Auditing of capsule, sterile production and packaging

Topic:-Capsule, sterile production, and packaging
Subject Name :-Audits & Regulatory Compliance
Subject Code:-MQA20T
Presented by:- Guided by :-
Rohit Mittal R. Dr. D. P. Damahe
2ndsem M.Pharm Associate Professor
Department of Pharmaceutical Quality Assurance
Smt. B. N. B. Swaminarayan Pharmacy College, Salvav– Vapi

Content
• Introduction
• Capsule
• Sterile production
• Packaging
• Question
• References
7/2/2022 Mittal Rohit Smt.BNB SPC,Salvav-vapi 2

Vendor audit
• A vendor audit is performed for a company that aims to attain an objective assessment of its contractors’ or
vendors’ compliance to the terms, conditions and intent of the contracts and/or agreements between two
entities.
• Vendor audits are necessary to effectively reduce cost and improve quality control throughout the procure-
to-pay system.
• The primary areas of assessment in a vendor audit are vendor viability, management responsibility, system
accuracy and data integrity, the latter of which being of particular importance in the modern business
environment.

Vendor audit
• The vendor audit provides assurance that the system is operating effectively and efficiently in the recording
and payment of goods/services of appropriate quality, at the right time, in sufficient quantity and at an
acceptable price.
• As a result, the reporting of the vendor audit is strictly to management, providing an opinion of the entity’s
operating processes and controls as well as third party’s adherence to the standards set forth by the
organization.
• The most desirable result of vendor audits is to achieve some level of cost reduction, which is achieved
through not only direct cost reduction, but also process improvements and risk mitigation to help prevent
future problems.

Vendor audit
Benefits of vendor audit
• Cost saving
• Process improvement
• Risk reduction
• Relationship building
• Helps management to achieve objectives

Supplier audit checklist
• A supplier audit is a formalized system of evaluating the reliability and competency of suppliers and
vendors to deliver quality service.
• Auditing suppliers are foundational in establishing strong customer-supplier relationships. Supplier audits
aim to assess and promote smooth operations in key business areas such as manufacturing, engineering,
invoicing, QA, and shipping.

• Supplier audit checklist is used to audit your supplier’s facility, record if the supplier meets the criteria, and
evaluate its suitability to be your supplier. The checklist can serve as a guide for the inspector to evaluate
the following areas:
• Management Responsibility
• Infrastructure, Sanitation, and Maintenance
• Traceability and Crisis Management
• Control of Materials
• Handling, Storage, and Delivery
• Calibration, Measuring, and Test Equipment
• Food Safety and HACCP Systems
• Manufacturing Quality Systems
• Regulatory Compliance

• The following is a list of benefits that can be realized by conducting a supplier audit:
• Adopt Organizational Quality Standards
The quality of your final product strongly depends on the quality of your suppliers.
• It makes sense to enforce the same set of standards across the supply chain to ensure consistency.
Compliance with customer quality management system requirements, industry standards and regulations
can be automatically tracked and measured within an electronic quality management system.
• A quality audit will uncover any noncompliant material and will set a plan in motion to ensure conformance
to industry standards.

 Practice Effective Document Management
A supplier audit will ensure all quality documents related to a supplier are in place and properly archived.
Important records for inspections, non conformances and supplier approvals are verified during the audit
process.
 Identify Areas of Potential Risk
Complete traceability and product genealogy of every part, subassembly and final assembly ensures
operational excellence throughout the product lifecycle. A supplier audit will identify any gaps in the
supplier quality process, manufacturing process, engineering change process, and shipping process,
allowing a manufacturer to close the loop on any deviations, non conformances or delays.

• Recover the Cost of Poor Quality
A supplier audit provides a comprehensive look at supply chain performance to identify winners and losers.
Suppliers can have a significant effect on the cost of quality. Many of the factors that contribute to the Cost
of Poor Quality (COPQ) stem from supplier-related activities.
• Improve Supplier Communication
A supplier audit improves collaboration between the manufacturer and its suppliers. Visibility into supplier-
related activities provides an open exchange of information and complete transparency on both sides of the
relationship.
• Improve Customer Satisfaction
A supplier audit clearly defines quality objectives and enhances the process of bringing high-quality goods
to market. Investigation into areas of risk identifies any adverse safety occurrence before it happens. With
firm compliance and quality standards in place, customer satisfaction with the end-product is sure to
improve.

Capsule
• Capsules are defined as unit solid dosage form of medicaments available as small containers (shells) made
• up of gelatin enclosing accurately measured drug substances.
• The term capsule is derived from the Latin word capsula, meaning a small container. Capsule occupy a
significant position in the drug development.
• They are often believed as the primary oral dosage form because of their manufacturing process compared
to other dosage forms.
• Gelatin has the property of disintegrating when it comes in contact with water, thereby releasing the
medicament completely. Instead, of gelatin, denatured gelatin, methyl cellulose and polyvinyl alcohol can
also be used to make the capsule shells.

Capsule
 There are mainly two types of capsules which are:
• Hard gelatin capsules
• Soft gelatin capsule
• Hard gelatin capsules which contain dry, powdered ingredients or miniature pellets made by e.g. processes
of extrusion or spheronization. These are made in two halves: a smaller-diameter “body” that is filled and
then sealed using a larger-diameter “cap”.
• Both of these classes of capsules are made from aqueous solutions of gelling agents, such as animal protein
(mainly gelatin) or plant polysaccharides or their derivatives (such as carrageenans and modified forms of
starch and cellulose).
• Other ingredients can be added to the gelling agent solution including plasticizers such as glycerin or
sorbitol to decrease the capsule's hardness.

Manufacturing Process for Capsule
Sampling of raw material Packaging
Analysis of raw material Finished good warehousing
Dispensing of raw material QA release for dispatch
Sifting of ingredient
Mixing and lubrication
Encapsulation and polishing
Inspection
Manufacturing

Audit for Capsule
 Manufacturing
• Equipment
• instrument calibration
 Packaging
• Packaging material
• Packaging operation
• Labels and labelling operation
 Reprocessing
 Finished product control
 Warehousing/distribution
 Environmental health and safety

Audit for Capsule
 Auditing an Oral Solid Solution Area
• Verify equipment identified in the batch record against field equipment is the same, noting calibration and
maintenance status.
• Determine if equipment is used for manufacturing more than one product.
• Determine that equipment is cleaned thoroughly by reviewing the equipment use, maintenance and
cleaning log.
• Determine how cleaning is documented.
• Ensure that critical equipment is qualified according to the facility’s established IQ/OQ procedure.
• Ensure that sterilization and cleaning has been validated.
• Review calibration status of balances.

Audit for Capsule
 What should be audited?
• An oral solid or oral solution/suspension audit should include an examination of the all of the six GMP
Systems:
• Quality
• Facility and Equipment
• QA Laboratory
• Material Handling
• Production
• Packaging and Labeling
• This training module will not include detailed information about the Packaging and Labeling system and
the Laboratory system for oral dose products. In-process control laboratories are often different from other
laboratories and part of the production area and in-process controls may be performed by operators. As an
auditor you need to cover these laboratories as including training of the staff.

Audit for Capsule
 Auditing an Oral Solid Solution Area
• Verify equipment identified in the batch record against field equipment is the same, noting calibration and
maintenance status.
• Determine if equipment is used for manufacturing more than one product.
• Determine that equipment is cleaned thoroughly by reviewing the equipment use, maintenance and
cleaning log.
• Determine how cleaning is documented.
• Ensure that critical equipment is qualified according to the facility’s established IQ/OQ procedure.
• Ensure that sterilization and cleaning has been validated.
• Review calibration status of balances.

Audit for Capsule
 Materials Receiving Area
• Ensure that approved procedures are in place for inspection, sampling, testing and release of incoming
materials (raw materials, packaging components, excipients, etc).
• Confirm, through observation, that procedures are being followed.
• Determine if raw materials, intermediate products, or final products require special storage conditions or
handling procedures.
• If special storage is needed, confirm that controls are in place to ensure these conditions are met
throughout the holding, manufacturing, packaging, and distribution process.
• Review calibration status of balances in the weighing area.

Audit for Capsule
 Utility systems
• Determine what type of water is used in the process and in equipment cleaning.
• Determine if any compressed gases or other utilities are used in the manufacturing process.
• Ensure that if any utilities contact the product they have been qualified.
• Ensure that if filters are used in the process they have been qualified or validated according to the
established approved facility procedures.
• Verify that there are air pressure differentials between corridors to process rooms as described in an
approved facility SOP and that they are documented.
• Ensure that there are dust filters in place within the air system and that they are regularly maintained and
recorded on a preventative maintenance schedule.
• Vacuum system.

Checklist for Capsule

Sterile products
• The manufacture of sterile medicinal products is a complex activity that requires additional controls and
measures to ensure the quality of products manufactured.
• Accordingly, the manufacturer’s Pharmaceutical Quality System (PQS) should encompass and address the
specific requirements of sterile product manufacture and ensure that all activities are effectively controlled
so that all final products are free from microbial and other contamination.
• The manufacture of sterile products should be carried out in clean areas, entry to which should be through
airlocks for personnel and/or for equipment and materials.
• Clean areas should be maintained to an appropriate cleanliness standard and supplied with air which has
passed through filters of an appropriate efficiency. The various operations of component preparation,
product preparation and filling should be carried out with appropriate technical and operational separation
measures within the clean area.
• For the manufacture of sterile medicinal products 4 grades of clean room can be distinguished.

Sterile products
• Airlocks should be designed and used to provide physical separation and to minimize microbial and
particulate contamination of the different areas, and should be present for material and personnel moving
from different grades, typically airlocks used for personnel movement are separate to those used for
material movement.
• They should be flushed effectively with filtered air. The final stage of the airlock should, in the at-rest state,
be the same grade as the area into which it leads. The use of separate changing rooms for entering and
leaving clean areas is generally desirable.
a) Personnel airlocks. A cascade concept should be followed for personnel In general hand washing facilities
should be provided only in the first stage of the changing rooms.
b) Material airlocks (used for materials and equipment).

Sterile products
• In order to establish a robust environmental monitoring program, i.e. locations, frequency of monitoring and
incubation conditions (e.g. time, temperature(s) and aerobic and or anaerobic), appropriate risk assessments
should be conducted based on detailed knowledge of the process inputs, the facility, equipment, specific
processes, operations involved and knowledge of the typical microbial flora found, consideration of other
aspects such as air visualization studies should also be included.
• These risk assessments should be re-evaluated at defined intervals in order to confirm the effectiveness of
the site’s environmental monitoring program, and they should be considered in the overall context of the
trend analysis and the contamination control strategy for the site.
• Routine monitoring for clean rooms, clean air devices and personnel should be performed “in operation”
throughout all critical stages, including equipment set up.
• The locations, frequency, volume and duration of monitoring should be determined based on the risk
assessment and the results obtained during the qualification.

Sterile products

Audit of Sterile products
• Inspect the component preparation area.
 Ensure that sterilization equipment (autoclave, dry heat oven, sterilizing tunnel) has been validated and is
properly maintained.
 Ensure that equipment used to wash/rinse containers and closures has been properly validated and
maintained.
 Ensure the required water quality is used for washing/rinsing
 Ensure that there are approved procedures for departmental processes, operation of/and maintenance of
equipment. Verify that operating procedures reflect those used during validation.
 Observe personnel to determine if they are appropriately gowned.
 Ensure that there is a documented training program in place for operators in this area.

• Inspect the microbiology laboratory.
 Review sterility testing program, performance and test results.
 Review all investigations for completeness and lot disposition decisions.
 Determine if there are any trends regarding false positive test results and the root cause.
• Review the Media Fill Procedure.
 Ensure there is a defined, approved program.
 Ensure that the media fill program is compliant with the applicable regulations and site Policy/Guideline
requirements.
 Ensure that all operators have participated in a media fill within the year.
 Ensure that media fills are performed for every aseptic filling line for every shift semi-annually.

 Verify the number of units filled during a media fill and assure that the media fill is representative of the
filling process. (For example: size and duration of fill; line speed; incubation (14 days and adequate
temperature to detect organisms and examination of each filled unit)
 Ensure that all staff that might be involved in the aseptic filling process participates in the media fill.
 Review media fill performance documentation and all associated deviation reports.
 Ensure that the number of units filled during the media fill trial is equivalent to the number of units placed
on incubation. Ensure that any variances in number are documented.

• Review the Environmental Monitoring Program.
 Ensure that there is a defined, approved program.
 Review training records for staff performing program sampling and testing.
 Ensure that the program is compliant with all worldwide regulatory and site policy/guideline requirements.
 Ensure that there are established alert and action limits that are appropriate.
 Review test results and associated investigations.
 Ensure that the program requires review of test results prior to release of product batches.
 Ensure that data is tracked for trends and reviewed by QC unit on a regular basis.

Audit for sterile product
 Premises:
• Design & layout of facilities
• Plant safety & security
• Sanitation
 Personnel:
• Hygiene
• Staff qualification
• Staff training
 Validation:
• Validation of new master formula
• Validation of equipment and instrument
 Documentation:
• Labels
• Process document
• SOP’s

Packaging
• Packaging is the act of enclosing or protecting the product using a container to aid its distribution,
identification, storage, promotion, and usage.
• In simple terms, packaging refers to designing and developing the wrapping material or container around a
product that helps to
• Identify and differentiate the product in the market,
• Transport and distribute the product,
• Store the product,
• Promote the product,
• Use the product properly.

Packaging
 Importance Of Packaging
• Often considered as an essential marketing subset, packaging forms the core distribution, storage, and sales
tool that can be a part of the product itself or an external container made of varied materials.
• Packaging is an essential element both for the seller and the customer. While the seller use it as a tool to
distribute, store, and promote; the customer uses it as an important identification and usage tool.
 Types of packaging
• Primary
• Secondary
• Tertiary

Packaging
 Functions Of Packaging
• Packaging plays a crucial role from the time a product is developed to the time a product is fully consumed.
These functions of packaging include:
• Contains the product: Most products need to be contained either during transportation, storage, or
consumption. Packaging makes sure the product is contained as and when required.
• Protects the product: Packaging protects the product and its quality, features, utility, etc. from being
damaged or contaminated during transportation, storage, and consumption.
• Aids product handling and usage: Proper packaging aids product handling and makes it easy to transport,
ship, and even use the product.
• Differentiates the product and makes it stand out: Packaging makes it easier for the customer to identify
and differentiate it from other products. Moreover, attractive packages have a property to stand out and
attract customers towards it.
• Forms a part of product marketing strategy: An attractive and/or informative package makes the product
stand out and have a promotional appeal. Packaging also acts as the final touchpoint that helps in product
promotion and sale.
• Provides customer convenience: Packaging is also a convenience tool that makes it convenient for the
customer to carry, transport, and use the product.
• Acts as a communication medium: Packaging along with labelling helps communicate the brand
identity, brand message, and product and company information to the customer.

Audit of Packaging
• Need A Packaging Audit?
• Every year is a new chance to re-evaluate your business, your goals, and most importantly your costs. What
better way to achieve your goals, than an annual packaging audit? The benefits of this service are huge, and
it’s something you can’t overlook.
• First of all, what actually is an annual packaging audit? A packaging audit is a program designed to identify
and analyze the products, packaging, and supply chain produced. The objective of the audit is to detect
problem areas that are bringing about extra costs, and areas where you can increase efficiency and decrease
costs.
• Keep reading to learn about the benefits of this service.
• Benefits of Packaging Audits
• Focus on your core business
• Identify your strengths and weaknesses
• Learn about alternate solutions
• Increase sales with new innovations
• Find and cut hidden costs
• Increase sustainability

Audit of Packaging
 Line clearance
• Line clearance is an essential element in product mix up prevention and needs to focus on:
• Input materials on the line from the previous batch
• Samples and waste from the previous batch
• Documents on the line from the previous batch
• Verification that any electronic data is wiped from consoles etc.
• Clearance after maintenance activity or major interruptions as appropriate

Audit of Packaging
 Contamination control
• The facilities should be designed and laid out to appropriately reduce the risk of contamination from the
environment and permit effective cleaning.
• Personnel gowning and hygiene practices are part of contamination control efforts that may be applicable.
The supplier should define the appropriate environmental conditions for handling and storage of the
component(s) being manufactured.
• Guidance for minimum conditions can be found in PS 9000 Pharmaceutical Packaging Materials, as well as
programs such as ISO 9001:2000 and ISO 9004:2000 for pharmaceutical packaging materials.

Audit of Packaging
 Validation and Qualification Ensure the processes are adequately validated, qualified and/or demonstrated
according to the quality critical parameters of the component being manufactured. This may be
demonstrated in the form of capability studies.
 Sampling
• There should be an SOP that defines package component sampling.
• The components sampled should be representative of the batch and sampling should be conducted to
prevent contamination from the sampling method.
• Any packaging materials that meet appropriate written specifications should be formally approved and
released for use.
• Any components that fail to meet such specifications must be rejected to prevent distribution. Samples
taken away from the line should not be returned to the line.
• They should be reconciled and placed in dedicated containers for destruction.

Audit of Packaging
 Documentation
• The appropriate SOPs and batch records must be followed when documenting any information or data
associated with a component manufacture. Other pertinent types of documentation include: ·
• Records of how and who set up a particular machine

Audit of Packaging
 Key Parameters of a Packaging Component Audit Prior to the audit ·
• Develop an understanding of the vendor manufacturing process specific to company requirements ·
• Obtain a list of company components that are manufactured at the site.
• Review recent rejections, complaints and issues, of the receiving site(s) and the respective statuses. ·
Review any Quality Agreements and relevant registration requirements.
• Review compliance status of the site by checking for service history, recalls associated with the site, recent
regulatory inspections (if applicable) and outcomes.
• Review previous audit reports and actions
 During the audit
• Perform a walk through of the manufacturing area.
• Ensure the production areas are clean and tidy.
• Ensure the fabric is in good condition and appropriate design for control of the process.

Questions
 Note on Auditing of packaging material ?
 Process of auditing of sterile product?
 Note on auditing of packaging material vendor ?
 Auditing of capsule manufacturing area ?

References

Auditing of capsule, sterile production and packaging

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