Regulatory Issues US and Abroad BIT 230 Chapters 9-11 Huxsoll
Dec 22, 2015
Regulatory IssuesUS and Abroad
BIT 230
Chapters 9-11 Huxsoll
Regulatory Affairs
Separate discipline that is part of product development team
Know laws enforced by FDACertain area of FDA presides over your
productLiaison between company and
government - CSO (Consumer Safety Officer)- point person from FDA
FDA
Review - law enforcement agency charged with the health and safety of food, drugs, cosmetics, medical devices
Division CDER - drugs CBER - biologics CDRH - devices/radiologic health CVM - veterinary medicine CFSAN - food safety and applied nutrition
FDA
SAFETY and
efficacy
FDA
Burden of proof for safety and efficacy evidence from product sponsor
FDA decides if there is enough evidence to approve product
needs ‘substantial evidence” (between preponderance of evidence and beyond a reasonable doubt)
rules often reactive to a crisis
FDA activities
Rulemaking - formulating, amending or repealing a rule disseminating info. To public
Adjudication - agency process for the formulation of an order (telling someone what to do responds to sponsor’s application for approval
to the FDA
Guidelines & Points to Consider
Guidelines - procedures and standards acceptable to the FDA communicate info that FDA has vast experience
Points to Consider - areas where FDA has little experience
Guidelines and PtC not enforceable requirements (like other aspects of FDA)
Product Characterization
See pages 142-143 -product definitionsDrug
cure, diagnose, treat prevent
Device instrument, apparatus, machine, implant,
reagent
Biological product virus, serum, toxin, vaccine, blood product
Regulatory functions
SubmissionsComplianceEnforcementMiscellaneous
Submission
File application with the FDANDA - new drug application - product not
yet recognized as safe and effectiveDevices - Class O, II, III; I and II need a
Premarket Notification- 90 day notice before goes into market; Class III needs FDA approval before commercial marketing begins
Submission cont’d
Biological products - requirements specialPLA - product license application, to
describe the productELA - establishment license application -to
describe the facilities used to manufacture the product
Submission cont’d
Remember three areas:
premarketing (IND)marketing (NDA)postmarketing (after on the market)
Compliance
GLP nonclinical laboratory studies
GMP set of rules for drugs, medical devices and
biologics
GCP inform subjects of test product in clinical trials
Other compliance areas
Study/data audits review raw data in reports
corporate policies and procedures self-imposed procedures for compliance
submissions commitments especially to coordinate manufacturing facilities
in different countries
Compliance
3 key points:
documentationdocumentationdocumentation
Enforcement
Civil or criminal penaltiesProduct liability suitsFrom Huxsoll page 147:
“ Enforcement is the end result of a lack of integration. It implies a failure in the systems designated to prevent mistakes and inadvertent or untested changes.”
Miscellaneous
State requirements for compliance (in addition to federal)
e.g in book- California State Board of Pharmacy says pharmacist responsible for manufacturing
State and federal laws for controlled substances
Incentives for orphan products
European Regulatory Issues
Chapter 10
One Europe
1995 “mutual regulation” for drug regulation by EU members
European Medicines Evaluation Agency (EMEA) - administering centralized procedure
Submit to agency and can get simultaneous approval in many European countries (for highly innovative products)
Other Products
Conventional products - submit filing to country of choice
Once approved there, other members of the EU will recognize the drug’s registration
Send to central agency only if concerns about original registration in Europe
European Drug Market
Small continent in comparison to some others, but one of largest drug markets outside the US (total population of Europe estimated at 400 million, down from # in textbook of close to 700 million)
Uses many medicinesApproval may be faster in EuropeRU 486 example
EC
1957 European Economic Community
France, Germany, Belgium, Italy, Luxembourg and Netherlands
Formed to achieve harmonization of laws and regulations for bringing drugs to market
Special organizations
Concertation procedure, for marketing products Recombinant DNA products transformed lines hybridoma and monoclonal antibody
procedures Referred to the CPMP (Committee for
Proprietary Medicinal Products)
Approval
Europe faster approval time lines than US (although not much; 417 vs. 452 days for US
For recombinant products, 411 in Europe vs. 548 days for approval in US’
FDA faster than EMEA on monoclonal antibody approval
Approvals cont’d
EMEA doesn’t have priority review like FDA does; may try and implement such a review
See and review handout from Tufts about EU/EMEA summary
Regulatory Issues in Japan
Chapter 11
The Ministry of Health & WelfareOversees social welfare, social security
and public health in JapanMade up of several bureaus, local
branches and affiliationsPAB(Pharmaceutical Affairs Bureau) one
of bureau for drugsPage 174 - chart (DO NOT need to know!)
PAB
Supervises domestic & foreign drug-related products
Director General of the PAB similar to head of FDA
8 divisions within PAB to deal with various aspects (biologics & antibiotics, safety, etc.)
Many functions similar to US (fee page 175)
CPAC
Central Pharmaceutical Affairs CouncilPowerful agency within ministryGovernment advisory committeeMakes recommendation for final approval
for drug manufacturing and importation of foreign drugs
Standards for Production
Japan has GLP, GMP and GCP regulations
for GCP, has guidelines for 14 therapeutic areas (page 177- DO NOT need to know)
Some bilateral agreements with countries to ensure quality
Several agencies within Japan work together develop guidelines
Drug Registration
Before 1983, formal partnership was needed with a Japanese country
1983 amendment, foreign drug producers can apply directly to import and sell drugs in Japan
Japan (along with Europe) prescribe our drugs
Terms
See page 181Cell culture, Seed cell lines, MCB and Cell
banks - similar definitions to the US terminology
CPAC says biologics should be considered entirely new drugs - must undergo complete preclinical and clinical testing again.
Manufacturing Criteria
Define origin and characteristics of seed cell line
Define method of prep, storage and maintenance of MCB
QA issuesStability of cells being used
Clinical Studies
Japan uses Phase I, II, and III testingSame as ours:
Phase 1: pharmacokinetics in healthy patients Phase II: small group with disease to look at
efficacy and continue looking at safety Phase III: larger group of patients with disease
to look at efficacy
Canada
Parallels drug approval process of FDA in US
Canadian drug approval
Why are drugs cheaper in Canada?
Canadian drug costs