Excellent Quality Assurance FINAL En

Dr. M. Pfeiffer, A_Quality Operations 1Istanbul, June 2004

An excellent Quality Assurance System is (the) key (to passing inspections…)

““Getting prepared for FDA or PIC Getting prepared for FDA or PIC inspections”inspections”

APV/IKEV Seminar on Good Manufacturing Practice: Compliance and Inspection, Istanbul,

June 10/11, 2004


Table of contents:

• Development of “quality” in the 20th century• ISO or GMP ?• Quality control and quality assurance versus quality

operations (= the “American approach”)

• Legal considerations (in Europe [qualified person], and in the U.S.)


“The magic triangle” in production processes

costs

quality

time

“Quality”, “time” and “costs” should be regarded as equal parameters in production.Keep in mind: “Quality improvement leads to cost reduction!”


Quality costs versus quality standards

costs

quality standard

cost of

preventing failurecost of

repairing failureintegratedtotal (sum)


The “iceberg theory”*

recalls

rejects

complaints

batch incidents

quality incidents

*David Sullivan: Maintenance of a Quality AssuranceSystem

number

of

events


Understanding “quality” in the 20th

century* (1/2)

≈1990≈1970≈1950≈19301910

Overall quality

concepts

Personnel oriented quality

challenge(s)

Quality assurance system(s)

Quality control

based on statistics

Quality control

QC QA QM TQM

*Qualitätsmanagement und Validierung, Editio Cantor Verlag


Understanding “quality” in the 20th

century* (2/2)

• QC: Quality control; separation of production and quality control (test of a single item)

• QA: Quality assurance; introduction of a statistical approach to quality control, a broader quality approach

• QM: Quality management; understanding quality as a general approach, with involvement of (nearly) all parts of a company

• TQM: Total quality management; broadest quality approach, integrates all parts of a company, including safety, environmental protection …

*Qualitätsmanagement und Validierung, Editio Cantor Verlag


EEC Directive 91/356/EEC

Commission Directive of 13 June 1991 lays down the principles and guidelines of good manufacturing practice for medicinal products for human use:Article 6, Quality ManagementThe manufacturer shall establish and implement an effective pharmaceutical quality assurance system, involving the active participation of the management and personnel of the different services involved.


Quality management system(s)

• EEC GMP Guide to Good Manufacturing Practice for Medicinal Products -> Chapter 1, Quality Management

• 18. Supplementary Guideline: Good Manufacturing Practice for Active Pharmaceutical Ingredients (API) (November 2000) -> Chapter 2, Quality Management

• FDA requirements for a quality management system• 21 CFR 210/211 (drugs) -> not mentioned


Which system: ISO or GMP* ?

1. You must have a system.2. The system must be GMP compliant (pharmaceuticals

!).• Use the tools and the methodology of ISO and TQM

to add to your GMP system in order to gain the utmost benefit !

3. A well designed and maintained QA system will allow you to relax … from time to time.

*FDA and GMP Compliance in Quality Assurance Units, 10-11.10.2000, Copenhagen/Denmark (D. Sullivan: “Maintenance of a Quality Assurance System”)


Degree of detail: GxP versus ISO*

degree ofdetail

low

high

specifity

GLP GCP

GMP

ISO

* source: www.gmp-navigator.com/daten/news/GMP_news_87.htm


ISO, GMP and TQM*

• ISO describes a system approach• but fails to set standards (ISO lets the organisation set

its own levels)• GMP has required national standards

• but lacks a system approach• TQM is a management approach

• to long term success centred on “quality” through customer satisfaction

• TQM is based on the participation of all members of an organisation in continually improving processes, products and services

* FDA and GMP Compliance in Quality Assurance Units, 10-11.10.2000, Copenhagen/Denmark (D. Sullivan: “Maintenance of a Quality Assurance System”)


Comparison: GMP and ISO*

product relatedsystem relatedmain emphasis

legally set standardsown standardsstandards

pharma specificall businessestype of business

detailedgeneraldegree of detail

health authorityneutral institutionsupervision

legally bindingvoluntarybinding nature

customer protectioncustomer satisfactionobjectives

GMPISO

*FDA and GMP Compliance in Quality Assurance Units, 10-11.10.2000, Copenhagen/Denmark (D. Sullivan: “Maintenance of a Quality Assurance System")


“Quality assurance” and “quality control” versus “quality operations”

Quality Control

Production

QualityAssurance

Quality Assurance

Quality Control

Production

QualityOperations


Involvement of Quality Operations in Production (1/2)

Head of Quality Operations Dept.

Quality ControlSupply Chain I

QA: QualifiedPerson Supply

Chain I

QA: QualifiedPerson Supply

Chain II

Quality ControlSupply Chain II

Head ofProduction

Supply Chain I Supply Chain II


Involvement of Quality Operations in Production (2/2)

QC QA Supply Chain

QualityOperations

Production


Legal Situation in the EEC (qualified person [QA])

• Key personnel according to the EEC Guide:• Head of production• Head of quality control• Qualified person (Annex 16 to the EU GMP Guide)

Chapter 2, EEC GMP Guide


Annex 16 EEC GMP Guide: QP

• Each batch of a finished product must be certified by a QP within the European Community (EC)/European Economic Area (EEA) before being released for sale or supply in the EC/EEA or for export.

• The relevant legislative requirements are contained in Article 22 of the Council Directive 75/319/EEC or in Article 30 of the Council Directive 81/851/EEC.

• Annex 16 of the EEC GMP Guide must be converted into national law.


Qualified person: Requirements

• The QP is the responsible person for batch release• Minimum requirements for a QP (Directive

83/2001/EEC, Article 49):• Academic degree (in pharmacy, medicine, chemistry

or biology)• Knowledge in certain subject areas• 2 years’ working experience

• in the manufacture of pharmaceuticals or• quality control


Batch release by the QP

• Before a batch is released by the QP, the QP must ensure that the following criteria are fulfilled:• the batch has been produced according to the

relevant registration• production has followed GMP requirements,• all manufacture and testing procedures are validated.• all necessary controls have been implemented,• full documentation is available,• all necessary audits have been performed,• and other quality relevant factors have been

considered.


FDA requirements (21 CFR 210/211 [1/2])

• 21 CFR 210: cGMP for manufacturing practice, processing, packaging, or holding of drugs (General)

• 21 CFR 211: cGMP for finished pharmaceuticals• § 211.22 There shall be a quality control unit that

shall have the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labelling, and drug products, and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated. The quality control unit shall be responsible for approving or rejecting drug products manufactured, processed, packed, or held under contract by another company.


FDA requirements (21 CFR 210/211 [2/2])

• §211.165 For each batch of drug product, there shall be appropriate laboratory determination of satisfactory conformance to final specification for the drug product … prior to release …

• §211.192 All drug product production and control records, including those for packaging and labelling, shall be reviewed and approved by the quality control unit …

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