Bulk and Sterile Manufacturing

• Bulk Compounding
– Mainly those drugs which are not commercially
available and modified formulations intended for
clinical/ investigational use
• Sterile preparation
– Sterile topical solutions, Small volume injectable,
I/V admixtures, TPN and special parenterals for
clinical/ investigational use
 Benefits
• Development of a close relationship between
physicians and pharmacists
• Promote economy for hospital
• Operation of formulary system
• Making drugs available that are not commercially
available
• Opportunity to develop new pharmaceutical
formulation
• Enhancing the prestige of pharmacist
 Control Systems
Decision of bulk and sterile preparation in
hospital depends upon certain control systems.
– Manufacturing Process Control
– Quality Control

– Budgetary Control
 Manufacturing Process Control
• Responsibility of pharmacist to make a
product that meet the high pharmaceutical
standards.
• Good manufacturing practice should be
followed
• Identity, strength, purity and quality control
• Sufficient packaging and labelling control.
• Palatability and stability should be considered
 Quality Control
• Validation
• Quality Control of Raw material
• Quality control of Instruments used
• Quality Control of Area to ensure specified
pharmaceutical environment
• Quality Control of Finished Product (including
label)
 Budgetary Control
• Also called economic consideration
• Regulate economic aspects of manufacturing program
• Feasibility of manufacturing depends upon budget.
Includes
– Manufacturing requirements
– Material requirements
– Manufacturing capacity
– Manufacturing staff
– Operating costs
• Manufacturing Requirement
– Includes quantitative estimation of manufacturing
frequency and the number of particular drugs to be
manufactured per annum
– Can be estimated in terms of rate or production
volume, batch quantity or manufacturing frequency.
– Depends on consumption rate
• Material requirement
– The estimated manufacturing requirements provides a
basis for the prediction of material requirements
– Includes raw material, containers, labels, ancillary
materials, boxes.
• Manufacturing capacity
– Availability of particular equipment and
manufacturing capacity of each equipment must be
considered
– Most of the times selection of equipment is based
upon economy and its multiple function performed
by single instrument.
– Selection of such equipment which is capable of
multifunction also prevent space allocation
problem
• Manufacturing Staff
– It is an important consideration in bulk and sterile manufacturing.
– Pharmacist as supervisor and supportive personnel
– Number of personnel should be optimum
– Too many personnel will increase the cost of manufacturing
– Too less personnel-------------
• Operating Cost
It includes
– Direct cost
• Cost being spent on purchase of materials
• Labour cost
– Indirect cost
• Maintenance of machinery
• Maintenance of building
• housekeeping
 Sterile Preparations
• It requires the same controlled environment as
that of bulk Manufacturing except additional
stringent environmental control is needed.
• Besides various control discussed
environmental control is also needed.
 Intravenous Additive Program
• Pharmacist is responsible for
– Preparation of final product under aseptic
condition
– Judicious choice of additive and mixing techniques
to avoid interaction
– Appropriate labelling
• Such products are prepared in aseptic
environment using laminar flow hood
Laminar Flow Hood
 Preparation of I/V additive solution

• Physician prescription order

• Label preparation (information on labels)
• Affixed upside down to the container----Why?
• Preparation is carried in laminer flow hood
• Final inspection before handing over
 TPN and Cytotoxic Drugs
• Preparation of TPN is the integral part of sterile preparation
• Stability and compatibility
• Facility and environment
• Personnel and training
• Documentation
• Manufacturing procedures
• Collection of materials and preparation
• Formulation
• Inspection
• Labelling and packaging
• Storage