Upload
others
View
3
Download
1
Embed Size (px)
Citation preview
3/5/09
1
GLP, quality assurance and some international guidelines
2
Introducing international guidelines – OECD, FDA,
More details about GLP
If you want to review a set of SOPs, look up our SOPs at
http://labanimals.no/ADFDsop/index.html
3
Describe what you do, and how you do it Then you should do what you have described
– Must be documented Minimum standards are introduced when
possible – Instruments – Animals – Environment
4
Better quality to increase competitiveness Avoid competition bias Safer products
Note: Animal welfare is not a main motivation, but has become more important
5
Laws - general and are enforced by legal system
Regulations, provisions
Recommendations Guidelines
ALL documents can be used in legal action – National authorities – WTO
6
Animal welfare act, Forskrift om forsøk med dyr
Occupational health regulations – Internkontrollforskriften, Arbeidsmiljølovcn
Rules of competition – OECD – CFR USA – …and similar in all countries
If OECD has guidelines, then these are de-facto standards
3/5/09
2
7
Arbeidsmiljøloven – Forskrift om internkontroll – Forskrift om kreftfremkallende stoffer – Forskrift om arbeid med biologiske faktorer
detaljer om arbeid med mikroorganismer Etc.
Occopational health and safety
8
international standardization is closely related to: – ISO 9001
Part of a family of quality systems: – Good manufacturing practise – Good clinical practice – Good documentation practise
9
“GLP” - an international standard – better science through standardization – standardization -> reproducibility – standardization - > avoid competitive edges
internationally, and product control – Scientific gains are obvious
GLP is about PRE-CLINICAL STUDIES – But could (should?) be implemented for all
activity in the animal unit
OECDs GLP guidelines 1
• Organization and personnel – Responsivbillities: Director, principal
investigator, all involved persons • Facilities
– buildings, • 4. Instruments, Materials,
Reagents
OECDs GLP 2
• 5 og 6 Test Systems, test objects – animals and animal products, other
organisms
• 7. Standard Operating Procedures = SOP – SOP, manuals, control, calibration – Forms to fill in to document the process
12
GLP: Work flow that must be documented: Ordering of animals, bedding, feed Reception of animals Acclimatization - quarantine & release from it Start of experiment Observations: Weight, inspection, clinical symptoms,
environmental parameters End of study - autopsy, histology Reporting Archives Inspections - internal & external
3/5/09
3
13
GLP differs from… AAALAC accreditation, that is primary concerned
about animal welfare (in a wide perspective) And has more specific demands
ISO 9001, that is a documenting system Very comprehensive system
----------------------------------------------------------- GLP includes internal Quality Assessment
You must have a QA unit with a master schedule for three kinds of inspections
GLP is compulsory for a test site (def)
• US standards • More details than OECD
– Code of Federal Regulations – Guidelines for industry
• detaljer -
• US Food and Drug Administration will check if you follow the CFRs
[Code of Federal Regulations] [Title 21, Volume 7] [Revised as of April 1, 2001]
From the U.S. Government Printing Office via GPO Access [CITE: 21CFR601.41]
[Page 38]
TITLE 21--FOOD AND DRUGS
DEPARTMENT OF HEALTH AND HUMAN SERVICES--(Continued)
PART 601--LICENSING--Table of Contents
Subpart E--Accelerated Approval of Biological Products for Serious or Life-Threatening Illnesses
Sec. 601.41 Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible morbidity.
FDA may grant marketing approval for a biological product on the basis of adequate and well-controlled clinical trials establishing that the biological product has an effect on a surrogate endpoint that is reasonably likely, based on epidemiologic, therapeutic, pathophysiologic, or other evidence, to predict clinical benefit or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity. Approval under this section will be subject to the requirement that the applicant study the biological product further, to verify and describe its clinical benefit, where there is uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical benefit to ultimate outcome. Postmarketing studies would usually be studies already underway. When required to be conducted, such studies must also be adequate and well-controlled. The applicant shall carry out any such studies with due diligence.
3/5/09
4
Application Avvik - when things go wrong
Inspections OECD
guidelines & development
• LD50 • Humane end points
– NB: Very similar to FELASA recommendations (www.lal.org.uk)
OECD and LD50
• Controversy over the procedure for 20 years (or more)
• LD50 = the dose that kills 50% of the animals in a toxicity test – Death = end point – Nominal variable = statistical problem
• PROBIT model
• GHS stepwise procedure
Classical LD50 (and still required by
some)
Dose # anim #dead
50 7 0 100 7 0 500 7 0 1000 7 3
2000 7 7
3/5/09
5
GHS stepwise procedure
26
Bottom line: The importance of training
• from – researchers and lawmakers
• FELASA guidelines
• to – Caretakers