An excellent Quality Assurance System is (the) key (to - °KEV
Transcript of An excellent Quality Assurance System is (the) key (to - °KEV
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
Dr. M. Pfeiffer, A_Quality Operations 2Istanbul, June 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.)
Dr. M. Pfeiffer, A_Quality Operations 3Istanbul, June 2004
“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!”
Dr. M. Pfeiffer, A_Quality Operations 4Istanbul, June 2004
Quality costs versus quality standards
costs
quality standard
cost of
preventing failurecost of
repairing failureintegratedtotal (sum)
Dr. M. Pfeiffer, A_Quality Operations 5Istanbul, June 2004
The “iceberg theory”*
recalls
rejects
complaints
batch incidents
quality incidents
*David Sullivan: Maintenance of a Quality AssuranceSystem
number
of
events
Dr. M. Pfeiffer, A_Quality Operations 6Istanbul, June 2004
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
Dr. M. Pfeiffer, A_Quality Operations 7Istanbul, June 2004
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
Dr. M. Pfeiffer, A_Quality Operations 8Istanbul, June 2004
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.
Dr. M. Pfeiffer, A_Quality Operations 9Istanbul, June 2004
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
Dr. M. Pfeiffer, A_Quality Operations 10Istanbul, June 2004
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”)
Dr. M. Pfeiffer, A_Quality Operations 11Istanbul, June 2004
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
Dr. M. Pfeiffer, A_Quality Operations 12Istanbul, June 2004
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”)
Dr. M. Pfeiffer, A_Quality Operations 13Istanbul, June 2004
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")
Dr. M. Pfeiffer, A_Quality Operations 14Istanbul, June 2004
“Quality assurance” and “quality control” versus “quality operations”
Quality Control
Production
QualityAssurance
Quality Assurance
Quality Control
Production
QualityOperations
Dr. M. Pfeiffer, A_Quality Operations 15Istanbul, June 2004
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
Dr. M. Pfeiffer, A_Quality Operations 16Istanbul, June 2004
Involvement of Quality Operations in Production (2/2)
QC QA Supply Chain
QualityOperations
Production
Dr. M. Pfeiffer, A_Quality Operations 17Istanbul, June 2004
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
Dr. M. Pfeiffer, A_Quality Operations 18Istanbul, June 2004
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.
Dr. M. Pfeiffer, A_Quality Operations 19Istanbul, June 2004
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
Dr. M. Pfeiffer, A_Quality Operations 20Istanbul, June 2004
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.
Dr. M. Pfeiffer, A_Quality Operations 21Istanbul, June 2004
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.
Dr. M. Pfeiffer, A_Quality Operations 22Istanbul, June 2004
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 …