CHAPTER-9

EQUIPMENTS AND RAW MATERIALS

CONTENTS:

9.1 Equipments
9.1.1 Design and Construction
9.1.2 Location
9.1.3 Installation
9.1.4 Cleaning and Maintenance
9.1.5 Qualification and Calibration
9.1.6 Documentation
9.1.7 Purchase Specifications for Equipment
9.2 Raw Material
9.2.1 Purchase of Materials
9.2.3 Receiving, handling and storage of materials
9.2.4 Sampling
9.2.5 Testing of Samples
9.2.6 Approval/Rejection of Materials
9.2.7 Labeling
9.2.8 Using Approved Materials
9.2.9 Handling Rejected Materials
9.2.10 Containers and Closures
9.3 Questions

(1.1)
Chapter-9 1.2 Pharmaceutical Quality Assurance

9.1 Equipment
 It may be defined as a physical entity which is used to carry out a
general or specific activity in the phase of plant.
 It can be a single piece for example tablet compression, weighing
machine etc.,
 Equipment is a integral system that is group of equipment come
together to perform single activities.
 The quality of the manufactured product much depends on the
suitability and level of the technology of the equipment used. Since it is
major requirement in the manufacture of the pharmaceutical product.
Life stages of Equipment:
Equipment management in the pharmaceutical industry has a life cycle and
the GMP requirement cover the life cycle of equipment.
It consist of following stages:
• Decision to purchase equipment
• Purchase of equipment
• Qualifying, installing, and validating equipment
• Using the equipment
• Preventive maintenance and revalidation
• Replacing the equipment Selection of Equipment
• Operating criteria (size, speed, effectiveness)
• Availability of spares and servicing.
• Cost
• Availability of process controls
• The frequency and ease of maintenance will significantly impact on
productivity and even quality.
• Equipment breakdown during processing could adversely affect quality.
Included in the maintenance evaluation should be the cleanability of the
equipment.
• This will involve accessibility to the parts to be cleaned and the relative ease
of disassembly and reassembly process.
• Environmental issues are important constraints
• Construction material and design.
• The type of process controls such as automatic weight adjustments on
tablet.

Purchase Specifications for Equipment:

Pharmaceutical industry equipment is quite expensive and therefore,
selecting the right equipment is a critical process.
Some of the most important factors to be considered in making this decision
are as follows:
Chapter-9 1.3 Pharmaceutical Quality Assurance

• Desired output capacity: Equipment purchased must be capable of

processing desired quantity of product at the desired speed of operation.
Understanding one’s production scale in terms of batch size requirements and
comparing this with the load capacity of the equipment being considered is an
important first step when choosing equipment.
• Product characteristics: The nature of the product, its reactivity, any
special conditions necessary to ensure retention of its safety, efficacy and
quality are all important while choosing equipment.
• Ease of operation: Equipment operation must be simple, and not involve
complex maneuvers or require special skills. The equipment must be easy for
the operator to operate after receiving proper training. It is important to strike
a balance between efficiency of performing the given operation and ease of
operating the equipment. Digitally enabled equipment can help to manage
manufacturing process better; it will however require special skills for
operation and the capacity of one’s workforce to learn those skills must be
considered.
• Ease of cleaning and maintenance: Equipment will require regular
cleaning and special, more thorough cleaning between batches of different
products. The time used for cleaning is time lost from the production run. So
equipment must be easy to clean (either in-place, or by disconnecting and
taking to a special cleaning area). It must also be easy to maintain and not
require frequent maintenance activities which again are a time-consuming
process.
• Equipment supplier: When buying equipment, price is often considered an
important criterion, but it is more important to focus on the quality
parameters on offer and the industry reputation of the supplier and how
reliable their product is, their customer service, and their capability to provide
equipment troubleshooting service when necessary.
Factors consideration while purchasing the materials
• Right source
• Right quality
• Right quantity
• Right price
• Right time
• Right mode of transportation

MAINTENANCE
The requirement that equipment be properly maintained is based on the
assertion that this ensures the constant performance of equipment to
specifications and that it reduces the likelihood of an unexpected breakdown
and consequent loss of data.
Maintenance may be carried out in two quite distinct ways:
Chapter-9 1.4 Pharmaceutical Quality Assurance

• Preventive maintenance; when parts are changed regularly based upon

the expected life of the part concerned. Planned maintenance of this type
may be a useful precaution for large items of equipment or items that do not
possess suitable backup or alternatives. Regular preventive maintenance
therefore reduces the risk of breakdown.
• Curative maintenance; when repairs are made in the case of a fault being
detected. This approach particularly applies to equipment such as modern
computer driven analyzers or electronic balances that do not easily lend
themselves to preventive maintenance. Back up for vital equipment should be
available whenever possible as well as back up in the event of service failures,
such as power cuts. A laboratory should have the ability to continue with
essential services to prevent animals or data being lost, and studies
irretrievably affected. For example, a laboratory carrying out animal studies
may, as a minimum, need a stand-by generator capable of maintaining the
animal room environment.
Early warning that equipment is malfunctioning is important; hence the
checking interval should be assigned to assure this. Alarms are very valuable,
particularly if problem occurs at a time when staff are not present in the
laboratory.

Raw Material
Between 1995 and 1996, Haiti saw incidents of around 80 children dying after
ingesting a cold-and-cough syrup. An investigation fixed the responsibility on
glycerol in the product being contaminated with diethylene glycol. This and
other such incidents highlight the need for drug product manufacturers to pay
attention to the quality of starting materials they use. While active
pharmaceutical ingredients (APIs) may be manufactured under cGMP (current
Good Manufacturing Practices), excipients may not be so produced, especially
the ones commonly used in other industries like cosmetics or food.
This makes it even more important to ensure these excipients are of a grade
suitable for pharmaceutical use. Containers and closures must also be
evaluated because they play a vital role in ensuring product stays stable and
safe throughout the shelf life.

All materials that used into the manufacturing of a finished drug (even though
it may be present in final product e.g. Certain solvents etc.,) and which are
consumed by person using it are called as raw materials. Raw materials can
be either active drug or inactive substances. E.g. Hard gelatin capsules: even
though it is used to fill the blend of medicine, it is not considered as package
materials because it is consumed by person using medicines.
Purchase Specification
Chapter-9 1.5 Pharmaceutical Quality Assurance

Written guidelines that precisely define the operational, physical and/or

chemical characteristics, as well as the quality and quantity of a particular
item to be acquired.
Mode of purchasing
• By Inspection
• By Sample
• By Description of brand
• By Grading
Steps involved in Purchase Specification
• Purchase requisition
• Selection of Supplies
• Inviting Quotation
• Placing the order
• Receiving the Material
• Checking the Material
• Recording of bills in books
• Releasing the payment to the supplier
• Staff involved in purchasing have a particular and thorough knowledge of
products and suppliers.
• Raw material can be purchased from supplier named in relevant
specifications or directly from producer.
• Specification established by manufacturer for the starting materials be
discussed with suppliers.
• Pharmacist or chemist, who is familiar with quality requirement of various
material purchase department can be head of purchase department.

1. Purchase of Materials: Purchasing must be done by staff with a

thorough knowledge of those materials and their suppliers. Materials
must be procured only from approved suppliers who have consented to
provide materials in keeping with quality specifications of the drug
product manufacturer. It is advisable for pharmaceutical manufacturers
to enter into contracts with specific vendors after performing a vendor
audit that provides an assurance of raw materials and packaging
materials of the desired level of safety and meeting quality standards.
2. Receiving, handling and storage of materials: Specific written
procedures must be prepared to describe how materials (both drug
components and drug containers and closures) will be received,
identified, stored, handled, sampled, tested, and accordingly approved
or rejected, and these procedures must be followed as written.
When receiving materials, the consignment must be visually examined
and the labels checked to confirm the content, quantity, integrity of
seals and to verify that there is no damage or contamination. Any
Chapter-9 1.6 Pharmaceutical Quality Assurance

damaged containers found must be separated, and details recorded

and informed to the supplier.
The materials must be stored under quarantine until samples have
been drawn and tests have been performed. They must not be issued
for use before approval.
Handling and storage of all materials in the storage area must be in
such a way that there is no contamination. Boxes or bags holding
containers and closures must be stored off the floor. The storage must
be done in a way that suitable space is left for proper cleaning and
inspection of the materials.
3. Sampling: Representative samples must be drawn from each
shipment of each lot. If different batches are present in a single
shipment, samples must be drawn from each of those. The quantity
must be sufficient to perform all required tests and reserve when
specified. Statistical criteria must also be used to determine quantity of
samples drawn. Containers must be cleaned before sampling to avoid
introducing contamination and resealed after sampling to prevent
contamination of the contents, and appropriately labeled to show
sample has been taken. Samples must be drawn from the bottom,
middle and top of the containers, and marked accordingly. Sample-
holding containers shall be labeled with details of name of material, lot
number, container number, date of sampling, and name of person
collecting the sample.
4. Testing of Samples: At least one specific test must be performed to
verify the material’s identity. Tests must be carried out to determine
conformity with predetermined specifications for quality, strength, and
purity. In case materials are supplied along with a certificate of analysis
by the supplier, the materials may be used without sampling and
testing, provided the supplier is a reliable, validated vendor and at
least one specific identity test has been performed and mentioned in
the certificate. Materials that are liable to contamination with
adulterants, or insect infestations or filth must be examined for such
contaminants. If materials are prone to microbial contamination,
microbiological tests must be performed to test for it.
5. Approval/Rejection of Materials: All materials that meet the
manufacturer’s quality requirements of identity, quality, purity and
strength and other tests are to be approved for use. Materials not
meeting these requirements must be rejected.
6. Labeling: Labels must carry the name of the product, the company’s
unique reference code, manufacturer’s name and address, and their
assigned batch number. It must also state the status of the contents
(For example – “Sampled”, “Quarantined”, “Approved” and
Chapter-9 1.7 Pharmaceutical Quality Assurance

“Rejected”), manufacturing and expiry dates and re-test date. When

attaching such labels, care must be taken that original information on
the supplier’s label is not lost. Approved materials must be so marked
while rejected materials must be conspicuously labeled and stored in a
separate area to avoid chances of mix-ups or misuse.
7. Using Approved Materials: Approved materials must be stored
properly and issued for use in a way such that earliest approved stock
is used first before more recently approved stock. Many companies use
a FEFO (First Expire First Out) system for stock rotation. Another
deciding factor is that the drug product’s shelf life must not exceed the
shelf life of the APIs.
If materials have been stored for very long period without usage, or if
they have been exposed to any condition that may have an adverse
effect on their quality or safety, they must be re-tested for the same
parameters as the initial test. Results of the re-test must be used to
determine if the materials are approved or rejected.
8. Handling Rejected Materials: Rejected materials must be identified
with appropriate labels and kept in quarantine until safely disposed.
Care must be taken to prevent use of such materials in manufacturing
operations.
9. Containers and Closures: Containers and closures are used for
packing of drug products must not be additive, reactive, or absorptive.
This is important to ensure they do not cause a change in the identity,
safety, quality, strength, or purity of the drugs beyond specifications.
Closures and containers must be capable of protecting the drug
product from external conditions that may cause its contamination or
deterioration. Containers and closures must be clean and if required,
sterilized to remove contamination by microorganisms and pyrogens.
Note: If computerized storage systems are used, they must be fully
validated to prove they work reliably.
Maintenance of Stores for Raw Materials:
Storage Area Specifications:
 Sufficient Capacity
 Clean, Dry, and maintained within acceptable temperature limit
 Designed and equipped reception area
 Ensuring of quarantine status
 Segregation for storage of rejected, recalled, or returned material.
 Safe and secure area for narcotics and highly active, dangerous, and
risky material ▪ First in First out Rule (FIFO)
▪ First expiring First out (FEFO)
Storage conditions:
 Room temperature should be 300C and Relative Humidity 60%.
Chapter-9 1.8 Pharmaceutical Quality Assurance

 Air conditioning Storage 25±20C and Relative Humidity 45-55%

 Low temperature Storage 2-80C.
 Separate area for sterile product storage in air condition.
 Light sensitive material in amber color container
 Hermetically sealed container.
Labeling of material in storage area:
 Designated name of product and internal code reference
 Batch no. given by supplier
 Status of content
 Expiry date or date beyond which retesting is necessary
 During fully computerized system used, labeling with all above
information need not to be necessary.
Check list before storage
 Integrity of package and seal
 Correspondence note for the order, delivery, and supplier’s label.
Check list during storage
 Separation of rejected, recalled, quarantine, on test, packaging
materials.
 Quality of materials
Released by Quality Control Department only.

Maintenance of raw materials

 Receipt of materials
I. Visual examination for all Incoming materials
• Intact container, lids, seals
• Evidence of any physical damage to the containers
• Evidence of rodents or insect specification
• Proper labeling in specified manner
II. Points to be checked and recorded
• Date of receipt
• Name of product, batch no., control no., assigned by manufacturer
• Quantity received against document
• Name of supplier
• Purchase order no.
• Excise gate pass etc.,
Storage of materials
I. External cleaning of container after receiving and before storage
II. Quantity verification
III. Storage in specified area as per condition
▪ A.C./Cool/Cold/Low Humidity area
IV. Storage as per quarantine status of the material
▪ Received, Sampled, Approved, Rejected
Chapter-9 1.9 Pharmaceutical Quality Assurance

Sampling of Materials
• Sampling responsibility
• Sampling formula used
• Method of sampling e.g. top, middle, bottom sample is required
1. Material wise quantity to be sampled as per requirement of analysis
2. Sampling room specification
• Temperature
• Relative Humidity
• Air pressure
3. Specific requirement for specialized product
• Sterile products
• Poisons or potent drugs
• Beta lactam products
• Sex hormones
• Steroids
4. Opening and closing of containers before and after sampling
5. Dress code of people doing sampling
6. Cleaning, Drying, Sanitization, of the utensils used for sampling
7. Identification of sampled containers
8. Sampled containers and sample collection containers should have following
details:
• Name of materials and manufacturer
• Batch no. for manufacturer
• Date of sampling
• Name & sign of Sampler etc.,
Control on Raw Materials:
 Quality assurance should make periodic sanitation and follow up to
assure that deficiencies are corrected.
 Raw materials with abnormally high microbial contamination may have
to be subjected to a sterilization procedure like heat treatment,
radiation, or crystallization from a bactericidal solvent like alcohol.
 Warehouses are the first operational area observed by the auditor to
check operational compliance with cGMP & FDA regulation.
 Following elements need to be considered when establishing
warehouses operation: cleanliness, floors, lightings & SOPs.

Questions
1. List out the important factors to be considered in equipment design and
location.
2. Name and explain the 3 most important criteria that matter when
purchasing equipment.
Chapter-9 1.10 Pharmaceutical Quality
Assurance

3. Describe the procedures followed for sampling and testing of raw materials.
4. Write a note on labelling of raw materials.
5. Explain the steps in the approval/rejection of raw materials by the QC
department.
location, design, construction and layout of premises is vital part of the Good
Manufacturing Practices (GMP) regulations.