Quality Assurance techniques

1. Presented by- Mr. Krushnakant Kisan Wable
Guided by- Mrs. Sonali Mahaparale

2. Emergent Trends in QA of drugs
 The quality assurance environment is a changing dramatically and forcing pharmaceutical companies to face new challenges.
Therefore some new recommendation are provided, that would allow pharmaceutical company to adhere good quality
assurance practice.
 ICH Q10 demonstrates industries and regulatory authorities support of an effect quality and systems, the idea of continuous
improvement of pharmaceutical life cycle management globally gaining importance
key recommendation-
 Adjust the corporate wide QA oganisation
 Develop and install business process.
 Design and implement QA related IT system.
 Communication with the management.
To adhere these recommendation QA unit at corporate level have to play leading role.

3. Key tasks for company QA unit-
There are four important task that CQA should implement-
Develop strategy, policy and standards.
 Design quality system, IT system.
 Audit and/or Monitor implementation progress.
 Report performance level.
Effective communication platform are crucial-
 The role of CQA manager is develop strategy for basic quality and compliance standard and monitor there implementation.
 Successful implementation is only achieved when all QA employee fully understand and identify with the quality strategy.
Supervision of quality is not good enough-
 Most of the survey confirmed that there company needed to place a greater attention on improving managerial supervision and quality
monitoring.(Latest regulation set out in ICH Q10 and Q8 supervision)
 Audits are most effective tool for monitoring and tracking quality and performance within manufacturing facility
 Risk based auditing technique are judged as a must for the efficient use of resources in future.

4. Validation variation –
 Many GMP audits conducted by FDA have discover that the original validation have never been updated.
 Product validation mainly based on annual product review.
 Product quality design go beyond annual product review and product quality review, they follow continuous
improvement and integrated quality risk management.
 All companies should employ stricter and more intense use of tool for preventive risk management.
 Quality control and validation strategy that is must be according to ICH standard.
Product and supply chain integrity-
 Product integrity is key element in supply chain protection.
 The main tool used by pharmaceutical company to protect product integrity include overt and covert physical
security embedded into labels, barcodes and tamperproof packaging.
 In future track and trace technology showing increasing importance.
Managing suppliers and third parties-
 The sourcing of pharmaceutical material represent one major quality risk that currently not fully addressed only
minority of corporations surveyed have been fully implemented quality control process for all third party source
product.
 Sourced material strictly required quality control are APIs, followed by intermediates and excipients.

5. HAZARD ANALYSIS AND CRITICAL CONTROL
POINT (HACCP) SYSTEM
Introduction-
 The HACCP system, which is science based and systematic, identifies specific hazards and measures for their
control to ensure the safety of food.
 HACCP is a tool to assess hazards and establish control systems that focus on prevention rather than relying
mainly on end-product testing.
 Any HACCP system is capable of accommodating change, such as advances in equipment design, processing
procedures or technological developments.
 HACCP can be applied throughout the food chain from primary production to final consumption and its
implementation should be guided by scientific evidence of risks to human health. As well as enhancing food
safety, implementation of HACCP can provide other significant benefits.
 In addition, the application of HACCP systems can aid inspection by regulatory authorities and promote
international trade by increasing confidence in food safety.

6. Seven principles of the HACCP system :

7. GUIDELINES FOR THE APPLICATION OF THE HACCP SYSTEM
The application of HACCP principles consists of the following tasks as identified in the Logic Sequence for Application of
HACCP
1. Assemble HACCP team-
 The person involved in food operation should have appropriate product specific knowledge and expertise is available for
the development of an effective HACCP plan. Optimally, this may be accomplished by assembling a multidisciplinary
team. Where such expertise is not available on site, expert advice should be obtained from other sources, such as, trade
and industry associations, independent experts, regulatory authorities, HACCP literature and HACCP guidance.
2. Describe product-
 A full description of the product should be drawn up, including relevant safety information such as: composition,
physical/chemical structure (including Aw, pH, etc.), microcidal /static treatments (heat treatment, freezing, brining,
smoking, etc.), packaging, durability and storage conditions and method of distribution.
3. Identify intended use-
 The intended use should be based on the expected uses of the product by the end user or consumer.

8. 4. Construct flow diagram
 The flow diagram should be constructed by the HACCP team.The flow diagram should cover all steps in the
operation for a specific product. The same flow diagram may be used for a number of products that are
manufactured using similar processing steps.
5. On-site confirmation of flow diagram
 The confirmation of the flow diagram should be performed by a person or persons with sufficient knowledge of
the processing operation.
6. List all potential hazards associated with each step, conduct a hazard analysis, and consider any measures to
control identified hazards-(principle 1)
 The HACCP team should list all of the hazards that may be reasonably expected to occur at each step according to
the scope from primary production, processing, manufacture, and distribution until the point of consumption.
 The HACCP team should next conduct a hazard analysis to identify for the HACCP plan, which hazards are of
such a nature that their elimination or reduction to acceptable levels is essential to the production of a safe food.
 Consideration should be given to what control measures, if any exist, can be applied to each hazard. More than
one control measure may be required to control a specific hazard(s) and more than one hazard may be controlled
by a specified control measure.

9. 7. Determine Critical Control Points (PRINCIPLE 2)
 There may be more than one CCP at which control is applied to address the same hazard.
 The determination of a CCP in the HACCP system can be facilitated by the application of a decision tree which
indicates a logic reasoning approach.
8. Establish critical limits for each CCP (PRINCIPLE 3)
 Critical limits must be specified and validated for each Critical Control Point.
 In some cases more than one critical limit will be elaborated at a particular step. Criteria often used include
measurements of temperature, time, moisture level, pH etc.
9. Establish a monitoring system for each CCP (PRINCIPLE 4)
 The monitoring procedures must be able to detect loss of control at the CCP. Further, monitoring should ideally
provide this information in time to make adjustments to ensure control of the process to prevent violating the critical
limits.
 Where possible, process adjustments should be made when monitoring results indicate a trend towards loss of
control at a CCP.

10. 10. Establish corrective actions (PRINCIPLE 5)
 Specific corrective actions must be developed for each CCP in the HACCP system. The actions must ensure that the
CCP has been brought under control. Actions taken must also include proper disposition of the affected product.
Deviation and product disposition procedures must be documented in the HACCP record keeping.
11. Establish verification procedures (PRINCIPLE 6)
 Establish procedures for verification. Verification and auditing methods, procedures and tests, including random
sampling and analysis, can be used to determine if the HACCP system is working correctly.
 Verification should be carried out by someone other than the person who is responsible for performing the monitoring
and corrective actions.
12. Establish Documentation and Record Keeping (PRINCIPLE 7)
 Efficient and accurate record keeping is essential to the application of a HACCP system.
 HACCP procedures should be documented.

11. GOOD AUTOMATED MANUFACTURING PRACTICE (GAMP)
 GAMP is a technical sub-committee of International Society For Pharmaceutical Engineering (ISPE), a set of
guideline for manufacturer and user of automated system in pharmaceutical industry.
 ISPE guide GAMP for validation of automated system.
 One of the prime principle of GAMP is quality can not be tested in to batch of product but must built in each stage
of manufacturing process, so GAMP covers all aspect of production, facility and equipment to training and hygiene
of staff.
 ISPE publish series of good practice guide for industry in several topics involved in drug manufacturing.
Purpose of GAMP-
 To help users understand the requirement for prospective validation of automated system.
 To help supplier to ensure that systems are developed according to good practice and to provide document
evidence that meet agreed specifications.

12. GAMP 5
 The New good automated manufacturing practice 5 guidelines were released in feb. 2008 at ISPE.
 This guidelines are latest, up-to-date thinking in the approach of validation of G×P computerize system.
 Purpose of guideline is that “provide cost effective framework of good practice to ensure that computerized system are fit
for use and compliance with regulation.”
Key concept of GAMP 5-
1. Product and process understanding.
2. Lifecycle approach within QMS .
3. Scalable lifecycle activity
4. Science based quality risk management.
5. Maximum supplier involvement.

13. Steps involved in GAMP 5
Perform initial risk assessment and determine system impact
Identify functions with impact on patient safety, product quality and data integrity
Perform risk assessment and identify control
Implement and verify appropriate control
Review risk and monitor control
Five stem process for risk management based on ICH guideline

14. Application Of GAMP 5 In Pharmaceutical Industry
 Monitoring manufacturing, production and storage environment in
pharmaceutical industry
 Freeze drying in pharmaceutical industry
 Monitoring autoclaving process in pharmaceutical industry
 Water purification in pharmaceutical industry.

15. REFERENCES
1. ICH Harmonized Tripartite guideline: pharmaceutical quality system Q10 ; june 2008. http://www.ich.org/
2. FDA http://www.fda.gov/
3. P. Lalasa and Vishal Gupta et. Al., review on application of GAMP 5 in pharmaceutical industry, JSS university, july-
sept 2013, volume-5, issue-3, ISSN 0975-9344
4. Hazard Analysis and Critical Control Point Principles and Application Guidelines, The National Advisory Committee
on Microbiological Criteria for Food (NACMCF), Journal of Food Protection, Vol. 61, No 9, 1998.
5. Federal Register, Vol. 61, No. 144, July 25, 1996, Final Rule, Pathogen Reduction; Hazard Analysis and Critical
Control Point (HACCP) Systems. 9 CFR Parts 304, 308, 310, 320, 327, 381, 416, and 417 [Docket No. 93–016F]