Quality & compliance excellence in pharmaceuticals

1. Presented by,
Anvita Jadhav
M.Pharm (IP) Sem I

2. What is Quality
 It can be defined in different ways
 Conformance to specifications measures how well the product or
service meets the targets and tolerances determined by its designers.
 Fitness for use focuses on how well the product performs its
intended function or use.
 Value for price paid is a definition of quality that consumers often
use for product or service usefulness.
 Support services provided are often how the quality of a product or
service is judged.
 A psychological criterion is a subjective definition that focuses on the
judgmental evaluation of what constitutes product or service quality.

3. Dimensions of Quality
Performance
Features
Reliability
Conformance
Durability
Serviceability
Aesthetics
Perceived quality

4. Difference between Pharmaceutical Product &
Consumer Goods
Pharmaceutical Product Consumer Goods
Development
• 2 – 3 years
Payer
• Customer
Regulation
• Low level of regulation
Development
• 10 – 15 years
Payer
• Mostly patient
Regulation
• Highly regulated

5. Sterile Product
 These products are by design required to be
free from living micro organisms, pyrogens,
& unacceptable particulate matter.
 Therefore it has more regulations than non
sterile product
 In addition to non sterile product quality
guidelines there are other procedures such as
– Sterilization, Aseptic processing and also
Premises Regulations, Equipments etc.

6. Guidelines of the Pharmaceutical Quality
WHO Guidelines
FDA Guidelines
ICH Guidelines

7. Quality
System
Facilities &
Equipment
System
Laboratory
Control
System
Packaging
&
Labeling
System
Production
System
Material
System

8. Facilities & Equipment
 Equipment must be located, designed, constructed, adapted,
and maintained to suit the operations to be carried out.
 Guidelines given by
 WHO Volume 2: good manufacturing practices and inspection
(Quality Assurance of Pharmaceuticals), 13.1 to 13.13
 US FDA: 21 CFR Part 211.63, 211.105, 211. 68, 211.72,
211.182
 Schedule M: 11.1 – 11.5

9. Material
 The main objective of a pharmaceutical plant is to produce
finished products for patients use from a combination of
materials (starting and packaging).
 Guidelines given by
 WHO Volume 2: good manufacturing practices and
inspection (Quality Assurance of Pharmaceuticals) 14.1 to
14.46
 US FDA: 21 CFR Part 211
 Schedule M: 10.1 – 10.10, 13.1 -13.6,

10. Production
 Production operations must follow clearly defined
procedures in accordance with manufacturing and marketing
authorizations, with the objective of obtaining products of the
requisite quality.
 Guidelines given by
 WHO Volume 2: good manufacturing practices and
inspection (Quality Assurance of Pharmaceuticals) 16.1 to
16.35
 US FDA: 21 CFR Part 211
 Schedule M: 8.1, 8.2, 9.1 – 9.5, 10.2, 24.1 – 24.3

11. Packaging & labeling
 All operations, including filling and labeling, that
a bulk product has to undergo in order to become
a finished product.
 Labels applied to containers, equipment or
premises should be clear, unambiguous and in
the company’s agreed format.
 Guidelines given by
 WHO Volume 2: good manufacturing practices
and inspection (Quality Assurance of
Pharmaceuticals)
 US FDA: 21 CFR Part 211

12. Laboratory Controls
 It is concerned with the organizational process
and the conditions under which laboratory
studies are planned, performed, monitored,
recorded, and reported.
 Guidelines given by:
 FDA: 21 CFR 58
 WHO: handbook of GLP

13. Clinical Practices
 Various regulations are involved clinical trials involving
human subjects. Guidelines include protection of human
rights as a subject in clinical trial. It also provides assurance
of the safety and efficacy of the newly developed
compounds.
 Guidelines given by
 WHO: Handbook for Good clinical practice
 ICH guidelines
 Schedule Y

14. General Practices Recently Applied in the
Pharmaceutical Industry
Quality risk
management
Quality by design
Corrective action and
preventive actions
Total quality
management

15.  The basic meaning focuses on target
populations of regulation, the extent to
which they comply with regulation, and
why they do so.
Compliance
Fulfillment/
Conformity

16. Compliance encourages-
Ethical behavior
Fosters the right values
Instills a culture of integrity

17. Regulatory Compliance
 The regulatory authorities are empowered to
issue and enforce regulations for the
manufacture of pharmaceutical products .
 Individual pharmaceutical companies produce
a set of internal guidelines, rules, and policies
to implement the regulation imposed by the
regulatory authorities.
 Regulatory compliance applied to statements

18. Compliance Program
to review policies & procedures through
which industry complies with the various
regulations
program to prevent & detect violations of
the regulation.

19. Strategies to achieve
Compliance
1
• Creating an Environment that Supports Compliance
2
• Making Compliance Part of Everyone's Job.
3
• Empowering the Regulatory Affairs/Quality Assurance Function
4
• Employ the Appropriate Skills to Obtain Cooperation
5
• Educating Other Departments.
6
• Selling the Benefits of Quality and Compliance.
7
• Using Internal Audits Effectively.
8
• Reviewing and Reporting Quality and Compliance Data.
9
• Explaining the Consequences of Noncompliance.

20. Quality Policies
 The ISO 9000 requires quality policies to ensure
that executive management has established system
for quality.
 Quality policies define numerous systems as well
as executive management’s commitment to
quality.

21. Purpose & intent of quality
policies
 Quality policies help industries to improve their
internal compliance & total quality system.
 By instituting & adhering to quality policies,
management obtains employees commitment to quality
system.
 The formulation of individual quality policies should
include the involved groups, depending on the
placement of responsibilities within the individual
organization.

22. Format & content of individual quality policies
 Executive management will probably determine who writes & edits the
individual quality policies.
 Policies should contain minimal information on specific procedure &
detailed information about structure, responsibility, & review.
 Definitions within policies are important to ensure that all parties are
speaking the same language & are understanding.
 The policy should define the responsibilities of individual department
implementing the policy & should ensure that adequate resources &
structure exist for successful implementation.

23. Validation
 Pharmaceutical validation can be defined as a
documented program, which provides a high
degree of assurance that a specific process will
consistently produce, a product meeting its pre-
determined specifications & quality attributes

24. Advantages of validation
Reduction of quality costs
Process optimization
Assurance of quality
Safety

25. CAPA – Compliance Tool
 CAPA is corrective and preventive action
 Corrective action: Action to eliminate the cause of
a detected nonconformity or other undesirable
situation.
 Preventive action: Action to eliminate the cause of
a potential nonconformity or other undesirable
potential situation.

26. CAPA Process
 Identification
 Impact / Risk Assessment
 Immediate Action
 Root Cause Investigation
 Conclusion and Quality Decision
 Action Plan
 Implementation and Follow-up

27. Documentation
 Document is a piece of written, typed,
printed or electronic matter that provides
information or evidence.
 In each case, key sections of the documents
are examined for compliance.

28. Documentation is essential-
 To define the specifications/procedures for all materials and methods of
manufacture control.
 To ensure that all personnel concerned with manufacturing know what to
do and when to do it.
 To ensure that authorized persons have all the information necessary to
decide whether or not to release a batch of a drug for sale.
 To ensure the existence of documented evidence, traceability and to
provide records and an audit trail that will permit investigation.
 To ensure the availability of the data needed for validation, review and
statistical analysis.

29. Categories of documents
 Specification (e.g. raw material, packaging material,
intermediate, finished product)
 Procedures (e.g. SOPs, STPs, process packaging instruction)
 Records & Reports
 Master Documents (e.g. MPCR, calibration master plan, site
master file etc.)
 Lists (e.g. certified vendors, employees, equipment, process
rooms)

30. Cost of Quality Compliance
Cost of Quality Compliance
Quality control
costs
Prevention costs
Costs of preparing and
implementing a quality
plan.
Appraisal costs
Costs of testing, evaluating,
and inspecting quality
Quality failure costs
Internal failure costs
Costs of scrap, rework,
and material losses.
External failure costs
Costs of failure at customer site,
including returns, repairs, and
recalls.

31. Effects of non compliance
 Complaints & adverse effects: Complaints about product is
an indicator of the product quality, & also about the
expectation of the consumer from the product.
 Recall of the product: A distributed product can be called
back for various reasons. Manufacturer or FDA officials found
out that the product is substandard.

32. Case Study
 The U.S. Food and Drug Administration had notified
(on 23/1/2014) Ranbaxy Laboratories, Ltd., that it is
prohibited from manufacturing and distributing
active pharmaceutical ingredients (APIs) from its
facility in Toansa, India, for FDA-regulated drug
products.
 The FDA’s inspection on Jan. 11, 2014, identified
significant CGMP violations. These included Toansa
staff retesting raw materials, intermediate drug
products, and finished API after those items failed
analytical testing and specifications, in order to
produce acceptable findings, and subsequently not
reporting or investigating these failures.

33. Reasons for Non compliance
1. Lack of Regulatory Knowledge
 Requirements are too complex to know and
understand.
 People cannot comply with regulations if
they do not understand what is required.

34. 2 Lack of willingness towards compliance
 Compliance is too costly
 Overly legalistic regulation
 Failure to monitor
 Deterrence failure.

35. 3. Lack of ability to achieve compliance
 Failures of administrative capacity
 Desired outcomes cannot be achieved

36. Quality Audit
 Auditors are typical part of regulatory
compliance for examine the data trail to
determine whether company policies and
procedures are followed.
 It has different categories –
1) Internal audits
2) External audits
3) Regulatory audits

37. Percentage of compliance:
 100% compliance: When the auditor is fully satisfied with
the compliance by the auditee by conforming that the auditee
meets all the requirements specified in the specific clause
 100% non compliance: When the auditor finds the
requirements of the specific clause in not all complied with by
the auditee.
 Partial compliance: When the auditor finds that the auditee
has not fully compiled but only part compliance is observed.

38. Compliance classifications (according to
US FDA)
 NAI – (No Action Indication)
No objectionable conditions or practices were found
during the inspection
 VAI – (Voluntary Actions Indicated)
Objectionable conditions were found and documented
but objectionable conditions do not meet the threshold
for regulatory action
 OAI – (Official FDA Action Indicated)
Regulatory violence is observed

39. Conclusion
Quality & safety should be priority of any
pharmaceutical industry.
Quality can be achieved by the compliance
excellence with the regulations.
Compliance program should be there to study
regulation & to implement them in best manner.
It is the responsibility of everyone.

40. Reference:
 Bhaskar Mazumder, Sanjib Bhattacharya and Abhishek Yadav, Total Quality
Management in Pharmaceuticals: A Review, International Journal of PharmTech
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Pharmaceutical Companies, International Journal of Research and Development in
Pharmacy and Life Sciences, Vol. 2, No.4, Pg. No. 493-498, June - July, 2013.
 Reham M. Haleem, Maissa Y. Salem, Faten A. Fatahallah, Laila E. Abdelfattah, Quality in
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 Achieving Quality and Compliance Excellence in Pharmaceuticals, Editor Madhu Raju
Saghee, Business Horizons, 2012.
 U.S. Pharmaceuticals, Compliance and Ethics Code of Conduct, Bristol-Myers Squibb
Company, January 1, 2009.

41.  Nancy Singer and Richard DeRisio, Optimizing Regulatory Compliance: Nine Strategies for
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Industry, 2005.
 Chapter 2 Compliance Failures, Reducing the Risk of Policy Failure: Challenges for Regulatory
Compliance, Organization for Economic Co-operation and Development, 2000.
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2012.
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