BTF1623

PROCESS
CONTROL
By: Dr Nadiya Abdul Halim
 TOPIC OUTLINE

Definition of process control and its relation to

1
validation

In-process control: raw material inspection,

2
cleaning and utilities
 PROCESS CONTROL AND ITS RELATION TO
VALIDATION

• Facilities and processes involved in the production of pharmaceuticals influence

product quality.
• The processes include raw materials, equipment inspection, and in-process controls.
• Important in good manufacturing practice.
• Monitors the online and offline performance of manufacturing practice, thus validating
it.
 RAW MATERIAL HANDLING

The dispensing All recipes and Material released into Only

(weighing) of raw formula must be dispensary must be approved
materials is one of the adhered for the tested and approved materials can
critical steps in the required batch-to- by quality control be used in the
production process. batch consistency (QC) operation.

It is critical that this
material is checked by the
dispensing operators and
only this material is used
for production
A rigid control must be Dispensary handles Materials can be
practiced in order to several classes of passed back to the
meet regulatory materials: (i) bought-in warehouse when only a
requirements product, (ii) In-house partial quantity is
manufactured materials, required from a large
(iii) active ingredients container
 Transfer to Production
Supplier Storage Area Demand
• Update computer
• Scan storage inventory
for empty
location

Computer Computer
Delivery Operation Operation
• Bulk
• Sacks • Scan storage
• Company
• Bottles for required
pallet
• Drums materials
• Secure/skin
• Packaging
components
Hold/Quarantine • Identify Transfer Transfer
• Label
• Sample
• Test • Dispensary/
• Fix • Unstack production
Accept/Reject • Repack silo
label
• Stack • Print label
Accept/Reject Collation Dispense • Update inventory-
recorder
• Return to
• Initiate reorder
supplier
procedure
• Order transport
• Restack
• Reload

Typical flow diagram for the handling of materials from supplier to the dispensary
 PROCESS CONTROL
DEFINITION OF VALIDATION
◦ As per FDA Nov 2008: The collection of data from the process design stage
throughout production, establishes scientific evidence that a process is capable of
consistently delivering quality products.
• Validation assures great importance for –quality assurance and cost reduction
• Validation produces product fit for the intended use.
• Quality, safety, and effectiveness may be designed and built into the product.
• Validation is a key element in assuring the quality of the product.
 Process parameters and controls are determined during
the validation of any process or system

It helps to determine the worst case and risks that may

arise during the manufacturing of the quality products

BENEFITS OF Validation helps to investigate the deviations caused

VALIDATION during the process

Deep study and understanding of the system and

equipment are made possible due to the validation

The risk of the regulatory non-compliance is minimized

after the validation.
 A validated process required less process control
and the finished product testing.

Batch to batch variations is minimized due to the

validation of processes, systems and equipment.

BENEFITS OF Reduces the production cost of the product.

VALIDATION
Increases the production of manufacturing facility
due to the minimized rework and rejection

Decreases the chances of the failure of the

batches.
 IMPORTANCE OF PROCESS CONTROL IN MONITORING
ON-LINE AND OFF-LINE PERFORMANCE
• In 2004, the U.S. FDA published aspirational guidance for the industry on process
analytical technology (PAT). It is a system for designing, analyzing, and controlling
the critical process parameters of a manufacturing process that affect the critical
quality attributes of raw and in-process materials and processes.

• The use of PAT to understand and control pharmaceutical manufacturing processes

(as appropriate) to ensure final product quality remains a worthy goal.

• The “PAT umbrella” comprises a broad suite of tools, including analytical, chemical,
physical, microbiological, mathematical, and risk analysis.

• PAT interfaces the process with the analytical instrument and may include a feedback
loop to modify the process conditions based upon real-time analysis. This real-time
data may aid both process control and product quality.
 IMPORTANCE OF PROCESS CONTROL IN
MONITORING ON-LINE AND OFF-LINE PERFORMANCE
◦ The goal of PAT is to consistently generate products with a predetermined level of quality.
◦ The tedious and empirical methods of batch manufacturing, consisting of time and labor-
intensive off-line sampling and analysis, to a more continuous and dynamic method of
manufacturing pharmaceuticals where process sensors and analyzers perform continuous
timely measurements of critical process parameters increasing end product quality levels.
◦ PAT emphasizes process understanding through the identification and real-time monitoring
and control of each of these variables using specific technological tools such as sensors,
analyzers, probes, and optical equipment located at predetermined critical measurement
points that accumulate large data sets.
◦ The resulting data is then analyzed and evaluated using multivariate analysis tools and
transposed into an electrical signal and fed upstream to adjust plant equipment to
compensate for variability in raw materials and equipment to produce a consistent product.
 IMPORTANCE OF PROCESS CONTROL IN MONITORING
ON-LINE AND OFF-LINE PERFORMANCE

• Analyzed data can also be utilized in continuous improvement strategies on

manufacturing processes through simulations and process modeling that identify key
areas within the process that are critical to quality.

• Identification and control of these key areas allow for the precise adjustment of plant
equipment and raw materials allowing for the optimization and automation of the
entire process stream and reducing the dependency on off-line analytics.
 PROCESS MONITORING
OFF-LINE PROCESS MONITORING

• Many of the variables within a process can be measured using off-line process
monitoring techniques, which generally consist of the manual sampling of material
from the process, for analysis in laboratory conditions.

• Off-line process monitoring has been used extensively in the pharmaceutical industry
and involves rigorous quality control (QC) procedures that must be constantly
repeated for each individual process such as sample collection, transport, preparation
and analysis of samples, prior to documentation and archiving of generated report
documents.
 PROCESS MONITORING
OFF-LINE PROCESS MONITORING

• Laboratories are a critical component of current drug manufacturing and require

complex, dynamic scheduling and skilled personnel to cope with the demands of
the supply chain, and can have a major impact on the overall supply chain service
level through its influence on cycle times, delivery times and quality levels.

• The time and labour-intensive nature of off-line laboratory analysis can also be
inefficient and a waste of valuable resources due to lengthy process time frames
from sample collection to results of the analysis.

• The process of off-line analysis also contains a large portion of non-value-added

(NVA) process steps.
 PROCESS MONITORING
ON/IN/AT-LINE PROCESS MONITORING

• The central point of PAT is the generation of product quality information in real-
time and the use of that information to control the critical process parameters of
a manufacturing process.

• Methods of obtaining this information generally depend on the process in

question and its suitability to various process monitoring solutions such as on-line,
in-line, and at-line process monitoring.
 PROCESS MONITORING
AT-LINE PROCESS MONITORING

• At-line process monitoring consists of the movement of process dedicated testing

equipment to the production line.

• The close proximity of the test equipment to the process reduces the time lag resulting
from the transport and documentation of samples from the process to the laboratory.

• This allows for a reduction in the reaction time to perform the necessary counter
measures to ensure product end quality.

• It is generally observed that at-line process monitoring equipment, while more robust and
insensitive towards process environments is less precise than off-line lab test equipment.
 PROCESS MONITORING
IN-LINE PROCESS MONITORING

• In-line process monitoring requires no sampling and takes timely measurements of

material in the process stream through use of a variety of either invasive sensors such as
immersive probes or non-invasive sensors such as optical sensors.
 PROCESS MONITORING
ON-LINE PROCESS MONITORING

• On-line process monitoring involves the redirection of a sample of material through

automatic extraction systems or recirculation loops, where the sampled material is
conveyed to the sensor locations and either returned to the process stream or safely
disposed of.

• This method is generally used in instances where modification required for the
integration of in-line process monitoring is either too costly, impractical, or where a
higher degree of precision is required, as on-line process monitoring offers an
opportunity to condition the sample before analysis to achieve higher quality results.
 THANK YOU
&
ALL THE BEST IN YOUR
FINALS!