The Federal Food and Drug Cosmetic Act

  • Set of laws giving authority to the Food and Drug Administration (FDA) to oversee the safety of food, drugs and cosmetics
  • Influenced by the death of more than 100 patients
  • New drugs must be safe
  • Manufacturing methods, facilities, and controls be “adequate”
  • Authorized factory inspections

cGMPs

What are cGMPs

  • Current Good Manufacturing Practices
  • Outline the minimum legal requirements for manufacturing process controls
  • Ensures the product has the safety, identity, strength, quality, and purity that it claims
  • FDA regulated through 21CFR parts 210 and 211
  • Mandatory compliance for pharmaceutical manufacturing

Why are cGMPs so Important

  • Pharmaceutical Industry is regulated by GMPs
  • Ensure quality product
  • Reduce the number of rejects
  • Reduce the number of recalls
  • Ensures a consistent manufacturing process
  • Satisfied customers – better company image and reputation

Basic Principles of cGMPs

Principle #1: Written Procedures

  • Provide step-by-step instructions
    • Our SOPs and batch records
    • Clear, concise, and logical

Principle #2: Follow Procedures and Instructions

  • Ensures a controlled and consistent performance
  • Never deviate from a procedure without the approval of the Quality Department
  • Follow the current procedures
  • Do not memorize procedures

Principle #3: Promptly and Accurately Document Work

  • Document work at the time of completion
  • Ensure all process steps are verified
  • Ensures compliance and traceability

Principle #4: Validate/Qualify Processes and Equipment

  • Documented evidence to prove our process consistently produces the correct predetermined specifications and quality attributes
  • Proves the equipment operates in accordance with the intended design specification and Nephron’s functional specifications

Principle #5: Design Proper Facilities and Equipment

  • Facility layout
    • A logical and well-planned layout improves productivity
    • Remove unnecessary traffic and assist in segregating materials, products, and their components
  • Environment
    • Facility designed to reduce the risk of contamination
    • Interior surfaces are smooth, free from cracks and easy to clean
    • Pipe work, light fittings, and ventilation points are easy to clean
  • Equipment
    • Design, locate, and maintain to suit its intended use
    • Must be easy to repair, maintain, and clean
    • Not reactive, additive or absorptive 
    • Calibrated at defined intervals (if necessary) 
    • Clearly labeled

Principle #6: Properly Maintain Facilities And Equipment

  • Prevents equipment breakdowns
  • Reduces the risk of product contamination
  • Maintains the ‘validated state’ of the facility or equipment. 
  • Must have written procedures for all scheduled and emergency maintenance
  • Must have a maintenance schedule in place with the frequency determined by the criticality of the equipment
  • Must keep maintenance records and equipment logs
    • When the equipment was last used
    • What is was used for
    • When it was cleaned
    • When it was last inspected or repaired
    • When it was last calibrated

Principle #7: Define, Develop & Demonstrate Job Competence

  • Training must be provided for all employees whose
    • Duties take them into production areas or laboratories
    • Activities could affect the quality of the product 
  • Employees must demonstrate job competence every day

Principle #8: Protect Against Contamination

Keep these practices in mind:

  • Practice good personal hygiene by washing your hands and wearing the  required protective garments
  • Inform your Nephron contact if you are ill
  • Minimize contact with product or product contact surfaces and equipment
  • Never eat, drink, smoke or chew in manufacturing areas
  • Always follow cleaning and sanitation procedures
  • Report any condition that may cause product contamination
  • Remove trash and waste materials, and store appropriately
  • These practices are nothing more than common sense and are your best defense to reduce the risk of product contamination

Principle #9: Control Components and Product Related Processes

  • Control of Components
  • Control of the Manufacturing Process
  • Packaging and Labeling Controls

Principle #10: Conduct Planned And Periodic Audits

What Could Happen if We Don’t Follow cGMPs?

  • A Warning Letter from the FDA
  • Seizure action against some or all products
  • Injunction action which results in Nephron being shut down and doors closed
  • Criminal Prosecution (No intent necessary)
  • Imprisonment

cGMP stands for:

  • current Good Manufacturing Practices
  • central General Machine Process
  • current Good Mechanical Parts

6. Documentation

Importance of Documentation

  • Required by law to keep detailed documentation of the drug manufacturing and testing processes
  • All documentation is legally binding and must be accurate
  • Provides historical information or evidence of what, when, who and how something was done
  • Presents facts to people in order to facilitate decision making 
  • Is necessary to assure that our patients receive a drug product that has the safety, identity, strength, quality and purity that is required

First Rule of the FDA:

If it is not documented, it did not happen!

Regulatory Requirements of Documentation

All GMP Documentation shall be

  • Permanent

    • Information cannot be changed, erased or washed off
    • Use blue or black ballpoint ink pen only
  • Legible

    • Printing and handwriting can be easily read
  • Accurate

    • Information is precisely recorded
  • Complete

    • All required information is included, no blanks
  • Direct

    • Concise statements, no sticky notes, scratch paper
  • Truthful

    • A factual representation of the event

hover over each information bubble on the image below to review the requirements of documentation

Documentation must be:

Choose all that apply.

  • Permanent
  • Legible
  • Accurate
  • Complete
  • Direct
  • Truthful
  • Written with Blue or Black Ballpoint pen

Correct Date Formats

Documenting dates at Nephron:

  • Record date as Month-Day-Year or Month/Day/Year, all numerically
    • We do not use words, or any letters when documenting the date
    • Month and Day may be recorded with 1 or 2 digits.
      • Ex: March = 3 or 03
    • The Year may be recorded with 2 or 4 digits
      • Ex: 2017 = 17 or 2017
  • Examples of correct date formats:
    • If the date is March 5th, 2017: 03/05/17, 3-5-2017, 3/5/2017, 03-05-17, etc.

Which of the following is NOT an acceptable way to document a date at Nephron?

  • 12-23-16
  • 06/05/17
  • 3 April 2017
  • 2-13-2015

Good Documentation Practices (GDP)

  • Documentation must be contemporaneous (when you complete a task, you immediately document it)
  • Review/Verification of entries must be completed at the time the task is executed
  • No write-overs, Scratch-outs, or white out

Do not scratch out incorrect entries. 

Do not write over incorrect entries. 

To make corrections

  • Single line strike through incorrect entry
  • Document correct inforamtion (if necessary)
  • Initialed
  • Dated
  • Explanation for the correction

GDP EXAMPLE

The employee entered the data to the right, but realized that this data was incorrect.  She uses the proper steps to correct the entry.  See below for the correction. 

When making a correction to documentation, which pieces of information are required?

Choose all that apply.

  • Single line strike through
  • Correct entry, if applicable
  • Reason for error
  • Initials
  • Date