This document discusses good manufacturing practices related to sanitation, prevention of cross-contamination and mix-ups, and processing of intermediates. It emphasizes that premises must be designed and maintained for good sanitation. Strict procedures and controls are needed to prevent cross-contamination between products during production through measures like segregation, air handling, cleaning, and labeling. Intermediates must also be stored and handled carefully according to specifications. Thorough cleaning and changeover procedures are required when switching between products to avoid mix-ups.

1. SANITATION OF MANUFACTURING PREMISES ;
MIX-UPS & CROSS CONTAMINATION,
PROCESSING OF INTERMEDIATES
Presented by
M .Manoj Kumar
H .t.no 636217885003
Under guidance of
Dr sandip sen Ph.D.
DEPARTMENT OF PHARMACEUTICAL SCIENCES
SRIKRUPA INSTITUTE OF PHARMACEUTICAL
SCIENCES
(Affiliated to osmania university)
(Approved by PCI;AICTE)

2. MANUFACTURING OPERATION AND CONTROL
 All manufacturing operations shall be carried out under the
supervision of technical staff approved by the Licensing
Authority
 Precautions against mix-up and cross contamination-
1. By proper air handling system, pressure differential,
segregation, status labelling and cleaning. Proper records and
SOP there of shall be maintained.
2. Processing of sensitive drugs and cytotoxic substances in
segregated areas
3. Proper labelling of materials and equipments

3. 4.Packaging lines shall be independent and adequately segregated
5.All printing and overprinting shall be authorized in writing
6.The manufacturing environment maintained at the required
levels of temperature, humidity and cleanliness

4. Sanitation premises
 Premises used for the
Manufacturing of products
Shall be of suitable design &
Construction so as to facilitate
Good sanitation.
 Ensure that the premises is
Neat & clean and is free of
Puddled water.
 Floorings of the equipment
Washing rooms could be sloped
To allow draining of water.

5.  Hand washing & well ventilated toilet facilities and changing
rooms shall be provided for personnel at suitable locations

6.  Suitable locker facilities shall be provided at appropriate locations
for the storage of employees clothing & personal property.

7.  The preparation , storage and consumption of food and
beverages shall be restricted to specific areas , such as meal
rooms & canteen.
 Facilities in such rooms must meet sanitary standards.
 Meal rooms & canteen rooms shall not have direct access to
controlled areas (ex: production area and areas used to store
materials used for production & finished products.
 Waste material shall not be allowed to accumulate. It shall be
collected in suitable receptacles for removal to collection
points outside the buildings and disposed of safely and in a
sanitary manner at regular & frequent intervals.
 Ensure that there are no harborages & breeding areas for pests
at the site

8. Rodenticide, insecticides, fumigating agents & sanitizing materials
used must not contaminate equipment, raw materials, packing
materials, in process materials or finished products. There shall be a
pest control programme , documents such as layout , trending and
expectations.
 Ensure that properly closed areas are used for storage of waste
materials.

9. There shall be written procedures assigning responsibility for
sanitation & describing cleaning schedules, methods , equipment
,materials to be used & facilities to be cleaned in sufficient detail.
Such written procedures shall be followed
and results shall be documented.
Pests are not allowed within the vicinity of the manufacturing plant

10. Cross contamination:
 Contamination of a starting material or intermediates or
finished products by another material or product during the
production is called cross contamination.
 The main sources of cross contamination are human beings,
equipment, air, raw materials and water.
 Human beings serve as carriers for microbial contamination
like staphylococcus species during manufacturing process. This
may also serve for introducing microbial species into
medicines which may be life threatening and may cause
allergic reactions. Sometimes the microbes may be resistant to
antimicrobials.
 Use of such cross contaminated drugs may cause sepsis in the
patients taking them

11.  Handling of Penicillin products need special caution as some
personnel may be sensitive to them. These may also be cross
contaminated during campaign process and may cause severe
anaphylactic reactions
 In cases where in same production line more than one drug is
manufactured which causes cross contamination
 Air carries many organic & inorganic particles which may
contaminate the product and degrades its quality
 Water may also contamination when the pipe that carries water
is not sanitized
Preventive measures
 To prevent cross contamination the personnel should be taught
of gowning practices and maintaining of personal hygiene.
 The personnel should wash their hands regularly.

12.  Penicillin like sensitive products should be handled carefully as
they may cross contaminate and cause fatal effects. Hence there
production should be carried in dedicated facilities
 Separation in time along suitable cleaning procedures ensures
that cross contamination doesn’t occur when more than one
product is produced in same line of production
 Proper air filtration systems should be installed to prevent
contamination by air with aptly designed air supply extraction
system. Filters should be cleaned regularly
 Pipes should be sanitized as per the written procedures

13. Mix Up
 Mix ups can be defined as presence of undesired material into
desirable material ,which can generally be visible seen
Ex: paracetamol mix with diclofenac
Tablet of one product into another ,which having different
size , shape
Sources
 Mix ups occur during labeling, packing, line clearance problems or
receipting
Preventive measures
 Physical segregation of the products with proper labeling and
identification details
 Proper design for the flow of materials
 Packing should be done in compliance with the written procedures

14. Good manufacturing practices to avoid Contamination
& Mix up
 Procedures should be clear and should be followed to achieve
the objective of quality for the product.
 All the procedures regarding materials and products regarding
their receipts, sampling, storage, cleaning, labeling, quarantine
and dispensing should be in accordance with written procedures
 Precautions should be taken so no deviations from procedures
and instructions occur and if deviations occur then they should
be treated as said in procedures
 To avoid discrepancies from acceptable limits yields and
quantities should be checked

15.  Operations on different products should not be conducted in the
same premises to prevent cross contamination or mix up
 At each step in processing every material and equipment
should be labeled with their indication, batch number and
strength. If applicable then the stage of production should also
be mentioned and few cases also mandate the name of the
previous product that is processed.
 The production premises should be accessed by only
personalized personnel
 Non medicinal products should not be produced in places
where the equipment and pharmaceutical products are
produced.
 Care should be taken so that the in process controls don’t
impact the product quality or any other product as in case of
mix up or cross contamination

16. INTERMEDIATE PRODUCTS
 Intermediate products should be kept under appropriate
conditions.
 Intermediate products purchased as such should be handled on
 receipt as though they were starting materials.
Specifications for intermediate and bulk products
 Specifications for intermediate and bulk products should be
available. The specifications should be similar to specifications
for starting materials or for finished products, as appropriate.
 Before any processing operation is started, steps should be taken
to ensure that the work area and equipment are clean and free
from any starting materials, products, product residues, labels or
documents not required for the current operation.
 Any necessary in-process controls and environmental controls
should be carried out and recorded.

17.  Means should be instituted of indicating failures of equipment or
of services (e.g. water, gas) to equipment. Defective equipment
should be withdrawn from use until the defect has been rectified.
After use, production equipment should be cleaned without delay
according to detailed written procedures and stored under clean
and dry conditions in a separate area or in a manner that will
prevent contamination.
 Time limits for storage of equipment after cleaning and before use
should be stated and based on relevant data.
 Containers for filling should be cleaned before filling. Attention
should be given to avoiding and removing any contaminants such
as glass fragments and metal particles.
 Any significant deviation from the expected yield should be
recorded and investigated.

18.  Checks should be carried out to ensure that pipelines and other
pieces of equipment used for the transportation of products
from one area to another are connected in the correct manner.
 Pipes used for conveying distilled or deionized water and,
where appropriate, other water pipes should be sanitized and
stored according to written procedures that detail the action
limits for microbiological contamination and the measures to
be taken.
 Measuring, weighing, recording, and control equipment and
instruments should be serviced and calibrated regularly. And
records maintained. To ensure satisfactory functioning,
instruments should be checked daily or prior to use for
performing analytical tests. The date of calibration and
servicing and the date when recalibration is due should be
clearly indicated on a label attached to the instrument.

19.  Repair and maintenance operations should not present any
hazard to the quality of the products.
 All IPQC checks should be carried out at pre - determined
stages and deviation should Be recorded and investigated
 Access to production area should be restricted only to
authorized person.
DOCUMENTS REQUIRED
1] B.P.C.R for each batch produced
2] calibration records

20. REFERENCES:
1. Pharmaceutical quality assurance by manohar A.
potdar
2. http://apps.who.int/medicinedocs/en/d/Js5517e/20.4
.html
3. https://www.slideshare.net/parth241989/gmppremis
es-112070804006