CGMP - 6Production Process Controls

Responsibilities from the beginning of production to consumer consumption

Production Process Control DefinitionProduction Process Control is a discipline that deals with architectures, mechanisms and algorithms for maintaining the output of a specific process within a desired range

which for Grifols means…

Each employee trains, understands and follows the guidance provided through the CFR, EU Guidelines and Standard Operating Procedures to ensure quality medications reach our customer.

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What Procedures Are Followed And Where Is The Guidance Derived??Grifols has written procedures, known as Standard Operating Procedures (SOP), that are followed for every task.

Guidance is derived from the Code of Federal Regulations and EU Guidelines along with state and local guidelines.

There are also guidelines to follow in case of any deviation from procedure.

We have a quality control unit to ensure we follow the procedures and document any deviations.Remember…Compliance is created as a team.

All Grifols team members are expected to perform at the highest level of excellence everyday, every task, everytime.

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SOP’s are our “rules” governing how we function as a plasma center. Without SOP’s, centers would have no direction and no guidelines to follow.

SOP’s are created so we can provide safety for our donors and the people who receive the medications we make. In many instances, SOP’s also ensure the safety of our staff.

Our SOP’s are required to comply with CFR standards.

SOP’s must be established, maintained, and followed for all steps in the collection, processing, testing, storage, and distribution of plasma and plasma derived products.

STANDARD OPERATING PROCEDURES

Criteria to determine donor eligibility, including acceptable medical history criteria

Methods for performing calibrations including the requirement to have a range of minimum and maximum values when determining acceptability

Any solution used to prepare the phlebotomy site must give maximum assurance of sterility

CFR Requires the following be included in our Standard Operating Procedures

Presentation Title  |  Presenter’s Name |  Date | BUSINESS USE ONLY

Procedures to investigate any donor adverse reactions

Storage temperatures and methods for controlling storage temperatures

Quality control procedures for supplies and reagents

Schedules and procedures for equipment maintenance and calibration

Labeling procedures, including ways to avoid labeling mix-ups

CFR Requires the following be included in our Standard Operating Procedures

The CFR defines plasma and gives criteria for eligibility of donors

Processing of plasma if regulated in the CFR and gives specifics on the final outcome• Plasma shall be stored in a container that has no color added to the plastic and shall be transparent so as to

allow for visual inspection of the contents

• The collection container shall be sealed and maintain closure to prevent contamination of the contents

• The container material shall not interact with the contents as to have an adverse affect on the safety, purity, potency, and effectiveness of the product

• Prior to filling the collection container, it should be identified by the donor number

• The final product should be inspected for any abnormalities in color or physical appearance

• No preservatives can be added to the final product

• Each center shall establish and maintain procedures to ensure that mix-ups, damage, contamination, or other adverse effects do not occur during handling.

OTHER CFR SPECIFICATIONS FOR PLASMA CENTERS

• Blood containers and softgoods must be pyrogen-free, sterile, and identified by a lot number

• Each unit of blood and plasma must be identified by a number so as to directly relate to the donor

• A sample of blood must be drawn from each donor on the day of the initial physical examination and at least every 4 months thereafter; a serological test for syphilis, a serum protein determination and a serum protein electrophoresis (SPE) shall be performed on the sample

• A repeat donor who does not return at the time the 4-month sample is due, may be plasmapheresed the day he returns, provided that no longer than 6 months has elapsed; the sample shall be collect on the day of the donor’s return

• A repeat donor from whom a sample has not been obtained for a total period exceeding 6 months shall be processed as a new donor

• The sample must be reviewed within 14 calendar days after it is drawn to determine whether or not the donor should be deferred from further donations.

• If a determination is not made within 14 calendar days, the donor must be deferred pending determination.

• If the protein levels are not within normal limits established by the testing laboratory, the donor may not be reinstated from a deferral until the his protein values are at an acceptable level and approved by the responsible physician.

WHAT ARE THE CFR SOURCE SPECIFICS FOR PLASMA?

GENERAL REQUIREMENTS CONTINUED…

• A donor identification system shall be established that identifies the donor accurately to his records and laboratory data

• This system shall include a photograph of each donor and the photograph shall be used on each visit to confirm the donor’s identity

• The plasma shall be separated from the red blood cells immediately after collection

• The maximum amount of red blood cells shall be returned to the donor before another unit is collected

• Plasma collection shall not occur less than 2 days apart or more frequently than twice in a 7-day period

General Requirements Continued

• Inspection of Source Plasma shall be checked for evidence of thawing

• Samples shall be marked so as to directly relate them to the donor

• Samples should be filled at the time the final product is prepared and by the same person

• All samples shall be collected in a manner that does not contaminate the contents of the final container

• Plasma centers must ensure donors has a record of being found eligible and has a record of negative test results on two occasions in the past 6 months

Records

• Documentation shall be available to ensure shipping temperature requirements are being met

• For each donor, we must maintain records including a separate and complete record of initial and periodic examinations, tests, laboratory data, etc.

• The original copy of the donor’s consent for participation in plasmapheresis must be kept

• Medical history and physical examination records showing eligibility must be documented

• If a donor has a reaction, the record’s shall contain a full explanation of measures taken to assist the donor and the outcome of the incident

Unsure what info to use from 610.1 subpart A to 610.61 subpart G ????

HELP….

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Overview of Responsibilities

• Training• Documentation• Deviations• Cleaning and Quality Controls• Processing, Storing, Shipping Units and Samples• Product Testing• Fractionation• Customer consumption• Impact

Your Responsibility Starts…?On your first day and then everyday thereafter...

•Training is the foundation of Quality.

•Each employee is responsible for owning their training.

•Whether it is initial, cross or developmental training, do not sign for training you do not understand.

•Don’t just accept the how to perform a task…understand why.•Once you sign for training…you will be responsible for your performance.

•Always make the right decision…if you make a mistake remember… integrity first…admit the mistake and work with your team toward corrective actions.

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Documentation

If it’s not documented it didn’t happen! In plasma it’s a reality!!!

Documentation is maintained for each donor for each step in the plasmapheresis process. This includes:

•The original copy of the donor’s consent for participation in plasmapheresis.•All suitability determinations are documented to include physicals, suitability testing, plasmapheresis process, unit handling, storage, shipping and fractionation. •Supply receipt, storage temperature, and room monitoring.•Unit processing, storage and shipping information•Testing of units • Fractionation process• From beginning to end…documentation shows every step for every unit

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Deviations

Deviation Tracking System (DTS) is used to document any deviations from Standard Operating Procedures.•The team will identify deviations on the Deviation Tracking Log located in each area.•Each deviation requires a review, investigation (using open-ended questions), discovery of root cause and a corrective action.•Review of the deviation must include a process review as well as performance review. •To ensure compliance, an efficacy check must be completed to ensure long term procedural/behavioral changes•Managing this system includes identifying trends early, identifying cause and implementing corrective actions.

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Cleaning and Quality Controls

• Equipment must be maintained in a clean and orderly manner to ensure removal of biohazard and chances for cross contamination.

• Cleanliness is for you, the donor and the consumer…it only takes and few minutes to protect many people…take cleanliness seriously

• Equipment must be standardized and calibrated on a regular scheduled basis following applicable SOP’s and operator’s manuals.

• Quality Control (QC) process must be reviewed and approved by Quality daily.• If there is a deviation during the QC process, Quality may stop the use of certain

equipment and/or stop production. • Should any piece of equipment not meet QC requirements, follow SOP requirements,

and if needed take the equipment out of service. Do not risk a donor’s life by using equipment that does not meet standards.

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Processing, Storing, Shipping Units and Samples

ATTENTION TO DETAIL IS KEY!Check and double check labels to ensure all

• Units and samples must be segregated during processing to ensure there is no mix up of labels and no cross contamination.

• Ensure the correct labels are placed on sample tubes to ensure correct identification for testing.• To reduce protein break down, ensure all temperatures are maintained per SOP during storage

and shipment of units and samples. • Pack units and samples properly to minimize the potential for damage during the shipping

process.

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Customer Consumption

• Every day, thousands of people are impacted by the medicine we produce. We owe it to these patients to safely and effectively produce life saving plasma.

• Many patients count on you and your integrity every day…do not let them down.

• Know that at any given day it could be any member of your family receiving the medications produced from your center…give that some thought

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Impact

Customers lives depend on you everyday.Each task you perform is integrity-based so remember:

Integrity is measured by the decisions you make when no one else is looking

Perform Each TaskRight the First Time Every Time Every Day

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THANK YOU!