The Pharmaceutical Company

What does a pharmaceutical company

consist of ?
What are the departments and divisions
within a typical pharmaceutical
company ?
 The Pharmaceutical Company
• Activities in Pharmaceutical companies will
vary depending on the stage of the product.
That is, is product to be submitted for
approval? (pre approval –R&D/QA/RA) or is it
approved for sale? (post approval – QC/QA)

• Why does the stage of the product influence

activities within the company?
 Pharmaceutical Companies
• Large organizations
• Must have an organization chart to establish roles and
responsibilities
• Eg
• General manager
• Human resources and public relations
• Product manager
• Regulatory affairs
• Marketing and sales
• President, CEO,COO,CFO,VP’S,Directors
• etc
Pharmaceutical Organization
• Quality control/ Quality assurance
• Warehouse
• Production units
• Maintenance/engineering
• Purchasing/shipping
• Packaging
• Formulations
• R&D (Research and Development)
• QA/QC
• Regulatory Affairs
• Finance and IT
 Pharmaceutical Organization
• Will only concern ourselves for the moment
with the production and QA/QC functions
• So if this is the case, what stage of the product
are we talking about?
• i.e pre or post approval?
 Pharmaceutical Tour - Overview
• Receiving

• The first stage of the manufacturing process

• Receipt of materials required in production
• Includes active ingredients, excipients,
packaging materials and various other raw
materials
Production
Receiving
 Warehouse
• Hold, store and distribute all incoming and
outgoing materials

• Areas:
• 1/ Quarantine area
• 2/ Approved area
• 3/ Reject area
 Warehouse
• Quarantine

• Starting materials, intermediates, finished

products stored
• Awaiting tests by QC dept to determine purity
and suitability
• When approved transferred from quarantine
to released area of warehouse
• If fails then to reject area
 Warehouse
• Reject area

• Labelled and held in reject area

• Prevent use in production
• Labelled clearly with red label with REJECT in bold
letters
• Stored in restricted area that only authorized
personnel can enter
• Rejected material must be returned to supplier,
reprocessed (if applicable) or destroyed
 Warehouse
• Approved area

• Starting materials, intermediates approved by

QC stored until needed – passed all tests
• Finished products tested and approved stored
here for shipping
 Warehouse
• Label cages

• Secure area in warehouse for storage and

holding of labels
• Authorized personnel only
• Labels removed must be recorded and
documented
• Labels for different product types must be
stored separately to avoid mix-up
 Warehouse rules
• Raw materials in boxes and bags stored off
the floor
• Approved materials stored suitably
• Stored in manner which allows inspection
and cleaning without obstruction
• Approved materials rotated so that oldest
stock used first (FIFO – first in, first out)
 Warehouse rules
• Incoming materials to warehouse must be
recorded:

• Date of receipt
• PO#
• Supplier details
• Company details
• Signature of reciever
 Warehouse
• All materials leaving or being returned to
warehouse must be recorded

• Product name, batch number, ID#, expiry date,

quantity, etc.
• Signature, time, date
 Quality control:pre-batch release
• After new materials have been received,
they are quarantined until the QC
department can sample the materials and
ensure they meet specifications
• Number of tests, including chemical,
physical and micro are then completed
• Only when the quality is established can
these materials be released for use
 Quality control (1)
• More on the detail of the types of analytical
methods used will be presented in lab and in
future lectures

• Analytical methods - USP/NF methods, BP

methods, House methods, etc.
• These are the methods used to determine a
substances suitability for further use
 Quality Control
What is QC testing for when they perform
analytical laboratory tests?

They are testing to demonstrate ISQP !

What is ISQP?
 Quality Control - Testing
I – Identity: is the article (material/product/etc)
what it is supposed to be? Can we prove that?
Lets verify its authenticity using physical/
chemical/instrumental tests

S – Strength: does the article posses the potency

it is said to have or must have? Lets prove it!
 Quality Control Testing
Q – Quality: does the article posses the
necessary quality attributes? Colour,
shape,size, etc. Will it perform as expected?
Physical tests – disintegration/dissolution/etc
P – Purity: is the article pure? Related to
potency, is the article free from impure
substances contained within? Why would this
matter?
 Weighing and blending
• With production ready to begin, weighing
materials according to the formulation of each
product is the first step
• Amounts of each ingredient are measured on
precision scales (calibrated regularly)
• Blending takes place immediately after weighing
• Blends are produced according to strict guidelines
in a variety of mixers (will see detail later)
 Weighing
• Weighing errors are very serious
• Check calibration of balance
• Balance must be level
• Record which balance used
• Batch number on ingredients and on
corresponding worksheet must be identical to
that on storage drums brought from
warehouse – why?
 Weighing procedure
• Place weighing bin and liner on centre of balance
• Tare
• Transfer ingredients from original drum into bin and
record weight
• Label weighing bin with ingredient name, batch
number and weight
• Reweigh original drum and record new weight
• Return unused materials
• Why weigh two containers? ie weighing bin and
original drum
 Production
• After completion of a powder blend (in the
case of solid dosage forms) or a liquid blend
(or ointment, cream etc) the product
moves forward to the production areas
• It may go to a capsule filling machine, a
tablet press, etc depending on the product
type
• We will look at the major production
equipment a bit later
 Production
During production of product, samples are
removed at specified times and tested. Why?
What types of tests might be suitable at this
stage?
When production is complete, samples are sent
to QC for a full range of analytical testing in
order to establish that the finished product
has the desired what?
 Coating and polishing

• In the case of capsules and tablets, they

now move on the coating and polishing
steps on their production
• We will discuss this section in more detail
later
 Packaging
• Bottling, blister packs etc
• The product is now packaged in a suitable
container
• We will discuss packaging testing and
packaging lines in more detail later in the
course
 Quality Control-product release

• Before any of the product is shipped, it is

tested in the QC lab to ensure that it meets
specifications
Tests are performed in order to demonstrate
product:
• Identity
• Strength
• Quality
• Purity
 Quality Control-product release
Examples-dissolution, disintegration, friability,
tablet hardness, stability tests, USP tests ( IR,
UV, TLC), assays, house tests, etc are all
performed on the product

Product can be accepted or rejected at this

stage based on test results – specifications
(limits) are set to ensure product meets
acceptable levels of quality
 Quality Control-product release
Note that if an article has to meet certain limits,
by definition the article will exceed (PASS) the
set limits or not reach (FAIL) the set limits

If testing for the presence of a compound(s) in a

test article, by definition that article either will
not contain that compound (negative) or will
contain that compound (positive)

There is a difference !
 Storage
• Back to the warehouse
• Approved or rejected areas
• Approved product is stored until ready to be
shipped
• Special storage conditions needed for many
products (temperature, humidity, etc)
 Shipping
• Product is palletized and shipped to the
customer or distributor
• Do shippers/receivers require higher
educational standards?
• Do shippers and receivers need to be trained
in GMP?
 Personnel
• Throughout this process, all staff must be
qualified and properly trained for whatever
function they carry out
• Safety, GMP, process understanding, equipment
operation – for production staff
• Only authorized staff allowed in production area
• Educational standards, proper protective clothing,
no eating/drinking in the workplace, personal
hygiene etc
 Personnel
• For laboratory staff (analytical),
documentation of training in Safety, GMP’,
GLP, SOP’s, use of Instruments and methods
and educational backgrounds must be
available and up to date.
• Why?
 Training
• Train all new staff
• Retrain continually all existing staff
• Proof of training and written records
• SOP training
• GMP, GLP training and education
Who conducts the training? How is successful
training demonstrated?
 Other documentation
• All records from all stages of production are kept
• Written evidence to show that process has followed
correct procedures
• Verbal instructions NOT acceptable
• All SOP’s must be available at point of use
• Batch production records
• (will detail later)
 Validation department - Preapproval
• Writes and executes validation protocols to
demonstrate that equipment, activities and
processes consistently produce products or
results that meet approved specs
• Validation of instruments is commonly known
as what?
• Verification of effective analytical method use
is commonly known as what?
 Validation department
• Validation conducted on manufacturing processes,
aseptic operations, equipment cleaning procedures,
equipment and computerized systems
• Also conducted on analytical methods used in
laboratories ( usually done by the R&D department.
Why?)
• Must be able to produce all related documentation
for all validation and calibration performed
 Regulatory affairs
• Responsible for knowing the regulatory requirements
for getting new products approved
• Know the government regulatory environment and
how to comply with it
• This is accomplished by keeping current on product
submission requirements (for Canada and the world),
guidances, protocols, recent trends and experience.
• RA will amass all data, oranize it, review it and be
responsible for sending it to the Reg agency
• RA will determine why and whenRegulatory agencies
need to be contacted
• RA will submit annual reports
 Quality Assurance
• Functions as the company’s internal quality auditing
and compliance group (police-ing)
• Most interested in global issues (GMP,GLP,product
quality) and less with the day-to-day testing and
release of products (QC)
• Ensure that company understands and is adhering to
GMP requirements
• Periodically conduct GMP training to personnel and
perform inspections in the company
Product Development -Preapproval
• Responsible for defining the details and specs of the
manufacturing process and final product
• Determine the form of the product, how it will be
produced, the non-medicinal ingredients and the
explicit way to make it
• Identify the critical control parameters ( CQA’s) of
the manufacturing process and write these in to the
final manufacturing documents. How are these CQA’s
determined?
• Will supervise/oversee clinical research activities
related to the proposed product
 Training department
• GMPs and GLP’s require that personnel be trained
in the tasks assigned to them
• These training needs must be identified,
coordinated, delivered and documented by
qualified staff. What defines “qualified” staff?
• Could be done within the department or by the
Training department itself ( depends on what the
training is about)
• The training department consists of personell
who are trained to be trainers. (e.g. HR
people, Communications people)