Presented by, Anvita Jadhav

M.Pharm (IP) Sem I

What is Quality

It can be defined in different ways

Conformance to specifications measures how well the product orservice meets the targets and tolerances determined by its designers.

Fitness for use focuses on how well the product performs itsintended function or use.

Value for price paid is a definition of quality that consumers oftenuse for product or service usefulness.

Support services provided are often how the quality of a product orservice is judged.

A psychological criterion is a subjective definition that focuses on thejudgmental evaluation of what constitutes product or service quality.

Dimensions of Quality

Performance

Features

Reliability

Conformance

Durability

Serviceability

Aesthetics

Perceived quality

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

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.

Guidelines of the Pharmaceutical Quality

WHO Guidelines

FDA Guidelines

ICH Guidelines

Quality

System

Facilities &

Equipment

System

Laboratory

Control

System

Packaging

&

Labeling

System

Production

System

Material

System

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

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,

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

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

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

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

General Practices Recently Applied in the

Pharmaceutical Industry

Quality risk management

Quality by design

Corrective action and preventive actions

Total quality management

The basic meaning focuses on target

populations of regulation, the extent to

which they comply with regulation, and

why they do so.

ComplianceFulfillment/

Conformity

Compliance encourages-

Ethical behavior

Fosters the right values

Instills a culture of integrity

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

made in the organizations own documents

Compliance Program

to review policies & procedures through

which industry complies with the various

regulations

program to prevent & detect violations of

the regulation.

Strategies to achieve

Compliance1 • 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.

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.

Purpose & intent of quality

policies

Quality policies help industries to improve theirinternal compliance & total quality system.

By instituting & adhering to quality policies,management obtains employees commitment to qualitysystem.

The formulation of individual quality policies shouldinclude the involved groups, depending on theplacement of responsibilities within the individualorganization.

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.

Validation

Pharmaceutical validation can be defined as adocumented program, which provides a highdegree of assurance that a specific process willconsistently produce, a product meeting its pre-determined specifications & quality attributes

Advantages of validationReduction of quality costs

Process optimization

Assurance of quality

Safety

CAPA – Compliance Tool

CAPA is corrective and preventive action

Corrective action: Action to eliminate the cause ofa detected nonconformity or other undesirablesituation.

Preventive action: Action to eliminate the cause ofa potential nonconformity or other undesirablepotential situation.

CAPA Process

Identification

Impact / Risk Assessment

Immediate Action

Root Cause Investigation

Conclusion and Quality Decision

Action Plan

Implementation and Follow-up

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.

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.

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)

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.

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.

Case Study

The U.S. Food and Drug Administration had notified(on 23/1/2014) Ranbaxy Laboratories, Ltd., that it isprohibited from manufacturing and distributingactive pharmaceutical ingredients (APIs) from itsfacility in Toansa, India, for FDA-regulated drugproducts.

The FDA’s inspection on Jan. 11, 2014, identifiedsignificant CGMP violations. These included Toansastaff retesting raw materials, intermediate drugproducts, and finished API after those items failedanalytical testing and specifications, in order toproduce acceptable findings, and subsequently notreporting or investigating these failures.

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.

2 Lack of willingness towards compliance

Compliance is too costly

Overly legalistic regulation

Failure to monitor

Deterrence failure.

3. Lack of ability to achieve compliance

Failures of administrative capacity

Desired outcomes cannot be achieved

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

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.

Compliance classifications (according to US FDA) NAI – (No Action Indication)

No objectionable conditions or practices were foundduring the inspection

VAI – (Voluntary Actions Indicated)Objectionable conditions were found and documentedbut objectionable conditions do not meet the thresholdfor regulatory action

OAI – (Official FDA Action Indicated)Regulatory violence is observed

Conclusion

Quality & safety should be priority of anypharmaceutical industry.

Quality can be achieved by the complianceexcellence with the regulations.

Compliance program should be there to studyregulation & to implement them in best manner.

It is the responsibility of everyone.

Reference:

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Industry, 2005.

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2012.

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http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm382736.htm

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